European Journal of Preventive Cardiology

Background Elevated resting heart rate (RHR) predicts mortality in older adults, primarily through cardiovascular disease (CVD). Prior cohort evidence suggests that RHR also predicts mortality in younger adults, but whether this association operates through cardiovascular or non-cardiovascular pathways has not been directly tested. Methods and Results We analyzed 3291 adults aged 20 to 49 years from NHANES 1999-2004 linked to mortality data through 2019 (median follow-up, 17.8 years; 120 deaths). RHR and heart rate reserve (HRR) were modeled per 10-bpm increment using Cox regression adjusted for demographic, lifestyle, and comorbidity covariates. Each 10-bpm RHR increase was associated with higher all-cause mortality (hazard ratio [HR], 1.26; 95% CI, 1.07-1.50; P=.007), driven by non-CVD mortality (HR, 1.28; 95% CI, 1.07-1.55; P=.009) rather than CVD mortality (HR, 1.15; 95% CI, 0.77-1.71; P=.51). A behavioral/external composite (accidents and NCHS residual causes, including suicide and liver disease) reached significance (HR, 1.35; P=.02), whereas a disease-oriented composite did not (P=.20). The association was absent before age 35 (HR, 0.98; P=.88) but pronounced at ages 35-39 (HR, 2.60; P=.001). HRR was not associated with any outcome. Conclusions In young US adults, elevated RHR predicted mortality through non-cardiovascular rather than cardiovascular pathways, concentrated among behavioral and external causes. The association emerged at age 35, below current screening thresholds. HRR under submaximal conditions carried no prognostic value. RHR in young adults may reflect global health vulnerability rather than cardiovascular risk alone.

Background: Regular exercise is a highly effective yet underutilized strategy to reduce cardiometabolic disease burden. Whether brief structured exercise programs confer lasting cardiometabolic benefits remains unclear. The STRRIDE-Prediabetes Reunion study examined legacy effects of exercise training on cardiorespiratory fitness, body composition, and cardiometabolic health. Methods: Seventy-three participants (71.3 {+/-} 7.2 years; 64% women; 77% White) completed Reunion assessments ~11 years after completing one of four 6-month interventions differing in exercise amount, intensity, and inclusion of diet-induced weight loss. Linear mixed effects models evaluated longitudinal trajectories; secondary analyses examined baseline-adjusted associations among short-term intervention response and Reunion outcomes. Results: Abdominal adiposity improved across all groups from baseline to Reunion, with waist circumference decreasing ~3 cm over the follow-up period. In contrast, cardiorespiratory fitness and fat-free mass declined significantly. A significant group by time interaction was observed for total fat mass (p=0.01), with continued fat mass reductions observed in women randomized to high amount exercise. After baseline adjustment, greater short-term intervention response was associated with more favorable Reunion outcomes across fitness, body composition, and cardiometabolic domains; fat-free mass showed the strongest association ({beta}=0.84, p<0.0001). Conclusions: In older adults with prediabetes, the STRRIDE-Prediabetes interventions produced several legacy health effects persisting more than a decade later. Legacy effects differed by sex and exercise dose, and short-term intervention response relative to baseline was associated with long-term outcomes, supporting targeted exercise strategies to preserve cardiometabolic health and functional independence with aging.

Background: Coronary artery calcium (CAC) scores inform subclinical atherosclerotic cardiovascular disease (ASCVD) burden, helping guide preventative treatments. However, prediction of cardiovascular (CV) events by CAC is largely limited to ASCVD outcomes. This study investigated whether a previously validated proteomic test for predicting a broad composite of four-year CV events could enhance the prognostic utility of CAC. Methods: We used a 27-protein CV risk score (Prot-CVR), derived from ~5,000 SomaScan? Assay plasma protein measurements, to predict four-year risk of a composite CV and mortality outcome (myocardial infarction, stroke/TIA, heart failure hospitalization, death) in 2,122 participants with ?1 CV risk factors from the Multi-Ethnic Study of Atherosclerosis (MESA) observational cohort at exam 5 and compared predictions to CAC Agatston scores. Discriminatory performance was assessed using C-Index and 4-year area under the curve (AUC). Cox Proportional Hazard (CoxPH) ratios were calculated for the composite outcome, ASCVD outcome (myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease death), and individual events. Changes in Prot-CVR and CAC scores from baseline to MESA exam 5 (+10-years) in CV event versus event-free participants were assessed using 2-tailed paired t-tests. CoxPH regression models of CV event status distributed by Prot-CVR, CAC, and relevant co-variates were evaluated for performance relative to individual models. Results: Individual Prot-CVR and CAC models predicting the composite outcome had comparable 4-year AUCs, but Prot-CVR had a higher C-index (0.68 (0.65-0.70) versus 0.63 (0.60-0.65), p=0.001) and greater hazard ratios for the composite outcome (p<0.001), death (p<0.001), and heart failure (p=0.015). A combined CoxPH model of Prot-CVR + CAC + Age had a higher 4-year AUC (0.72, p<0.05) and C-Index (0.71, p<0.05) than Prot-CVR or CAC alone. Both Prot-CVR and CAC scores detected an increase in risk prior to an approaching CV event in ~10-year sensitivity-to-change analysis. For 49.6% of MESA population with CAC=0 at baseline, Prot-CVR was greater in composite event versus event free participants at 4 years (0.23 versus 0.15, p=0.006) and full follow-up (0.18 versus 0.13, p<0.001). Conclusion: Protein testing complements CAC for CV risk assessment although the improvement is modest. Prot-CVR may resolve which patients with CAC=0 are at heightened CV risk.

BACKGROUND: Coronary artery disease (CAD) and Impaired Cognitive (IC) disease share sociodemographic, genetic, and clinical factors, but the association of IC with statin use in CAD remains unclear. OBJECTIVES: To determine the association between IC and statin use in CAD based on APO (e) genotype, sex, and lipid levels. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective study of AllofUS (AoU) participants with CAD (Age [&ge;]60 yrs) enrolled from 2017 to 2023. We defined CAD as having a history of angina/myocardial infarction/chronic ischemic heart disease or having percutaneous coronary intervention/CABG, and IC defined as mild cognitive impairment or all cause dementia, using ICD/SNOMED codes. MEASURES: We assessed the association between IC and statin use using logistic regression analysis, while adjusting for clinical factors, sociodemographics, and APO (e) genotypes before and after propensity score matching. We further performed stratified analysis by sex, and APO (e) genotypes. We finally assessed the association between IC and statin users, based magnitude on the change in lipid levels before CAD and after IC (TC: Total cholesterol, LDL: low density lipoprotein, HDL: High Density Lipoprotein). Significance was defined at p < 0.05. RESULTS: The cohort included 22,089 participants with CAD and 1343 with IC. Thirty-nine percent of participants were females, 77% were European, 13% were African American, and 9% were of Admixed American ancestry. The proportion of IC was higher (6.8% vs 3.5%, p<0.001) in statin users (n=17,191) vs non-statin users (n=4,898). IC was significantly associated with statin use (OR:1.70;1.40-2.10, p = 4.9e-7) after adjustment for clinical factors, sociodemographics, and APO (e) genotypes. After propensity-score matching between IC and CAD, we observed an association between IC and statin use (OR:1.55;1.24-1.94, p =1e-4). In stratified analysis, the association between IC and statin use was strongest in the APO e3/e3 group (OR:2.04;1.53-2.75, p = 1e-6), and in females (OR:2.20;1.60-3.06, p = 2.e-6) compared to males (OR:1.43;1.10-1.90, p = 0.01). We finally observed an increased magnitude of association between IC and statin users having higher HDL increase (> 10 mg/dl: OR:1.95;1.44-2.66, p=1e-5) as compared to statin users with lesser HDL increase (<=; 10mg/dl: OR:1.61;1.22-2.15, p=8e-4). CONCLUSION: In the AllofUS cohort, IC was significantly associated with statin use in CAD participants. We observed the strongest association in the APO e3/e3 group, among females, and with a greater increase in HDL levels in statin users.

Background: People with ischemic heart disease (IHD) remain at high risk of recurrent major cardiovascular events despite contemporary therapy. Over two decades, a translational research program has evaluated pressure pain sensitivity (PPS) as a non-invasive marker of central autonomic dysfunction and a mutual risk phenotype in IHD and type 2 diabetes. A PPS-guided non-pharmacological intervention has been shown to substantially reduce five-year all-cause mortality in IHD. Methods: In a randomized controlled trial, 213 adults with stable IHD and elevated PPS, suggesting ANSD, were allocated to PPS-guided intervention (n=106) or control (n=107). The active group received three months of structured education (daily PPS self-measurement, cutaneous sensory nerve stimulation, supportive mental and physical exercises, telemedical feedback) followed by self-directed continuation. Controls received a booklet on general stress-management. The primary endpoint for this prespecified secondary analysis was a composite of eight major cardiovascular events. Results: Over 5 years, at least one major adverse cardiovascular event occurred in 19.8% of the PPS-guided group versus 43.8% of controls (odds ratio 0.32, 95% CI 0.17-0.62, P=0.0003). Incidence rates were directionally in favor of active intervention across all event categories (P=0.004). Conclusions: A brief PPS-guided non-pharmacological intervention, followed by self-directed continuation, was associated with a marked long-term reduction in major adverse cardiovascular events, complementing previously reported large reductions in all-cause mortality in the same cohort. Within the context of a multi-decade PPS research program, these findings support PPS-guided care as a low-resource autonomic intervention ready for pragmatic scale-up testing as an adjunct to cardiometabolic care.

Lipoprotein(a) (Lp(a)) is associated with atherothrombosis through several mechanisms, including putative antifibrinolytic properties. In the ASPREE randomized trial of daily low-dose aspirin for primary prevention in older adults, 72% of trial participants in Australia provided baseline blood samples from which Lp(a) and related oxidized phospholipids and plasminogen have been measured in a specialized laboratory at University of California San Diego. Recent findings from our group suggest that aspirin may benefit older individuals with genotypes associated with elevated lipoprotein(a). We present an analysis plan to address key hypotheses relating to whether the effects of aspirin on cardiovascular disease might vary based on a person's measured levels of lipoprotein(a), oxidized phospholipid levels present on protein carriers apoB-100 (OxPL-apoB), Lp(a) (OxPL-apo(a)) and plasminogen (OxPL-PLG), and plasminogen. The analysis plan also articulates safety analyses involving major hemorrhage.

Objective To evaluate the associations between maternal history of psychiatric disorders and the risk cardiovascular disease (CVD) in offspring. Design Population based cohort study. Setting Nationwide health registers in Sweden. Participants All 4 171 005 liveborn singletons in Sweden from 1973 to 2014. Follow-up started at birth and ended until the first diagnosis of CVD, death, emigration, or December 31st, 2023, whichever occurred first. Exposures for observational studies Maternal psychiatric disorders diagnosed before delivery (n=208,680, 5.0%). Main outcome measures The primary outcome was the first diagnosis of CVD in offspring, identified through hospital registers. Additional outcomes included specific CVD subtypes. To address potential familial confounding, a cousin comparison was performed, comparing the risk of CVD in offspring born to mothers who were biological sisters. Mediation analyses examined the roles of congenital heart disease, small for gestational age, and preterm birth. Results During up to 51 years of follow-up, 307 596 (7.4%) offspring had a diagnosis of CVD. Maternal history of psychiatric disorders was associated with a higher risk of overall CVD both in the full cohort (hazard ratio 1.19, 95% confidence interval 1.17 to 1.21) and the cousin-comparison cohort (n=1 577 113; 1.08, 1.03 to 1.13). In disease-specific analyses, a prominent association with heart failure was robustly observed in both the full cohort (1.59, 1.37 to 1.85) and the cousin comparison cohort (1.51, 1.06 to 2.17). Mediation analyses indicated that congenital heart disease mediated 9.5% of the association between maternal psychiatric disorders and offspring CVD risk. Preterm birth and small for gestational age contributed minimally (<3%) to the observed associations. Conclusions Maternal history of psychiatric disorders was associated with an increased risk of CVD up to early middle-age in offspring. Congenital heart disease partly mediated this association.

Background: Hypertensive disorders of pregnancy (HDP) are a risk factor for early cardiovascular disease in women, perhaps related to adverse cardiovascular reactivity to physiologic stress. Objectives: To evaluate the association of HDP subtypes with exercise stress echocardiography parameters. Methods: This retrospective cohort study linked exercise stress echocardiograms with delivery records. HDP was classified as none, gestational hypertension (GH), and preeclampsia (PEC). We compared features of treadmill exercise stress echocardiography among HDP groups, adjusted for maternal demographic characteristics, time between delivery and stress testing, resting blood pressure (BP), and exercise duration. Results: Among 885 women with matching delivery and exercise echocardiography records (41.4plus-or-minus sign7.4 years at exercise exam), 92 (10.4%) experienced GH and 39 (4.4%) experienced PEC. Women with PEC were referred for exercise stress testing 3.1 years earlier following delivery (p<0.001) and had shorter exercise duration (lower case Greek beta]=-69.6 seconds [95% CI -115.9, -23.4], p=0.003) than those without HDP. Women with GH had higher peak exercise systolic BP (lower case Greek beta=8.96 mmHg [95% CI 4.89, 13.04], p<0.001), diastolic BP (lower case Greek beta=2.67 mmHg [95% CI 0.24, 5.10], p=0.031), and pulse pressure (lower case Greek beta=8.25 mmHg [95% CI 4.11, 12.39], p<0.001) than those without HDP. Women with GH and PEC were twice as likely to have concentric remodeling and more adverse diastolic parameters on echocardiography than those without HDP (p<0.05). Conclusions: Exercise stress echocardiography may detect subclinical cardiovascular dysfunction in midlife women following HDP, with adverse findings differing by subtype: GH was associated with higher peak exercise BP and PEC with lower exercise capacity.

Background: Higher METS-IR has been shown to be associated with a higher risk of major adverse cardiovascular events, but data are lacking regarding cardiac arrhythmias. Objectives: The aim of this study was to assess the association between METS-IR and atrial fibrillation/flutter, ventricular arrhythmia and bradyarrhythmia. Methods: Data from the Atherosclerosis Risk in Communities study spanning 1987 to 2013 was utilized for this analysis. METS-IR scores were assessed at baseline (1987-1989) and arrhythmia episodes were identified using ICD-9 codes. Multivariate-adjusted Cox proportional hazard models were constructed to evaluate the relationship between METS-IR and arrhythmia risk, with dose-response analyses conducted. In addition, we analyzed the predictive value of METS-IR for arrhythmias. Results: Over a mean follow-up of 21.9 years, 2493 cases of AF, 688 cases of bradyarrhythmia, and 1315 cases of ventricular arrhythmia were recorded. Each interquartile range increase in METS-IR was associated with a 49% higher risk of atrial fibrillation(P<0.001), 29% higher risk of bradyarrhythmia(P<0.001), and 42% higher risk of ventricular arrhythmia(P<0.001). After correction for relevant confounders, the METS-IR index was significantly and positively associated with the risk of new-onset atrial fibrillation, bradyarrhythmia, and ventricular arrhythmia (P overall<0.05, P for non-linearity>0.05). Most of the results of the subgroup analyses were not significantly different. The inclusion of METS-IR in the base model improves the predictive value of the risk of arrhythmogenesis. Conclusions: There is a significant association between METS-IR and increased risk of arrhythmias.

Background The use of Assisted Reproductive Technology (ART) is increasing worldwide. These treatments involve ovarian stimulation to enable multiple follicle recruitment, hence inducing supraphysiological estrogen levels. While most long-term follow-up of women undergoing ART has concerned cancer incidence, the long-term safety regarding cardiovascular and metabolic diseases remains under-explored. This study was performed to assess the risk of acute myocardial infarction, cerebral ischemic conditions, intracranial hemorrhage, type 2 diabetes mellitus, heart failure, aortic aneurysm or dissection, and chronic kidney disease in women that conceived with ART, and to investigate the role of the underlying infertility and its risk factors. Methods and Findings Swedish national registers allowed us to follow a nationwide cohort of 380,756 women from their first birth between 1992 and 2002 until the end of 2023. The safety of ART was evaluated by comparing women with infertility who conceived with and without ART, while adjusting for baseline differences in age, body mass index, country of origin, socioeconomic factors, pre-existing comorbidity, smoking and year. The role of infertility was additionally explored by comparing all women with and without infertility adjusting for age, as well as the aforementioned baseline characteristics. Cumulative risks were plotted using inverse-probability weighted Kaplan-Meier curves. To facilitate the comparison of groups we also estimated risk differences and ratios at 10-, 20-, and 30-years of follow-up. Use of ART was not associated with cardiovascular disease except for an excess risk of cerebral ischemic conditions, with a 30 year risk ratio of 1.43 (1.09; 1.89). With the exception of cerebral ischemic conditions, intracranial hemorrhage, aortic dissection, and chronic kidney disease, women with a history of infertility exhibited consistently higher risk of all outcomes, adjustment for differences in baseline characteristics explained some but not all of these elevated risks. Conclusions With the exception of ischemic cerebral conditions, the findings provide reassurance regarding the long-term cardiometabolic safety of ART use, while adding to the growing literature suggesting that infertility can act as a marker of womens cardiovascular and metabolic disease.

Introduction: Calcific aortic stenosis (CAS) is a progressive valvular disease characterized by lipid accumulation, inflammation, and osteogenic remodeling. Emerging evidence implicates gut microbiota-derived metabolites in cardiovascular pathology, yet their contribution to valvular disease remains poorly defined. The aim of this study was to investigate gut microbiota and metabolite signatures in patients with CAS and explore causal relationships using Mendelian randomization (MR). Methods: In a prospective cohort of 54 patients with CAS and 41 age, sex, BMI-balanced non-CAS controls, we performed integrated microbiome and metabolomic profiling. Gut microbial composition was assessed by 16S rRNA sequencing, and circulating levels of tryptophan derivatives, short-chain fatty acids, bile acids, and TMA/TMAO-related metabolites were quantified. MR analyses were performed to assess causal contributions of key metabolic and inflammatory markers to CAS. Results: Baseline characteristics were comparable between groups. CAS patients exhibited a distinct tryptophan metabolic profile, characterized by higher concentrations of inflammatory kynurenine-pathway metabolites and lower indole-3-sulfate. With consistent effect sizes despite modest statistical significance after multiple testing correction. Pathway-level analyses supported preferential routing of tryptophan toward inflammatory host metabolism. In contrast, global microbiota diversity and overall community structure were preserved. However, CAS was associated with depletion of specific Firmicutes taxa, including Eubacterium coprostanoligenes, a key cholesterol-converting bacterium mediating intestinal cholesterol-to-coprostanol transformation. MR analyses suggested LDL cholesterol and lipoprotein(a) as upstream triggers of CAS, whereas ALPL and tryptophan/kynurenine metabolites appear downstream and might reflect systemic inflammation and local metabolic consumption. Sex-stratified analyses revealed enhanced kynurenine pathway activation in males, whereas females exhibited relatively higher TMAO and indole-related metabolites. Conclusion: CAS is characterized by a focused gut-host metabolic reprogramming defined by inflammatory tryptophan catabolism and loss of cholesterol-transforming microbial functions, rather than global dysbiosis. These findings identify a potential gut, valve metabolic axis contributing to valvular calcification, with potential sex-specific effects.

Introduction Cardiovascular disease (CVD) remains Vietnam's leading cause of mortality, yet no comprehensive national analysis of burden trends and future projections exists. This study characterizes Vietnam's CVD burden from 1990 to 2023 and projects burden through 2050. Methods Using Global Burden of Disease 2023 data, we analyzed CVD prevalence, incidence, mortality, and disability-adjusted life years (DALYs) in Vietnam from 1990 to 2023, stratified by sex and age. Joinpoint regression quantified temporal trends. Decomposition analysis separated contributions of population growth, aging, and epidemiological change. ARIMA modeling, validated against pre-pandemic and COVID 19 periods, projected burden through 2050. Results Despite age-standardized CVD prevalence below global estimates, stroke mortality and DALYs rates exceeded global benchmarks. Age-standardized CVD mortality (ASMR) declined significantly (average annual percentage change [APC]:-1.34%), yet absolute deaths nearly doubled from 121,611 to 223,068. Population aging contributed 140.9% to observed mortality increases while epidemiological improvements averted over 102,000 deaths. Male age-standardized CVD mortality was approximately twice that of females. High systolic blood pressure remained the leading attributable risk factor, while high BMI and alcohol use showed the largest rank escalations. CVD incidence reversed its declining trend during 2019 - 2023 (APC:+0.69%). By 2050, ASMR are projected to decline by 51.0% (218.8 to 107.1 per 100,000 [95%CI: 64.1 - 150.2]), while absolute deaths are projected to increase by 43.4% (206,677 to 296,335 [95%CI: 272,323 - 320,348]). Conclusions Vietnam faces a demographic paradox of improving age-specific outcomes alongside a rising absolute burden driven by population aging, demanding urgent reorientation toward aging-specific prevention, hypertension control, and chronic cardiovascular care.

Background: Comprehensive assessment of hypertension-mediated organ damage (HMOD) across multiple organ systems in sub-Saharan Africa is limited. We assessed the prevalence and correlates of multidomain HMOD in a geographically diverse population in Ghanaian adult. Methods: This cross-sectional secondary analysis of the Ghana Heart Study, which included 1,106 adults aged [&ge;]18 years from four Ghanaian regions between September 2016 and March 2017. Multidomain HMOD was determined using a pre-specified 9-domain composite score [&ge;]2, using an ESH/ESC 2018 guideline-informed selection of HMOD domain with baPWV instead of carotid-femoral PWV (cfPWV), due to device unavailability, and a threshold of [&ge;]14 m/s which was derived from analysis within the cohort. LODO sensitivity analyses were used to address issues of predictor-outcome circularity. We used logistic regression models to examine association between each predictor and multidomain HMOD, adjusted for age, systolic blood pressure, body mass index, presence of dyslipidaemia and smoking status. We also performed receiver operating characteristic (ROC) analysis to determine correlates of multidomain HMOD and compare the discriminative ability of each predictor against the others. Results: The mean age of participants was 46.9{+/-}17.2 years of which 58% were females. Multidomain HMOD was observed in 21.3% (235/1,106; zero-imputation lower bound 21.2%) of participants studied. There was a marked increase in the prevalence of multidomain HMOD with advancing age. Thus, while 8.6% (44/ 511) of adults<45years had multidomain HMOD, 20.6% (63/306) of 45- to 59-yr-olds and 44.4% (128/ 288) of individuals [&ge;]60 years had multidomain HMOD. HMOD-positive adults were older (59.1{+/-}8.4 vs 43.6{+/-}13.4y, p<0.001), had higher systolic BP (147{+/-}22 vs 123{+/-}21 mmHg, p<0.001), and had higher prevalence of hypertension (73% vs 28%, p<0.001) than their HMOD-negative counterparts. Using the primary (circular) specification, the strongest co-occurrence among all domains of HMOD was observed between peripheral artery disease and other HMOD (OR 41.2, 95% CI 20.7-81.6; p<0.001) followed by valvular burden and other HMOD (OR 14.4, 95% CI 4.8-43.8; p<0.001) and between ECG-LVH and other HMOD (OR 9.0, 95% CI 5.9-13.8; p<0.001) (S2 Table). After LODO correction to remove the self-inclusive co-occurrence between each predictor domain and the outcome (all p-values calculated in S2 Table), there was no significant association between the remaining 8 HMOD domains and the prevalence of multidomain HMOD (all p-values>0.05; S2 Table). This was not the case for baPWV, however. Thus, whereas the AUC of the best performing non-self-inclusive HMOD domain (ECG-CMD) only reached 0.688{+/-}0.016 (vs 0.827{+/-}0.008 for self-inclusive AUC calculated for the sake of interest only and provided as supplementary material), baPWV demonstrated good discriminative capacity (LODO-adjusted AUC = 0.702, 95% CI 0.654-0.751; S3 Fig). However, this AUC did not significantly exceed that for age alone (AUC = 0.752; {Delta}AUC = -0.050, 95% CI ?0.103 to 0.03; p=0.106; S3 Fig). Most importantly, after adjustment for SBP (a direct mediator in this pathway), the LODO AUC for baPWV did not exceed that for the single variable age (S3 Fig), indicating that baPWV does not possess independent discriminative power for multidomain HMOD above and beyond the information provided by SBP and age. Importantly, however, the adjusted OR for baPWV did not reach statistical significance (OR 1.094, 95% CI 0.986-1.213; p=0.091), suggesting that while circularity prevented validation of biological association, it did not prove the absence of association altogether. Sensitivity analysis (estimating total as opposed to direct effect) in which SBP was excluded from the regression model to estimate the total effect of baPWV on the prevalence of HMOD showed that, indeed, the OR for baPWV was significantly elevated (OR 1.261; 95% CI 1.150-1.382; p<0.001) in this specification. The effect of SBP, a direct mediator in this pathway, therefore apparently accounted for the non-significance in the original model entirely. Formal mediation analysis using the aforementioned specification yielded that SBP indeed mediated 69.9% (95% CI 41.3-128.8%) of the effect of baPWV on the prevalence of HMOD. Conclusions: One in five Ghanaian adults has hypertension-mediated organ damage in multiple HMOD domains. baPWV has good discriminative power for HMOD risk prediction in a Ghanaian adult population under the non-circular LODO estimand (LODO- adjusted AUC = 0.702; 95% CI: 0.654, 0.751) than the PCE (AUC = 0.496; 95% CI: 0.438, 0.555; {Delta}AUC = +0.206; p < 0.001). However, baPWV LODO AUC (0.702) was not statistically significantly greater than age alone (AUC = 0.752; 95% CI: 0.730, 0.774; {Delta}AUC = -0.050, p = 0.106). AUC for self- inclusive model was provided in supplementary materials for the reader's perusal, and that AUC (0.827; 95% CI: 0.794, 0.860) is circular. The prevalence of ECG-LVH was substantially higher (42%) than that of echocardiographic- LVH (5.9%) in this Black African population. These findings support further research on the role of baPWV for HMOD risk prediction in a Ghanaian adult population. Prospective validation of baPWV would be needed before clinical use.

BackgroundNeighborhood social vulnerability may shape cardiovascular health (CVH), but its association with Lifes Essential 8 (LE8), and whether changes in vulnerability track with changes in CVH during midlife, are unclear. We examined cross-sectional and longitudinal associations of the Social Vulnerability Index (SVI) with LE8 and assessed differences by SVI domain, LE8 component, race, and sex. MethodsWe analyzed CARDIA participants at Year 15 (Y15; 2000-2001; n = 3,168; mean age 40 years) and Year 30 (Y30; 2015-2016; n = 2,267; mean age 55 years). Residential addresses were geocoded and linked to 2000 and 2016 SVI. Participants were stratified by SVI quartiles. CVH scores were calculated from LE8 metrics (range 0-100; higher is better CVH), excluding sleep. Using multivariable linear regression adjusted for age, sex, race, and educational attainment, we estimated LE8 differences across SVI quartiles and associations of 15-year SVI change/residential mobility with change in LE8. Cox models estimated incident CVD associations. ResultsHigher SVI was associated with lower LE8 at both exams. Adjusted Q4 vs Q1 differences in overall LE8 were -5.34 points (95% CI, -6.90 to -3.78) at Y15 and -4.60 points (95% CI, -6.51 to -2.69) at Y30. Among the four SVI domains, SES and household characteristics drove most of the disparity in LE8 scores (Y30 Q4 vs. Q1: SES {Delta} = -6.98; household {Delta} = -6.56 points). Component-level differences across quartiles of SVI were largest for nicotine exposure at Y15 (-13.09 points) and physical activity at Y30 (-13.09 points). Changes in SVI and residential mobility were not significantly associated with change in LE8. ConclusionHigher social vulnerability was associated with significantly lower CVH. Socioeconomic and household factors, along with behavioral gaps in nicotine exposure and physical activity, may be key targets for community-level interventions to improve cardiovascular health equity.

Background Myocardial remodeling precedes symptomatic heart failure, which is important to detect early. We assessed feasibility and clinical correlates of a novel integrated assessment of myocardial remodeling in a large rural cohort in the Southeastern United States. Methods Echoes were obtained with AI assistance (Caption guidance) in 3100 adults in the NHLBI-funded RURAL cohort study. Of those, 1895 had quantifiable global longitudinal strain (GLS), left ventricular mass (LVM), and left atrial volume (LAV). LV-LA Health was based on a simple count of sex-specific abnormalities (0-3), indexed to body surface area (BSA) or height (Table 1). Relationships with demographics and risk factors were compared with Spearman correlation and Mantel-Haenszel tests, with moderate and severe results combined. Results Median (IQR) age was 49 (40-58). Impaired LV-LA Health is common even in a low PREVENT cardiovascular (CV) risk population (median 10-year risk 3.3%; 25th, 75th 1.2,7.2) with preserved ejection fraction (EF; 60%; 57,62). The prevalence of abnormalities differed greatly by indexing method: 18.2% with BSA (15.1% mild; 3.1% mod/severe) vs 51% with height (38.3% mild; 12.7% mod/severe) (Figure 1). LV-LA impairment increased with age, PREVENT CV risk score and cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity); all p<0.001. Impairment was more common in Black vs White people (p<0.001) and differed by sex only with height indexation. Conclusions A novel LV-LA health composite of routinely acquired echocardiographic measures identifies substantial subclinical cardiac remodeling in a middle-aged rural community cohort, not detected by PREVENT score or ejection fraction. This is the first application of this framework in a large, unselected community sample. Indexation method affects prevalence, with BSA likely underestimating risk in adiposity-enriched populations. Findings suggest a high rural burden and longitudinal evaluation with future CV events is ongoing.

Background: Resting electrocardiogram (ECG) are associated with heart failure (HF) events, even though it is not currently recommended in risk assessment. Objective: To examine the association between ECG abnormalities and incident HF events according to the 2023 PREVENT HF equation. And identify a subgroup of individuals who are misclassified as being at low risk. Design: Secondary data analysis from the REasons for Geographic And Racial Differences in Stroke (REGARDS) prospective cohort, including study participants without baseline HF. Exposure: ECG abnormalities were classified by Minnesota Code (MC) as normal, only minor, or any major abnormality at baseline (2003-2007). Outcome: Participants were followed for expert adjudicated incident HF hospitalizations/ deaths through December 2021. Results: Among 20,923 participants (mean age at baseline 63.6 years, 53.7% female), 26.0% of the sample was classified as low risk (<3%), 17.5% as borderline risk (3-<5%), 27.5% as intermediate risk (5%-<10%), and 29.0% as high risk (10%). Compared to those without ECG abnormality, the adjusted HR for incident HF was 1.56 (95% CI 1.35-1.80) for any minor abnormality and 2.56 (2.18-3.00) for any major abnormality. 43.5% of the population were in the less than 5% risk by PREVENT among whom 45.8% had any ECG abnormalities. The fully adjusted HR for only minor ECG abnormalities in the <3% was 1.47 (95% CI 0.72-3.01), and the fully adjusted HR for any major ECG abnormality was 5.22 (95% CI 2.42-11.30). In the borderline risk group, the fully adjusted HR for only minor ECG abnormalities was 1.37 (95% CI 0.89 - 2.11), and the fully adjusted HR for any major ECG abnormality was stronger than the HR in the intermediate and high-risk groups; 3.05 (95% CI 1.85 - 5.03). Conclusion: ECG abnormalities were common and associated with HF events across all PREVENT risk groups, especially in the low/borderline risk groups with major ECG abnormalities.

Background: Postoperative atrial fibrillation (POAF) affects up to 50% of cardiac surgery patients and is linked to higher morbidity, longer hospital stays and increased thromboembolic risk. Early identification of at-risk patients remains challenging. Calcitonin (CT), a hormone with anti-fibrotic effects, may serve as a novel biomarker. Methods: In 491 patients undergoing elective cardiac surgery, baseline serum CT was measured preoperatively using CT-specific enzyme-linked immunosorbent assay (ELISA). Patients with pre-existing AF were excluded. Associations between CT levels and POAF incidence and onset were evaluated using logistic regression, Cox proportional hazards models, and Kaplan-Meier analysis. Results: Among 248 patients with detectable CT levels, 88 patients developed POAF. Higher baseline CT was independently associated with lower risk of POAF (OR 0.68 per 5 pg/ml increase; 95% CI 0.51-0.89; P = 0.009) and delayed arrhythmia onset (adjusted HR 0.941; 95% CI 0.898-0.980, P = 0.0026) after adjusting for covariates. Kaplan-Meier analysis demonstrated a graded relationship between increasing CT levels and reduced cumulative incidence of POAF. In this cohort, baseline CT showed greater discriminative ability than CRP and BNP, although overall model performance remained moderate. Conclusion. Higher preoperative circulating CT levels are associated with reduced risk and delayed onset of POAF following cardiac surgery. These findings suggest that calcitonin may have the potential as a biomarker for perioperative risk stratification in POAF. Given the observational design and single-centre setting, further validation in independent cohorts and studies integrating mechanistic insights are warranted.

BACKGROUNDSmooth muscle cells (SMCs) comprise the majority of cells in human atherosclerotic lesions and are thought to be a major source of cholesterol-overloaded foam cells in human and mouse atheromas. However, the transcriptomic profile, specific markers, and biologic itinerary of SMC foam cells relative to macrophage foam cells remain poorly defined. METHODSSingle-cell RNA sequencing (scRNA-seq) was performed on fresh coronary artery segments from heart transplant recipients with early- to intermediate-stage atherosclerosis. Gene expression in a putative SMC foam cell cluster was compared with cultured SMCs loaded with aggregated low-density lipoprotein (agLDL) or cholesterol-methyl-{beta}-cyclodextrin (Chol-M{beta}CD). Candidate markers distinguishing SMC from macrophage foam cells were validated using additional publicly-available scRNA-seq datasets, Xenium spatial transcriptomics, and immunofluorescence microscopy of human coronary atheromas. Pathway analysis was performed using Gene Set Enrichment Analysis Hallmark gene sets. RESULTSA distinct SMC foam cell cluster derived from fibromyocytes ("lipomyocytes") was identified using markers induced by in vitro cholesterol loading. agLDL loading reproduced the lipomyocyte transcriptional profile, whereas Chol-M{beta}CD induced an inflammatory phenotype colocalizing with macrophages rather than lipomyocytes. Lipomyocytes highly expressed SERPINE1, encoding plasminogen activator inhibitor-1 (PAI-1), and CFH, encoding complement factor H, which were validated in human coronary lesions by spatial transcriptomics and immunofluorescence microscopy. Compared with macrophage foam cells, lipomyocytes demonstrated distinct pathway activation, including enrichment of extracellular matrix, coagulation and angiogenesis pathways. CONCLUSIONSSMC foam cells, or lipomyocytes, represent a distinct foam cell phenotype with unique markers and biologic programs that differ from macrophage foam cells during atherosclerotic plaque development. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LISmooth muscle cell (SMC) foam cells, or lipomyocytes, arise from fibromyocytes and exhibit a transcriptomic profile that is markedly distinct from that of macrophage foam cells. C_LIO_LIIn vitro loading of SMCs with aggregated LDL recapitulates the gene expression profile of SMC foam cells in human coronary atheromas, whereas loading with cyclodextrin-bound cholesterol does not. C_LIO_LIPlasminogen activator inhibitor 1 (PAI-1, encoded by SERPINE1) and Complement Factor H are specific markers of SMC foam cells and are not expressed by macrophage foam cells. C_LI What Are the Clinical Implications?O_LISMCs contribute a substantial proportion, and potentially the majority, of foam cells in atherosclerotic lesions. C_LIO_LIDefining the biological trajectory of SMC foam cells within plaques is critical for understanding their roles in plaque progression, rupture and thrombosis, and for establishing their relevance as a distinct therapeutic target to reduce major cardiovascular events. C_LI

Background: Over half of U.S. women have hypertension, a strong but modifiable risk factor for cardiovascular diseases. Personal care products (PCPs) are widely used in daily life and contain endocrine disrupting chemicals that can alter hormonal regulation of blood pressure. However, the relationship between PCPs and hypertension has not been well studied. We investigated whether patterns of PCP use were associated with incident hypertension in a large prospective cohort study of U.S. women. Methods: Sister Study participants were recruited in 2003-2009 and followed until September 30, 2021. Usage frequency of 41 PCPs in the 12 months before baseline was self-reported. Latent class analyses identified groups with similar PCP use patterns ("infrequent," "moderate," or "frequent"). At baseline, we excluded women with prevalent hypertension, antihypertensive medication users, or those missing hypertension status. Multivariable Cox regression was used to estimate associations between PCP use and incident self-reported hypertension. Results: During a mean follow-up of 11.4 years, 10,099 women developed hypertension. Frequent PCP use was associated with higher hypertension risk [HR=1.08 (95% CI: 1.03, 1.13); p-trend=0.003], with a 4.1% population attributable risk. Frequent users of beauty products had higher risk than infrequent users [HR=1.11 (95% CI: 1.05, 1.16)]. Moderate and frequent users of hygiene products also had increased risk [HR=1.07 (95% CI: 1.01, 1.13); HR=1.13 (95% CI: 1.08, 1.19)]. Conclusions: Frequent PCP use, especially beauty and hygiene products, was associated with incident hypertension. Our findings implicate everyday chemicals as modifiable cardiovascular risk factors and highlight the need to identify pathogenic components in widely used consumer products.

Abstract Background: Heart Failure is a complex clinical syndrome of growing public health concern in sub-Saharan Africa, yet the data from Sierra Leone are absent. The aim of the study is to characterise the clinical profile, etiological and temporal trends of hospitalised HF patients at Choithrams Memorial Hospital (CMH), Freetown, Sierra Leone, to confirm specific management strategies. Methods: This single-center, retrospective observational cohort study analysed data on HF patients (>18years) admitted at the CMH between January 2021 to 31 December 2025. The clinical definition of HF was based on the Framingham criteria and the European Society of Cardiology (ESC) guidelines , including standard echocardiographic parameters. All variables, including patients demographics, HF. phenotype, aetiology, medical history and hospital outcomes were extracted from the digital record. Non-parameteric tests, multivariable logistic regression to identify variables associated with etiology, Wilcoxon rank-sum test to compare groups and Kruskal-Wallis test to analyse trends over time were utilised. Result: A total of 765 patients were included in the study, with a median age of 53 years (IQR 42-61) and male predominance of 55.3%. Patients with recurrent HF (60.9%) were more common than those with de novo HF (39.1%), were older (54 years vs 53 years), had a higher comorbidity burden (34% vs 4%, p < 0.001), and presented with a cold-wet hemodynamic profile (18.4% vs 8.4%, p < 0.001). HFrEF (61.3%) was the most predominant phenotype, though HFpEF increased with age. Dilated Cardiomyopathy (37.0%), Hypertensive Heart Disease (31.2%) and Valvular Heart Failure (17.1%) were the leading etiologies, while ischemic heart disease (6.3%) was relatively uncommon. A majority of the patients were referred (77.9%), and 50.8% presented with NYHA IV. The strongest independent predictor for HF was hypertensive heart disease [AOR = 17.81; C.I 95%: (3.13-48.76), p <0.001]. An analysis of the trends in etiologies and demographics over the five-year period demonstrated no significant changes (all p-values > 0.05 for age, sex, aetiology, and most comorbidities). Conclusion: HF affects the younger adult population in Sierra Leone and is mainly caused by DCM and HHD. The late case presentations, the high prevalence of recurrent HF, and the associated high burden of comorbidities emphasize an urgent need to develop and implement improved strategies for the prevention, early detection, and long-term management of HF within Sierra Leone's healthcare system.