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Park Y, Hwang WM. Management of Elderly Patients with Chronic Kidney Disease. Yonsei Med J 2025; 66:63-74. [PMID: 39894039 PMCID: PMC11790406 DOI: 10.3349/ymj.2024.0178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 09/23/2024] [Accepted: 10/08/2024] [Indexed: 02/04/2025] Open
Abstract
Chronic kidney disease (CKD) is highly prevalent among elderly patients, and as the global population ages, the number of elderly patients with CKD is increasing. Elderly patients require additional considerations beyond those required for their younger counterparts, such as comorbidities, frailty, and geriatric syndromes. In this review, we primarily focus on these additional considerations specific to elderly patients and discuss the assessment of CKD and its management strategies, including blood pressure and glycemic control; dyslipidemia, anemia, and electrolyte and metabolic acidosis management; and medication dosage, among others, as well as polypharmacy and nonpharmacological management. Furthermore, the concept of conservative kidney management and the practical recommendations of the Korean Society of Geriatric Nephrology for elderly patients with end-stage kidney disease requiring dialysis therapy are discussed. In particular, the aging rate in Korea is exceptionally high; therefore, it is crucial to pay more attention to the increase in elderly patients with CKD. A more palliative approach, rather than intensive treatment strategies, may be necessary for these patients. In a world with an abundance of information, shared decision-making with patients is of great importance, and it is essential to keep in mind that this holds true for elderly patients as well.
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Affiliation(s)
- Yohan Park
- Division of Nephrology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon, Korea
| | - Won Min Hwang
- Division of Nephrology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon, Korea.
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Yang JW. Blood Pressure Control in Elderly Chronic Kidney Disease Patients. Electrolyte Blood Press 2022; 20:57-63. [PMID: 36688210 PMCID: PMC9827045 DOI: 10.5049/ebp.2022.20.2.57] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/02/2022] [Accepted: 12/12/2022] [Indexed: 01/05/2023] Open
Abstract
In elderly chronic kidney disease (CKD) patients, isolated systolic hypertension is common, the rate of renal function decline is slow, and there is a high possibility of physical damage due to side effects such as drug use-related orthostatic hypotension. Therefore, there are still many questions about whether lowering blood pressure in elderly patients will actually improve prognosis. Since many blood pressure-related clinical studies exclude advanced CKD and the elderly, it is particularly difficult to define target blood pressure in these populations. A randomized controlled trial is needed to establish optimal blood pressure targets and treatment strategies in elderly patients with CKD. This review seeks to summarize the guidelines available at this time.
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Affiliation(s)
- Jae Won Yang
- Division of Nephrology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.,The Korean Society of Geriatric Nephrology, Seoul, Republic of Korea
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Wang X, Carcel C, Woodward M, Schutte AE. Blood Pressure and Stroke: A Review of Sex- and Ethnic/Racial-Specific Attributes to the Epidemiology, Pathophysiology, and Management of Raised Blood Pressure. Stroke 2022; 53:1114-1133. [PMID: 35344416 DOI: 10.1161/strokeaha.121.035852] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Raised blood pressure (BP) is the leading cause of death and disability worldwide, and its particular strong association with stroke is well established. Although systolic BP increases with age in both sexes, raised BP is more prevalent in males in early adulthood, overtaken by females at middle age, consistently across all ethnicities/races. However, there are clear regional differences on when females overtake males. Higher BP among males is observed until the seventh decade of life in high-income countries, compared with almost 3 decades earlier in low- and middle-income countries. Females and males tend to have different cardiovascular disease risk profiles, and many lifestyles also influence BP and cardiovascular disease in a sex-specific manner. Although no hypertension guidelines distinguish between sexes in BP thresholds to define or treat hypertension, observational evidence suggests that in terms of stroke risk, females would benefit from lower BP thresholds to the magnitude of 10 to 20 mm Hg. More randomized evidence is needed to determine if females have greater cardiovascular benefits from lowering BP and whether optimal BP is lower in females. Since 1990, the number of people with hypertension worldwide has doubled, with most of the increase occurring in low- and-middle-income countries where the greatest population growth was also seen. Sub-Saharan Africa, Oceania, and South Asia have the lowest detection, treatment, and control rates. High BP has a more significant effect on the burden of stroke among Black and Asian individuals than Whites, possibly attributable to differences in lifestyle, socioeconomic status, and health system resources. Although pharmacological therapy is recommended differently in local guidelines, recommendations on lifestyle modification are often very similar (salt restriction, increased potassium intake, reducing weight and alcohol, smoking cessation). This overall enhanced understanding of the sex- and ethnic/racial-specific attributes to BP motivates further scientific discovery to develop more effective prevention and treatment strategies to prevent stroke in high-risk populations.
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Affiliation(s)
- Xia Wang
- The George Institute for Global Health (X.W., C.C., M.W., A.E.S.), University of New South Wales, Sydney, Australia
| | - Cheryl Carcel
- The George Institute for Global Health (X.W., C.C., M.W., A.E.S.), University of New South Wales, Sydney, Australia.,Sydney School of Public Health, Sydney Medical School, The University of Sydney, New South Wales, Australia (C.C.)
| | - Mark Woodward
- The George Institute for Global Health (X.W., C.C., M.W., A.E.S.), University of New South Wales, Sydney, Australia.,The George Institute for Global Health, School of Public Health, Imperial College London, United Kingdom (M.W.)
| | - Aletta E Schutte
- The George Institute for Global Health (X.W., C.C., M.W., A.E.S.), University of New South Wales, Sydney, Australia.,School of Population Health (A.E.S.), University of New South Wales, Sydney, Australia.,Hypertension in Africa Research Team, Medical Research Council Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa (A.E.S.)
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Zhu J, Chen N, Zhou M, Guo J, Zhu C, Zhou J, Ma M, He L. Calcium channel blockers versus other classes of drugs for hypertension. Cochrane Database Syst Rev 2022; 1:CD003654. [PMID: 35000192 PMCID: PMC8742884 DOI: 10.1002/14651858.cd003654.pub6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated. OBJECTIVES To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events. SEARCH METHODS For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to 1 September 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted the authors of relevant papers regarding further published and unpublished work and checked the references of published studies to identify additional trials. The searches had no language restrictions. SELECTION CRITERIA Randomised controlled trials comparing first-line CCBs with other antihypertensive classes, with at least 100 randomised hypertensive participants and a follow-up of at least two years. DATA COLLECTION AND ANALYSIS Three review authors independently selected the included trials, evaluated the risk of bias, and entered the data for analysis. Any disagreements were resolved through discussion. We contacted study authors for additional information. MAIN RESULTS This update contains five new trials. We included a total of 23 RCTs (18 dihydropyridines, 4 non-dihydropyridines, 1 not specified) with 153,849 participants with hypertension. All-cause mortality was not different between first-line CCBs and any other antihypertensive classes. As compared to diuretics, CCBs probably increased major cardiovascular events (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.09, P = 0.03) and increased congestive heart failure events (RR 1.37, 95% CI 1.25 to 1.51, moderate-certainty evidence). As compared to beta-blockers, CCBs reduced the following outcomes: major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92), stroke (RR 0.77, 95% CI 0.67 to 0.88, moderate-certainty evidence), and cardiovascular mortality (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence). As compared to angiotensin-converting enzyme (ACE) inhibitors, CCBs reduced stroke (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence) and increased congestive heart failure (RR 1.16, 95% CI 1.06 to 1.28, low-certainty evidence). As compared to angiotensin receptor blockers (ARBs), CCBs reduced myocardial infarction (RR 0.82, 95% CI 0.72 to 0.94, moderate-certainty evidence) and increased congestive heart failure (RR 1.20, 95% CI 1.06 to 1.36, low-certainty evidence). AUTHORS' CONCLUSIONS For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.
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Affiliation(s)
- Jiaying Zhu
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
- Department of Emergency, Gui Zhou Provincial People's Hospital, Guiyang, China
| | - Ning Chen
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Muke Zhou
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Jian Guo
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Cairong Zhu
- Epidemic Disease & Health Statistics Department, School of Public Health, Sichuan University, Chengdu, China
| | - Jie Zhou
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Mengmeng Ma
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Li He
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
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Zhu J, Chen N, Zhou M, Guo J, Zhu C, Zhou J, Ma M, He L. Calcium channel blockers versus other classes of drugs for hypertension. Cochrane Database Syst Rev 2021; 10:CD003654. [PMID: 34657281 PMCID: PMC8520697 DOI: 10.1002/14651858.cd003654.pub5] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated. OBJECTIVES To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events. SEARCH METHODS For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to 1 September 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted the authors of relevant papers regarding further published and unpublished work and checked the references of published studies to identify additional trials. The searches had no language restrictions. SELECTION CRITERIA Randomised controlled trials comparing first-line CCBs with other antihypertensive classes, with at least 100 randomised hypertensive participants and a follow-up of at least two years. DATA COLLECTION AND ANALYSIS Three review authors independently selected the included trials, evaluated the risk of bias, and entered the data for analysis. Any disagreements were resolved through discussion. We contacted study authors for additional information. MAIN RESULTS This update contains five new trials. We included a total of 23 RCTs (18 dihydropyridines, 4 non-dihydropyridines, 1 not specified) with 153,849 participants with hypertension. All-cause mortality was not different between first-line CCBs and any other antihypertensive classes. As compared to diuretics, CCBs probably increased major cardiovascular events (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.09, P = 0.03) and increased congestive heart failure events (RR 1.37, 95% CI 1.25 to 1.51, moderate-certainty evidence). As compared to beta-blockers, CCBs reduced the following outcomes: major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92), stroke (RR 0.77, 95% CI 0.67 to 0.88, moderate-certainty evidence), and cardiovascular mortality (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence). As compared to angiotensin-converting enzyme (ACE) inhibitors, CCBs reduced stroke (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence) and increased congestive heart failure (RR 1.16, 95% CI 1.06 to 1.28, low-certainty evidence). As compared to angiotensin receptor blockers (ARBs), CCBs reduced myocardial infarction (RR 0.82, 95% CI 0.72 to 0.94, moderate-certainty evidence) and increased congestive heart failure (RR 1.20, 95% CI 1.06 to 1.36, low-certainty evidence). AUTHORS' CONCLUSIONS For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.
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Affiliation(s)
- Jiaying Zhu
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Ning Chen
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Muke Zhou
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Jian Guo
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Cairong Zhu
- Epidemic Disease & Health Statistics Department, School of Public Health, Sichuan University, Chengdu, China
| | - Jie Zhou
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | | | - Li He
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
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Okamura K, Yano Y, Takamiya Y, Shirai K, Urata H. Efficacy and safety of a combination antihypertensive drug (olmesartan plus azelnidipine): "Issues with hypertension studies in real-world practice". Clin Exp Hypertens 2020; 42:438-448. [PMID: 31756122 DOI: 10.1080/10641963.2019.1693586] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Background: This study investigated whether a combination drug containing an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB) could provide effective antihypertensive therapy.Methods: A multicenter, prospective, open-label study was conducted at the clinics of Clinical Research Network. The subjects had uncontrolled blood pressure (BP) despite ARB or CCB monotherapy. The effect on both office and home BP was examined after patients switched to a combination drug (REZ: containing 20 mg of olmesartan [OL] and 16 mg of azelnidipine [AZ]).Results: A total of 78 patients were enrolled. After switching to REZ, a significant and sustained reduction of office BP was observed. The proportion of patients who achieved the target for both office and home BP was an increase from 0% to 55%. Switching from amlodipine to REZ resulted in a significant and sustained decrease of office and home BP. There was also a significant decrease of home pulse rate (PR), but office PR was unchanged. To determine the accuracy of the BP and PR values reported by patients, the frequency of each number as the first digit was determined. The frequency of "0" was extremely high for both office and home BP values, and the same was noted for home PR values.Conclusion: The results of this study suggested that switching from a single drug to combination therapy with REZ could achieve a stronger antihypertensive effect. However, concern was raised regarding the methods of BP and PR measurement and recording in this clinical trial involving general practitioners.
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Affiliation(s)
- Keisuke Okamura
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Chikushino, Fukuoka, Japan
| | - Yuiko Yano
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Chikushino, Fukuoka, Japan
| | - Yosuke Takamiya
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Chikushino, Fukuoka, Japan
| | - Kazuyuki Shirai
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Chikushino, Fukuoka, Japan
| | - Hidenori Urata
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Chikushino, Fukuoka, Japan
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Nagai K, Yamagata K, Iseki K, Moriyama T, Tsuruya K, Fujimoto S, Narita I, Konta T, Kondo M, Kasahara M, Shibagaki Y, Asahi K, Watanabe T. Antihypertensive treatment and risk of cardiovascular mortality in patients with chronic kidney disease diagnosed based on the presence of proteinuria and renal function: A large longitudinal study in Japan. PLoS One 2019; 14:e0225812. [PMID: 31800605 PMCID: PMC6892527 DOI: 10.1371/journal.pone.0225812] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 11/13/2019] [Indexed: 11/18/2022] Open
Abstract
Several recent clinical trials and meta-analyses have shown that lowering blood pressure reduces the risk of cardiovascular disease. However, current evidence that describes general demographics in blood pressure and mortality with chronic kidney disease is sparse in Japan. Using a population-based longitudinal cohort that received annual health checkups in Japan in 2008, hypertensive status, self-reported use of antihypertensive drugs, and prognosis were examined through 2012. Chronic kidney disease was defined as positive proteinuria or estimated glomerular filtration rate <60 ml/min/1.73 m2. Subjects were 40 to 74 years old (n = 227,204) with median 3.6 years follow-up period, and patients with and without chronic kidney disease were analyzed separately (n = 183,586 and n = 43,618, respectively). Cardiovascular disease mortality, comprising coronary heart diseases and stroke as entered in the national death registry using ICD-10 coding, was examined. Among all subjects, 346 deaths (96 in chronic kidney disease and 250 in non-chronic kidney disease) due to cardiovascular disease occurred. Compared with cardiovascular disease mortality in chronic kidney disease patients with untreated normal blood pressure, the multivariable adjusted hazard ratio was 3.08 (95% confidence interval: 1.75–5.41) for those with untreated hypertension, 2.30 (1.31–4.03) for those who became normotensive after treatment, and 3.28 (1.91–5.64) for those who remained hypertensive despite treatment. In non-chronic kidney disease subjects, the ratios were 1.90 (1.33–5.41), 1.95 (1.35–2.80), and 1.77 (1.18–2.66), respectively. These results from a nationwide cohort could be one of representative demographics of controlling blood pressure and cardiovascular disease deaths when treating patients with chronic kidney disease in Japan in recent years. Even after development and spread of anti-hypertensive drugs, preventing development of hypertension is preferable, because any hypertension treatment status comparing untreated normal blood pressure was a risk of cardiovascular mortality at baseline year.
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Affiliation(s)
- Kei Nagai
- University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Kunihiro Yamagata
- University of Tsukuba, Tsukuba, Ibaraki, Japan
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
- * E-mail:
| | - Kunitoshi Iseki
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
- Okinawa Heart and Renal Association, Okinawa, Japan
| | - Toshiki Moriyama
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
- Health Care Center, Osaka University, Suita, Japan
| | - Kazuhiko Tsuruya
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
- Nara Medical University, Nara, Japan
| | - Shouichi Fujimoto
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
- University of Miyazaki, Miyazaki, Japan
| | - Ichiei Narita
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
- Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Tsuneo Konta
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
- Yamagata University Graduate School of Medical Science, Yamagata, Japan
| | - Masahide Kondo
- University of Tsukuba, Tsukuba, Ibaraki, Japan
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
| | - Masato Kasahara
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
- Institute for Clinical and Translational Science, Nara Medical University Hospital, Nara, Japan
| | - Yugo Shibagaki
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
- St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Koichi Asahi
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
- Iwate Medical University, Morioka, Japan
| | - Tsuyoshi Watanabe
- The Steering Committee for “Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkups”, Tsukuba, Ibaraki, Japan
- Fukushima Rosai Hospital, Iwaki, Japan
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Cheung AK, Chang TI, Cushman WC, Furth SL, Ix JH, Pecoits-Filho R, Perkovic V, Sarnak MJ, Tobe SW, Tomson CR, Cheung M, Wheeler DC, Winkelmayer WC, Mann JF, Bakris GL, Damasceno A, Dwyer JP, Fried LF, Haynes R, Hirawa N, Holdaas H, Ibrahim HN, Ingelfinger JR, Iseki K, Khwaja A, Kimmel PL, Kovesdy CP, Ku E, Lerma EV, Luft FC, Lv J, McFadden CB, Muntner P, Myers MG, Navaneethan SD, Parati G, Peixoto AJ, Prasad R, Rahman M, Rocco MV, Rodrigues CIS, Roger SD, Stergiou GS, Tomlinson LA, Tonelli M, Toto RD, Tsukamoto Y, Walker R, Wang AYM, Wang J, Warady BA, Whelton PK, Williamson JD. Blood pressure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2019; 95:1027-1036. [DOI: 10.1016/j.kint.2018.12.025] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 11/30/2018] [Accepted: 12/06/2018] [Indexed: 12/30/2022]
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Gregg LP, Hedayati SS. Management of Traditional Cardiovascular Risk Factors in CKD: What Are the Data? Am J Kidney Dis 2018; 72:728-744. [PMID: 29478869 PMCID: PMC6107444 DOI: 10.1053/j.ajkd.2017.12.007] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 12/06/2017] [Indexed: 12/22/2022]
Abstract
Patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) are 10 times more likely to die of cardiovascular (CV) diseases than the general population, and dialysis-dependent patients are at even higher risk. Although traditional CV risk factors are highly prevalent in individuals with CKD, these patients were often excluded from studies targeting modification of these risks. Although treatment of hypertension is beneficial in CKD, the best target blood pressure has not been established. Trial data showed that renin-angiotensin-aldosterone blockade may prevent CV events in patients with CKD. The risks of aspirin may equal the benefits in NDD-CKD samples, and there are no trials testing aspirin in dialysis-dependent patients. Lipid-lowering therapy improves CV outcomes in NDD-CKD, but not in dialysis-dependent patients. Strict glycemic control prevents CV events in nonalbuminuric individuals, but showed no benefit in those with baseline albuminuria with albumin excretion > 300mg/g, and there are no data in dialysis-dependent patients. Data for lifestyle modifications, such as weight loss, physical activity, and smoking cessation, are mostly observational and extrapolated from non-CKD samples. This comprehensive review summarizes the best existing evidence and current clinical guidelines for modification of traditional risk factors for the prevention of CV events in patients with CKD and identifies knowledge gaps.
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Affiliation(s)
- L Parker Gregg
- Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX; Division of Nephrology, Medical Service, Veterans Affairs North Texas Health Care System, Dallas, TX.
| | - S Susan Hedayati
- Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX
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Raman M, Green D, Middleton RJ, Kalra PA. Comparing the impact of older age on outcome in chronic kidney disease of different etiologies: a prospective cohort study. J Nephrol 2018; 31:931-939. [PMID: 30187380 PMCID: PMC6244557 DOI: 10.1007/s40620-018-0529-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 08/22/2018] [Indexed: 11/30/2022]
Abstract
Background In older patients with chronic kidney disease (CKD), the risk of progression to end stage renal disease and cardiovascular death both differ compared to younger patients. This likely reflects differences in case mix and co-morbid burdens. We sought to establish the extent to which age itself is an independent biomarker of adverse outcome in CKD. Methods This was an analysis of the Salford Kidney Study, a prospective, longitudinal, observational study of 2,667 patients with eGFR < 60 ml/min/1.73 m2. Patients were divided into four age groups (< 55, 55–65, 65–75 and > 75 years). Within group adjusted hazard ratios for death in older compared to younger patients were calculated for different primary renal diseases. A competing risk model of death and renal replacement therapy (RRT) as outcomes was performed. Results The median age of the cohort was 67.1 years [interquartile range (IQR): 55.6–75.3] and median eGFR 30.8 ml/min/1.73 m2 (IQR: 20.6–43.2). Follow up was 3.5 ± 2.9 years. Overall, the adjusted HR for death in patients aged > 75 years compared to those < 55 years was 4.4 (95% CI 3.4–5.9), p < 0.001. The HR for death differed between primary renal diseases and CKD stages. In diabetic nephropathy, the HR was 3.0 (1.8–5.3, p < 0.001), in glomerulonephritis the HR was 12.2 (5.6–25.5, p < 0.001). The cumulative incidence of RRT was < 0.1 at 10 years for patients > 75 years, compared with 0.50 in those < 55 years. Death was more likely at 20 months in those aged 75 years or older (0.17) than at 10 years in those aged < 55 years (0.10). Conclusion This study demonstrates that the risk associated with older age shows significant variability between primary renal diseases. This is whilst acknowledging that observational studies carry the risk of hidden bias not adjusted for in the statistical model. Electronic supplementary material The online version of this article (10.1007/s40620-018-0529-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Maharajan Raman
- Vascular Research Group, Department of Renal Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Darren Green
- Vascular Research Group, Department of Renal Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK. .,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
| | - Rachel J Middleton
- Vascular Research Group, Department of Renal Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Philip A Kalra
- Vascular Research Group, Department of Renal Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
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11
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Kim-Mitsuyama S, Soejima H, Yasuda O, Node K, Jinnouchi H, Yamamoto E, Sekigami T, Ogawa H, Matsui K. Cardiovascular and renal protective role of angiotensin blockade in hypertension with advanced CKD: a subgroup analysis of ATTEMPT-CVD randomized trial. Sci Rep 2018; 8:3150. [PMID: 29453374 PMCID: PMC5816600 DOI: 10.1038/s41598-018-20874-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 01/25/2018] [Indexed: 12/29/2022] Open
Abstract
The ATTEMPT-CVD study was prospective randomized active-controlled trial and the main findings had been reported. According to baseline GFR and albuminuria categories, we divided the patients of the ATTEMPT-CVD study into 2 subgroups: (Group 1) the patients with at least one of eGFR of <45 ml/min per 1.73 m2 and UACR of ≥300 mg/g creatinine, defined as G3b and/or A3; (Group 2) the patients except for Group 1, defined as the other patients. In patients with G3b and/or A3, the incidence of cardiovascular events was significantly less in ARB group than in non-ARB group (11 vs 22, respectively) (HR = 0.465: 95%CI = 0.224-0.965; P = 0.040). UACR was significantly less in ARB group than in non-ARB group during follow-up period in patients with G3b and/or A3 (P = 0.0003), while eGFR, plasma BNP levels, and blood pressure were comparable between ARB and non-ARB groups. Allocation to ARB therapy was a significant independent prognostic factor for cardiovascular events in patients with G3b and/or A3 (P = 0.0268). On the other hand, in the other patients, the occurrence of cardiovascular events was comparable between ARB and non-ARB groups. In patients with advanced CKD, ARB-based therapy may confer greater benefit in prevention of cardiovascular events than non-ARB therapy.
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Affiliation(s)
- Shokei Kim-Mitsuyama
- Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
| | - Hirofumi Soejima
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
- Health Care Center, Kumamoto University, Kumamoto, Japan
| | - Osamu Yasuda
- Department of Sports and Life Sciences, National Institute of Fitness and Sports in Kanoya, Kanoya, Japan
| | - Koichi Node
- Department of Cardiovascular Medicine, Saga University, Saga, Japan
| | | | - Eiichiro Yamamoto
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Taiji Sekigami
- Division of Internal Medicine & Diabetes and Endocrine, Sekigami Clinic, Yatsushiro, Japan
| | - Hisao Ogawa
- National Cerebral and Cardiovascular Center, Suita, Japan
| | - Kunihiko Matsui
- Department of General and Community Medicine, Kumamoto University Hospital, Kumamoto, Japan
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12
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Hagiwara H, Nishikawa R, Fukuzawa K, Tohkin M. The Survey of the Compliance Situation to the Antihypertensive Therapy Guideline by Analyzing Japanese National Claims Data. YAKUGAKU ZASSHI 2017; 137:893-901. [DOI: 10.1248/yakushi.17-00038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Hiromi Hagiwara
- Department of Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University
| | - Ryouhei Nishikawa
- Department of Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University
| | - Kazuki Fukuzawa
- Department of Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University
| | - Masahiro Tohkin
- Department of Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University
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13
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Drapak I, Perekhoda L, Tsapko T, Berezniakova N, Tsapko Y. Cardiovascular Calcium Channel Blockers: Historical Overview, Development and New Approaches in Design. J Heterocycl Chem 2017. [DOI: 10.1002/jhet.2837] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Iryna Drapak
- Department of General, Bioinorganic, Physical and Colloidal Chemistry; Lvivs'kyj nacional'nyj medychnyj universytet imeni Danyla Halyc'koho; Lviv 58666 Ukraine
| | - Lina Perekhoda
- Department of Medicinal Chemistry; Nacional'nyj farmacevtychnyj universytet; Kharkiv 199318 Ukraine
| | - Tetiana Tsapko
- Department of Medicinal Chemistry; Nacional'nyj farmacevtychnyj universytet; Kharkiv 199318 Ukraine
| | - Natalia Berezniakova
- Department of Medicinal Chemistry; Nacional'nyj farmacevtychnyj universytet; Kharkiv 199318 Ukraine
| | - Yevgen Tsapko
- Department of Inorganic Chemistry; Nacional'nyj farmacevtychnyj universytet; Kharkiv 199318 Ukraine
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14
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Tamargo J, Ruilope LM. Investigational calcium channel blockers for the treatment of hypertension. Expert Opin Investig Drugs 2016; 25:1295-1309. [DOI: 10.1080/13543784.2016.1241764] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
- J Tamargo
- Department of Pharmacology, School of Medicine, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain. CIBER of Cardiovascular Diseases
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15
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Raman M, Green D, Middleton RJ, Kalra PA. OLDER PEOPLE WITH CHRONIC KIDNEY DISEASE: DEFINITION, AND INFLUENCE OF BIOMARKERS AND MEDICATIONS UPON CARDIOVASCULAR AND RENAL OUTCOMES. J Ren Care 2016; 42:150-61. [PMID: 27364740 DOI: 10.1111/jorc.12164] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Chronic kidney disease (CKD) is a global problem. With an ageing population the burden on the health services has increased due to the growing number of older people with CKD. This group of individuals is far different to the younger CKD population and their risk of cardiovascular death is far greater than the risk of progressing to end stage kidney disease (ESKD). OBJECTIVE In this review we explore the role of certain biomarkers and medications in predicting the risk of progression to ESKD and death in old people with CKD. METHODS An electronic literature search of EMBASE and MEDLINE databases was performed using Healthcare Databases Advanced Search (HDAS) in December 2014. RESULTS Albuminuria is a key biomarker in predicting the risk of death and progression to ESKD. Cystatin C appears to be superior in predicting the risk of cardiovascular and non-cardiovascular death compared to GFR or creatinine. Several inflammatory biomarkers can be used to predict the risk of death and progression to CKD but measuring and monitoring them in routine clinical practice will be expensive and impractical. The effects of long-term RAAS inhibition in older people are not well established. Older people especially those with CKD receive suboptimal secondary preventive measures. Due to multiple comorbidities older people with CKD are usually receiving a number of medications. This can potentially lead to significant adverse drug events (ADE) due to drug interactions. CONCLUSION Novel non-traditional risk factors like albuminuria, Cystatin C and inflammatory biomarkers play an important role in predicting their risk of death and progression to ESKD. The efficacy and safety of medications in older people with CKD is not well established and requires more extensive, focused study.
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Affiliation(s)
- Maharajan Raman
- Vascular Research Group, Salford Royal NHS Foundation Trust, Salford, UK.,Institute of Population Health, University of Manchester, Manchester, UK
| | - Darren Green
- Vascular Research Group, Salford Royal NHS Foundation Trust, Salford, UK.,Institute of Population Health, University of Manchester, Manchester, UK
| | - Rachel J Middleton
- Vascular Research Group, Salford Royal NHS Foundation Trust, Salford, UK.,Institute of Population Health, University of Manchester, Manchester, UK
| | - Philip A Kalra
- Vascular Research Group, Salford Royal NHS Foundation Trust, Salford, UK.,Institute of Population Health, University of Manchester, Manchester, UK
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Fukuda M, Ogiyama Y, Sato R, Miura T, Fukuta H, Mizuno M, Kiyono K, Yamamoto Y, Hayano J, Ohte N. L/T-type calcium channel blocker reduces non-Gaussianity of heart rate variability in chronic kidney disease patients under preceding treatment with ARB. J Renin Angiotensin Aldosterone Syst 2016; 17:1470320316643905. [PMID: 27094219 PMCID: PMC5843923 DOI: 10.1177/1470320316643905] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Accepted: 03/12/2016] [Indexed: 11/23/2022] Open
Abstract
Introduction: Increased sympathetic nerve activity has been suggested in patients with chronic kidney disease (CKD). Pathologic sympathetic activity can alter heart rate variability (HRV), and the altered HRV has prognostic importance, so that reducing sympathetic activity may be an important strategy. Novel nonlinear HRVs, including deceleration capacity (DC), have greater predictive power for mortality. We have recently proposed an increase in a non-Gaussianity index of HRV, λ25s, which indicates the probability of volcanic heart rate deviations of departure from each standard deviation level, as a marker of sympathetic cardiac overdrive. L/T-type calcium channel blocker (L/T-CCB), azelnidipine, decreases sympathetic nerve activity in experimental and clinical studies. Methods: In 43 hypertensive patients with CKD under treatment with an angiotensin receptor blocker (ARB), we investigated whether 8-week add-on L/T-CCB treatment could restore HRV. Results: Means of all normal-to-normal intervals over 24 h (p<0.0001) and DC (p=0.002) increased, and λ25s (p=0.001) decreased regardless of gender, age, renal function or blood pressure, while no significant changes were observed in the other HRVs. Conclusions: Reduction of λ25s is useful to assess the effect of sympathoinhibitory treatment. Further studies are needed to investigate if the restoration of HRV is directly associated with the improvement of prognosis in patients with CKD.
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Affiliation(s)
- Michio Fukuda
- Department of Cardio-Renal Medicine and Hypertension, Nagoya, Japan
| | - Yoshiaki Ogiyama
- Department of Cardio-Renal Medicine and Hypertension, Nagoya, Japan
| | - Ryo Sato
- Department of Cardio-Renal Medicine and Hypertension, Nagoya, Japan
| | - Toshiyuki Miura
- Department of Cardio-Renal Medicine and Hypertension, Nagoya, Japan
| | - Hidekatsu Fukuta
- Department of Cardio-Renal Medicine and Hypertension, Nagoya, Japan
| | - Masashi Mizuno
- Department of Cardio-Renal Medicine and Hypertension, Nagoya, Japan
| | - Ken Kiyono
- Department of Mechanical Science and Bioengineering, Osaka University, Osaka, Japan
| | - Yoshiharu Yamamoto
- Department of Physical and Health Education, University of Tokyo Graduate School of Education, Tokyo, Japan
| | - Junichiro Hayano
- Department of Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Nobuyuki Ohte
- Department of Cardio-Renal Medicine and Hypertension, Nagoya, Japan
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17
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Ma J, Wang XY, Hu ZD, Zhou ZR, Schoenhagen P, Wang H. Meta-analysis of the efficacy and safety of adding an angiotensin receptor blocker (ARB) to a calcium channel blocker (CCB) following ineffective CCB monotherapy. J Thorac Dis 2016; 7:2243-52. [PMID: 26793346 DOI: 10.3978/j.issn.2072-1439.2015.12.39] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND We conducted this meta-analysis to systematically review and analyze the clinical benefits of angiotensin receptor blocker (ARB) combined with calcium channel blocker (CCB) following ineffective CCB monotherapy. METHODS PubMed was searched for articles published until August 2015. Randomized controlled trials (RCTs) evaluating the clinical benefits of ARB combined with CCB following ineffective CCB monotherapy were included. The primary efficacy endpoint of the studies was normal rate of blood pressure, the secondary efficacy endpoints were the response rate and change in blood pressure from baseline. The safety endpoint of the studies was incidence of adverse events. Differences are expressed as relative risks (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and weighted mean differences (WMDs) with 95% CIs for continuous outcomes. Heterogeneity across studies was tested by using the I(2) statistic. RESULTS Seven RCTs were included and had sample sizes ranging from 185 to 1,183 subjects (total: 3,909 subjects). The pooled analysis showed that the on-target rate of hypertension treatment was significantly higher in the amlodipine + ARB group than in the amlodipine monotherapy group (RR =1.59; 95% CI, 1.31-1.91; P<0.01). The response rate of systolic blood pressure (SBP) (RR =1.28; 95% CI, 1.04-1.58; P<0.01) and diastolic blood pressure (DBP) (RR =1.27; 95% CI, 1.12-1.44; P=0.04) were significantly higher in the amlodipine + ARB group than in the amlodipine monotherapy group. The change in SBP (RR =-3.56; 95% CI, -7.76-0.63; P=0.10) and DBP (RR =-3.03; 95% CI, -6.51-0.45; P=0.09) were higher in hypertensive patients receiving amlodipine + ARB but the difference did not reach statistical significance. ARB + amlodipine treatment carried a lower risk of adverse events relative to amlodipine monotherapy (RR =0.88; 95% CI, 0.80-0.96; P<0.01). CONCLUSIONS The results of our meta-analysis demonstrate that adding an ARB to CCB after initial ineffective CCB monotherapy, significantly improved blood pressure control and the percentage of on-target hypertension treatment with significantly reduced incidence of adverse events compared with continued CCB monotherapy.
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Affiliation(s)
- Jin Ma
- 1 Department of Cardiology, Yangpu Hospital, Tongji University, Shanghai 20090, China ; 2 Graduate School, Dalian Medical University, Dalian 116044, China ; 3 Department of Laboratory Medicine, General Hospital of Ji'nan Military Region, Ji'nan 250031, China ; 4 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 5 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China ; 6 Cleveland Clinic, Imaging Institute and Heart&Vascular Institute, Cleveland, USA
| | - Xiao-Yan Wang
- 1 Department of Cardiology, Yangpu Hospital, Tongji University, Shanghai 20090, China ; 2 Graduate School, Dalian Medical University, Dalian 116044, China ; 3 Department of Laboratory Medicine, General Hospital of Ji'nan Military Region, Ji'nan 250031, China ; 4 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 5 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China ; 6 Cleveland Clinic, Imaging Institute and Heart&Vascular Institute, Cleveland, USA
| | - Zhi-De Hu
- 1 Department of Cardiology, Yangpu Hospital, Tongji University, Shanghai 20090, China ; 2 Graduate School, Dalian Medical University, Dalian 116044, China ; 3 Department of Laboratory Medicine, General Hospital of Ji'nan Military Region, Ji'nan 250031, China ; 4 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 5 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China ; 6 Cleveland Clinic, Imaging Institute and Heart&Vascular Institute, Cleveland, USA
| | - Zhi-Rui Zhou
- 1 Department of Cardiology, Yangpu Hospital, Tongji University, Shanghai 20090, China ; 2 Graduate School, Dalian Medical University, Dalian 116044, China ; 3 Department of Laboratory Medicine, General Hospital of Ji'nan Military Region, Ji'nan 250031, China ; 4 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 5 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China ; 6 Cleveland Clinic, Imaging Institute and Heart&Vascular Institute, Cleveland, USA
| | - Paul Schoenhagen
- 1 Department of Cardiology, Yangpu Hospital, Tongji University, Shanghai 20090, China ; 2 Graduate School, Dalian Medical University, Dalian 116044, China ; 3 Department of Laboratory Medicine, General Hospital of Ji'nan Military Region, Ji'nan 250031, China ; 4 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 5 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China ; 6 Cleveland Clinic, Imaging Institute and Heart&Vascular Institute, Cleveland, USA
| | - Hao Wang
- 1 Department of Cardiology, Yangpu Hospital, Tongji University, Shanghai 20090, China ; 2 Graduate School, Dalian Medical University, Dalian 116044, China ; 3 Department of Laboratory Medicine, General Hospital of Ji'nan Military Region, Ji'nan 250031, China ; 4 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 5 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China ; 6 Cleveland Clinic, Imaging Institute and Heart&Vascular Institute, Cleveland, USA
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Chen YC, Zhu W, Zhong SP, Zheng FC, Gao FF, Zhang YM, Xu H, Zheng YS, Shi GG. Characterization and bioactivity of novel calcium antagonists - N-methoxy-benzyl haloperidol quaternary ammonium salt. Oncotarget 2015; 6:43759-69. [PMID: 26544729 PMCID: PMC4791264 DOI: 10.18632/oncotarget.6086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 10/06/2015] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND AND PURPOSE Calcium antagonists play an important role in clinical practice. However, most of them have serious side effects. We have synthesized a series of novel calcium antagonists, quaternary ammonium salt derivatives of haloperidol with N-p-methoxybenzyl (X1), N-m-methoxybenzyl (X2) and N-o-methoxybenzyl (X3) groups. The objective of this study was to investigate the bioactivity of these novel calcium antagonists, especially the vasodilation activity and cardiac side-effects. The possible working mechanisms of these haloperidol derivatives were also explored. EXPERIMENTAL APPROACH Novel calcium antagonists were synthesized by amination. Compounds were screened for their activity of vasodilation on isolated thoracic aortic ring of rats. Their cardiac side effects were explored. The patch-clamp, confocal laser microscopy and the computer-fitting molecular docking experiments were employed to investigate the possible working mechanisms of these calcium antagonists. RESULTS The novel calcium antagonists, X1, X2 and X3 showed stronger vasodilation effect and less cardiac side effect than that of classical calcium antagonists. They blocked L-type calcium channels with an potent effect order of X1 > X2 > X3. Consistently, X1, X2 and X3 interacted with different regions of Ca2+-CaM-CaV1.2 with an affinity order of X1 > X2 > X3. CONCLUSIONS The new halopedidol derivatives X1, X2 and X3 are novel calcium antagonists with stronger vasodilation effect and less cardiac side effect. They could have wide clinical application.
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Affiliation(s)
- Yi-Cun Chen
- Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Wei Zhu
- Geneheal Biotechnology Co., Ltd, Guangzhou 510000, Guangdong, China
| | - Shu-Ping Zhong
- Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
| | - Fu-Chun Zheng
- Department of Pharmacy, the First Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Fen-Fei Gao
- Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Yan-Mei Zhang
- Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Han Xu
- Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Yan-Shan Zheng
- Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Gang-Gang Shi
- Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China
- Department of Cardiovascular Diseases, the First Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong, China
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Abe M, Soma M. Multifunctional L/N- and L/T-type calcium channel blockers for kidney protection. Hypertens Res 2015; 38:804-6. [PMID: 26423789 DOI: 10.1038/hr.2015.106] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Masanori Abe
- Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Masayoshi Soma
- Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.,Division of General Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
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Nagai K, Yamagata K, Ohkubo R, Saito C, Asahi K, Iseki K, Kimura K, Moriyama T, Narita I, Fujimoto S, Tsuruya K, Konta T, Kondo M, Watanabe T. Annual decline in estimated glomerular filtration rate is a risk factor for cardiovascular events independent of proteinuria. Nephrology (Carlton) 2015; 19:574-80. [PMID: 24899111 DOI: 10.1111/nep.12286] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2014] [Indexed: 11/28/2022]
Abstract
AIMS Chronic kidney disease is a risk factor of the development of cardiovascular disease (CVD). However, it is not clear whether decline of glomerular filtration rate (GFR), not reduced GFR, is a risk factor for the incidence of CVD independent of proteinuria. METHODS By using a population-based 521 123 person-years longitudinal cohort receiving annual health checkups from 2008 to 2010, we examined whether the annual decline of estimated GFR is a risk factor for CVD development independent of proteinuria. RESULTS During the follow-up period, there were 12 041 newly developed CVD events, comprising 4426 stroke events and/or 8298 cardiac events. As expected, both reduced estimated GFR and proteinuria were risk factors for the development of CVD in our study population. Moreover, annual decline of estimated GFR was a significant and independent risk factor for the incidence of CVD (HR [95% CI], 1.23 [1.18-1.28] in males or 1.14 [1.10-1.18] in females for -10% per year) with covariant adjustment for proteinuria and reduced estimated GFR. CONCLUSION Annual decline of GFR is an independent risk factor for CVD. Serial measurement of both creatinine and proteinuria would be better to predict the incidence of CVD in the general population.
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Affiliation(s)
- Kei Nagai
- Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
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Differential effectiveness of ARB plus CCB therapy and high-dose ARB therapy in high-risk elderly hypertensive patients: subanalysis of the OSCAR study. Hypertens Res 2014; 38:199-207. [PMID: 25471234 DOI: 10.1038/hr.2014.164] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Revised: 09/26/2014] [Accepted: 10/23/2014] [Indexed: 01/01/2023]
Abstract
The OSCAR study was a multicenter prospective randomized study that examined the relative benefit of combined ARB (olmesartan 20 mg per day) plus calcium channel blocker (CCB) therapy vs. high-dose ARB monotherapy (olmesartan 40 mg per day) for prevention of cardiovascular events in elderly Japanese hypertensive patients. The present subanalysis of patients enrolled in the OSCAR study (n = 1078) was performed to assess whether baseline eGFR coupled with cardiovascular disease (CVD) could predict the relative benefit of these two treatments. Patients with baseline CVD (n = 769) and patients without baseline CVD (n = 309) were divided into two groups based on baseline eGFR; (i) patients with eGFR of < 60 ml min(-1) 1.73 m(-)(2) and (ii) those with eGFR of ⩾ 60 ml min(-1) 1.73 m(-2). There was a significant treatment-subgroup interaction among these four subgroups in relation to the incidence of primary outcome events(P = 0.007 for interaction). In patients with CVD and with eGFR of <60 ml min(-1) 1.73 m(-2), ARB plus CCB therapy was associated with a lower incidence of primary events than high-dose ARB therapy and the difference of the relative risk was statistically significant (hazard ratio: 3.525, 95% confidence interval (CI): 1.676-7.412, P < 0.001). The greater benefit of ARB plus CCB therapy vs. high-dose ARB therapy in this subgroup was associated with less visit-to-visit variability of systolic BP and diastolic BP. In conclusion, baseline eGFR coupled with baseline CVD seems to be a predictor of the relative efficacy of ARB plus CCB therapy vs. high-dose ARB therapy in the elderly hypertensive patients. ARB plus CCB therapy appears to be superior to high-dose ARB therapy for preventing cardiovascular events in the patients with CVD and with eGFR of <60 ml min(-1) 1.73 m(-2).
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Lee J, Lee H, Jang K, Lim KS, Shin D, Yu KS. Evaluation of the pharmacokinetic and pharmacodynamic drug interactions between cilnidipine and valsartan, in healthy volunteers. DRUG DESIGN DEVELOPMENT AND THERAPY 2014; 8:1781-8. [PMID: 25336921 PMCID: PMC4199974 DOI: 10.2147/dddt.s68574] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
PURPOSE Although cilnidipine and valsartan are widely coadministered to patients with hypertension, their drug-drug interaction potential has not been investigated. This study compared the pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles of cilnidipine and valsartan, both alone and in combination, in healthy male subjects. PATIENTS AND METHODS Fifty-four subjects, enrolled into an open-label, single-dose, three-treatment, three-period crossover study, randomly received cilnidipine (10 mg), valsartan (160 mg), or both according to one of six sequences. Blood samples were collected at baseline and up to 24 hours after drug administration in each period. Plasma concentrations of cilnidipine and valsartan were determined by liquid chromatography with tandem mass spectrometry. Maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to the last measurable time (AUC(last)) were estimated using a noncompartmental method. Tolerability was evaluated by assessing adverse events (AEs), vital signs, electrocardiograms, and clinical laboratory tests. Blood pressure was also measured for PD assessment. RESULTS A total of 51 subjects completed the study. The PK profile of cilnidipine was not significantly affected by coadministered valsartan; the geometric mean ratio and 90% confidence interval (90% CI) of AUC(last) for cilnidipine with and without valsartan was 1.04 (0.98-1.10). Likewise, cilnidipine did not affect the PK of valsartan; the geometric mean ratio (90% CI) of AUC(last) for valsartan with and without cilnidipine was 0.94 (0.83-1.07). Coadministration of cilnidipine and valsartan reduced blood pressure in an additive way. No serious AEs were reported, and both cilnidipine and valsartan were well tolerated. CONCLUSION Coadministered cilnidipine and valsartan do not cause a significant PK or PD interaction, and they are well tolerated.
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Affiliation(s)
- Jieon Lee
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea
| | - Howard Lee
- Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Kyungho Jang
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea
| | - Kyoung Soo Lim
- Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, Republic of Korea
| | - Dongseong Shin
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea
| | - Kyung-Sang Yu
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea
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Rafiq K, Nishiyama A, Konishi Y, Morikawa T, Kitabayashi C, Kohno M, Masaki T, Mori H, Kobori H, Imanishi M. Regression of glomerular and tubulointerstitial injuries by dietary salt reduction with combination therapy of angiotensin II receptor blocker and calcium channel blocker in Dahl salt-sensitive rats. PLoS One 2014; 9:e107853. [PMID: 25233358 PMCID: PMC4169441 DOI: 10.1371/journal.pone.0107853] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Accepted: 08/15/2014] [Indexed: 12/24/2022] Open
Abstract
A growing body of evidence indicates that renal tissue injuries are reversible. We investigated whether dietary salt reduction with the combination therapy of angiotensin II type 1 receptor blocker (ARB) plus calcium channel blocker (CCB) reverses renal tissue injury in Dahl salt-sensitive (DSS) hypertensive rats. DSS rats were fed a high-salt diet (HS; 4% NaCl) for 4 weeks. Then, DSS rats were given one of the following for 10 weeks: HS diet; normal-salt diet (NS; 0.5% NaCl), NS + an ARB (olmesartan, 10 mg/kg/day), NS + a CCB (azelnidipine, 3 mg/kg/day), NS + olmesartan + azelnidipine or NS + hydralazine (50 mg/kg/day). Four weeks of treatment with HS diet induced hypertension, proteinuria, glomerular sclerosis and hypertrophy, glomerular podocyte injury, and tubulointerstitial fibrosis in DSS rats. A continued HS diet progressed hypertension, proteinuria and renal tissue injury, which was associated with inflammatory cell infiltration and increased proinflammatory cytokine mRNA levels, NADPH oxidase activity and NADPH oxidase-dependent superoxide production in the kidney. In contrast, switching to NS halted the progression of hypertension, renal glomerular and tubular injuries. Dietary salt reduction with ARB or with CCB treatment further reduced blood pressure and partially reversed renal tissues injury. Furthermore, dietary salt reduction with the combination of ARB plus CCB elicited a strong recovery from HS-induced renal tissue injury including the attenuation of inflammation and oxidative stress. These data support the hypothesis that dietary salt reduction with combination therapy of an ARB plus CCB restores glomerular and tubulointerstitial injury in DSS rats.
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Affiliation(s)
- Kazi Rafiq
- Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan
- * E-mail:
| | - Akira Nishiyama
- Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Yoshio Konishi
- Division of Nephrology and Hypertension, Osaka City General Hospital, Osaka, Japan
| | - Takashi Morikawa
- Division of Nephrology and Hypertension, Osaka City General Hospital, Osaka, Japan
| | - Chizuko Kitabayashi
- Division of Nephrology and Hypertension, Osaka City General Hospital, Osaka, Japan
| | - Masakazu Kohno
- Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Hirohito Mori
- Department of Gastroenterology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Hiroyuki Kobori
- Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Masahito Imanishi
- Division of Nephrology and Hypertension, Osaka City General Hospital, Osaka, Japan
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Abstract
This paper summarizes the pharmacological properties of calcium channel blockers (CCBs), their established therapeutic uses for cardiovascular disorders and the current improvement of their clinical effects through drug combinations. Their identification resulted from study of small molecules including coronary dilators, which were named calcium antagonists. Further experiments showed that they reduced contraction of arteries by inhibiting calcium entry and by interacting with binding sites identified on voltage-dependent calcium channels. This led to the denomination calcium channel blockers. In short-term studies, by decreasing total peripheral resistance, CCBs lower arterial pressure. By unloading the heart and increasing coronary blood flow, CCBs improve myocardial oxygenation. In long-term treatment, the decrease in blood pressure is more pronounced in hypertensive than in normotensive patients. A controversy on the safety of CCBs ended after a large antihypertensive trial (ALLHAT) sponsored by the National Heart, Lung, and Blood Institute. There are two main types of CCBs: dihydopyridine and non-dihydropyridine; the first type is vascular selective. Dihydropyrines are indicated for hypertension, chronic, stable and vasospastic angina. Non-dihydropyridines have the same indications plus antiarrythmic effects in atrial fibrillation or flutter and paroxysmal supraventricular tachycardia. In addition, CCBs reduced newly formed coronary lesions in atherosclerosis. In order to reach recommended blood pressure goals, there is a recent therapeutic move by combination of CCBs with other antihypertensive agents particularly with inhibitors acting at the level of the renin-angiotensin system. They are also combined with statins. Prevention of dementia has been reported in hypertensive patients treated with nitrendipine, opening a way for further studies on CCBs' beneficial effect in cognitive deterioration associated with aging.
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Chrysant SG. Effectiveness of the fixed-dose combination of olmesartan/amlodipine/hydrochlorothiazide for the treatment of hypertension in patients stratified by age, race and diabetes, CKD and chronic CVD. Expert Rev Cardiovasc Ther 2014; 11:1115-24. [PMID: 24073676 DOI: 10.1586/14779072.2013.827449] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The prevalence of hypertension is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and chronic cardiovascular disease (CVD), as well as in black and elderly subjects. In addition, these subjects have the lowest control of blood pressure (BP) among the hypertensive population, and also the risk of having a morbid or fatal cardiovascular event >20% in 10 years. For these reasons, aggressive control of BP to <130/80 mm Hg for these subjects is strongly recommended by National and International guidelines. To accomplish this goal, combination therapy with two or more antihypertensive drugs with a complementary mechanism of action is necessary. Drugs that block the renin-angiotensin system (RAS) in combination with a calcium channel blocker (CCB) and a diuretic have been shown to be the most effective combinations to accomplish this goal. However, this will require the administration of multiple drugs given separately, which will decrease the patient compliance and adherence to treatment. Poor patient compliance and adherence to treatment is a major factor for poor BP control. Several studies have shown that patient compliance is inversely related to the number of drugs being administered. To overcome this problem, several dual and triple-drug, fixed-dose combinations with a RAS blocker, a CCB and a diuretic have been developed and marketed, which are easier to administer, and have been shown to increase patient compliance and adherence to treatment. In this concise review, the effectiveness and safety of the fixed-dose, triple-combination of the RAS blocker olmesartan medoxomil, the CCB amlodipine besylate and the diuretic hydrochlorothiazide, as well as other similar combinations for the treatment of hypertension, will be discussed. These drug combinations have been shown to be effective, safe and well tolerated by most patients.
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Affiliation(s)
- Steven G Chrysant
- Department of Cardiology, University of Oklahoma College of Medicine, 5700 Mistletoe Court, Oklahoma City, OK 73142, USA +1 405 721 6662 +1 405 721 8417
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Chapter 6. Hypertension associated with organ damage. Hypertens Res 2014. [DOI: 10.1038/hr.2014.9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Chrysant SG, Chrysant GS. The age-related hemodynamic changes of blood pressure and their impact on the incidence of cardiovascular disease and stroke: new evidence. J Clin Hypertens (Greenwich) 2014; 16:87-90. [PMID: 24373633 PMCID: PMC8031888 DOI: 10.1111/jch.12253] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Accepted: 11/29/2013] [Indexed: 11/29/2022]
Abstract
There is a linear change in blood pressure (BP) with the advancement of age from predominantly diastolic BP (DBP) in the young to predominantly systolic BP (SBP) in the old. This change is caused by the stiffening of the large arteries and the loss of elastic recoil as a result of replacement of the elastic fibers with collagen fibers. The result of this ageing process leads to an increase in pulse wave velocity and widening of pulse pressure. These hemodynamic changes are associated with an increased incidence in cardiovascular diseases (CVDs) and strokes. Recently, an inverse relationship with stroke risk was noted when the DBP was <71 mm Hg in persons older than 60 years. Accordingly, when treating SBP in the elderly, care should be taken not to lower the DBP below this level in order to minimize the risk for CVD and stoke.
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Rafiq K, Sherajee SJ, Hitomi H, Nakano D, Kobori H, Ohmori K, Mori H, Kobara H, Masaki T, Kohno M, Nishiyama A. Calcium channel blocker enhances beneficial effects of an angiotensin II AT1 receptor blocker against cerebrovascular-renal injury in type 2 diabetic mice. PLoS One 2013; 8:e82082. [PMID: 24339994 PMCID: PMC3858271 DOI: 10.1371/journal.pone.0082082] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Accepted: 10/29/2013] [Indexed: 11/19/2022] Open
Abstract
Recent clinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calcium channel blockers (CCBs) elicits beneficial effects on cardiovascular and renal events in hypertensive patients with high cardiovascular risks. In the present study, we hypothesized that CCB enhances the protective effects of an angiotensin II type 1 receptor blocker (ARB) against diabetic cerebrovascular-renal injury. Saline-drinking type 2 diabetic KK-Ay mice developed hypertension and exhibited impaired cognitive function, blood-brain barrier (BBB) disruption, albuminuria, glomerular sclerosis and podocyte injury. These brain and renal injuries were associated with increased gene expression of NADPH oxidase components, NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Treatment with the ARB, olmesartan (10 mg/kg/day) reduced blood pressure in saline-drinking KK-Ay mice and attenuated cognitive decline, BBB disruption, glomerular injury and albuminuria, which were associated with a reduction of NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Furthermore, a suppressive dose of azelnidipine (3 mg/kg/day) exaggerated these beneficial effects of olmesartan. These data support the hypothesis that a CCB enhances ARB-associated cerebrovascular-renal protective effects through suppression of NADPH oxidase-dependent oxidative stress in type 2 diabetes.
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Affiliation(s)
- Kazi Rafiq
- Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan
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The Authors Reply. Kidney Int 2013; 84:1047-8. [PMID: 24172735 PMCID: PMC3898315 DOI: 10.1038/ki.2013.313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Fukuda M, Miura T. Awaiting the OSCAR subanalysis of subjects according to the presence of proteinuria. Kidney Int 2013; 84:1047. [DOI: 10.1038/ki.2013.310] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Woo KT, Wong KS, Choong HL, Foo MW, Tan HK, Chan CM. Angiotensin receptor blocker and calcium channel blocker combination prevents cardiovascular events in CKD better than high-dose ARB alone. Kidney Int 2013; 84:214-5. [DOI: 10.1038/ki.2013.124] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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The Authors Reply:. Kidney Int 2013; 84:215-6. [DOI: 10.1038/ki.2013.127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Garnock-Jones KP. Irbesartan/amlodipine: a review of its use in adult patients with essential hypertension not adequately controlled with monotherapy. Am J Cardiovasc Drugs 2013; 13:141-50. [PMID: 23516133 DOI: 10.1007/s40256-013-0014-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Combination therapy is often required in patients with hypertension, and fixed-dose single-pill combinations have been shown to provide an easier regimen for patients, improving adherence. Irbesartan/amlodipine (Aprovasc®) is an angiotensin-receptor blocker/calcium-channel blocker fixed-dose single-pill combination, whose constituent drugs exert additive effects when coadministered. In two randomized, open-label, multicentre, phase III trials, fixed-dose combination therapy with irbesartan/amlodipine was more effective than continuation of irbesartan or amlodipine monotherapy in patients with hypertension not adequately controlled with initial irbesartan or amlodipine monotherapy; there was a significantly greater decrease from baseline in mean seated home systolic blood pressure (primary endpoint) with the fixed-dose combination. The fixed-dose combination was also associated with a greater decrease in mean seated home diastolic blood pressure and mean seated office systolic and diastolic blood pressure than monotherapy. The fixed-dose combination of irbesartan/amlodipine was well tolerated in these patients; most treatment-emergent adverse events were of mild or moderate severity. The most frequent adverse event was peripheral oedema, generally associated with amlodipine treatment.
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Affiliation(s)
- Karly P Garnock-Jones
- Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand.
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Chrysant SG. Treating blood pressure to prevent strokes: The age factor. World J Cardiol 2013; 5:22-27. [PMID: 23539515 PMCID: PMC3610003 DOI: 10.4330/wjc.v5.i3.22] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2013] [Revised: 02/27/2013] [Accepted: 03/07/2013] [Indexed: 02/06/2023] Open
Abstract
The importance of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP), on the incidence of coronary heart disease (CHD) and stroke are known. However, the importance of blood pressure (BP)-age shifts regarding the stroke incidence is not clearly known. The BP changes with the advancement of age from the predominance of DBP in the young to the predominance of SBP in the old. This change is due to the stiffening of the large arteries as a result of the aging process and the replacement of the elastic fibers with collagen fibers. This change results in the loss of compliance and the elastic recoil of these vessels leading to increase in pulse wave velocity, central SBP and widening of pulse pressure leading to an increased incidence of CHD and strokes. It has been demonstrated epidemiologically that the SBP rises linearly with age, whereas the DBP rises up to the age of 45-50 years, and then begins to decline after the age of 60 years leading to a progressive widening of PP. Several studies have shown an inverse relationship between DBP and CHD, whereas no such relationship has been demonstrated for stroke. However, a recent study showed an inverse relationship with DBP and stroke when it dropped below 71 mmHg in subjects 50 years of age or older. In contrast, there was a positive association between BP and stroke when both SBP and DBP were ≥ 71 mmHg. These findings suggest that in treating systolic hypertension in the elderly to reduce stroke risk, attention should be paid on the potential harm of low DBP and the widening of PP regarding CHD and stroke. The implications of BP shifts with age and the potential risks of low DBP regarding the risk of stroke will be discussed in this concise review.
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The OSCAR for cardiovascular disease prevention in chronic kidney disease goes to blood pressure control. Kidney Int 2013; 83:20-2. [DOI: 10.1038/ki.2012.364] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Nistala R, Sowers JR. Hypertension: Synergy of antihypertensives in elderly patients with CKD. Nat Rev Nephrol 2012. [PMID: 23183840 DOI: 10.1038/nrneph.2012.264] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Ravi Nistala
- Diabetes and Cardiovascular Center, University of Missouri School of Medicine, One Hospital Drive, Columbia, MO 65212, USA
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