Identification and single-base gene-editing functional validation of a cis-EPO variant as a genetic predictor for EPO-increasing therapies.

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are currently under clinical development for treating anemia in chronic kidney disease (CKD), but it is important to monitor their cardiovascular safety. Genetic variants can be used as predictors to help inform the potential risk of adverse effects associated with drug treatments. We therefore aimed to use human genetics to help assess the risk of adverse cardiovascular events associated with therapeutically altered EPO levels to help inform clinical trials studying the safety of HIF-PHIs. By performing a genome-wide association meta-analysis of EPO (n = 6,127), we identified a cis-EPO variant (rs1617640) lying in the EPO promoter region. We validated this variant as most likely causal in controlling EPO levels by using genetic and functional approaches, including single-base gene editing. Using this variant as a partial predictor for therapeutic modulation of EPO and large genome-wide association data in Mendelian randomization tests, we found no evidence (at p < 0.05) that genetically predicted long-term rises in endogenous EPO, equivalent to a 2.2-unit increase, increased risk of coronary artery disease (CAD, OR [95% CI] = 1.01 [0.93, 1.07]), myocardial infarction (MI, OR [95% CI] = 0.99 [0.87, 1.15]), or stroke (OR [95% CI] = 0.97 [0.87, 1.07]). We could exclude increased odds of 1.15 for cardiovascular disease for a 2.2-unit EPO increase. A combination of genetic and functional studies provides a powerful approach to investigate the potential therapeutic profile of EPO-increasing therapies for treating anemia in CKD.

Residential proximity to agricultural pesticide use and cardiovascular disease risk factors among adult Latina women in California's Salinas Valley.

Cardiovascular disease is a leading cause of death worldwide. There is limited evidence that exposure to current-use pesticides may contribute to cardiovascular disease risk. We examined the association between residential proximity to the application of agricultural pesticides and cardiovascular risk factors among 484 adult women in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a cohort based in an agricultural region of California. Outcome assessment was completed between 2010 and 2013. Using participant residential addresses and California's Pesticide Use Reporting database, we estimated agricultural pesticide use within one km of residences during the 2-year period preceding outcome assessment. We used Bayesian Hierarchical Modeling to evaluate associations between exposure to 14 agricultural pesticides and continuous measures of waist circumference, body mass index, and blood pressure. Each 10-fold increase in paraquat application around homes was associated with increased diastolic blood pressure (ß=2.60 mm Hg, 95% Credible Interval (CrI): 0.27-4.89) and each 10-fold increase in glyphosate application was associated with increased pulse pressure (ß=2.26 mm Hg, 95% CrI: 0.09-4.41). No meaningful associations were observed for the other pesticides examined. Our results suggest that paraquat and glyphosate pesticides may affect cardiovascular disease development in women with chronic environmental exposure.

Adults prenatally exposed to the Dutch Famine exhibit a metabolic signature associated with a broad spectrum of common diseases.

BACKGROUND: Exposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type 2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to identify the metabolic changes that are associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and subsequently assess their link to disease. METHODS: NMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases. RESULTS: Prenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2-0.3 SD, p < 3 × 10-3). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type 2 diabetes from the UK Biobank (r = 0.77, p = 3 × 10-27), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r = 0.67, p = 1 × 10-18). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 ≤ r ≤ 0.9, p < 3.2 × 10-4). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index. CONCLUSIONS: Prenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity.

Single and 7-day handgrip and squat exercise prevents endothelial ischemia-reperfusion injury in individuals with cardiovascular disease risk factors.

Whole body exercise provides protection against endothelial ischemia-reperfusion (IR) injury. In this crossover study, we examined the effects of 1) single bout of local exercise (handgrip, squats) on endothelial responses to IR, and 2) if 7 days of daily local exercise bolsters these effects in individuals with cardiovascular disease (CVD) risk factors. Fifteen participants (9 women, 58 ± 5 yr, ≥2 CVD risk factors) attended the laboratory for six visits. Subsequent to familiarization (visit 1), during visit 2 (control) brachial artery flow-mediated dilation (FMD) was measured before and after IR (15-min upper-arm ischemia, 15-min reperfusion). One week later, participants were randomized to 4 × 5-min unilateral handgrip (50% maximal voluntary contraction, 25 rpm) or squat exercises (15 rpm), followed by IR plus FMD measurements. Subsequently, home-based exercise was performed (6 days), followed by another visit to the laboratory for the IR protocol plus FMD measurements (18-24 h after the last exercise bout). After a 2-wk washout period, procedures were repeated with the alternative exercise mode. For a single exercise bout, we found a significant IR injury × exercise mode interaction (P < 0.01) but no main effect of injury (P = 0.08) or condition (P = 0.61). A lower post-IR FMD was evident after control (pre-IR: 4.3 ± 2.1% to post-IR: 2.9 ± 1.9%, P < 0.01) but not after handgrip (pre-IR: 3.8 ± 1.6% to post-IR: 3.4 ± 1.5%, P = 0.31) or squats (pre-IR: 3.9 ± 1.8% to post-IR: 4.0 ± 1.9%, P = 0.74). After 7 days of daily exercise, we found no change in FMD post-IR following handgrip (pre-IR: 4.3 ± 1.9% to post-IR: 4.7 ± 3.2%) or squats (pre-IR: 3.7 ± 2.1% to post-IR: 4.7 ± 3.0%, P > 0.05). Single bouts of dynamic, local exercise (handgrip, squats) provide remote protection against endothelial IR-induced injury in individuals with CVD risk factors, with 1-wk daily, home-based exercise preserving these effects for up to 24 h following the last exercise bout.NEW & NOTEWORTHY We show that single bouts of dynamic handgrip and squat exercise provide remote protection against endothelial ischemia-reperfusion (IR)-induced injury in individuals with cardiovascular disease (CVD) risk factors, with 1-wk daily, home-based exercise preserving these effects for up to 24 h following the last exercise bout.

Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm.

BACKGROUND: Typical bone proteins, such as sclerostin and periostin, have been associated with cardiovascular disease (CVD). Simultaneously, several risk scores have been developed to predict CVD in the general population. Therefore, we aimed to evaluate the association of these bone proteins related to CVD, with the main vascular risk scales: Framingham Risk Score (FRS), REGICOR and SCORE2-Diabetes, in patients with type 2 diabetes. We focus in particular on the SCORE2-Diabetes algorithm, which predicts 10-year CVD risk and is specific to the study population. METHODS: This was a cross-sectional study including 104 patients with type 2 diabetes (62 ± 6 years, 60% males). Clinical data, biochemical measurements, and serum bioactive sclerostin and periostin levels were collected, and different risk scales were calculated. The association between bioactive sclerostin or periostin with the risk scales was analyzed. RESULTS: A positive correlation was observed between circulating levels of bioactive sclerostin (p < 0.001) and periostin (p < 0.001) with SCORE2-Diabetes values. However, no correlation was found with FRS or REGICOR scales. Both serum bioactive sclerostin and periostin levels were significantly elevated in patients at high-very high risk of CVD (score ≥ 10%) than in the low-moderate risk group (score < 10%) (p < 0.001 for both). Moreover, analyzing these proteins to identify patients with type 2 diabetes at high-very high vascular risk using ROC curves, we observed significant AUC values for bioactive sclerostin (AUC = 0.696; p = 0.001), periostin (AUC = 0.749; p < 0.001), and the model combining both (AUC = 0.795; p < 0.001). For diagnosing high-very high vascular risk, serum bioactive sclerostin levels > 131 pmol/L showed 51.6% sensitivity and 78.6% specificity. Similarly, serum periostin levels > 1144 pmol/L had 64.5% sensitivity and 76.2% specificity. CONCLUSIONS: Sclerostin and periostin are associated with vascular risk in the SCORE2-Diabetes algorithm, opening a new line of investigation to identify novel biomarkers of cardiovascular risk in the type 2 diabetes population.

Improvements in markers of inflammation and coagulation potential following a 5-day high-fat diet rich in cottonseed oil vs. Olive oil in healthy males.

Low-grade inflammation is believed to be a risk factor for chronic diseases and is nutritionally responsive. Cottonseed oil (CSO), which is rich in n-6 polyunsaturated fats, has been shown to lower cholesterol and other chronic disease risk factors. The purpose of this secondary analysis was to determine the comparative responses of markers of inflammation and coagulation potential of healthy adult males consuming diets rich in CSO vs. olive oil (OO). METHODS: Fifteen normal-weight males, ages 21.7 ± 2.58y, completed a randomized crossover trial. Each intervention consisted of a 3-day lead-in diet and a 5-day outpatient, controlled feeding intervention (CSO or OO). There was a 2 to 4-week washout period between interventions. The 5-day intervention diets were 35 % carbohydrate, 15 % protein, and 50 % fat, enriched with either CSO or OO (44 % of total energy from oil). At pre- and post- diet intervention visits, a fasting blood draw was collected for analysis of markers of inflammation (Tumor Necrosis Factor Alpha (TNF-α), Interleukin-6 (IL-6), C-Reactive Protein (CRP)) and coagulation potential (Tissue Factor (TF), Plasminogen Activator Inhibitor-1 (PAI-1)). RESULTS: The CSO-enriched diets reduced TNF-α (CSO: -0.12 ± 0.02 pg/ml, OO: -0.01 ± 0.05 pg/ml; p < 0.01) and TF (CSO: -0.59 ± 0.68 pg/ml, OO: 1.13 ± 0.83 pg/ml; p = 0.02) compared to OO diets. There were no differences in IL-6, CRP, or PAI-1 between diets. CONCLUSION: A 5-day, CSO-enriched diet may be sufficient to reduce inflammation and coagulation potential compared to OO-enriched diets in a healthy male population which could have implications in chronic disease prevention.

Association of Cancer and Its Interaction with Conventional Risk Factors on Cardiovascular Disease Risk.

INTRODUCTION: We sought to examine the association of cancer history with the incidence of individual cardiovascular disease events and to clarify whether the history of cancer modifies the relationship between conventional cardiovascular risk factors and incident cardiovascular disease. METHODS: This retrospective cohort study used the JMDC Claims Database, including 3,531,683 individuals. The primary endpoint was the composite cardiovascular disease outcome, which included myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. RESULTS: During a follow-up, 144,162 composite endpoints were recorded. Individuals with a history of cancer had a higher risk of developing composite cardiovascular disease events (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.22-1.29). The HRs for myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation were 1.11 (95% CI 0.98-1.27), 1.15 (95% CI 1.10-1.20), 1.11 (95% CI 1.05-1.18), 1.39 (95% CI 1.34-1.44), and 1.22 (95% CI 1.13-1.32), respectively. Individuals who required chemotherapy for cancer had a higher risk of developing cardiovascular disease. Although conventional risk factors (e.g., overweight/obesity, hypertension, and diabetes) were associated with incident composite cardiovascular disease even in individuals with a history of cancer, the total population-attributable fractions of conventional risk factors were less in individuals with a history of cancer. CONCLUSION: Individuals with a history of cancer (particularly those requiring chemotherapy) have a higher risk of cardiovascular disease. Traditional risk factors are important in the development of cardiovascular disease in individuals with and without a history of cancer. In individuals with a history of cancer, however, the total population-attributable fractions of conventional risk factors decreased.

Cortical and subcortical brain networks predict prevailing heart rate.

Resting heart rate may confer risk for cardiovascular disease (CVD) and other adverse cardiovascular events. While the brainstem's autonomic control over heart rate is well established, less is known about the regulatory role of higher level cortical and subcortical brain regions, especially in humans. This study sought to characterize the brain networks that predict variation in prevailing heart rate in otherwise healthy adults. We used machine learning approaches designed for complex, high-dimensional data sets, to predict variation in instantaneous heart period (the inter-heartbeat-interval) from whole-brain hemodynamic signals measured by fMRI. Task-based and resting-state fMRI, as well as peripheral physiological recordings, were taken from two data sets that included extensive repeated measurements within individuals. Our models reliably predicted instantaneous heart period from whole-brain fMRI data both within and across individuals, with prediction accuracies being highest when measured within-participants. We found that a network of cortical and subcortical brain regions, many linked to visceral motor and visceral sensory processes, were reliable predictors of variation in heart period. This adds to evidence on brain-heart interactions and constitutes an incremental step toward developing clinically applicable biomarkers of brain contributions to CVD risk.

Noninvasive liver fibrosis markers are independently associated with carotid atherosclerosis risk in patients with nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is considered an independent risk factor for cardiovascular disease (CVD). The overall morbidity and mortality of CVD increase with higher fibrosis stage in NAFLD. Carotid atherosclerosis (CAS) is an important predictor of cardiovascular events. However, the relationship between liver fibrosis degree and the risk of CAS in NAFLD patients remains uncertain. We aimed to investigate the relationship between noninvasive liver fibrosis markers and CAS risk in patients with NAFLD. MATERIALS AND METHODS: This study included 3,302 participants with NAFLD. Participants were divided into a CAS group and a non-CAS group based on carotid artery ultrasound results. They were then stratified into quartiles using various noninvasive liver fibrosis markers (fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aminotransferase to platelet ratio index (APRI), aminotransferase to alanine aminotransferase ratio (AAR), AAR-to-platelet ratio index (AARPRI), and Forns index) to assess the associations between these markers and the risk of CAS. RESULTS: In the NAFLD population, individuals with CAS exhibited elevated levels of blood pressure, glucose, lipids, and noninvasive liver fibrosis markers (p < 0.001). The higher quartiles of noninvasive liver fibrosis markers, including FIB-4, mFIB-4, AAR, AARPRI, and Forns index, were significantly associated with increased risks of CAS, even after adjusting for multiple CVD risk factors. CONCLUSIONS: In individuals with NAFLD, increased noninvasive liver fibrosis markers were independently associated with elevated CAS risk, which may be beneficial in assessing the risk of CVD in individuals with NAFLD.

Benign Prostatic Hyperplasia and Incident Cardiovascular Disease.

BACKGROUND: Data regarding the relationship between benign prostatic hyperplasia (BPH) and incident cardiovascular disease (CVD) are scarce. We aimed to clarify the association of BPH with the risk of developing CVD using a nationwide epidemiological database. METHODS AND RESULTS: This retrospective observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2022, including 2,370,986 men (median age 44 years). The primary endpoints were myocardial infarction (MI), angina pectoris (AP), stroke, heart failure (HF), and atrial fibrillation (AF), which were assessed separately. BPH was observed in 48,651 (2.1%) men. During a mean (±SD) follow-up of 1,359±1,020 days, 7,638 MI, 52,167 AP, 25,355 stroke, 58,183 HF, and 16,693 AF events were detected. Hazard ratios of BPH for MI, AP, stroke, HF, and AF were 1.04 (95% confidence interval [CI] 0.92-1.18), 1.31 (95% CI 1.25-1.37), 1.26 (95% CI 1.18-1.33), 1.21 (95% CI 1.16-1.27), and 1.15 (95% CI 1.07-1.24), respectively. We confirmed the robustness of our primary findings through a multitude of sensitivity analyses. In particular, a history of BPH was associated with a higher risk of developing CVD, even in participants without obesity, hypertension, diabetes, or dyslipidemia. CONCLUSIONS: Our analysis of a nationwide epidemiological dataset demonstrated that BPH was associated with a greater risk of developing CVD in middle-aged men.

Awareness of Being Prescribed Antihypertensive Medications and Cardiovascular Outcomes.

BACKGROUND: Hypertension is a major cause of cardiovascular disease (CVD). In patients with hypertension, unawareness of the disease often results in poor blood pressure control and increases the risk of CVD. However, data in nationwide surveys regarding the proportion of unaware individuals and the implications of such on their clinical outcomes are lacking. We aimed to clarify the association between unawareness of being prescribed antihypertensive medications among individuals taking antihypertensive medications and the subsequent risk of developing CVD. METHODS AND RESULTS: This retrospective cohort study analyzed data from the JMDC Claims Database, including 313,715 individuals with hypertension treated with antihypertensive medications (median age 56 years). The primary endpoint was a composite of myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Overall, 19,607 (6.2%) individuals were unaware of being prescribed antihypertensive medications. During the follow-up period, 33,976 composite CVD endpoints were documented. Despite their youth, minimal comorbidities, and the achievement of better BP control with a reduced number of antihypertensive prescriptions, unawareness of being prescribed antihypertensive medications was associated with a greater risk of developing composite CVD. Hazard ratios of unawareness of being prescribed antihypertensive medications were 1.16 for myocardial infarction, 1.25 for angina pectoris, 1.15 for stroke, 1.36 for heart failure, and 1.28 for atrial fibrillation. The results were similar in several sensitivity analyses, including the analysis after excluding individuals with dementia. CONCLUSIONS: Among individuals taking antihypertensive medications, assessing the awareness of being prescribed antihypertensive medications may help identify those at high risk for CVD-related events.

High-sensitivity C-reactive protein among people living with HIV on highly active antiretroviral therapy: a systemic review and meta-analysis.

The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10­1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76­1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.

Changes in Atherosclerotic Cardiovascular Disease Risk Scores in a Predominantly Black Cohort with HIV and Associated Comorbidities: A Preliminary Study.

INTRODUCTION: People with HIV (PWH) have an increased risk of atherosclerotic cardiovascular disease (ASCVD) compared to non-PWH, but the reasons for this increased risk remain elusive. We investigated the change in ASCVD risk scores over 4 years to identify clinical factors associated with change in risk scores or high-risk scores. METHODS: We conducted a preliminary study using retrospective analysis of PWH, between 40 and 75 years old, seen at the Evelyn Jordan Center with at least two routine HIV visits. We collected clinical and demographic data and calculated the ASCVD risk scores using the Pooled Cohort Equation. Exploratory analyses examined change in risk score categories over time. Final adjusted analysis examined factors associated with change in continuous risk scores over time. RESULTS: Our sample included 187 PWH; 166 were black/African American and 79 were female. We found no significant change in ASCVD risk score over time. The risk score was significantly higher in PWH with hepatitis C (7.34%; 95% CI: 2.59, 12.09; p = 0.003) and trended higher in those with dual hepatitis B/C and hepatitis B compared to those without hepatitis (p = 0.07). CONCLUSION: We found that ASCVD risk did not change over a 4-year period among predominantly black young PWH, but infection with hepatitis C and dual hepatitis B/C were associated with higher ASCVD risk scores. Our findings illustrate the need for further longitudinal studies evaluating change in cardiovascular disease (CVD) risk and investigating viral hepatitis as an added potential contributor to increased CVD risk in high-risk, vulnerable populations.

Investigating the interplay of smoking, cardiovascular risk factors, and overall cardiovascular disease risk: NHANES analysis 2011-2018.

BACKGROUND: This study explores the intricate relationship between smoking, cardiovascular disease (CVD) risk factors and their combined impact on overall CVD risk, utilizing data from NHANES 2011-2018. METHODS: Participants were categorized based on the presence of CVD, and we compared their demographic, social, and clinical characteristics. We utilized logistic regression models, receiver operating characteristics (ROC) analysis, and the chi-squared test to examine the associations between variables and CVD risk. RESULTS: Significant differences in characteristics were observed between those with and without CVD. Serum cotinine levels exhibited a dose-dependent association with CVD risk. The highest quartile of cotinine levels corresponded to a 2.33-fold increase in risk. Smoking, especially in conjunction with lower HDL-c, significantly increases CVD risk. Combinations of smoking with hypertension, central obesity, diabetes, and elevated triglycerides also contributed to increased CVD risk. Waist-to-Height Ratio, Visceral Adiposity Index, A Body Shape Index, Conicity Index, Triglyceride-Glucose Index, Neutrophil, Mean platelet volume and Neutrophil to Lymphocyte ratio demonstrated significant associations with CVD risk, with varying levels of significance post-adjustment. When assessing the combined effect of smoking with multiple risk factors, a combination of smoking, central obesity, higher triglycerides, lower HDL-c, and hypertension presented the highest CVD risk, with an adjusted odds ratio of 14.18. CONCLUSION: Smoking, when combined with central obesity, higher triglycerides, lower HDL-c, and hypertension, presented the highest CVD risk, with an adjusted odds ratio of 14.18.

Associations of 10-year atherosclerotic cardiovascular disease risk scores with cerebral small vessel disease: the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study.

BACKGROUND: 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores were useful for predicting large vessel disease, but the relationships between them and cerebral small vessel disease (CSVD) were unclear. Our study aimed to evaluate associations of 10-year ASCVD risk scores with CSVD and its magnetic resonance imaging (MRI) markers. METHODS: Community-dwelling residents from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study were included in this cross-sectional study. At baseline, we collected data related to the Framingham Risk Score (FRS), pooled cohort equation (PCE), prediction for ASCVD risk in China (China-PAR) and Systematic COronary Risk Evaluation model 2 (SCORE2), and classified participants into low, moderate and high groups. Participants underwent brain MRI scans. We evaluated white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS) according to criteria of Wardlaw and Rothwell, and calculated total CSVD score and modified total CSVD score. RESULTS: A total of 3063 participants were included, and 53.5% of them were female. A higher FRS was associated with higher total CSVD score (moderate vs. low: cOR 1.89, 95% CI 1.53-2.34; high vs. low: cOR 3.23, 95%CI 2.62-3.97), and the PCE, China-PAR or SCORE2 score was positively related to total CSVD score (P < 0.05). Moreover, higher 10-year ASCVD scores were associated with higher odds of WMH (P < 0.05), lacunes (P < 0.05), CMBs (P < 0.05) and BG-EPVS (P < 0.05). CONCLUSIONS: The 10-year ASCVD scores were positively associated with CSVD and its MRI markers. These scores provided a method of risk stratification in the population with CSVD.

Loneliness status transitions and risk of cardiovascular disease among middle-aged and older adults.

BACKGROUND AND AIMS: Loneliness is a risk factor for cardiovascular disease (CVD), and the levels at which individuals experience it can transition over time. However, the impact of increased loneliness or decreased loneliness on later CVD risk remains unexplored. We aimed to identify the age-specific association between loneliness status transitions and subsequent CVD incidences in middle-aged and older adults. METHODS AND RESULTS: Data was extracted from the China Health and Retirement Longitudinal Study (CHARLS) on 8463 adults to evaluate how loneliness status transitions across two data collection points were associated with the subsequent CVD incidence at a five-year follow-up. Loneliness status transitions were divided into four categories: stable low loneliness, decreased loneliness, increased loneliness, and stable high loneliness. Data were analyzed using a Cox-proportional hazards model with age subgroups, accounting for covariates at baseline. During follow-up, the incidence rate of CVD per 1000 person-years was lower for the stable low loneliness group and decreased loneliness group compared to the increased loneliness and stable high loneliness group. Increased loneliness is associated with the highest risk of overall CVD and heart disease (HR 2.44, P < 0.001; HR 2.34, P < 0.001), while stable high loneliness is associated with the highest risk of stroke among the four loneliness categories (HR 4.29, P < 0.05). The age-specific analyses revealed no statistically significant interaction in terms of loneliness status transitions and age group. CONCLUSION: Increased loneliness and stable high loneliness are associated with higher CVD risk. In clinical practice, it is important to monitor patients' loneliness status transitions to reduce CVD incidences.

A cross-sectional study of the relationship between physical activity, diet quality, and high-sensitivity C-reactive protein in US adults.

BACKGROUND AND AIMS: High-sensitivity C-reactive protein (hs-CRP) is associated with many diseases, especially cardiovascular disease (CVD). Research into the independent and integrated relationships of physical activity and diet quality with hs-CRP across sex-specific cohorts is lacking. METHODS AND RESULTS: National Health and Nutrition Examination Survey data (2015-2018) was used to examine the relationship between physical activity and diet quality with hs-CRP and hs-CRP classified CVD risk using multiple multinormal logistic regression adjusted for covariates including demographics. Physical activity was measured using a self-reported survey and further categorized to those who met (MPAR) or did not meet (NPAR) national recommendations. Diet quality was measured using the Healthy Eating Index-2015, and further categorized to higher (HDQ) and lower (LDQ) diet quality. hs-CRP was also categorized as low, average, and high CVD risk using established cut-points. Physical activity was inversely related to hs-CRP in males (p < 0.001) whereas diet quality was inversely related to hs-CRP in females (p = 0.031). Compared to those with NPAR and LDQ, the hs-CRP for males with NPAR and HDQ and females with MPAR and HDQ was 1.18 mg/L and 0.75 mg/L lower respectively. Although, diet quality was inversely associated with high CVD risk in both sexes (p < 0.05), the lowest proportion of high and average CVD risk was observed in males and females with MPAR and HDQ. CONCLUSION: Physical activity and diet-quality lowered CVD risk regardless of sex. However, the independent effects of physical activity and diet quality on hs-CPR differs between sexes.

COPD is associated with increased cardiovascular disease risk independent of phenotype.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide that frequently presents with concomitant cardiovascular diseases. Despite the pathological distinction between individual COPD phenotypes such as emphysema and chronic bronchitis, there is a lack of knowledge about the impact of COPD phenotype on cardiovascular disease risk. Thus, this study aimed to utilize a nationally representative sample to investigate cardiovascular disease prevalence in patients with COPD with emphysema and chronic bronchitis phenotypes. METHODS: Data from 31,560 adults including 2504 individuals with COPD, collected as part of the National Health and Nutrition Examination Survey (1999-2018), were examined. RESULTS: A significantly increased cardiovascular disease risk, including coronary heart disease, heart failure, myocardial infarction and stroke, was identified in patients with COPD among all disease phenotypes. Particularly, compared to those without COPD, individuals with chronic bronchitis presented with 1.76 (95% CI: 1.41-2.20) times greater odds, individuals with emphysema with 2.31 (95% CI: 1.80-2.96) times greater odds, while those with a concurrent phenotype (combined chronic bronchitis and emphysema) exhibited 2.98 (95% CI: 2.11-4.21) times greater odds of reporting cardiovascular diseases. CONCLUSION: Our data confirms that patients with COPD present an elevated risk of developing cardiovascular disease among all phenotypes, with the most marked increase being in those with concurrent chronic bronchitis and emphysema phenotypes. These findings emphasize the need for awareness and appropriate cardiovascular screening in COPD.

Reproductive milestones across the lifespan and cardiovascular disease risk in women.

Cardiovascular disease (CVD) is the leading cause of death for women across the developed and developing world. Beyond traditional cardiovascular risk factors, a number of reproductive milestones have been recognized. The goal of this White Paper, issued by the International Menopause Society in conjunction with World Menopause Day 2023, is to highlight female reproductive milestones in terms of potential cardiovascular risk and to review recommendations for minimizing that risk. The primary milestones discussed relate to menstrual cyclicity, adverse pregnancy outcomes, breast cancer treatments and menopause. Each of these categories has a number of permutations that have been shown in observational studies to be associated with increased cardiovascular risks. In current clinical care, recognition of these reproductive milestones has been encouraged so patients can be informed and motivated to engage in primary prevention of CVD early in their life course rather than retrospectively later in life. Options for specifically targeted care with specialist teams are designed to enhance success with risk identification, screening and possible detection of CVD and, optimally, primary or secondary prevention of CVD. Promoting cardiovascular health of women has far-reaching effects for themselves, their families and their progeny. It is time to make women's cardiovascular health a priority.

Characteristics of and changes in the cardiometabolic measures of Japanese workers grouped according to their vegetables and salt intake through workplace cafeteria meals.

OBJECTIVE: This study aimed to objectively evaluate the diet consumed in a workplace cafeteria to group Japanese workers according to vegetables and salt intake and estimate the association of these groups with changes in cardiometabolic measurements. DESIGN: This longitudinal observational study estimated the food and nutrient intake of Japanese workers from data recorded in the cafeteria system of their workplace. The primary outcomes included cardiometabolic measures obtained via regular health check-ups conducted at the workplace. The participants were divided into four groups according to high or low vegetables and salt intake based on their respective medians and the association of each group with cardiometabolic measurement changes was estimated using robust regression with MM-estimation. SETTING: A Japanese automobile manufacturing factory. SUBJECTS: The study included 1,140 men and women workers with available cafeteria and health check-up data. RESULTS: An inverse marginal association was observed between changes in triglyceride levels and high vegetables and low salt intake (ß: -9.93, 95% confidence interval [CI]: -20.45, 0.59, p: 0.065) with reference to low vegetables and high salt intake. This association was stronger in participants who used the cafeteria more frequently (>71 days; ß: -13.55, 95% CI: -25.51, -1.60, p: 0.027). CONCLUSIONS: The participants in the higher vegetables and lower salt intake group were more likely to exhibit decreased triglyceride levels. These findings encourage using workplace cafeteria meals to promote the health of workers.