Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis, which might progress due to inflammation. This systematic review assessed the association of specific inflammatory biomarkers with morbidity and mortality in PAD patients. MEDLINE and EMBASE databases were systematically searched for studies assessing evidence between inflammatory biomarkers and morbidity and mortality risks in PAD patients. Results were reported as Hazard Ratios (HR), Odds Ratios (OR), or mean and standard deviation. Effect estimates for high-sensitivity C-reactive protein (hs-CRP) were pooled using a random-effects model and respectively displayed in forest plots. The study reviewed a total of 7024 records, out of which 26 studies were included for qualitative synthesis and nine for quantitative synthesis. A total of 4673 patients were analyzed in the meta-analysis. Elevated baseline IL-6 levels were consistently linked to poor outcomes, including loss of patency and composite endpoints, such as major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Tumor necrosis factor-α (TNF-α) and related biomarkers were associated with adverse outcomes like mortality and patency loss. Elevated IL-1 levels predicted worse cardiovascular outcomes and IL-1 receptor antagonist levels indicated recurrence or new lesions post-surgery. Hs-CRP was statistically significantly associated with all-cause mortality and MALE in the pooled analysis. The study highlights the ability of inflammatory biomarkers to predict clinical outcomes in PAD patients. The strength of these associations varies based on the specific biomarker and clinical context.

Inflammation has been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. We evaluated immune-related biomarkers regarding their ability, individually and as a composite score, to predict 20-year ASCVD incidence in an apparently healthy adult population.

A cohort of 1270 adults, who were free of ASCVD at baseline, with a 20-year follow-up from the prospective ATTICA study, were included in this analysis. Immune-related biochemical markers independently predictive of 20-year ASCVD risk were identified, and an aggregate biomarker score was developed. The incremental predictive value of this score beyond the SCORE2 was assessed using area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Three immune-related biomarkers -interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and fibrinogen-showed the best predictive ability of 20-year ASCVD risk and were subsequently integrated into an aggregate biomarker score (ImmActScore), exhibiting a range from 0 (6 % absolute risk) to 4 (63 % absolute risk). Individual ImmActScore was independently associated with 20-year ASCVD risk (multi-adjusted HR per 1-unit:1.24, 95 %CI:1.05-1.46, p = 0.011). The 38.5 % of the 20-year incident ASCVD could be attributed to ImmActScores of ≥1. Integrating ImmActScore into the SCORE2 model yielded a continuous NRI of 0.603 and a categorical NRI of 18.4 % in the 40-50 year age group.

Assessing immune-related pathways may offer additional potential for long-term ASCVD risk stratification. A combined measure of IL-6, TNF-α and fibrinogen levels was associated with ASCVD events over a 20-year period. Further validation in independent cohorts is warranted.

Background: Walking ability is important for the quality of life of older adults. A self-reported walking ability index (WAI) covering the difficulty and ease of walking captures a broader spectrum of walking ability in healthy older persons. Methods: Using metabolomics in the Health, Aging and Body Composition study, we identified Year 2 metabolites cross-sectionally and longitudinally related to WAI (0-9, higher scores indicate better walking ability) using probabilistic index models and multinomial logistic models, respectively. Results: Among 2334 participants (mean age 74.6 years, 51% women, 37% Black), 27% scored 0-5, 36% scored 6-8, and 37% scored 9 at Year 2. Over 4 years, 52% maintained a stable WAI, 6% improved, while 42% declined (22% 1-2 points and 20% >2 points decline). We identified 81 metabolites significantly associated with both poorer concurrent WAI and faster decline, including higher acylcarnitine species, shorter-chain saturated diglycerides and triglycerides, and TCA cycle intermediates (cis-aconitic, fumaric, and malic acids), and lower phospholipids levels. Eighteen additional metabolites were only associated with faster WAI decline: higher short-chain saturated triglycerides and energy metabolism markers (ATP/ADP/AMP) and lower margaric acid and glycine levels. Notably, those with improved WAI, despite poorer baseline WAI and lifestyles, showed more favorable metabolic profiles than others. Conclusions: Metabolites linked to the TCA cycle and energy metabolism, as well as inflammation and protein catabolism, were related to mobility function. Some metabolites might be particularly important for the early detection of older adults at risk of mobility decline. Metabolic profiles may also help identify older individuals (i.e., with improving WAI) with greater metabolic resilience to lifestyle risk factors and health conditions.

To investigate the associations between periodontal inflammation-as determined by the periodontal inflamed surface area (PISA)-and serum inflammatory markers in community-dwelling older adults in Japan.

This cross-sectional study included 470 adults (mean age: 73.1 years). The composite inflammatory marker z-score (CIMZ) was calculated as the sum of the participants' individual z-scores for C-reactive protein (CRP), interleukin-1beta (IL-1β), IL-6 and tumour necrosis factor-α (TNF-α). The associations of PISA (quartiles) with individual biomarkers (continuous, log-transformed) and CIMZ (dichotomized, highest quartile or not) were assessed using linear or Poisson regression models.

Compared with participants in the lowest PISA quartile (Q1), those in Q3 and Q4 had significantly (p < 0.05) higher CRP and IL-6 levels. Statistically significant linear trends (ptrend < 0.05) across the PISA quartiles were observed for CRP and IL-6. The multivariable adjusted prevalence ratios (95% confidence intervals) of high CIMZ (reference: Q1) were 1.20 (0.68-2.14), 1.66 (0.96-2.88) and 1.90 (1.08-3.34) (ptrend = 0.01) in individuals in PISA Q2-Q4.

Older adults with high periodontal inflammation had high serum CRP and IL-6 concentrations and composite summary inflammatory indicator values. Periodontal inflammation is a potential modifiable factor of elevated inflammatory status among older adults in Japan.

Metabolic-inflammatory states are central to multiorgan mechanisms of aging, but precise functional biomarkers of physiological aging remain less clear.

In the Health, Aging, and Body Composition study, we defined metabolomic profiles of the Healthy Aging Index (HAI), a composite of cardiovascular, lung, cognitive, metabolic, and renal function (0-10, with higher scores indicating poorer health) in a split set design from 2015 older participants (mean age 73.6 years; 50% women; 35% Black). We used standard regression to identify metabolomic correlates of Year 1 and Year 10 HAI, change in HAI over time, and mortality. A metabolite score of HAI was developed using LASSO regression.

We identified 42 metabolites consistently associated with Year 1 and Year 10 HAI, as well as change in HAI: 13 lipids, 4 amino acids, and 4 metabolites of other classes were associated with worse and worsening HAI while 20 lipids and 1 amino acid was associated with better and improving HAI. Most of these associations were no longer significant after additionally adjusting for inflammation biomarkers. A higher metabolite score of Year 1 HAI was associated with greater HAI deterioration over time (hold-out "test" set beta 0.40 [0.15-0.65]) and higher mortality (hold-out "test" set hazard ratio: 1.43 [1.23-1.67]).

A multiorgan healthy aging phenotype was linked to lipid metabolites, suggesting potential pathways related to mitochondrial function, oxidative stress, and inflammation. Metabolomics of HAI at older age were related to worsening health and mortality, suggesting potential links between metabolism and accelerated physiological aging.

Chronic inflammation is linked to cardiovascular disease, cancer, and other non-communicable diseases. Dietary factors like fibre and protein may affect inflammation, but limited evidence exists exploring how they interact. This study investigated associations between dietary fibre, protein sources, and the inflammatory marker C-reactive protein (CRP) in older adults.

This cross-sectional analysis included 128,612 UK Biobank participants aged 60+ years with CRP measurements and dietary data from multiple 24 h recalls. Fibre intake was reported as total fibre (g/day). Protein intake included total, animal, and vegetable protein (g/day). Robust regression analysis examined associations between quintiles of fibre, protein, and CRP, adjusted for demographics, lifestyle factors, and multimorbidity. Analyses were stratified by health status (with and without multimorbidity).

Higher fibre and vegetable protein intakes were inversely associated with CRP, while higher animal and total protein were positively associated with CRP in people with no multimorbidity. Specifically, participants in the highest quartile of dietary fibre had CRP levels that were 0.42 mg/L lower compared with the lowest quartiles. In contrast, those with the highest total protein and animal protein intakes had CRP levels that were 0.24 mg/L and 0.40 mg/L higher, respectively. In people with multimorbidity, fibre exhibited an inverted U-shaped association with the strongest association in participants in the highest quintile of intake. Vegetable protein had an inverse association with CRP. Animal and total protein had strong positive linear associations with CRP. Notably, high animal protein coupled with low dietary fibre intake resulted in CRP levels that were 0.65 mg/L higher compared with low animal protein and high dietary fibre intake.

Higher fibre and vegetable protein intakes were associated with lower inflammation in older adults. In promoting protein intake to maintain muscle mass and function, future studies should investigate replacing animal with vegetable protein to concomitantly reduce age-related inflammation.

Unintentional weight loss in older populations is linked to greater mortality and morbidity risks. This study aims to understand the metabolic mechanisms of unintentional weight loss and their relationship with body composition changes in older adults. We investigated plasma metabolite associations with weight and body composition changes over 5 years in 1335 participants (mean age 73.4 years at Year 1, 51% women, and 33% Black) from the Health, Aging and Body Composition (Health ABC) study. Multinomial logistic regressions were used to examine associations of the 442 metabolites with weight loss > 5% over 5 years with/without an intention, weight gain > 5%, and fluctuating weight relative to weight stability. Metabolite associations with unintentional weight loss differed from other weight change patterns. Lower levels of essential amino acids, phospholipids, long-chain polyunsaturated triglycerides, cholesterol esters, and uridine were associated with higher odds of unintentional weight loss versus weight stability after adjusting for age, sex, race, and Year 1 BMI categories. Losses in fat mass and muscle mass each attenuated > 20% of the associations between many metabolites, such as phospholipids and essential amino acids, and unintentional weight loss. DXA whole-body fat mass loss (mean 3% annually) further attenuated 9 metabolite associations by > 50% after CT muscle loss (mean 2% annually) adjustment. Lipids and amino acids related to energy and protein balance were associated with unintentional weight loss in older adults. Fat and muscle mass losses partially attenuated these associations, suggesting connections of these metabolic pathways with muscle, and particularly adiposity dynamics.

Population ageing is increasing in prevalence in most developed countries. Ageing is the decline of functional properties at the cellular, tissue, and organ level. Biochemical changes that occur in all organisms that experience biological ageing are referred to as the "Hallmarks of ageing". Inflammation is a common denominator of the hallmarks of ageing, being mechanistically involved in most age-related health consequences. Inflamm-ageing refers to age-related changes in the inflammatory and immune systems which somehow drive the ageing process towards healthy or unhealthy ageing. Current evidences, support that, reversing the age-related pro-inflammatory status of inflamm-ageing, is able to modulate most hallmarks of ageing. Inflamm-ageing is associated with increased levels of pro-inflammatory molecules (e.g. cytokines, chemokines), ultimately producing a chronic low-grade inflammatory state typically observed in older individuals. It is commonly accepted that, the balance between pro- and anti-inflammatory cytokines/chemokines is one of the factors determining whether healthy or unhealthy ageing occurs. Malnutrition and nutritional imbalances, are highly prevalent in the elderly, playing a role in driving the balance of pro- and anti-inflammatory immunoactive molecules. In particular, malnutrition is a major risk factor for sarcopenia, a phenomenon characterized by loss of muscle mass, which is often referred to as the biological basis for frailty. Given the close relationship between malnutrition and sarcopenia, there is also evidence for a link between malnutrition and frailty. Indeed, changes in cytokine/chemokine levels in elderly patients with malnutrition were demonstrated. The demonstration that specific cytokines play a role in modulating appetite and nutrient sensing and taste reception, provided further evidence for the existence of a link between inflamm-ageing, nutrition and cytokines in shaping the trajectory of ageing. The present review will overview current evidence supporting the role of specific circulating cytokines and chemokines in the relationship between ageing, inflammation, and malnutrition.

Resveratrol, a natural polyphenolic compound, has potent antioxidant and anti-inflammatory properties, leading to beneficial effects against cardiovascular diseases. The purpose of this study was to determine whether resveratrol induces protective effects against aging-induced cardiac remodeling, mitochondrial dysfunction, and mitochondria-mediated apoptosis in the heart.

Thirty-two male Fischer 344 rats were divided into 4 groups: 2 groups that were orally treated with resveratrol (50 mg/kg/day) for 6 weeks (young and old resveratrol groups), and 2 control groups (young and old control groups). Mitochondrial function and mitochondria-mediated apoptotic pathway were analyzed in cardiac muscle fibers from the left ventricle.

Resveratrol significantly reduced cardiac hypertrophy and remodeling in aging hearts. In addition, resveratrol significantly ameliorated aging-induced mitochondrial dysfunction (e.g., decreased oxygen respiration and increased hydrogen peroxide emission) and mitochondria-dependent apoptotic signaling (the Bax/Bcl-2 ratio, mitochondrial permeability transition pore opening sensitivity, and cleaved caspase-3 protein levels). Resveratrol also significantly attenuated aging-induced apoptosis (determined via cleaved caspase-3 staining and TUNEL-positive myonuclei) in cardiac muscles.

This study demonstrates that resveratrol treatment has a beneficial effect on aging-induced cardiac remodeling by ameliorating mitochondrial dysfunction and inhibiting mitochondria-mediated apoptosis in the heart.

The term early life stress encompasses traumatic events occurring before the age of 18 years, such as physical abuse, verbal abuse, household dysfunctions, sexual abuse, childhood neglect, child maltreatment, and adverse childhood experiences. Adverse psychological experiences in early life are linked to enduring effects on mental and physical health in adulthood. In this review, we first describe the effects and potential mechanisms of early life stress on the components of the vasculature. Next, we dive into the impact of early life stress on the vasculature across the lifespan through alterations of the epigenetic landscape. Finally, we consolidate the critical gaps in knowledge for focusing future research including the potential for resilience in combatting the impact of early life stress on vascular health.

To clarify whether the high-density lipoprotein cholesterol/C reactive protein (HDL-C/CRP) ratio can be used as a new prognosticator of all-cause mortality in patients with chronic heart failure (CHF) (New York Heart Association (NYHA) cardiac class III/IV).

Retrospective study.

Several papers have revealed that HDL-C and CRP can act as anti-inflammatory and pro-inflammatory factors, respectively, to affect disease progression in patients with heart failure, and the balance of the two has been shown to affect the prognosis of patients with heart failure with preserved ejection fraction (HFpEF), but none of the above studies involved patients with the more severe forms of heart failure with mildly reduced ejection fraction and heart failure with reduced ejection fraction; therefore, the present study is to extend the balance of HDL-C and CRP to the whole range of types of patients CHF to further confirm its importance.

This study is from a single centre in Yunnan Province, China.

After excluding ineligible patients, we finally included 1192 patients with CHF from January 2017 to October 2021.

The primary outcome was all-cause mortality in patients with CHF between January 2017 and October 2021. No secondary outcome measures were performed.

All patients were divided into four groups according to the quartiles of the HDL-C/CRP ratio. Using the Kaplan-Meier analysis, the risk of all-cause mortality was always the highest for Q1 (HDL-C/CRP<0.395) and the lowest for group Q4 (HDL-C/CRP≥3.4163). Cox univariate and multivariate regression analyses showed that HDL-C/CRP was consistently an independent risk factor for death from CHF. Based on the receiver operating characteristic curve, the area under the curve for HDL-C/CRP was 0.7254 (p<0.001), with a sensitivity of 65.5% and a specificity of 69.6%.

The HDL-C/CRP ratio is an independent prognostic indicator of all-cause mortality in patients with CHF in NYHA cardiac function class III/IV, which has good specificity and sensitivity. Patients with lower levels of the HDL-C/CRP ratio are at a greater risk of death than patients with higher levels of the HDL-C/CRP ratio.

Strokes are a leading cause of death and disability among African Americans in the United States. Biological markers to predict stroke remain elusive; thus, our objective was to investigate whether inflammation, as measured by high-sensitivity C-reactive protein (hs-CRP), was associated with stroke incidence among African Americans enrolled in the Jackson Heart Study (JHS).

Baseline hs-CRP levels were categorized in quintiles: quintile 1 (0.0084 mg/L); quintile 2 (0.0085-0.0189 mg/L); quintile 3 (0.0190-0.036 mg/L); quintile 4 (0.037-0.0675 mg/L); quintile 5 (≥0.0676 mg/L). Nonfatal stroke incidence was ascertained from passive community surveillance through annual phone calls and adjudicated via hospital records. At baseline, stroke risk factors/covariates were compared across quintiles using a one-way analysis of variance and a chi-square test. The association between baseline hs-CRP levels and stroke incidence was determined using a Cox regression analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI).

In the unadjusted model, hs-CRP levels in quintile 2 (HR, 1.48; 95% CI, 0.96-2.29), quintile 3 (HR, 1.44; 95% CI, 0.93-2.24), and quintile 4 (HR, 1.09; 95% CI, 0.68-1.74) were not associated with stroke incidence when compared with quintile 1 (reference). However, individuals within quintile 5 (HR, 1.78; 95% CI, 1.17-2.72) exhibited a significantly increased risk for stroke compared with those in the reference quintile. This risk persisted after adjusting for stroke risk factors (demographics, anthropometrics, health condition covariates, health behavioral risk factors, and cardiovascular disease history) for quintile 5 (HR, 1.87; 95% CI, 1.17-2.98) compared with reference quintile 1.

An increased and independent risk of nonfatal stroke appears at the highest quintile of hs-CRP values (≥0.0676 mg/L) among JHS participants.

This study aims to understand the metabolic mechanisms of unintentional weight loss in older adults. We investigated plasma metabolite associations of subsequent weight change over 2 years in 1536 previously weight stable participants (mean age 74.6 years, 50% women, 35% Black) from the Health, Aging and Body Composition (Health ABC) Study. Multinomial logistic regressions were used to examine associations of the 442 metabolites with weight loss with/without an intention and weight gain >3% annually relative to weight stability. The metabolite associations of unintentional weight loss differed from those of intentional weight loss and weight gain. Lower levels of aromatic amino acids, phospholipids, long-chain poly-unsaturated triglycerides, and higher levels of amino acid derivatives, poly-unsaturated fatty acids, and carbohydrates were associated with higher odds of unintentional weight loss after adjusting for age, sex, race, and BMI categories. Prevalent diseases attenuated four and lower mid-thigh muscle mass and poorer appetite each attenuated 2 of 77 identified metabolite associations by >20%, respectively. Other factors (e.g., energy expenditure, diet, and medication) attenuated all associations by <20%. While 16 metabolite associations were attenuated by 20%-48% when adjusting for all these risk factors, 47 metabolite associations remained significant. Altered amino acid metabolism, impaired mitochondrial fatty acid oxidation, and inflammaging implicated by identified metabolites appear to precede unintentional weight loss in Health ABC older adults. Furthermore, these pathways seem to be associated with prevalent diseases especially diabetes, lower muscle mass, and poorer appetite.

This research aims to investigate the connection between systemic inflammatory response and metabolic syndrome (MetS) across different age groups, with the aim of proposing more targeted recommendations.

This study enrolled 15 959 adults from the 2001-2018 National Health and Nutrition Examination Survey of whom 6739 were diagnosed with MetS. After dividing the systemic immune-inflammation index (SII) into 4 quartiles, the Kruskal-Wallis test and weighted chi-square test were employed to assess statistical differences. Weighted multivariable logistic regression analysis, subgroup analysis, sensitivity analysis, and restricted cubic spline were employed to examine the relationship between SII and MetS.

Our study revealed that SII exhibits a quantitative association with MetS [odds ratio (OR) = 1.56; 95% confidence interval (CI): 1.37-1.79; P < .001]. Elevated SII is an independent risk factor for the 5 components of MetS. Different age groups and alcohol consumption status could modify the connection between SII and MetS. This connection was statistically significant in the 18 to 65 age group but not in the elderly subgroup (OR = 1.08; 95% CI, .95-1.23; P = .248). Multiple imputation confirmed the robustness of our results. Moreover, the connection exhibits an inverted U-shaped curve.

Our research highlights the predictive significance of SII in forecasting the incidence of MetS in young and middle-aged populations. The differences in inflammatory mechanisms across various age groups necessitate further research for exploration.

Metabolic syndrome (MetS) is a global public health problem that significantly impacts human health and quality of life. The relationship between MetS and the C-reactive protein-albumin-lymphocyte (CALLY) index is uncertain.

This study analyzed the data of 7,534 individuals from the National Health and Nutrition Examination Survey cycles (2003-2010 cycles). Weighted logistic regression and weighted restricted cubic spline (RCS) curve analyses were used to identify the relationships between the CALLY index and MetS, as well as its components.

Of the 7,534 participants, 2,086 were diagnosed with MetS. The estimated prevalence of MetS decreased with an increase in the CALLY index (P < 0.001). Multivariable logistic regression analysis showed that the odds ratio of MetS was 0.25 (95% confidence interval 0.20-0.32, P < 0.001) in the highest CALLY index quartile compared with the lowest quartile after adjusting for confounding variables. The RCS curve analysis revealed non-linear relationships between the CALLY index and MetS or its components.

This study revealed an inverse relationship between the CALLY index and MetS risk. The CALLY index might be valuable for identifying individuals who are at a high risk of MetS.

Not applicable.

Chronic coronary artery disease (CAD) remains a significant global healthcare burden. Current risk assessment methods have notable limitations in early detection and risk stratification. Hence, there is an urgent need for innovative biomarkers that facilitate the premature CAD diagnosis, ultimately leading to reduction in associated morbidity and mortality rates. This review comprehensively examines recent advances in emerging biomarkers for CAD detection. Our analysis delves into various aspects of these biomarkers such as their mechanisms of action, roles in the pathophysiology of the disease, and different measurement techniques employed in clinical practice. Comparative assessment of biomarker performance between CAD patients and control groups was also presented relying on their sensitivity, specificity, and area under the curve at specific cutoff points. In this regard, prominent biomarkers including Tenascin-C, IL-37, PTX3, transthyretin, soluble interleukin-6 receptor α, and miR-15a are identified as having high diagnostic potential for chronic CAD that indeed showcase promising performance metrics. These findings underscore the role of novel biomarkers in enhancing CAD risk stratification and improving patient outcomes through early intervention. However, the pursuit of an ideal and inclusive biomarker continues due to the multifaceted nature of CAD. Future randomized controlled trials are essential to bridge the gap between research findings and clinical practice in order to augment the practical application of these biomarkers in routine healthcare settings.

Despite significant advances in imaging modalities for diagnosing coronary artery disease (CAD), there remains a need for novel diagnostic approaches with high predictive values and fewer limitations. Circulating biomarkers, including cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8), cell adhesion molecules such as soluble vascular cell adhesion molecule-1 (sVCAM-1), peptides secreted by endothelial cells such as endothelin-1 (ET-1), and enzymes involved in extracellular matrix remodeling such as a disintegrin and metalloproteinase with thrombospondin motifs-1 (ADAMTS-1) offer a promising alternative. This study aimed to evaluate the correlation between the plasma levels of selected biomarkers and the presence and severity of CAD. We enrolled 40 patients admitted for elective coronary angiography. CAD was defined as having at least one coronary artery stenosis ≥ 50%. The severity of CAD was assessed using the Gensini Score (GS). IL-8 levels were significantly higher in the CAD group, with a mean of 9.78 (SD 0.46) compared to 8.37 (SD 0.40) in the non-CAD group (p = 0.0228). No significant differences were observed for the other biomarkers between the groups. A positive Spearman correlation was found between IL-8 levels and the GS (ρ = 0.39, p = 0.017). These findings suggest that IL-8 may have potential as an additional tool for diagnosing or excluding atherosclerosis. Further studies with larger sample sizes are needed to validate its clinical utility.

Despite earlier research demonstrating the immunomodulatory effects of acute and chronic exercise in many medical illnesses, there is a lack of literature evaluating the acute and chronic effects of exercise on the cytokine levels in individuals with bipolar disorder (BD) or schizophrenia (SCH). This study aims to examine the acute effects of resistance exercise on cytokines and the chronic effects of resistance exercise by 10 weeks on cytokine levels, symptoms of disease, and muscular strength in individuals with BD and SCH. The included individuals (N=10) performed a single session of band-elastic resistance exercises (six exercises, 3 sets of 12-15 repetitions, 60 seconds of interval between sets). A sub-sample (N=6) of individuals performed a supervised band-elastic resistance exercise program (2 times a week, for 10 weeks, 6 exercises, 3 sets of 12-15 repetitions, 60 seconds of interval). We verified for acute effects: IL-2 (P=0.0085) and IL-4 (P=0.0253) levels increased, while IL-6 decreased (P=0.0435), and for chronic effects: increased IL-2 and IL-4 levels (significant effect size - Pre vs Post), a decrease in disease symptoms, and an increase in muscular strength. This study adds to what is already known about how resistance exercises affect people with BD and SCH in both short-term (systemic cytokines levels) and long-term (symptoms of disease, muscular strength, and systemic cytokines levels).

Aging is the primary risk factor for heart disease, the leading global cause of death. Right ventricular (RV) function predicts survival in several age-related clinical contexts, yet no therapies directly improve RV function, in large part due to a poor mechanistic understanding of RV aging and how it is distinct from the widely studied left ventricle (LV). To address this gap, we comprehensively quantified RV functional and morphological remodeling with age. We further aimed to identify molecular mechanisms of RV aging thus we performed RNAseq on RV and LV from male and female young (4 months) and aged (19-21 months) C57BL6 mice. Contrary to the concentric hypertrophic remodeling and diastolic dysfunction that occurs in the LV, the aging RV underwent eccentric remodeling with significant dilation and impaired systolic function. Transcriptomic data were also consistent with ventricle-specific aging, with few genes (13%) similarly shared between ventricles with aging. KEGG analysis identified shared aging genes in inflammatory and immune cell pathways that were confirmed by flow cytometry that demonstrated higher percent of GR1+ myeloid cells in both ventricles. Unique RV aging genes enriched in the biosynthesis of saturated fatty acids, PPAR signaling, and butanoate metabolism, and we identified putative novel RV-specific aging genes. Together, we suggest that the RV and LV are unique cardiac chambers that undergo distinct remodeling with age. These robust differences may explain why therapies designed from LV-based studies fail to improve RV function and suggest that future efforts emphasizing ventricular differences may elucidate new therapies for healthy cardiac aging.

The aim of the PAROBRAIN study was to examine the association of periodontal health with microstructural white matter integrity and cerebral small vessel disease (CSVD) in the Hamburg City Health Study, a large population-based cohort with dental examination and brain magnetic resonance imaging (MRI).

Periodontal health was determined by measuring clinical attachment loss (CAL) and plaque index. Additionally, the decayed/missing/filled teeth (DMFT) index was quantified. 3D-FLAIR and 3D-T1-weighted images were used for white matter hyperintensity (WMH) segmentation. Diffusion-weighted MRI was used to quantify peak width of skeletonized mean diffusivity (PSMD).

Data from 2030 participants were included in the analysis. Median age was 65 years, with 43% female participants. After adjusting for age and sex, an increase in WMH load was significantly associated with more CAL, higher plaque index and higher DMFT index. PSMD was significantly associated with the plaque index and DMFT. Additional adjustment for education and cardiovascular risk factors revealed a significant association of PSMD with plaque index (p < .001) and DMFT (p < .01), whereas effects of WMH load were attenuated (p > .05).

These findings suggest an adverse effect of periodontal health on CSVD and white matter integrity. Further research is necessary to examine whether early treatment of periodontal disease can prevent microstructural brain damage.

Aging is a dynamic and progressive process characterized by the gradual accumulation of cellular damage. The continuous functional decline in the intrinsic capacity of living organisms to precisely regulate homeostasis leads to an increased susceptibility and vulnerability to diseases. Among the factors contributing to these changes, body composition-comprised of fat mass and lean mass deposits-plays a crucial role in the trajectory of a disability. Particularly, visceral and intermuscular fat deposits increase with aging and are associated with adverse health outcomes, having been linked to the pathogenesis of sarcopenia. Adipose tissue is involved in the secretion of bioactive factors that can ultimately mediate inter-organ pathology, including skeletal muscle pathology, through the induction of a pro-inflammatory profile such as a SASP, cellular senescence, and immunosenescence, among other events. Extensive research has shown that natural compounds have the ability to modulate the mechanisms associated with cellular senescence, in addition to exhibiting anti-inflammatory, antioxidant, and immunomodulatory potential, making them interesting strategies for promoting healthy aging. In this review, we will discuss how factors such as cellular senescence and the presence of a pro-inflammatory phenotype can negatively impact body composition and lead to the development of age-related diseases, as well as how the use of polyphenols can be a functional measure for restoring balance, maintaining tissue quality and composition, and promoting health.

Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions. The causal relationship between olfaction with memory dysfunction deserves particular attention because this sensory system has the only direct projection to memory centers. Mechanisms that may underlie the connections between medical conditions and olfactory loss include inflammation as well as neuroanatomical and environmental factors, and all 139 of the medical conditions listed here are also associated with inflammation. Olfactory enrichment shows efficacy for both prevention and treatment, potentially mediated by decreasing inflammation.

Cardiovascular diseases (CVDs) are a leading global health concern. Emerging evidence suggests a potential protective role of well-being in reducing CVD risk.

We conducted a cohort analysis using the UK Biobank data set, encompassing 121 317 participants. We assessed the well-being of participants using a well-being index derived from baseline questionnaires. Well-being categories were derived by latent class analysis using general happiness and satisfaction with family, friendships, health, and finance situations. The relationship between well-being and 4 major CVDs was analyzed using Cox proportional hazards models and Mendelian randomization. The study also examined the impacts of well-being on lifestyle factors and inflammatory markers, and its mediating role in the well-being-CVD relationship. Higher well-being was associated with a significantly reduced risk of various CVDs. Latent class analysis identified 4 distinct well-being groups (low, variable, moderate-to-high, and high satisfaction), with higher satisfaction levels generally associated with lower risk of CVDs. Mendelian randomization suggested potential causal relationships between well-being and reduced risk of CVDs. Participants with greater well-being demonstrated healthier behaviors and lower levels of inflammatory markers. Mediation analysis indicated that lifestyle and inflammatory markers partially mediated the relationship between well-being and CVDs.

This study demonstrates a robust inverse association between well-being and the risks of CVDs, suggesting that enhancing well-being may be a viable strategy for CVD prevention. The role of lifestyle factors and inflammation as a mediator provides insight into possible biological pathways linking psychological states and cardiovascular health.

A standardized measure for inflammaging is lacking. We introduced the inflammatory age (iAge) as a quantification method and explored its associations with age-related traits and diseases in an older Chinese cohort.

Inflammatory markers including white blood cell count (WBC), neutrophils, lymphocytes, monocytes, C-reactive protein, platelets and albumin were measured. Quantitative real-time polymerase chain reaction was used to measure telomere length. Traditional multivariable linear, partial least squares, and logistic regression were used.

iAge was constructed based on WBC, neutrophils, monocytes and albumin, which were associated with telomere length independently. A higher iAge indicated a heavier aging-related inflammation burden. Per 1-year increase in iAge was associated with higher body mass index (β 0.86 (95 % CI 0.67, 1.05) kg/m2), waist circumference (β 2.37 (95 % CI 1.85, 2.90) cm), glycosylated hemoglobin A1c (β 0.06 (95 % CI 0.02, 0.10) %), systolic blood pressure (β 1.06 (95 % CI 0.10, 2.03) mmHg), triglycerides (β 0.05 (95 % CI 0.01, 0.08) mmol/L), 10-year cardiovascular diseases risk (β 0.05 (95 % CI 0.02, 0.08) %), diabetes (OR 1.22 (95 % CI 1.02, 1.46)), hypertension (OR 1.21 (95 % CI 1.04, 1.42)) and metabolic syndrome risks (OR 1.25 (95 % CI 1.04, 1.51)), and lower fasting plasma glucose (β -0.016 (95 % CI -0.024, -0.007) mmol/L), total cholesterol (β -0.06 (95 % CI -0.12, -0.01) mmol/L) and high-density lipoprotein cholesterol (β -0.05 (95 % CI -0.07, -0.03) mmol/L).

The newly introduced iAge, derived from inflammatory markers and telomere length, aligns with various metabolic dysfunctions and age-related disease risks, underscoring its potential ability in identifying aging-related phenotypes.

Growth differentiation factor 15 (GDF-15) is a member of the TGFβ superfamily secreted by many cell types and found at higher blood concentrations as chronological age increases (1). Given the emergence of GDF-15 as a key protein associated with aging, it is important to understand the multitude of conditions with which circulating GDF-15 is associated.

We pooled data from 1,174 randomly selected Health ABC Study (Health ABC) participants and 1,503 Cardiovascular Health Study (CHS) participants to evaluate the risk of various conditions and age-related outcomes across levels of GDF-15. The primary outcomes were (1) risk of mobility disability and falls; (2) impaired cognitive function; (3) and increased risk of cardiovascular disease and total mortality.

The pooled study cohort had a mean age of 75.4 +/-4.4 years. Using a Bonferroni-corrected threshold, our analyses show that high levels of GDF-15 were associated with a higher risk of severe mobility disability (HR: 2.13 [1.64, 2.77]), coronary heart disease (HR: 1.47 [1.17, 1.83]), atherosclerotic cardiovascular disease (HR: 1.56 [1.22, 1.98]), heart failure (HR: 2.09 [1.66, 2.64]), and mortality (HR: 1.81 [1.53, 2.15]) when comparing the highest and lowest quartiles. For CHS participants, analysis of extreme quartiles in fully adjusted models revealed a 3.5-fold higher risk of dementia (HR: 3.50 [1.97, 6.22]).

GDF-15 is associated with several age-related outcomes and diseases, including mobility disability, impaired physical and cognitive performance, dementia, cardiovascular disease, and mortality. Each of these findings demonstrates the importance of GDF-15 as a potential biomarker for many aging-related conditions.

The incidence of frailty and cardiovascular disease (CVD) increases as the population ages. There is a bidirectional relationship between frailty and CVD, and both conditions share several risk factors and underlying biological mechanisms. Frailty has been established as an independent prognostic marker in patients with CVD. Moreover, its presence significantly influences both primary and secondary prevention strategies for adults with CVD while also posing a barrier to the inclusion of these patients in pivotal clinical trials and advanced cardiac interventions. This review discusses the current knowledge base on the relationship between frailty and CVD, how managing CVD risk factors can modify frailty, the influence of frailty on CVD management, and future directions for frailty detection and modification in patients with CVD.

Objectives: The aim of this nationwide longitudinal cohort study is to determine the risk of congestive heart failure (CHF) associated with a seropositive rheumatoid arthritis (RA) population in Korea. Methods: In this study, National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data from 2002 to 2003 were used. The cohort was followed up with for 12 years until December of 2015. Seropositive RA was defined as a patient prescribed with a disease-modifying anti-rheumatic drug (DMARD) among patients with the International Classification of Diseases code M05 (seropositive RA). Patients who were diagnosed before 2004 were excluded. The seropositive RA group consisted of 2765 patients, and a total of 13,825 patients were in the control group. The Kaplan-Meier method was used to calculate the 12-year CHF incidence rate for each group. A Cox proportional hazards regression analysis was used to estimate the hazard ratio of CHF. Results: The hazard ratio of CHF in the seropositive RA group was 2.41 (95% confidence interval (CI): 1.40-4.14) after adjusting for age and sex. The adjusted hazard ratio of CHF in the seropositive RA group was 2.50 (95% CI: 1.45-4.30) after adjusting for age, sex, income, and comorbidities. In females aged ≥65 and aged <65, the incidence rates in the non-hypertension, non-diabetes mellitus, and non-dyslipidemia subgroups were significantly higher in the seropositive RA group than in the control group. Conclusions: This nationwide longitudinal cohort study shows an increased risk of CHF in patients with seropositive RA.

Uric acid (UA) and C-reactive protein (CRP) may interact synergistically to accelerate the initiation and progression of cardiovascular disease (CVD). This study investigated the effects of a combination of high UA and high CRP on the risks of CVD.

A total of 90,270 participants recruited from the Kailuan study were included, who were divided into four groups according to the presence/absence of hyperuricemia and inflammation. Cox regression was applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CVD. C-statistics, net classification index (NRI), and integrated discrimination improvement (IDI) were used to compare the incremental predictive of UA, CRP, and their combined effects on CVD. Mediation analysis was to explore the impact of CRP on the association between UA and CVD. Over a median follow-up of 14.95 years, we identified 11398 incident CVD cases. Compared to the low UA/low CRP group, the high UA/low CRP, low UA/high CRP and high UA/high CRP groups showed progressively higher risks of CVD, HR (95% CI): 1.18(1.10-1.27), 1.27(1.21-1.33) and 1.50 (1.33-1.69), respectively. The incorporation of UA and CRP into the traditional China-PAR model led to improvement in the C-statistic, NRI, and IDI, and was better than incorporation of either UA or CRP alone. Mediation analysis showed that CRP mediated the association between UA and CVD, accounting for 11.57% of the total effects.

High UA/high CRP is associated with increased risks of CVD. Incorporation of both UA and CRP provided additional value for risk stratification.

Heart disease remains a prominent global health concern, with cardiovascular disease (CVD) standing as a leading cause of death worldwide. Preventing heart disease not only decreases the risk of premature death but also mitigates complications like heart attacks, strokes, and arrhythmias, thereby enhancing overall health and quality of life. The economic burden of heart disease treatment highlights the importance of implementing preventive measures, such as lifestyle changes and early interventions, which can alleviate healthcare costs. These strategies, targeting risk factors like hypertension (HTN), diabetes mellitus (DM), dyslipidemia, and obesity, not only prevent heart disease but also reduce the risk of other health issues. Herein, this review covers various preventive measures, including dietary interventions, exercise, controlling HTN, DM, cholesterol, and weight, smoking cessation, and pharmacological interventions. By critically analyzing the guidelines and leveraging robust data alongside variations in recommendations, this review aims to elucidate effective primary prevention strategies for CVD.

The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet may slow cognitive decline in older adults. A potential mechanism could be possible anti-inflammatory properties of the MIND-diet.

To examine whether adherence to the MIND diet at baseline is associated with the odds of mild cognitive impairment (MCI) and changes in biomarkers of inflammation (High-sensitivity C-reactive Protein(hsCRP), interleukin-6(IL-6)) over three years in adults ≥70 years.

Adherence to the MIND diet was assessed by food frequency questionnaire (FFQ) at baseline and after three years. Presence of MCI based on the Montreal Cognitive Assessment (MoCA) was defined as <26 (MCI26), or <24 (MCI24). We performed a minimally adjusted model controlling for sex, prior fall, linear spline at age 85, time, treatment and study site. The fully adjusted model also adjusted for education, BMI, physical activity, depression score, daily energy intake, and comorbidity score. To assess the change in inflammatory markers from baseline, we used linear-mixed-effect models adjusted for the same variables plus the respective baseline concentrations. Sensitivity analyses accounting for practice effects of repeated cognitive tests using the reliable change index for both MoCA cut-offs were done.

We included 2028 of 2157 DO-HEALTH participants (60.5% women; mean age 74.88 years) with complete data. Adherence to the MIND diet at baseline was not associated with cognitive decline over three years, neither at MoCA < 26 (OR (95%CI) = 0.99 (0.94-1.04)) nor at MoCA < 24 (OR (95%CI) = 1.03 (0.96-1.1)). Applying the reliable change index to the two cut-offs confirmed the findings. Further, the MIND diet adherence was not associated with the change in MoCA score from baseline in DO-HEALTH. For inflammatory biomarkers MIND-diet baseline adherence was not associated with changes in hsCRP or IL-6.

Adherence to the MIND-diet was neither associated with the odds of MCI, nor with hsCRP or IL-6 at baseline. Moreover, change in MIND-diet over three years was not associated with changes in hsCRP or IL-6.

Previous studies investigating the effect of oral supplementation of paricalcitol on reactive protein levels in chronic kidney disease (CKD) patients reported inconsistent findings. In this systematic review and meta-analysis, we have analyzed and interpreted the results obtained from previous randomized clinical trials on the effect of paricalcitol on C-reactive protein in CKD patients in the literature.

MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched until January 2023 and related articles were obtained through a careful screening process allowing extraction of required data from selected articles. The effect size was calculated using a random effect model and weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity among studies was evaluated using Cochran's Q test and I2.

Amongst the 182 articles obtained from the initial search, 4 studies (6 arms) were finally included in the meta-analysis. Pooled analysis shows that C-reactive protein levels significantly decrease after oral supplementation with paricalcitol (WMD: -2.55 mg/L, 95% CI (-4.99 to -0.11; P = 0.04). The studies used in this meta-analysis showed significant heterogeneity (I2 = 66.3% and P = 0.01).

Oral paricalcitol supplementation in CKD patients can significantly reduce C-reactive protein levels, which may prevent CKD progression.

Elevation of systemic inflammatory markers were found to correlate with increased disease extent, reduced lung function and higher risk of future severe exacerbations in patients with bronchiectasis. Although a significant correlation of circulating hs-CRP levels with HRCT scores and resting oxygen saturation in patients with stable-state non-cystic fibrosis (CF) bronchiectasis was suggested, there is little data on the relationship between hs-CRP and the prognosis of bronchiectasis and a lack of data on the role of hs-CRP in predicting bronchiectasis exacerbation.

A prospective study was conducted on Chinese patients with non- CF bronchiectasis from 1st October to 31st December 2021. Baseline serum hs-CRP were obtained at stable-state. The follow-up period lasted for one year. Co-primary endpoints were the development of any bronchiectasis exacerbation and hospitalized bronchiectasis exacerbation.

Totally 123 patients were included. Higher hs-CRP was associated with increased risk to develop any bronchiectasis exacerbation, adjusted odds ratio (aOR) of 2.254 (95% CI = 1.040-4.885, p = 0.039), and borderline significantly increased hospitalized bronchiectasis exacerbation with aOR of 1.985 (95% CI = 0.922-4.277, p = 0.080).

Baseline serum hs-CRP level at stable-state can predict risk of bronchiectasis exacerbation, which is reflecting chronic low-grade inflammation in bronchiectasis.

We examined the relationship between baseline olfactory performance and incident significant depressive symptoms and longitudinal depression trajectories in well-functioning older adults. Inflammation and cognitive status were examined as potential mediators.

Older adults (n = 2 125, 71-82 years, 51% female, 37% Black) completed an odor identification task at Year 3 (our study baseline) of the Health, Aging, and Body Composition study. Cognitive assessments, depressive symptoms, and inflammatory markers were ascertained across multiple visits over 8 years. Discrete-time complementary log-log models, group-based trajectory models, and multivariable-adjusted multinomial logistic regression were employed to assess the relationship between baseline olfaction and incident depression and longitudinal depression trajectories. Mediation analysis assessed the influence of cognitive status on these relationships.

Individuals with lower olfaction had an increased risk of developing significant depressive symptoms at follow-up (hazard ratio = 1.04, 95% confidence interval [CI]: 1.00, 1.08). Of the 3 patterns of longitudinal depression scores identified (stable low, stable moderate, and stable high), poorer olfaction was associated with a 6% higher risk of membership in the stable moderate (relative risk ratio [RRR] = 1.06, 95% CI: 1.02, 1.10)/stable high (RRR = 1.06, 95% CI: 1.00, 1.12) groups, compared to the stable low group. Poor cognitive status, but not inflammation, partially mediated the relationship between olfactory performance and incident depression symptom severity.

Suboptimal olfaction could serve as a prognostic indicator of vulnerability for the development of late-life depression. These findings underscore the need for a greater understanding of olfaction in late-life depression and the demographic, cognitive, and biological factors that influence these relationships over time.

Inflammation can be defined as a complex biological response that is produced by body tissues to harmful agents like pathogens, irritants, and damaged cells and thereby acts as a protective response incorporating immune cells, blood vessels, and molecular mediators. Histamine, serotonin, bradykinin, leukotrienes (LTB4), prostaglandins (PGE2), prostacyclins, reactive oxygen species, proinflammatory cytokines like IL-1, IL-11, TNF- anti-inflammatory cytokines like IL-4, IL-10, IL-11, IL-6 and IL-13, etc. all have different effects on both pro and anti-inflammatory mediators. Incorporation of combinatorial chemistry and computational studies have helped the researchers to design xanthones moieties with high selectivity that can serve as a lead compound and help develop potential compounds that can act as effective COX-2 inhibitors. The study aims to design and develop different series of substituted hydroxyxanthone derivatives with anti-inflammatory potential.

The partially purified synthetic xanthone derivatives were orally administered to the carrageenan induced paw oedemic rat models at the dose of 100 mg/kg, and their effect in controlling the degree of inflammation was measured at the time interval of 30 min, 1, 2, 3, 4 and 6 hrs. respectively. Further, these compounds were also subjected to modern analytical studies like UV, IR, NMR and mass spectrometry or their characterization.

The results drawn out of the in silico, in vitro, in vivo and analytical studies concluded that the hydroxyxanthone derivatives can obstruct the enzyme COX-2 and produce anti-inflammatory action potentially.

With the aim to evaluate the compounds for their anti-inflammatory activity, it was observed that the newly designed xanthonic compounds also possess a safe toxicity margin and hence can be utilized by the researchers to develop hybrid xanthonic moieties that can specifically target the enzyme COX-2.

A fluorescence antibody microarray has been developed for the determination of relevant cardiovascular disease biomarkers for the analysis of human plasma samples. Recording characteristic protein molecular fingerprints to assess individual's states of health could allow diagnosis to go beyond the simple identification of the disease, providing information on its stage or prognosis. Precisely, cardiovascular diseases (CVDs) are complex disorders which involve different degenerative processes encompassing a collection of biomarkers related to disease progression or stage. The novel approach that we propose is a fluorescent microarray chip has been developed accomplishing simultaneous determination of the most significant cardiac biomarkers in plasma aiming to determine the CVD status stage of the patient. As proof of concept, we have chosen five relevant biomarkers, C-reactive protein (CRP) as biomarker of inflammation, cystatin C (CysC) as biomarker of renal failure that is directly related with heart failure, cardiac troponin I (cTnI) as already established biomarker for cardiac damage, heart fatty acid binding protein as biomarker of ischemia (H-FABP), and finally, NT-proBNP (N-terminal pro-brain natriuretic peptide), a well-established heart failure biomarker. After the optimization of the multiplexed microarray, the assay allowed the simultaneous determination of 5 biomarkers in a buffer solution reaching LODs of 15 ± 5, 3 ± 1, 24 ± 3, 25 ± 3, and 3 ± 1 ng mL-1, for CRP, CysC, H-FABP, cTnI, and NT-proBNP, respectively. After solving the matrix effect, and demonstrating the accuracy for each biomarker, the chip was able to determine 24 samples per microarray chip. Then, the microarray has been used on a small pilot clinical study with 29 plasma samples from clinical patients which suffered different CVD and other related disorders. Results show the superior capability of the chip to provide clinical information related to the disease in terms of turnaround time (1 h 30 min total assay and measurement) and amount of information delivered in respect to reference technologies used in hospital laboratories (clinical analyzers). Despite the failure to detect c-TnI at the reported threshold, the microarray technology could be a powerful approach to diagnose the cardiovascular disease at early stage, monitor its progress, and eventually providing information about an eminent potential risk of suffering a myocardial infarction. The microarray chip here reported could be the starting point for achieving powerful multiplexed diagnostic technologies for the diagnosis of CVDs or any other pathology for which biomarkers have been identified at different stages of the disease.