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Affiliation(s)
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Cited by Other Article(s) |
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1
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von Känel R. Stress-Induced Hypercoagulability: Insights from Epidemiological and Mechanistic Studies, and Clinical Integration. Semin Thromb Hemost 2025; 51:381-400. [PMID: 38914118 DOI: 10.1055/s-0044-1787660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/26/2024]
Abstract
By integrating findings from comprehensive reviews, meta-analyses, and cutting-edge genetic studies, this article illuminates the significance of stress-induced hypercoagulability in clinical medicine. In particular, the findings from numerous prospective cohort studies indicate that stress and hemostatic factors of a hypercoagulable state are associated with increased incident risk and poor prognosis for atherosclerotic cardiovascular disease and venous thromboembolism. Mendelian randomization studies suggest that these associations are partially causal. The review synthesizes extensive research on the link between acute and chronic stress and hypercoagulability, outlining a potential pathway from stress to thrombosis risk. Consistent with the allostatic load concept, acute stress-induced hypercoagulability, initially adaptive, can turn maladaptive under chronic stress or excessive acute stress, leading to arterial or venous thrombotic events. Individuals with predisposing factors, including atherosclerosis, thrombophilia, or immobilization, may exhibit an increased risk of thrombotic disease during stress. Contextual sociodemographic characteristics, the stress experience, and coping resources additionally modulate the extent of stress-induced hypercoagulability. Research into the neuroendocrine, cellular, and molecular bases reveals how stress influences platelet activation coagulation and fibrinolysis. The activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, along with vagal withdrawal, and the effects of catecholamines, cortisol, and vasopressin, are the central mechanisms involved. Hemoconcentration, inflammation, endothelial dysfunction, and thrombopoiesis additionally contribute to stress-induced hypercoagulability. Further research is needed to prove a causal link between chronic stress and hypercoagulability. This includes exploring its implications for the prevention and management of thrombotic diseases in stressed individuals, with a focus on developing effective psychosocial and pharmacological interventions.
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Affiliation(s)
- Roland von Känel
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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2
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Tomoda F, Koike T, Nitta A, Kurosaki H, Sugimori H, Oh-Hara M, Kinugawa K. Urinary levels of cortisol but not catecholamines are associated with those of 8-hydroxy-2'-deoxyguanosine in uncomplicated primary hypertension. J Hypertens 2023; 41:1571-1577. [PMID: 37642591 DOI: 10.1097/hjh.0000000000003507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/31/2023]
Abstract
OBJECTIVES The relationships between stress hormones and oxidative DNA damage have not yet been explored in human hypertension. We investigated the associations of urinary levels of cortisol or catecholamines with those of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage in primary hypertension. METHODS Untreated 156 primary hypertensives without apparent cardiovascular diseases were entered into the study. Following blood sampling after an overnight fast, 24-h blood pressure monitoring and 24-h urinary sampling were performed simultaneously to determine 24-h averaged values for blood pressure and urinary levels of cortisol, catecholamines and 8-hydroxy-2'-deoxyguanosine. RESULTS Urinary cortisol significantly correlated positively with urinary 8-hydroxy-2'-deoxyguanosine in all studied participants (r = 0.334, P < 0.001). Contrary, either urinary adrenaline or urinary noradrenaline did not significantly correlate with urinary 8-hydroxy-2'-deoxyguanosine (r = 0.050, P = 0.553 or r = 0.063, P = 0.435). Additionally, the positive association of urinary cortisol with urinary 8-hydroxy-2'-deoxyguanosine remained highly significant after the adjustments for multiple confounders of oxidative stress such as age, gender, body mass index, smoking status, 24-h blood pressure, C-reactive protein and estimated glomerular filtration rate (partial r = 0.323, P < 0.001), although only approximately 10% of the variance in urinary cortisol was attributable to differences in urinary 8-OHdG (partial r2 = 0.104). Thus, our data indicate that cortisol but not catecholamines could at least partially contribute to the occurrence of oxidative DNA damage in primary hypertensives. CONCLUSION The present study suggested the possibility that the overactivation of hypothalamic-pituitary-adrenal axis rather than sympathoadrenal system could enhance oxidative stress and attendant DNA oxidation in uncomplicated primary hypertension.
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Affiliation(s)
- Fumihiro Tomoda
- The Faculty of Health Science, Fukui Health Science University, Fukui
- The Second Department of Internal Medicine
| | | | - Atsumi Nitta
- The Department of Pharmaceutical Therapy & Neuropharmacology, University of Toyama, Toyama, Japan
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3
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Walther LM, Wirtz PH. Physiological reactivity to acute mental stress in essential hypertension-a systematic review. Front Cardiovasc Med 2023; 10:1215710. [PMID: 37636310 PMCID: PMC10450926 DOI: 10.3389/fcvm.2023.1215710] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 07/27/2023] [Indexed: 08/29/2023] Open
Abstract
Objective Exaggerated physiological reactions to acute mental stress (AMS) are associated with hypertension (development) and have been proposed to play an important role in mediating the cardiovascular disease risk with hypertension. A variety of studies compared physiological reactivity to AMS between essential hypertensive (HT) and normotensive (NT) individuals. However, a systematic review of studies across stress-reactive physiological systems including intermediate biological risk factors for cardiovascular diseases is lacking. Methods We conducted a systematic literature search (PubMed) for original articles and short reports, published in English language in peer-reviewed journals in November and December 2022. We targeted studies comparing the reactivity between essential HT and NT to AMS in terms of cognitive tasks, public speaking tasks, or the combination of both, in at least one of the predefined stress-reactive physiological systems. Results We included a total of 58 publications. The majority of studies investigated physiological reactivity to mental stressors of mild or moderate intensity. Whereas HT seem to exhibit increased reactivity in response to mild or moderate AMS only under certain conditions (i.e., in response to mild mental stressors with specific characteristics, in an early hyperkinetic stage of HT, or with respect to certain stress systems), increased physiological reactivity in HT as compared to NT to AMS of strong intensity was observed across all investigated stress-reactive physiological systems. Conclusion Overall, this systematic review supports the proposed and expected generalized physiological hyperreactivity to AMS with essential hypertension, in particular to strong mental stress. Moreover, we discuss potential underlying mechanisms and highlight open questions for future research of importance for the comprehensive understanding of the observed hyperreactivity to AMS in essential hypertension.
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Affiliation(s)
- Lisa-Marie Walther
- Biological Work and Health Psychology, University of Konstanz, Konstanz, Germany
- Centre for the Advanced Study of Collective Behaviour, University of Konstanz, Konstanz, Germany
| | - Petra H. Wirtz
- Biological Work and Health Psychology, University of Konstanz, Konstanz, Germany
- Centre for the Advanced Study of Collective Behaviour, University of Konstanz, Konstanz, Germany
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4
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Oida M, Suzuki S, Arita T, Yagi N, Otsuka T, Kishi M, Semba H, Kano H, Matsuno S, Kato Y, Uejima T, Oikawa Y, Hoshino S, Matsuhama M, Inoue T, Yajima J, Yamashita T. Seasonal Variations in the Incidence of Ischemic Stroke, Extracranial and Intracranial Hemorrhage in Atrial Fibrillation Patients. Circ J 2020; 84:1701-1708. [PMID: 32863288 DOI: 10.1253/circj.cj-20-0134] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Ischemic stroke (IS) and major bleeding, which are serious adverse events in patients with atrial fibrillation (AF), could have seasonal variations, but there are few reports. METHODS AND RESULTS In the Shinken Database 2004-2016 (n=22,018), 3,581 AF patients (average age, 63.5 years; 2,656 men, 74.2%; 1,388 persistent AF, 38.8%) were identified. Median CHADS2and HAS-BLED scores were both 1 point. Oral anticoagulants were prescribed for 2,082 (58.1%) patients (warfarin, 1,214; direct oral anticoagulants [DOACs], 868). Incidence and observation period (maximum 3 years) of IS, extracranial hemorrhage (ECH), and intracranial hemorrhage (ICH) were counted separately for the northern hemisphere seasons. During the mean follow-up period of 2.4 years, there were totals of 90 IS, 73 ECH, and 33 ICH cases. The respective incidence rates per 1,000 patient-years in spring, summer, autumn, and winter were 8.5, 8.8, 7.5, and 16.8 for IS, 7.2, 9.7, 3.8, and 13.1 for ECH, and 2.7, 1.9, 3.8, and 7.0 for ICH. The number of patients with DOACs relatively increased among those with ECH in summer. CONCLUSIONS Significant seasonal variations were observed for IS, ECH, and ICH events in AF patients, and were consistently the highest in winter. A small peak of ECH was observed in summer, which seemed, in part, to be related to increased DOAC use.
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Affiliation(s)
- Mitsunori Oida
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Shinya Suzuki
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Takuto Arita
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Naoharu Yagi
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Takayuki Otsuka
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Mikio Kishi
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Hiroaki Semba
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Hiroto Kano
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Shunsuke Matsuno
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Yuko Kato
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Tokuhisa Uejima
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Yuji Oikawa
- Department of Cardiovascular Medicine, The Cardiovascular Institute
| | - Satoshi Hoshino
- Department of Cardiovascular Surgery, The Cardiovascular Institute
| | - Minoru Matsuhama
- Department of Cardiovascular Surgery, The Cardiovascular Institute
| | - Tatsuya Inoue
- Department of Cardiovascular Surgery, The Cardiovascular Institute
| | - Junji Yajima
- Department of Cardiovascular Medicine, The Cardiovascular Institute
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5
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Koudouovoh-Tripp P, Hüfner K, Egeter J, Kandler C, Giesinger JM, Sopper S, Humpel C, Sperner-Unterweger B. Stress Enhances Proinflammatory Platelet Activity: the Impact of Acute and Chronic Mental Stress. J Neuroimmune Pharmacol 2020; 16:500-512. [PMID: 32757120 PMCID: PMC8087592 DOI: 10.1007/s11481-020-09945-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 07/12/2020] [Indexed: 01/04/2023]
Abstract
The role of platelets in hemostasis and thrombosis has long been recognized, recently their contribution to immunological and inflammatory processes is emerging. Platelets could be the missing link between cardiovascular disease, chronic stress and depressive symptoms. Both physical and mental stressors cause platelet activation reflected by changes in platelet bioactivity and aggregation. Here we evaluate the proinflammatory platelet response to acute and chronic mental stress. In a prospective study design an acute mental stress test was administered to 55 healthy male participants once without and once in the presence of chronic mental stress. Blood was collected prior to and at three time points following an acute mental stress test (0, 30, 60 min). Platelet proinflammatory activation markers, were assessed using FACS analysis and aggregability was measured in response to ADP or epinephrine using PFA-100. A linear mixed model was used for analysis. Chronic mental stress lead to a significant increase in state anxiety (p < 0.001), depressive symptoms (p = 0.045) and perceived stress (p = 0.001). The factor “chronic mental stress” was significantly associated with increased numbers of CD63+ platelets (p = 0.009). The factor “acute mental stress” was associated with alterations in CD62P+ platelets (p < 0.001), CD63+ platelets (p = 0.011), PAC-1+ platelets (p < 0.001) as well as platelet leucocyte aggregates (p = 0.019). The recovery of CD62P function following the acute mental stress exposure was significantly impaired by chronic stress (p = 0.023). Aggregation was affected by chronic and acute mental stress. In conclusion, mental stress is linked to an increased and prolonged proinflammatory platelet bioactivity. This proinflammatory and immunomodulatory stimuli could help to explain the link between mental and somatic disorders.
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Graphical Abstract
- Pia Koudouovoh-Tripp
- Department of Psychiatry, Psychotherapy and Psychosomatics, Division of Psychiatry I, Medical University Innsbruck, Innsbruck, Austria
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- Katharina Hüfner
- Department of Psychiatry, Psychotherapy and Psychosomatics, Division of Psychiatry II, Medical University Innsbruck, Innsbruck, Austria.
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- Jonas Egeter
- Department of Psychiatry, Psychotherapy and Psychosomatics, Division of Psychiatry II, Medical University Innsbruck, Innsbruck, Austria
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- Christina Kandler
- Department of Psychiatry, Psychotherapy and Psychosomatics, Division of Psychiatry II, Medical University Innsbruck, Innsbruck, Austria
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- Johannes M Giesinger
- Department of Psychiatry, Psychotherapy and Psychosomatics, Division of Psychiatry II, Medical University Innsbruck, Innsbruck, Austria
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- Sieghart Sopper
- Clinic for Hematology and Oncology, Flow Cytometry Unit, Medical University Innsbruck, Innsbruck, Austria
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- Christian Humpel
- Laboratory of Psychiatry and Exp. Alzheimer's Research, Medical University Innsbruck, Innsbruck, Austria
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- Barbara Sperner-Unterweger
- Department of Psychiatry, Psychotherapy and Psychosomatics, Division of Psychiatry II, Medical University Innsbruck, Innsbruck, Austria
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Yu Z, Shibazaki M, Otsuka H, Takada H, Nakamura M, Endo Y. Dynamics of Platelet Behaviors as Defenders and Guardians: Accumulations in Liver, Lung, and Spleen in Mice.
Biol Pharm Bull 2020;
42:1253-1267. [PMID:
31366863 DOI:
10.1248/bpb.b18-00975]
[Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Systemic platelet behaviors in experimental animals are often assessed by infusion of isotope-labeled platelets and measuring them under anesthesia. However, such procedures alter, therefore may not reveal, real-life platelet behaviors. 5-Hydroxytryptamine (5HT or serotonin) is present within limited cell-types, including platelets. In our studies, by measuring 5HT as a platelet-marker in non-anesthetized mice, we identified stimulation- and time-dependent accumulations in liver, lung, and/or spleen as important systemic platelet behaviors. For example, intravenous, intraperitoneal, or intragingival injection of lipopolysaccharide (LPS, a cell-wall component of Gram-negative bacteria), interleukin (IL)-1, or tumor necrosis factor (TNF)-α induced hepatic platelet accumulation (HPA) and platelet translocation into the sinusoidal and perisinusoidal spaces or hepatocytes themselves. These events occurred "within a few hours" of the injection, caused hypoglycemia, and exhibited protective or causal effects on hepatitis. Intravenous injection of larger doses of LPS into normal mice, or intravenous antigen-challenge to sensitized mice, induced pulmonary platelet accumulation (PPA), as well as HPA. These reactions occurred "within a few min" of the LPS injection or antigen challenge and resulted in shock. Intravenous injection of 5HT or a catecholamine induced a rapid PPA "within 6 s." Intravenous LPS injection, within a minute, increased the pulmonary catecholamines that mediate the LPS-induced PPA. Macrophage-depletion from liver and spleen induced "day-scale" splenic platelet accumulation, suggesting the spleen is involved in clearing senescent platelets. These findings indicate the usefulness of 5HT as a marker of platelet behaviors, and provide a basis for a discussion of the roles of platelets as both "defenders" and "guardians."
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Affiliation(s)
- Zhiqian Yu
- Department of Disaster Psychiatry, International Research Institute for Disaster Science, Tohoku University
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- Masahiro Shibazaki
- Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University
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- Hirotada Otsuka
- Laboratory of Veterinary Anatomy, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University
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- Haruhiko Takada
- Department of Microbiology and Immunology, Graduate School of Dentistry, Tohoku University
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- Masanori Nakamura
- Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University
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- Yasuo Endo
- Division of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Tohoku University
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7
Dias A, Franco E, Janzer S, Koshkelashvili N, Bhalla V, Rubio M, Amanullah S, Hebert K, Figueredo VM. Incidence and predictors of stroke during the index event in an ethnically diverse Takotsubo cardiomyopathy population.
FUNCTIONAL NEUROLOGY 2017;
31:157-62. [PMID:
27678209 DOI:
10.11138/fneur/2016.31.3.157]
[Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Takotsubo cardiomyopathy (TTS) is a peculiar clinical condition often affecting postmenopausal women after a stressful trigger. The underlying mechanisms have not been completely elucidated but several hypotheses have been advanced, with catecholamine cardiotoxicity, microvascular dysfunction and coronary artery spasm each suggested to play a role. The incidence of stroke after TTS appears to range from 0% to 7.7%, and interestingly TTS has been described as both a cause and a complication of stroke. We sought to assess the incidence and predictors of stroke during the index event (peri-index event stroke) in a heterogeneous TTS population. We conducted a retrospective descriptive study reviewing patients who were discharged with a diagnosis of TTS from the Einstein Medical Center, Philadelphia, PA and Danbury Hospital, Danbury, CT in the period between 2003 and 2014. A total of Incidence and predictors of stroke during the index event in an ethnically diverse Takotsubo cardiomyopathy population 206 patients met the modified Mayo Clinic criteria and were included in the study. The patients' overall mean age was 67.8 years; 87% (n=179) were females and 25% (n=53) were African Americans. The following incidence rates were found: stroke 7%, in-hospital heart failure 26.7%, and in-hospital death 7%. On multivariate analysis independent predictors (expressed as odds ratios with 95% confidence intervals) of periindex event stroke were: i) African American race (OR 3.2, 95% CI 1.2-10.2, p=0.048); ii) hypertension (OR 10.5, 95% CI 1.3-88, p=0.03). ACE inhibitor use was a protective factor for developing peri-index event stroke (OR 0.15, 95% CI 0.04-0.5, p=0.001). There was a trend towards dual antiplatelet therapy (DAPT) being protective for stroke (OR 0.3, 95% CI 0.05-1.1, p=0.08). The incidence of peri-index event stroke was 7%. African American race and hypertension were found to be independent predictors of peri-index event stroke. Prospective clinical trials are needed to confirm these findings and to better determine the impact of hypertension as a risk factor for stroke and to assess the role of DAPT in preventing it.
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8
Yu Z, Saito H, Otsuka H, Shikama Y, Funayama H, Sakai M, Murai S, Nakamura M, Yokochi T, Takada H, Sugawara S, Endo Y. Pulmonary platelet accumulation induced by catecholamines: Its involvement in lipopolysaccharide-induced anaphylaxis-like shock.
Int Immunopharmacol 2016;
43:40-52. [PMID:
27939824 DOI:
10.1016/j.intimp.2016.11.034]
[Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 10/29/2016] [Accepted: 11/29/2016] [Indexed: 11/15/2022]
Abstract
Intravenously injected lipopolysaccharides (LPS) rapidly induce pulmonary platelet accumulation (PPA) and anaphylaxis-like shock (ALS) in mice. Macrophages reportedly release catecholamines rapidly upon stimulation with LPS. Here, we examined the involvement of macrophage-derived catecholamines in LPS-induced PPA and ALS. A catecholamine or Klebsiella O3 (KO3) LPS was intravenously injected into mice, with 5-hydroxytryptamine in the lung being measured as a platelet marker. The tested catecholamines induced PPA, leading to shock. Their minimum shock-inducing doses were at the nmol/kg level. The effects of epinephrine and norepinephrine were inhibited by prazosin (α1 antagonist) and by yohimbine (α2 antagonist), while dopamine's were inhibited only by prazosin. Use of synthetic adrenergic α1- and/or α2-agonists, platelet- or macrophage-depleted mice, a complement C5 inhibitor and C5-deficient mice revealed that (a) α2-receptor-mediated PPA and shock depend on both macrophages and complements, while α1-receptor-mediated PPA and shock depend on neither macrophages nor complements, (b) the PPA and ALS induced by KO3-LPS depend on α1- and α2-receptors, macrophages, and complements, and (c) KO3-LPS-induced PPA is preceded by catecholamines decreasing in serum. Together, these results suggest the following. (i) Catecholamines may stimulate macrophages and release complement C5 via α2-receptors. (ii) Macrophage-derived catecholamines may mediate LPS-induced PPA and ALS. (iii) Moderate PPA may serve as a defense mechanism to remove excess catecholamines from the circulation by promoting their rapid uptake, thus preventing excessive systemic effects. (iv) The present findings might provide an insight into possible future pharmacological strategies against such diseases as shock and acute respiratory distress syndrome.
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Affiliation(s)
- Zhiqian Yu
- Division of Molecular Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Department of Disaster Psychiatry, International Research Institute for Disaster Science, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
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- Hiroko Saito
- Laboratory of Pharmacology, Faculty of Pharmaceutical Science, Aomori University, 2-3-1 Koubata, Aomori 030-0943, Japan
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- Hirotada Otsuka
- Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
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- Yosuke Shikama
- Division of Molecular Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503, Japan
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- Hiromi Funayama
- Division of Molecular Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Division of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Department of Pediatric Dentistry, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan
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- Mai Sakai
- Department of Disaster Psychiatry, International Research Institute for Disaster Science, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
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- Shigeo Murai
- Laboratory of Pharmacology, Faculty of Pharmaceutical Science, Aomori University, 2-3-1 Koubata, Aomori 030-0943, Japan
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- Masanori Nakamura
- Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
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- Takashi Yokochi
- Department of Microbiology and Immunology, Aichi Medical University, Nagakute, Aichi 48-1955, Japan
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- Haruhiko Takada
- Division of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
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- Shunji Sugawara
- Division of Molecular Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
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- Yasuo Endo
- Division of Molecular Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
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9
Dias A, Franco E, Koshkelashvili N, Bhalla V, Pressman GS, Hebert K, Figueredo VM. Antiplatelet therapy in Takotsubo cardiomyopathy: does it improve cardiovascular outcomes during index event?
Heart Vessels 2015;
31:1285-90. [PMID:
26266632 DOI:
10.1007/s00380-015-0729-2]
[Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2015] [Accepted: 08/05/2015] [Indexed: 10/23/2022]
Abstract
Plasma catecholamines may play an important role in Takotsubo cardiomyopathy (TCM) pathophysiology. Patients with disproportionately high catecholamine responses to stressful events are prone to worse clinical outcomes. Catecholamines stimulate platelet activation and, therefore, may determine the clinical presentation and outcomes of TCM. We conducted a retrospective, descriptive study TCM patients admitted between 2003 and 2013 to Einstein Medical Center, Philadelphia, PA, USA and Danbury Hospital, Danbury, CT, USA. A total of 206 patients met Modified Mayo TCM criteria. Using a multiple logistic model, we tested whether aspirin, dual antiplatelet therapy (DAPT) aspirin + clopidogrel, beta blocker, statin, or ACE inhibitor use were independent predictors of major adverse cardiovascular events (MACE) during the index hospitalization. MACE was defined as in-hospital heart failure, in-hospital death, stroke or respiratory failure requiring mechanical ventilation. Incidence of in-hospital heart failure was 26.7 %, in-hospital death was 7.3 %, stroke was 7.3 % and MACE was 42.3 %. In a multiple logistic regression model (adjusted for gender, race, age, physical stressor, hypertension, diabetes, hyperlipidemia, smoking history, body mass index, initial left ventricular ejection fraction, single antiplatelet therapy, DAPT, beta blocker, statin, and ACE inhibitor) aspirin and DAPT at the time of hospitalization were independent predictors of a lower incidence of MACE during the index hospitalization (aspirin: OR 0.4, 95 % CI (0.16-0.9), P = 0.04; DAPT: OR 0.23; 95 % CI (0.1-0.55); P < 0.01. Physical stressor itself was also found to be an independent predictor of worse MACE: OR 5.1; 95 % CI (2.4-11.5); P < 0.01. In our study, aspirin and DAPT were independent predictors of a lower incidence of MACE during hospitalization for TCM. Prospective clinical trials are needed to confirm the findings of this study.
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Affiliation(s)
- Andre Dias
- Department of Cardiology, Einstein Medical Center, 5501 Old York Road, Philadelphia, PA, 19141, USA. .,Western Connecticut Health Network, Danbury, CT, USA.
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- Emiliana Franco
- Department of Cardiology, Einstein Medical Center, 5501 Old York Road, Philadelphia, PA, 19141, USA.,Western Connecticut Health Network, Danbury, CT, USA
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- Vikas Bhalla
- Department of Cardiology, Einstein Medical Center, 5501 Old York Road, Philadelphia, PA, 19141, USA
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- Gregg S Pressman
- Department of Cardiology, Einstein Medical Center, 5501 Old York Road, Philadelphia, PA, 19141, USA
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- Kathy Hebert
- Department of Cardiology, University of Miami, Miami, FL, USA
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- Vincent M Figueredo
- Department of Cardiology, Einstein Medical Center, 5501 Old York Road, Philadelphia, PA, 19141, USA.,Sidney Kimmel College of Medicine at Thomas Jefferson University, Philadelphia, PA, USA
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10
Núñez-Gil IJ, Bernardo E, Feltes G, Escaned J, Mejía-Rentería HD, De Agustín JA, Vivas D, Nombela-Franco L, Jiménez-Quevedo P, Macaya C, Fernández-Ortiz A. Platelet function in Takotsubo cardiomyopathy.
J Thromb Thrombolysis 2014;
39:452-8. [DOI:
10.1007/s11239-014-1109-y]
[Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Koudouovoh-Tripp P, Sperner-Unterweger B. Influence of mental stress on platelet bioactivity.
World J Psychiatry 2012;
2:134-47. [PMID:
24175179 PMCID:
PMC3782187 DOI:
10.5498/wjp.v2.i6.134]
[Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2011] [Revised: 10/10/2012] [Accepted: 10/23/2012] [Indexed: 02/05/2023] Open
Abstract
It is well established that various mental stress conditions contribute, or at least influence, underlying pathophysiological mechanisms in somatic, as well as in psychiatric disorders; blood platelets are supposed to represent a possible link in this respect. The anculeated platelets are the smallest corpuscular elements circulating in the human blood. They display different serotonergic markers which seem to reflect the central nervous serotonin metabolism. They are known as main effectors in haematological processes but recent research highlights their role in the innate and adaptive immune system. Platelets are containing a multitude of pro-inflammatory and immune-modulatory bioactive compounds in their granules and are expressing immune-competent surface markers. Research gives hint that platelets activation and reactivity is increased by mental stress. This leads to enhanced cross talk with the immune system via paracrine secretion, receptor interaction and formation of platelet leucocyte-aggregates. Recently it has been demonstrated that the immune system can have a remarkable impact in the development of psychiatric disorders. Therefore platelets represent an interesting research area in psychiatry and their role as a possible biomarker has been investigated. We review the influence of mental stress on what is termed platelet bioactivity in this article, which subsumes the mainly immune-modulatory activity of platelets in healthy volunteers, elderly persons with chronic care-giving strain, patients with cardiovascular diseases who are prone to psychosocial stress, as well as in patients with posttraumatic stress disorder. Research data suggest that stress enhances platelet activity, reactivity and immune-modulatory capacities.
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Affiliation(s)
- Pia Koudouovoh-Tripp
- Pia Koudouovoh-Tripp, Clinic for Biological Psychiatry, Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria
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12
Blood rheology and platelet function in untreated early-stage essential hypertensives complicated with metabolic syndrome.
Int J Hypertens 2012;
2012:109830. [PMID:
22570768 PMCID:
PMC3337609 DOI:
10.1155/2012/109830]
[Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2011] [Accepted: 02/28/2012] [Indexed: 11/22/2022] Open
Abstract
We examined whether hemorheology and platelet function are affected in essential hypertensives (EHTs) of the World Health Organization stage I when complicated with metabolic syndrome (Mets). In 156 untreated EHTs, blood viscosity and platelet surface markers were determined. Blood viscosity was significantly elevated in 54 subjects with Mets compared with 102 subjects without Mets. Hematocrit and plasma viscosity increased in the group with Mets, although red blood cell rigidity index “k” did not differ between groups. As a whole group, blood viscosity correlated positively with hematocrit and plasma viscosity. Additionally, plasma viscosity correlated positively with plasma leptin, triglyceride, homeostasis model assessment index, C-reactive protein, and plasma fibrinogen, but negatively with high-density lipoprotein cholesterol. In contrast, no differences were seen in platelet surface markers between groups. In conclusion, EHTs of the early stage complicated with Mets are characterized by increased blood viscosity due to hemoconcentration and increased plasma viscosity.
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13
Austin AW, Patterson SM, von Känel R. Hemoconcentration and hemostasis during acute stress: interacting and independent effects.
Ann Behav Med 2012;
42:153-73. [PMID:
21562905 DOI:
10.1007/s12160-011-9274-0]
[Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND
Acute psychological stress can produce significant hemoconcentration as well as prothrombotic changes in blood, both of which may have potentially harmful effects on the cardiovascular system. It is unclear whether these effects are independent or have influence on each other.
PURPOSE
This review discusses research investigating the effects of acute psychological stress on hemoconcentration and hemostasis and explores future directions for psychohematology research. Physiology, associations with cardiovascular disease, and relationships between acute psychological stress are discussed independently for hemoconcentration and hemostasis, followed by an examination of the effects of stress-hemoconcentration on hemostasis.
CONCLUSIONS
Traditional methods of adjusting for stress-hemoconcentration effects (e.g., calculated plasma volume or hematocrit level corrections) may not be appropriate when examining stress-induced changes in hemostasis. The effects of acute stress on hemostasis should be examined in conjunction with hemoconcentration.
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14
Ishikawa S, Suga H, Fukushima M, Yoshida A, Yoshida Y, Sunagawa M, Hisamitsu T. Blood fluidity enhancement by electrical acupuncture stimulation is related to an adrenergic mechanism.
J Acupunct Meridian Stud 2011;
5:21-8. [PMID:
22309904 DOI:
10.1016/j.jams.2011.11.003]
[Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2011] [Accepted: 09/09/2011] [Indexed: 10/14/2022] Open
Abstract
We have reported that electrical acupuncture stimulation (ACU) increases blood fluidity by decreasing platelet aggregation. In this study, we investigated the mechanism causing the increase of blood fluidity. The effects of ACU on blood fluidity and platelet adhesion were examined using a Micro Channel Array Flow Analyzer (MC-FAN) and a laser scattering platelet aggregometer (PA-20). Male Wistar rats (7-8 weeks old) were used in the study. ACU (1 or 100 Hz, 3-5 V), which causes slight muscle twitching, was applied to the ZuSanli (ST-36) acupoint for 15 or 60 minutes once/day. Blood samples were collected from the inferior vena cava. ACU applied to ST-36 revealed significant increases in blood fluidity, while platelet adhesion activity decreased, regardless of the difference of stimulus time. The acupuncture had an immediate effect. Even if naloxone was administered during acupuncture stimulus, the blood flow time shortened in a similar way, as in the only acupuncture stimulus group. In addition, the effect of acupuncture on blood fluidity was inhibited by a β-antagonist. The results indicate that ACU affects blood fluidity depending on the acupoints, and that the effect of ACU might involve an endogenous adrenergic mechanism.
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Affiliation(s)
- Shintaro Ishikawa
- Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
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15
Ishikawa S, Murai M, Sato T, Sunagawa M, Tokita E, Aung SK, Asano K, Hisamitsu T. Promotion of Blood Fluidity by Inhibition of Platelet Adhesion Using Electroacupuncture Stimulation.
J Acupunct Meridian Stud 2011;
4:44-53. [DOI:
10.1016/s2005-2901(11)60006-x]
[Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2010] [Accepted: 11/02/2010] [Indexed: 11/12/2022] Open
16
von Känel R, Kudielka BM, Haeberli A, Stutz M, Fischer JE, Patterson SM. Prothrombotic changes with acute psychological stress: combined effect of hemoconcentration and genuine coagulation activation.
Thromb Res 2008;
123:622-30. [PMID:
18614205 DOI:
10.1016/j.thromres.2008.05.014]
[Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2008] [Revised: 05/19/2008] [Accepted: 05/27/2008] [Indexed: 10/21/2022]
Abstract
INTRODUCTION
Acute psychosocial stress accelerates blood coagulation and elicits hemoconcentration which mechanisms are implicated in acute coronary thrombotic events. We investigated the extent to which the change in prothrombotic measures with acute stress reflects hemoconcentration and genuine activation of coagulation.
MATERIAL AND METHODS
Twenty-one middle-aged healthy men underwent three sessions of a combined speech and mental arithmetic task with one-week intervals. Coagulation and plasma volume were assessed at baseline, immediately post-stress, and 45 min post-stress at sessions one and three. Measures of both visits were aggregated to enhance robustness of individual biological stress responses. Changes in eight coagulation measures with and without adjustment for simultaneous plasma volume shift were compared.
RESULTS
From baseline to immediately post-stress, unadjusted levels of fibrinogen (p=0.028), clotting factor VII activity (FVII:C) (p=0.001), FVIII:C (p<0.001), FXII:C (p<0.001), and von Willebrand factor (VWF) (p=0.008) all increased. Taking into account hemoconcentration, fibrinogen (p=0.020) and FVII:C levels (p=0.001) decreased, activated partial prothrombin time (APPT) shortened (p<0.001) and prothrombin time (PT) was prolonged (p<0.001). Between baseline and 45 min post-stress, unadjusted (p=0.050) and adjusted (p=0.001) FVIII:C levels increased, adjusted APTT was prolonged (p=0.017), and adjusted PT was shortened (p=0.033). D-dimer levels did not significantly change over time.
CONCLUSIONS
Adjustment for stress-hemoconcentration altered the course of unadjusted levels of several prothrombotic factors. After adjustment for hemoconcentration, APPT was shortened immediately post-stress, whereas 45 min post-stress, FVIII:C was increased and PT was shortened. Procoagulant changes to acute stress may reflect both hemoconcentration and genuine activation of coagulation molecules and pathways.
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Affiliation(s)
- Roland von Känel
- Department of General Internal Medicine, University Hospital / INSELSPITAL, CH-3010 Bern/ Switzerland.
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17
Wirtz PH, Ehlert U, Emini L, Rüdisüli K, Groessbauer S, von Känel R. Procoagulant stress reactivity and recovery in apparently healthy men with systolic and diastolic hypertension.
J Psychosom Res 2007;
63:51-8. [PMID:
17586337 DOI:
10.1016/j.jpsychores.2007.01.014]
[Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2006] [Revised: 01/16/2007] [Accepted: 01/18/2007] [Indexed: 11/23/2022]
Abstract
OBJECTIVE
The aim of this study was to investigate whether systemic systolic hypertension (SHT) and diastolic hypertension (DHT) are associated with an exaggerated response of factor VII clotting activity (FVII:C), factor VIII clotting activity (FVIII:C), fibrinogen, and d-dimer to acute psychosocial stress.
METHODS
We performed the 15-min Trier Social Stress Test (i.e., combination of task preparation, job interview and mental arithmetic) in a sample of 42 middle-aged apparently healthy and unmedicated men with normal and elevated blood pressure (BP) (i.e. screening systolic and/or diastolic BP>or=130/85 mmHg). Blood samples for coagulation measures were obtained immediately pre and post stress and 20 min and 60 min thereafter. Repeated measures analyses of covariance controlled for age, body mass index, screening mean arterial BP, and resting level of coagulation factors.
RESULTS
There was a stress-by-DHT interaction for changes across all time points in FVII:C (P=.027), FVIII:C (P=.018), and d-dimer (P=.011) explaining between 14% and 17% of the variance. Compared to subjects without DHT, diastolic hypertensives had higher FVII:C immediately post stress (P=.085, Cohen's d=.60) and at 20-min recovery (P=.19, d=.46), higher FVIII:C at 20- (P=.028, d=.78) and at 60-min (P=.035, d=.75) recovery, and higher D-dimer at 20-min recovery (P=.10, d=.58). A significant stress-by-SHT interaction for fibrinogen (P=.050) became nonsignificant when controlling for covariates.
CONCLUSION
Diastolic hypertension exaggerated the acute procoagulant response to stress in middle-aged men. This effect was particularly observed during recovery of hypercoagulability from stress. The findings suggest a psychobiological mechanism linking stress with an increased atherothrombotic risk in hypertensive individuals.
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Affiliation(s)
- Petra H Wirtz
- Department of Clinical Psychology and Psychotherapy, University of Zurich, Zurich, and Department of General Internal Medicine, University Hospital Berne, Switzerland
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18
Torres SJ, Nowson CA. Effect of a weight-loss program on mental stress–induced cardiovascular responses and recovery.
Nutrition 2007;
23:521-8. [PMID:
17560080 DOI:
10.1016/j.nut.2007.04.016]
[Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2006] [Revised: 04/24/2007] [Accepted: 04/26/2007] [Indexed: 11/17/2022]
Abstract
OBJECTIVE
We assessed the effect of weight loss on blood pressure (BP) and pulse rate during rest, psychological stress, and recovery after stress.
METHODS
Two groups of men completed two mental stress tests 12 wk apart. The control group continued their usual diet, whereas the weight-loss group underwent a dietary weight-loss program in which they were randomized to a high-fruit/vegetable and low-fat dairy diet or a low-fat diet.
RESULTS
Fifty-five men with a baseline BP of 125.9 +/- 6.9/83.6 +/- 7.1 mmHg (mean +/- SD) completed the study (weight-loss group, n = 28; control group, n = 27). The weight-loss group lost weight (mean +/- SEM, -4.3 +/- 0.3 versus +0.4 +/- 0.4 kg, P = 0.001) compared with controls and had a significant decrease in resting systolic BP (SBP; -2.0 +/- 1.1% versus +2.0 +/- 1.1%, P < 0.05). There was a greater decrease in SBP (P < 0.05) and pulse rate (P < 0.05) at all time points during the stress test in the weight loss compared with the control group. At week 12, SBP in 23 (82%) subjects in the weight-loss group and 24 (89%) in the control group returned to resting levels, with recovering levels in the weight-loss group returning to resting levels 6.1 +/- 2.6 min earlier than in the control group (P < 0.05). There was an overall greater decrease in diastolic BP (DBP; P < 0.05) and DBP during recovery up to 27 min after stress (P < 0.05) in the high-fruit/vegetable and low-fat dairy diet group (n = 14) compared with the low-fat diet group (n = 14).
CONCLUSION
A 5% loss of weight decreased BP during rest and returned SBP to resting levels faster, thus decreasing the period of increased BP as a result of mental stress, which is likely to lower the risk of cardiovascular disease in the long term.
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Affiliation(s)
- Susan J Torres
- Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia.
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19
Waki H, Liu B, Miyake M, Katahira K, Murphy D, Kasparov S, Paton JFR. Junctional Adhesion Molecule-1 Is Upregulated in Spontaneously Hypertensive Rats.
Hypertension 2007;
49:1321-7. [PMID:
17420334 DOI:
10.1161/hypertensionaha.106.085589]
[Citation(s) in RCA: 82] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Junctional adhesion molecule-1 (JAM-1) forms part of the tight junction between adjacent endothelial cells. Using microarray technology, we showed previously that JAM-1 was differentially expressed in the brain stem of spontaneously hypertensive rats compared with normotensive Wistar-Kyoto (WKY) rats. In this study, we quantified the expression of JAM-1 in the brain stem of spontaneously hypertensive rats and WKY rats and established whether any differential expression was confined to this region of the brain or was ubiquitous throughout the central nervous system and, indeed, the whole body. Because the nucleus tractus solitarii plays a pivotal role in arterial pressure regulation, we assessed whether JAM-1 in this region affects the chronic regulation of arterial pressure. Real time RT-PCR revealed that JAM-1 mRNA was upregulated in multiple regions of the brain and all of the peripheral vascular beds studied. In the nucleus tractus solitarii, the level of JAM-1 mRNA was significantly higher in both young (3-week-old, prehypertensive) and adult male spontaneously hypertensive rats (15 to 18 weeks old) than that of age-matched WKY rats (fold differences; prehypertensives: 1.01+/-0.06 versus 1.59+/-0.13; n=10; P<0.01; adult: 1.08+/-0.14 versus 2.86+/-0.57; n=10; P<0.01). After adenoviral-mediated expression of JAM-1 in the nucleus tractus solitarii of adult WKY rats (15 weeks old; n=6), systolic pressure was increased from 120+/-4 to 132+/-4 mm Hg (P<0.01). Our data suggest that JAM-1 expression in the spontaneously hypertensive rat is upregulated throughout the body compared with the WKY rat and that this is not secondary to the hypertension. When JAM-1 is expressed in the nucleus tractus solitarii, it raises arterial pressure, suggesting a novel prohypertensive role for this protein within the brain stem.
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Affiliation(s)
- Hidefumi Waki
- Department of Physiology, Bristol Heart Institute, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.
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20
Thrall G, Lane D, Carroll D, Lip GYH. A systematic review of the effects of acute psychological stress and physical activity on haemorheology, coagulation, fibrinolysis and platelet reactivity: Implications for the pathogenesis of acute coronary syndromes.
Thromb Res 2007;
120:819-47. [PMID:
17321571 DOI:
10.1016/j.thromres.2007.01.004]
[Citation(s) in RCA: 96] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2006] [Revised: 09/28/2006] [Accepted: 01/01/2007] [Indexed: 12/18/2022]
Abstract
Physical activity and psychological stress are two potential triggers for the onset of acute coronary syndromes (ACS). To examine the mechanisms underlying this association, we systematically reviewed the literature to determine the effects of acute psychological stress and physical activity on haemorheology and haemostasis. Studies examining the haemorheological and haemostatic response to an acute bout of physical activity (i.e. <60 min) or laboratory psychological stress task were eligible for inclusion. The experimental evidence, although compromised by various methodological weaknesses, suggests that low and moderate intensity physical activity may be cardio-protective through beneficial effects on fibrinolytic system. High levels of physical activity, and psychological to a lesser extent, have been consistently associated with robust changes in haemorheology and haemostasis. Such findings imply that such activities may have the potential to trigger the onset of ACS, although in reality this may be limited sedentary individual and/or those with pre-existing vascular disease. In addition, the data also suggest that individuals may be at a greatest risk of stress-induced thrombogenesis in the period immediately following physical activity or psychological stress, rather than during the activity per se. In conclusion, psychological stress and physical activity may act as potential triggers for the onset of ACS via effects on haemostasis and haemorheology.
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Affiliation(s)
- Graham Thrall
- Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, England
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21
Wirtz PH, Ehlert U, Emini L, Rüdisüli K, Groessbauer S, Mausbach BT, von Känel R. The role of stress hormones in the relationship between resting blood pressure and coagulation activity.
J Hypertens 2006;
24:2409-16. [PMID:
17082723 DOI:
10.1097/hjh.0b013e32801098e5]
[Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND
Systemic hypertension confers a hypercoagulable state. We hypothesized that resting mean blood pressure (MBP) interacts with stress hormones in predicting coagulation activity at rest and with acute mental stress.
METHODS
We measured plasma clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, epinephrine and norepinephrine, and saliva cortisol in 42 otherwise healthy normotensive and hypertensive medication-free men (mean age 43 +/- 14 years) at rest, immediately after stress, and twice during 60 min of recovery from stress.
RESULTS
At rest, the MBP-by-epinephrine interaction predicted FVII:C (beta = -0.33, P < 0.04) and D-dimer (beta = 0.26, P < 0.05), and the MBP-by-cortisol interaction predicted D-dimer (beta = 0.43, P = 0.001), all independent of age and body mass index (BMI). Resting norepinephrine predicted fibrinogen (beta = 0.42, P < 0.01) and D-dimer (beta = 0.37, P < 0.03), both independent of MBP. MBP predicted FVIII:C change from rest to immediately post-stress independent of epinephrine (beta = -0.37, P < 0.03) and norepinephrine (beta = -0.38, P < 0.02). Cortisol change predicted FVIII:C change (beta = -0.30, P < 0.05) independent of age, BMI and MBP. Integrated norepinephrine change from rest to recovery (area under the curve, AUC) predicted D-dimer AUC (beta = 0.34, P = 0.04) independent of MBP. The MBP-by-epinephrine AUC interaction predicted FVII:C AUC (beta = 0.28) and fibrinogen AUC (beta = -0.30), and the MBP-by-norepinephrine AUC interaction predicted FVIII:C AUC (beta = -0.28), all with borderline significance (Ps < 0.09) and independent of age and BMI.
CONCLUSIONS
MBP significantly altered the association between stress hormones and coagulation activity at rest and, with borderline significance, across the entire stress and recovery interval. Independent of MBP, catecholamines were associated with procoagulant effects and cortisol reactivity dampened the acute procoagulant stress response.
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Affiliation(s)
- Petra H Wirtz
- Department of Clinical Psychology and Psychotherapy, University of Zurich, Switzerland
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22
Thrall G, Lip GYH. Haemoconcentration and the hypercoagulable state associated with mental stress.
Thromb Res 2005;
115:171-3. [PMID:
15617738 DOI:
10.1016/j.thromres.2004.08.021]
[Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2004] [Indexed: 10/26/2022]
23
Fogari R, Zoppi A. Is the effect of antihypertensive drugs on platelet aggregability and fibrinolysis clinically relevant?
Am J Cardiovasc Drugs 2005;
5:211-23. [PMID:
15984904 DOI:
10.2165/00129784-200505040-00001]
[Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Hypertension is associated with decreased fibrinolytic potential, mainly expressed as elevated plasma plasminogen activator inhibitor type 1 (PAI-1) levels, and increased platelet aggregability, which may account in part for the increased risk of atherosclerosis and its clinical complications in hypertensive patients. The effects of antihypertensive drugs on this prothrombotic state have been investigated and controversial findings have been reported, possibly because of differences in study designs, patients selected, and methodology used. Scarce and conflicting data exist about the effects of diuretics and beta-adrenoceptor antagonists on the fibrinolytic system, whereas ACE inhibitors have generally been reported to improve the fibrinolytic balance by decreasing plasma PAI-1 levels, calcium channel antagonists have been shown to increase tissue plasminogen activator (tPA) activity, and angiotensin II type 1 (AT(1)) receptor antagonists seem to exert neutral effects. beta-Adrenoceptor antagonists, calcium channel antagonists, and AT(1)-receptor antagonists have been reported to exert anti-aggregatory effects on platelets, while contrasting data exist about the influence of ACE inhibitors. Clinical implications of the changes induced by antihypertensive drugs on the fibrinolytic balance and platelet function are still debated. In particular, the question of whether these changes may translate into different degrees of cardiovascular protection in hypertensive patients remains unanswered. While awaiting more information from clinical trials, the choice of antihypertensive drugs, particularly in high-risk patients, should take into account effects beyond their BP-lowering efficacy. Selected agents should have a favorable, or at least neutral, impact on fibrinolytic function and platelet activity.
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Affiliation(s)
- Roberto Fogari
- Department of Internal Medicine and Therapeutics, Clinica Medica II, I.R.C.C.S. Policlinico San Matteo, University of Pavia, Pavia, Italy.
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24
Preckel D, von Känel R. Regulation of Hemostasis by the Sympathetic Nervous System: Any Contribution to Coronary Artery Disease?
HEARTDRUG : EXCELLENCE IN CARDIOVASCULAR TRIALS 2004;
4:123-130. [PMID:
19169370 PMCID:
PMC2629605 DOI:
10.1159/000078415]
[Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Within the last two decades, hemostasis factors have emerged as 'new' risk factors for coronary artery disease. Historical studies on the physiology of the sympathetic nervous system (SNS) attributed accelerated blood clotting to the components of the fight-flight response. Although this has not been demonstrated, exaggerated clotting related to SNS hyperactivity might confer an increased arterial thrombotic risk. This review outlines the effects of sympathetic activation as mimicked by adrenergic infusions and as elicited by mental stress and physical exercise, and the molecular mechanisms involved. A selective review of the pertinent literature was undertaken. Sympathetic activation provokes a simultaneous increase in molecules of both the coagulation and fibrinolysis pathways within minutes, resulting in net hypercoagulability as a part of normal human physiology. Catecholamines and adrenergic receptors interact to mediate hemostatic changes. Exaggerated procoagulant changes in individuals with a preexistent atherosclerotic disease, in those experiencing ongoing stressful life circumstances and in the physically untrained might confer a thrombotic threat with sympathetic activation. Initial evidence suggests that nonselective β-adrenergic blockade may attenuate clotting acceleration upon SNS activation. Prospective studies are needed to demonstrate whether exaggerated clotting as elicited by the SNS is associated with an increased risk of cardiovascular morbidity and mortality. If confirmed, intervention studies targeted at reducing this risk, for example with drugs, psychotherapy (including stress management) and regular physical exercise, would be warranted.
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Affiliation(s)
- Daniel Preckel
- Institute for Behavioral Sciences, Swiss Federal Institute of Technology, Zurich
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- Roland von Känel
- Institute for Behavioral Sciences, Swiss Federal Institute of Technology, Zurich
- Department of General Internal Medicine, University Hospital Bern, Bern, Switzerland
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25
Steptoe A, Magid K, Edwards S, Brydon L, Hong Y, Erusalimsky J. The influence of psychological stress and socioeconomic status on platelet activation in men.
Atherosclerosis 2003;
168:57-63. [PMID:
12732387 DOI:
10.1016/s0021-9150(02)00453-7]
[Citation(s) in RCA: 32] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE
Circulating monocyte- and neutrophil-platelet aggregates are sensitive markers of in vivo platelet activation. Socioeconomic status is inversely associated with risk of coronary heart disease. We assessed the impact of psychological stress on leukocyte-platelet aggregates in men from higher and lower socioeconomic status groups.
METHODS
Participants were 37 healthy non-smoking men aged 30-59 years, divided by occupation into higher and lower social status groups. Blood was drawn at baseline, immediately following stressful behavioural tasks, and at 30 and 75 min post-stress, and aggregates were analysed using flow cytometry. Cardiovascular and subjective stress responses were also monitored.
RESULTS
There were significant increases following stress in monocyte-, neutrophil-, lymphocyte- and total leukocyte-platelet aggregates (all P<0.05). The largest responses were in monocyte-platelet (21% increase) and neutrophil-platelet (16.7% increase) aggregates. Lower socioeconomic status men had greater numbers of leukocyte-platelet aggregates throughout, but the magnitude of stress responses did not vary with social status. The increase in monocyte- and leukocyte-platelet aggregates was associated with systolic blood pressure stress responsivity.
CONCLUSIONS
Psychological stress induces platelet activation as indexed by leukocyte-platelet aggregates, and correlations with cardiovascular stress reactions suggest that sympathoadrenal responses may be responsible. Platelet activation may be a mechanism through which social position influences cardiovascular disease risk.
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Affiliation(s)
- Andrew Steptoe
- Department of Epidemiology and Public Health, Psychobiology Group, University College London, UK.
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26
von Kanel R, Dimsdale JE, Adler KA, Dillon E, Perez CJ, Mills PJ. Effects of nonspecific beta-adrenergic stimulation and blockade on blood coagulation in hypertension.
J Appl Physiol (1985) 2003;
94:1455-9. [PMID:
12482765 DOI:
10.1152/japplphysiol.00892.2002]
[Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
A hypercoagulable state might contribute to increased atherothrombotic risk in hypertension. The sympathetic nervous system is hyperactive in hypertension, and it regulates hemostatic function. We investigated the effect of nonspecific beta-adrenergic stimulation (isoproterenol) and blockade (propranolol) on clotting diathesis in hypertension. Fifteen hypertensive and 21 normotensive subjects underwent isoproterenol infusion in two sequential, fixed-order doses of 20 and then 40 ng. kg(-1). min(-1) for 15 min/dose. Thirteen subjects were double-blind studied after receiving placebo or propranolol (100 mg/day) for 5 days each. In hypertensive subjects, isoproterenol elicited a dose-dependent increase in plasma von Willebrand factor (vWF) antigen [F(2,34) = 5.02; P = 0.032] and a decrease in D-dimer [F(2,34) = 4.57; P = 0.040], whereas soluble tissue factor remained unchanged. Propranolol completely abolished the increase in vWF elicited by isoproterenol [F(1,12) = 10.25; P = 0.008] but had no significant effect on tissue factor and D-dimer. In hypertension, vWF is readily released from endothelial cells by beta-adrenergic stimulation, which might contribute to increased cardiovascular risk. However, beta-adrenergic stimulation alone may not be sufficient to trigger fibrin formation in vivo.
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Affiliation(s)
- Roland von Kanel
- Department of Psychiatry, University of California, San Diego, California 92093, USA
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27
Xu YJ, Rathi SS, Chapman DC, Arneja AS, Dhalla NS. Mechanisms of lysophosphatidic acid-induced DNA synthesis in vascular smooth muscle cells.
J Cardiovasc Pharmacol 2003;
41:381-7. [PMID:
12605016 DOI:
10.1097/00005344-200303000-00006]
[Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
In order to investigate the signal transduction mechanisms of lysophosphatidic acid (LPA)-induced vascular smooth muscle (VSM) DNA synthesis, rat aortic A10 cells were used as an experimental model and [ H]-thymidine incorporation was used as an index of DNA synthesis. LPA caused dose- and time-dependent increase in DNA synthesis in A10 VSM cells. LPA (10 microM) also stimulated the activity of casein kinase II (CKII) in a time-dependent manner. The inhibitors of CKII, daidzein and 5,6-dichlorobenzimidazole riboside, diminished the LPA-induced increase in CKII activity and DNA synthesis. The LPA-stimulated activities of extracellularly regulated kinases (ERK) and p38 kinases as well as the stimulatory effects of LPA on DNA synthesis were blocked by ERK inhibitor, PD98059, and p38 kinase inhibitor, SB203580. The LPA-induced increase in intracellular free Ca and the LPA-induced DNA synthesis were not affected by Ca channel blockers, verapamil and diltiazem, as well as a Ca -dependent protein phosphatase (calcineurin) inhibitor, cyclosporine A. These data suggest that the LPA-induced DNA synthesis in VSM cells may be mediated by a signal transduction mechanism involving CKII, ERK, and p38 K.
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Affiliation(s)
- Yan-Jun Xu
- Institute of Cardiovascular Sciences, St Boniface General Hospital Research Center, Departments of Physiology and Internal Medicine, University of Manitoba, Winnipeg, Canada
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28
Preston RA, Jy W, Jimenez JJ, Mauro LM, Horstman LL, Valle M, Aime G, Ahn YS. Effects of severe hypertension on endothelial and platelet microparticles.
Hypertension 2003;
41:211-7. [PMID:
12574084 DOI:
10.1161/01.hyp.0000049760.15764.2d]
[Citation(s) in RCA: 370] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The molecular mechanisms by which extreme blood pressure elevation leads to vascular injury are not defined. To explore the hypothesis that activation of endothelium and platelets as manifested by increased concentrations of circulating endothelial microparticles and platelet microparticles could play a role in this target organ injury, we conducted a cross-sectional study of these markers in 3 groups: (1) untreated patients referred specifically for treatment of severe uncontrolled hypertension; (2) untreated patients with established mild hypertension; and (3) normotensive volunteer subjects. By ANOVA, endothelial (P=0.002) and platelet (P=0.01) microparticles were greatest in the severely hypertensive group. There was a significant correlation between both of these markers and blood pressure, even in the setting of multiple risk factors. Our results suggest that these markers may be useful and specific for pressure-induced endothelial and platelet activation in hypertension. Furthermore, because of the combined effects of endothelial and platelet microparticles on coagulation, leukocytes, and endothelium, it is possible that they may play a pathogenic role in mediating target organ injury in severe hypertension.
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Affiliation(s)
- Richard A Preston
- Division of Clinical Pharmacology, Department of Medicine, University of Miami School of Medicine, Miami, Fla., USA.
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29
Nomura S, Kanazawa S, Fukuhara S. Effects of efonidipine on platelet and monocyte activation markers in hypertensive patients with and without type 2 diabetes mellitus.
J Hum Hypertens 2002;
16:539-47. [PMID:
12149659 DOI:
10.1038/sj.jhh.1001447]
[Citation(s) in RCA: 81] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2001] [Revised: 03/19/2002] [Accepted: 04/03/2002] [Indexed: 11/10/2022]
Abstract
We compared the levels of microparticles, platelet activation markers, soluble cell adhesion molecules, and soluble selectins between hypertensive patients with and without type 2 diabetes and control subjects. Binding of anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib monoclonal antibodies to platelets did not differ significantly between the hypertensive patients and controls, but platelet expression of activation markers (CD62P, CD63, PAC-1, and annexin V) was higher in the hypertensive patients. Platelet-derived microparticle (PDMP) and monocyte-derived microparticle (MDMP) levels were significantly higher in the hypertensive patients than in the controls. Soluble ICAM-1, VCAM-1, P-selectin, and E-selectin levels were also higher in the hypertensive patients, and they were significantly higher in the hypertensive patients with diabetes. After treatment with efonidipine, the levels of PDMPs, CD62P-, CD63-, PAC-1-, and annexin V-positive platelets, sICAM-1, sVCAM-1, sP-selectin, and sE-selectin all decreased significantly. The MDMP levels decreased, and the decrease was significant in the hypertensive patients with diabetes. These findings suggest that administration of efonidipine to hypertension patients with diabetes may prevent the development of cardiovascular complications caused by cell adhesion molecules or activated platelets and monocytes.
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Affiliation(s)
- S Nomura
- First Department of Internal Medicine, Kansai Medical University, Moriguchi, Osaka, Japan.
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