Clinical Cardiovascular Disease Research Articles

Extent of vascular plaque predicts future cardiovascular events in patients with systemic lupus erythematosus.

Patients with SLE have increased prevalence of clinical cardiovascular disease (CVD) and subclinical atherosclerosis. Although 30-40% of patients with SLE have vascular plaque on ultrasound scanning, this study is the first to consider the relationship between total burden of plaque and subsequent CVD risk. One hundred patients with SLE and without any previous clinical CVD underwent vascular ultrasound scans of both carotid and both common femoral bifurcations between 2011 and 2013. Clinical, serological, demographic and treatment data were collected at baseline. Patients were followed till 2020 to identify those who developed new onset coronary disease or stroke. Statistical analysis to identify factors associated with increased risk of developing CVD events was carried out. Thirty-six patients had plaque at baseline. During follow-up five patients (all had baseline plaque) developed coronary disease and two, without baseline plaque, developed lacunar strokes. Mean (s.d.) age of these patients was 46.5 (4.5) years. Patients with three or more baseline bifurcations with plaque were 10 times more likely to develop CVD than those with 0-2 bifurcations with plaques (OR 9.9, P = 0.009). TPA > 16mm2 was associated with six-fold increased risk of CVD (OR = 6.44, P = 0.028). Patients with disease duration > 14 years were more likely than those with disease duration < 14 years to develop CVD (OR 8.3 P = 0.043). The number of bifurcations with plaque and TPA in patients with SLE may be valuable in assessing risk of CVD and deciding on clinical measures to reduce this risk.

Midlife determinants of healthy cardiovascular aging: The Atherosclerosis Risk in Communities (ARIC) study

Background and aimsRisk factor cutoffs are derived from associations with clinical cardiovascular disease (CVD), but how these risk factors associate with preserved cardiovascular health into old age is not well studied. We investigated midlife determinants of healthy versus nonhealthy cardiovascular aging in the Atherosclerosis Risk in Communities (ARIC) study. MethodsARIC participants were categorized by cardiovascular status in older age (mean age 75.8 ± 5.3 years, range 66–90): healthy, subclinical disease (assessed by biomarkers and left ventricular function), clinical CVD (coronary heart disease, stroke, or heart failure), or prior death. We examined associations of midlife (mean age 52.1 ± 5.1 years) systolic and diastolic blood pressure (SBP, DBP), low-density lipoprotein cholesterol (LDL-C), triglycerides, hemoglobin A1c (HbA1c), and body mass index (BMI) with cardiovascular status in older age using multinomial logistic regression analyses. ResultsCompared with healthy status, odds for subclinical disease (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.09–1.55) and clinical CVD (OR 1.87, 95% CI 1.53–2.29) at older age increased starting with midlife SBP 120–129 mmHg, whereas odds for death increased starting with SBP 110–119 mmHg (OR 1.29, 95% CI 1.10–1.52); findings were similar for DBP. Odds for subclinical disease increased for HbA1c ≥ 6.5% and BMI starting at 30–<35 kg/m2; odds for clinical CVD or death increased starting at HbA1c 5.5–5.9%, LDL-C >160 mg/dL, and BMI 30–<35 kg/m2. ConclusionsMore-stringent levels of modifiable risk factors in midlife beyond current clinical practice and guidelines were associated with preserved cardiovascular health in older age.

Risk for Cardiovascular Death Associated With Waist Circumference and Diabetes: A 9-Year Prospective Study in the Wan Shou Lu Cohort.

BackgroundIt has been reported that obesity and diabetes are both risk factors for the development of cardiovascular diseases (CVDs). However, recent articles reported that compared with body mass index, waist circumference (WC) can better reflect obesity, more closely related to visceral fat tissue which is positively associated with an increased risk of cardiovascular death. Moreover, few studies have investigated the prognostic value of both WC and diabetes during a long-term follow-up. We aimed to investigate whether the higher level of WC measurements and diabetes were able to predict cardiovascular mortality in the general population.MethodsIn this prospective cohort study, a total of 1,521 consecutive subjects free of clinical CVD were included. The endpoint was cardiovascular death. The Kaplan–Meier method and Cox regression models were used to evaluate the cumulative risk of the outcome at different WC levels with or without diabetes.ResultsDuring a median follow-up of 9.2 years, 265 patients died due to cardiovascular conditions. Kaplan–Meier survival estimates indicated that the patients with higher levels of WC (WC > 94 cm) coexisted with diabetes had a significantly increased risk of cardiovascular death (log-rank p < 0.05). After adjustment for potential confounders, multiple COX regression models showed that the incidence of cardiovascular death was significantly higher when patients with high WC coexisted with diabetes mellitus (hazard ratio: 3.78; 95% CI: 3.35–3.98; p < 0.001).ConclusionPatients with high WC and diabetes represent a high-risk population for cardiovascular death. WC and diabetes may provide incremental prognostic value beyond traditional risks factors.

Investigation of the Relationship between Cardiovascular Biomarkers and Brachial-Ankle Pulse Wave Velocity in Hemodialysis Patients.

Brachial–ankle pulse wave velocity (baPWV) and cardiovascular (CV) biomarkers are correlated with clinical cardiovascular diseases (CVDs) in patients with kidney disease. However, limited studies evaluated the relationship between baPWV and CV biomarkers in hemodialysis patients. This study investigated the relationship between circulating CV biomarkers and baPWV in patients on hemodialysis. Hemodialysis patients were enrolled between August 2016 and January 2017 for the measurement of baPWV, traditional CV biomarkers, including high-sensitivity troponin-T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), and novel CV biomarkers, including Galectin-3, Cathepsin D, placental growth factor, Endocan-1, and Fetuin-A. The independent association was assessed by multivariate-adjusted linear regression analysis to control for potential confounders. The final analysis included 176 patients (95 men and 81 women) with a mean age of 60 ± 11 y old. After adjusting for age and sex, hsTnT (p < 0.01), NT-proBNP (p = 0.01), Galectin-3 (p = 0.03), and Cathepsin D (p < 0.01) were significantly directly correlated with baPWV. The direct correlation with baPWV existed in multivariable linear regression models with a β of 0.1 for hsTnT and 0.1 for Cathepsin D. The direct relationship between baPWV and CV biomarkers, particularly with hsTnT and Cathepsin D, may be helpful for risk stratification of hemodialysis patients.

Glycated Hemoglobin as an Integrator of Cardiovascular Risk in Individuals Without Diabetes: Lessons from Recent Epidemiologic Studies.

Prediabetes, or dysglycemia in the absence of diabetes, is a prevalent condition typically defined by a glycated hemoglobin (HgbA1c) of 5.7- < 6.5%. This article reviews current contemporary data examining the association between prediabetes and cardiovascular disease (CVD) as well as HgbA1c as a continuous measure of cardiovascular risk across the glycemic spectrum. Dysglycemia in the prediabetic range is associated with an increased risk of both subclinical and clinical CVD, including atherosclerotic CVD, chronic kidney disease, and heart failure. Several recent large, prospective studies demonstrate roughly linear risk with increasing HgbA1c, even below the threshold for prediabetes. "High-risk" patients with prediabetes have similar CVD risk as those with diabetes. HgbA1c below the threshold for diabetes stratifies CVD risk. Use of HgbA1c as a continuous measure, rather than simply dichotomized, may inform current and future prevention strategies. Given the high population attributable risk associated with prediabetes, targeted prevention strategies in this population warrant dedicated study.

Inclisiran: A Novel Small Interfering RNA Drug for Low-Density Lipoprotein Reduction.

Inclisiran increases the number of low-density lipoprotein surface receptors expressed on hepatocytes using small interfering RNA directed against proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA. This novel mechanism can reduce low-density lipoprotein by ≈50%, like reductions achieved with high-intensity statins or PCSK9-inhibiting monoclonal antibodies. Inclisiran is indicated in the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, unable to achieve target LDL concentrations with diet and maximally tolerated statin therapy. It is more expensive than PCSK9-inhibiting monoclonal antibodies and still lacks clinical evidence for the expected reduction in atherosclerotic cardiovascular disease events when added to statin therapy. Although some patients experience injection-site reactions of mild or moderate severity, current evidence suggests a strong safety profile with total and serious adverse events approximating that of placebo. The dosing protocol of inclisiran offers its biggest clinical advantage over PCSK9-inhibiting monoclonal antibodies, being administered only every 6 months after initial baseline and 3-month doses rather than every second or fourth week. Unlike PCSK9-inhibiting monoclonal antibodies, inclisiran has not as yet been noted to induce neutralizing antidrug antibodies that can impact drug efficacy. Thus, inclisirin is a novel small interfering RNA molecule that provides further options in the management of hypercholesterolemia refractory to statins alone. However, cost and evidence considerations suggest it should not supplant adjunctive therapy with the PCSK9-inhibiting monoclonal antibodies, despite having an efficacy, safety, tolerability, and drug interaction profile superior to other antihypercholesterolemic options such as lomitapide, niacin, bile acid sequestrants, and bempedoic acid.

Reduced cardiovascular risks in women with endometriosis or polycystic ovary syndrome carrying a common functional IGF1R variant.

STUDY QUESTIONIs the increased future cardiovascular risk seen in women with endometriosis or polycystic ovary syndrome (PCOS) mitigated by functional insulin-like growth factor-1 receptor (IGF1R) single-nucleotide polymorphism (SNP) rs2016347 as previously shown in women with hypertensive disorders of pregnancy?SUMMARY ANSWERThis cohort study found that women with endometriosis or PCOS who carry a T allele of IGF1R SNP rs2016347 had a reduced future risk of developing cardiovascular disease (CVD) and associated risk factors, with risk reduction dependent on cohort era.WHAT IS KNOWN ALREADYWomen with endometriosis or PCOS have been shown to have an increased future risk of CVD and associated risk factors with limited predictive ability.STUDY DESIGN, SIZE, DURATIONThis retrospective cohort study took place in the Nurses’ Health Study 2 (NHS2), which enrolled 116 430 participants in 1989 who were followed through 2015. The study population was analyzed in its entirety, and subdivided into entry (pre-1989) and after entry (post-1989) exposure cohorts. All NHS2 participants were eligible for inclusion in the study, 9599 (8.2%) were excluded for missing covariates.PARTICIPANTS/MATERIALS, SETTING, METHODSThe NHS2 enrolled female registered nurses from 14 different states who ranged in age from 25 to 42 years at study entry. Data were collected from entry and biennial questionnaires, and analysis conducted from November 2020 to June 2021. Cox proportional hazard models were used to assess risk of CVD, hypertension (HTN), hypercholesterolemia (HC) and type 2 diabetes, both with and without genotyping for rs2016347.MAIN RESULTS AND THE ROLE OF CHANCEWhile women without endometriosis or PCOS, as a whole, demonstrated no impact of genotype on risk in either cohort, women with endometriosis carrying a T allele had a lower risk of CVD (hazard ratio (HR), 0.48; 95% CI, 0.27–0.86, P = 0.02) and HTN (HR, 0.80; 95% CI, 0.66–0.97, P = 0.03) in the pre-1989 cohort, while those in the post-1989 cohort had a decrease in risk for HC (HR, 0.76; 95% CI, 0.62–0.94, P = 0.01). Women with PCOS in the post-1989 cohort showed a significant protective impact of the T allele on HTN (HR, 0.44; 95% CI, 0.27–0.73, P = 0.002) and HC (HR, 0.62; 95% CI, 0.40–0.95, P = 0.03).LIMITATIONS, REASONS FOR CAUTIONData on specific endometriosis lesion locations or disease stage, as well as on PCOS phenotypes were lacking. In addition, data on systemic medical treatments beyond the use of oral contraceptives were missing, and these treatments may have confounded the results.WIDER IMPLICATIONS OF THE FINDINGSThese findings implicate systemic dysregulation of the insulin-like growth factor-1 axis in the development of HTN, HC and clinical CVD in endometriosis and PCOS, suggesting a common underlying pathogenetic mechanism.STUDY FUNDING/COMPETING INTEREST(S)The NHS2 infrastructure for questionnaire data collection was supported by National Institute of Health (NIH) grant U01CA176726. This work was also supported in part by NIH and National Cancer Institute grant U24CA210990; as well, research effort and publication costs were supported by the Elizabeth MA Stevens donor funds provided to the Buck Institute for Research on Aging. The authors declare they have no conflicts of interest.TRIAL REGISTRATION NUMBERN/A.

Study protocol: MyoFit46\u2014the cardiac sub-study of the MRC National Survey of Health and Development

BackgroundThe life course accumulation of overt and subclinical myocardial dysfunction contributes to older age mortality, frailty, disability and loss of independence. The Medical Research Council National Survey of Health and Development (NSHD) is the world’s longest running continued surveillance birth cohort providing a unique opportunity to understand life course determinants of myocardial dysfunction as part of MyoFit46–the cardiac sub-study of the NSHD.MethodsWe aim to recruit 550 NSHD participants of approximately 75 years+ to undertake high-density surface electrocardiographic imaging (ECGI) and stress perfusion cardiovascular magnetic resonance (CMR). Through comprehensive myocardial tissue characterization and 4-dimensional flow we hope to better understand the burden of clinical and subclinical cardiovascular disease. Supercomputers will be used to combine the multi-scale ECGI and CMR datasets per participant. Rarely available, prospectively collected whole-of-life data on exposures, traditional risk factors and multimorbidity will be studied to identify risk trajectories, critical change periods, mediators and cumulative impacts on the myocardium.DiscussionBy combining well curated, prospectively acquired longitudinal data of the NSHD with novel CMR–ECGI data and sharing these results and associated pipelines with the CMR community, MyoFit46 seeks to transform our understanding of how early, mid and later-life risk factor trajectories interact to determine the state of cardiovascular health in older age.Trial registration: Prospectively registered on ClinicalTrials.gov with trial ID: 19/LO/1774 Multimorbidity Life-Course Approach to Myocardial Health- A Cardiac Sub-Study of the MCRC National Survey of Health and Development (NSHD).

New Adjunct Therapy for Elevated Lipid Levels.

Inclisiran (Leqvio) has been approved as adjunct therapy, along with diet and statin therapy, to treat adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional reduction in low-density lipoprotein cholesterol despite maximal statin therapy.Inclisiran is administered subcutaneously by a nurse or other health care provider.

Interpersonal Trauma and Risk of Incident Cardiovascular Disease Events Among Women.

BackgroundTraumatic experiences have been linked to risk for cardiovascular disease (CVD). Interpersonal violence is a trauma that is prevalent in women. Among midlife women followed up for 2 decades, we examined whether interpersonal violence (childhood abuse, adulthood abuse, or intimate partner violence [IPV]) was related to increased risk of subsequent clinical CVD events.Methods and ResultsA total of 2201 women, aged 42 to 52 years at baseline, underwent up to 16 in‐person visits over 22 years. Measures included questionnaires (including of childhood physical/sexual abuse, adult physical/sexual abuse, and IPV), physical measures, phlebotomy, and reported CVD events (myocardial infarction, stroke, heart failure, and revascularization). Death certificates were collected. Relationships between childhood abuse, adult abuse, and IPV with incident fatal/nonfatal CVD were tested in Cox proportional hazards models. Women with a childhood abuse history had increased risk for incident CVD (versus no abuse; hazard ratio [HR] [95% CI], 1.65 [1.12–2.44]; P=0.01; adjusted for demographics and CVD risk factors); associations were strongest for childhood sexual abuse. Adult abuse was not significantly associated with CVD. Women with IPV had a doubling of risk for incident CVD in demographic‐adjusted models (versus no IPV; IPV: HR [95% CI], 2.06 [1.01–4.23]; P=0.04; no partner: HR [95% CI], 1.79 [0.91–3.53]; P=0.09); systolic blood pressure partially mediated relationships between IPV and CVD.ConclusionsChildhood abuse, particularly sexual abuse, was associated with increased risk of CVD in women. IPV was associated with risk for CVD, with the higher systolic blood pressure among IPV‐exposed women important in these associations. Interpersonal violence prevention may contribute to CVD risk reduction in women.

Estimating the Direct Effect between Dietary Macronutrients and Cardiometabolic Disease, Accounting for Mediation by Adiposity and Physical Activity.

Assessing the causal effects of individual dietary macronutrients and cardiometabolic disease is challenging because distinguish direct effects from those mediated or confounded by other factors is difficult. To estimate these effects, intake of protein, carbohydrate, sugar, fat, and its subtypes were obtained using food frequency data derived from a Swedish population-based cohort (n~60,000). Data on clinical outcomes (i.e., type 2 diabetes (T2D) and cardiovascular disease (CVD) incidence) were obtained by linking health registry data. We assessed the magnitude of direct and mediated effects of diet, adiposity and physical activity on T2D and CVD using structural equation modelling (SEM). To strengthen causal inference, we used Mendelian randomization (MR) to model macronutrient intake exposures against clinical outcomes. We identified likely causal effects of genetically predicted carbohydrate intake (including sugar intake) and T2D, independent of adiposity and physical activity. Pairwise, serial- and parallel-mediational configurations yielded similar results. In the integrative genomic analyses, the candidate causal variant localized to the established T2D gene TCF7L2. These findings may be informative when considering which dietary modifications included in nutritional guidelines are most likely to elicit health-promoting effects.

Atorvastatin Induces Mitochondria-Dependent Ferroptosis via the Modulation of Nrf2-xCT/GPx4 Axis.

As one of the cornerstones of clinical cardiovascular disease treatment, statins have an extensive range of applications. However, statins commonly used have side reactions, especially muscle-related symptoms (SAMS), such as muscle weakness, pain, cramps, and severe condition of rhabdomyolysis. This undesirable muscular effect is one of the chief reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. Moreover, the underlying mechanism of muscle cell damage is still unclear. Here, we discovered that ferroptosis, a programmed iron-dependent cell death, serves as a mechanism in statin-induced myopathy. Among four candidates including atorvastatin, lovastatin, rosuvastatin, and pravastatin, only atorvastatin could lead to ferroptosis in human cardiomyocytes (HCM) and murine skeletal muscle cells (C2C12), instead of human umbilical vein endothelial cell (HUVEC). Atorvastatin inhibits HCM and C2C12 cell viability in a dose-dependent manner, accompanying with significant augmentation in intracellular iron ions, reactive oxygen species (ROS), and lipid peroxidation. A noteworthy investigation found that those alterations particularly occurred in mitochondria and resulted in mitochondrial dysfunction. Biomarkers of myocardial injury increase significantly during atorvastatin intervention. However, all of the aforementioned enhancement could be restrained by ferroptosis inhibitors. Mechanistically, GSH depletion and the decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPx4), and xCT cystine–glutamate antiporter (the main component is SLC7A11) are involved in atorvastatin-induced muscular cell ferroptosis and damage. The downregulation of GPx4 in mitochondria-mediated ferroptosis signaling may be the core of it. In conclusion, our findings explore an innovative underlying pathophysiological mechanism of atorvastatin-induced myopathy and highlight that targeting ferroptosis serves as a protective strategy for clinical application.

The clinical and molecular cardiometabolic fingerprint of an exploratory psoriatic arthritis cohort is associated with the disease activity and differentially modulated by methotrexate and apremilast.

Objectives(1) To evaluate clinical and molecular cardiovascular disease (CVD) signs and their relationship with psoriatic arthritis (PsA) features and (2) to identify a clinical patient profile susceptible to benefit from methotrexate (MTX) and/or apremilast regarding CVD risk.MethodsThis cross‐sectional study included 100 patients with PsA and 100 age‐matched healthy donors. In addition, an exploratory cohort of 45 biologically naïve patients treated for 6 months with apremilast, MTX or combined therapy according to routine clinical practice was recruited. Extensive clinical and metabolic profiles were obtained. Ninety‐nine surrogate CVD‐related molecules were analysed in plasma and peripheral blood mononuclear cells (PBMCs). Hard cluster analysis was performed to identify the clinical and molecular phenotypes. Mechanistic studies were performed on adipocytes.ResultsCardiometabolic comorbidities were associated with disease activity and long‐term inflammatory status. Thirty‐five CVD‐related proteins were altered in the plasma and PBMCs of PsA patients and were associated with the key clinical features of the disease. Plasma levels of some of the CVD‐related molecules might distinguish insulin‐resistant patients (MMP‐3, CD163, FABP‐4), high disease activity (GAL‐3 and FABP‐4) and poor therapy outcomes (CD‐163, LTBR and CNTN‐1). Hard cluster analysis identified two phenotypes of patients according to the rates of cardiometabolic comorbidities with distinctive clinical and molecular responses to each treatment.Conclusions(1) Novel CVD‐related proteins associated with clinical features could be emerging therapeutic targets in the context of PsA and (2) the pleiotropic action of apremilast could make it an excellent choice for the management of PsA patients with high CVD risk, targeting metabolic alterations and CVD‐related molecules.

Abstract P040: Dyslipidemia And The Incidence Of Subclinical And Clinical Cardiovascular Disease In Adolescents And Young Adults: The Strong Heart Family Study (SHFS)

Introduction: Dyslipidemia is characterized by high levels of total cholesterol (TC), LDL cholesterol (LDL-C), triglycerides (TG), or low levels of HDL cholesterol (HDL-C) and is an established risk factor for subclinical and clinical cardiovascular disease (CVD) among adults. Although several investigations exist in older American Indian (AI) adults, the data on AI adolescents and young adults are scarce. Hypothesis: Dyslipidemia will be prevalent, and the incidence of subclinical and clinical CVD will be higher in young AI with than without baseline dyslipidemia. Methods: We evaluated AI participants from the SHFS, who were 14-39 years old at the baseline examination, 2001-2003 (n=1,436). To measure lipids, we drew blood after a 12-hour fast and defined dyslipidemia as any of the following: TC ≥ 200 mg/dL, LDL-C ≥ 100 mg/dL, TG ≥ 150 mg/dL, HDL-C &lt; 40 mg/dL for men, HDL-C &lt; 50mg/dL for women, non-HDL-C ≥ 130 mg/dL or taking lipid lowering medication. We used carotid ultrasound to detect atherosclerotic plaque at baseline and at the follow-up examination, 2006-2009. We identified CVD events through 2019 with a median follow-up of 17.8 years. We used log-rank tests to determine if the incidence of plaque or CVD events differed according to different categories of dyslipidemia. Results: Prevalence of dyslipidemia was 42%, 65%, and 73% for participants &lt;20, 20-29, and 30-39 years old, respectively. During follow-up, 109 (9.9%) participants had incident plaque (of 1,107 plaque free participants) and 128 (9%) had a fatal or non-fatal CVD event (of 1,424 CVD free participants). Plaque incidence was higher in participants with high TC, LDL-C, TG, non-HDL-C, and dyslipidemia at baseline. CVD incidence was higher for participants with high TC, TG, and non-HDL-C (Table 1). Conclusions: AI adolescents and young adults have an unexpectedly high prevalence of dyslipidemia, which leads to higher incident plaque and CVD events later in life. These data provide evidence for the benefits of lipid screening and intervention among this population.

Abstract P075: An Innovative Statistical Approach To Investigate The Association Of Movement Behaviors On High-sensitivity C-reactive Protein: The Jackson Heart Study

Introduction: Over the course of 24 hours, humans engage in multiple movement behaviors including sleep, physical activity (PA), and sedentary behavior (SB) that are each associated with high-sensitivity C-reactive protein (hs-CRP). Traditional regression models do not allow for the estimation of the relative contributions of each of these behaviors on hs-CRP as they are correlated and sum to 100% of the whole day. Compositional and isotemporal substitution analyses will allow us to estimate how exchanging one behavior for another influences hs-CRP. We hypothesize an equal time amount substitution of PA (subtraction) with SB will be associated with higher hs-CRP, while substitution of sleep or SB with PA will be associated with lower hs-CRP. Methods: The Jackson Heart Study (JHS) was designed to investigate cardiovascular disease risk factors among African Americans in the Jackson, MS area. PA was self-reported via the JHS PA Cohort survey and used to calculate minutes per day of total PA. Usual nightly hours of sleep was self-reported using the JHS Sleep History Form. As compositional analysis examines proportions of a whole, SB was calculated as remaining time during the day after PA and sleep. Blood samples of hs-CRP (mg·dl -1 ) were measured by the immunoturbidimetric CRP-latex assay method. Due to being skewed right, hs-CRP was natural logarithmic transformed. Iso-temporal substitutions were calculated as a substitution in one movement behavior of 15 minutes for another while maintaining the third. Models adjusted for age, sex, smoking status, education, body mass index, and metabolic syndrome criteria. Results: The mean age of the 3,716 participants was 61.94 years (SD; 12.06) and the majority of participants were female (63.5%). The median hs-CRP concentration was 0.29 mg·dl -1 (IQR; 0.12, 0.65). Most of daily minutes was spent in SB (72.12%), followed by sleep (26.30%), and PA (1.58%). When replacing 15 minutes of PA for SB or sleep, the predicted hs-CRP was 0.03 mg·dl -1 (95% CIs; -0.00, 0.06) greater than the hs-CRP of the average participant. Substituting 15 minutes of SB for PA was associated with a predicted lowering of hs-CRP of 0.01 mg·dl -1 (-0.02, 0.00) and was similar for substituting 15 minutes of sleep for PA 0.01 mg·dl -1 (-0.03, 0.00). Substituting 15 minutes of SB for sleep, or sleep for SB was associated with no predicted change in hs-CRP (0.00 mg·dl -1 ). Conclusions: Efforts should strive to increase, or at the very least, maintain PA levels to improve measures of systemic inflammation. Future research could aim to tie the proportion of time each day spent in each movement activity to cardiovascular disease risk factors and subclinical or clinical cardiovascular disease.

Soluble Fms-like tyrosine kinase-1 (sFlt-1) is associated with subclinical and clinical atherosclerotic cardiovascular disease: The Dallas Heart Study

Background and aimsSoluble Fms-like tyrosine kinase-1 (sFlt-1) plays a role in angiogenesis, atherogenesis, and preeclampsia. The relationship of sFlt-1 with markers of subclinical atherosclerosis and future atherosclerotic cardiovascular disease (ASCVD) events in a generally healthy population is unknown. MethodsParticipants in the Dallas Heart Study with sFlt-1 measured were included (n = 3292). Abdominal aortic atherosclerosis was measured by MRI and coronary artery calcium (CAC) by CT. The cohort was also followed for subsequent ASCVD events (CV death, MI, stroke, unstable angina, revascularization). Multivariable linear and logistic regression analyses and Cox regression analyses were performed adjusting for demographics and traditional cardiac risk factors. ResultssFlt-1 levels were higher in older individuals, males, and African Americans, and tracked with most traditional risk factors. sFlt-1 was significantly associated with higher prevalence of aortic plaque [OR 1.33 (95% CI 1.02–1.73)], greater abdominal aortic wall thickness (p<0.01) and aortic plaque area (p<0.02) but no difference in coronary artery calcification. There were 322 ASCVD events over 12 years of follow-up. Higher sFlt-1 levels associated with increased ASCVD events in unadjusted (16.1% vs. 8.9%, p<0.001, quartile 4 vs. quartile 1) and adjusted analyses (HR 1.58 [1.14–2.18], p<0.01, quartile 4 vs. quartile 1). Findings were unchanged when analyzing sFlt-1 as a continuous variable or when excluding those with a history of ASCVD. ConclusionsIn a population-based cohort, sFlt-1 is associated with measures of subclinical aortic atherosclerosis and clinical ASCVD events. Future studies are warranted on the therapeutic potential of targeting sFlt-1 for atherosclerotic disease.

Abstract P082: Association Of Breast Arterial Calcification With Atrial Fibrillation Among Postmenopausal Women

Coronary artery calcium (CAC) is independently associated with incident atrial fibrillation (AF). Breast arterial calcification (BAC), commonly seen in mammograms, correlates with CAC and cardiovascular outcomes. However, whether BAC is associated with AF is unknown. We examined the association of BAC presence and gradation with prevalent or incident AF in the MINERVA cohort of 5,059 post-menopausal women (60-79 years), free of clinical cardiovascular disease, recruited after mammography screening at Kaiser Permanente Northern California between 2012-2015. Incident AF cases were identified between entry and 12/31/2020, and prevalent cases up to 5 years before entry. Both prevalent and incident AF were ascertained using hospital discharge diagnostic and outpatient ICD-9 and ICD-10 codes plus natural language processing of ECG reports and progress notes in the electronic health record. We measured the quantity of BAC using a densitometry method. A total of 469 AF events were ascertained during 6.5 years of follow-up (132 prevalent, 335 incident). In multivariable logistic regression adjusting for age and ethnicity (Model 1), BAC presence (BAC &gt; 0 mg) vs absence (BAC=0 mg) was associated with 1.26 (95% CI:1.02-1.55; p=0.03) increased odds of prevalent or incident AF; further adjustment for body mass index, hypertension, diabetes, cholesterol lowering drugs, anticoagulant use, hs-CRP, e-GFR, sleep apnea and early menopause increased the strength of association between BAC and AF. However, there was no clear dose-response association, although women in the upper tertile of BAC when BAC was present exhibited the highest odds of prevalent or incident AF (adjusted OR=1.91; 95% CI=1.43-2.57; p=&lt;0.001). In sensitivity analysis restricting to incident AF events, the independent association persisted (data not shown). In conclusion, presence of mammographic BAC and more severe BAC may provide additional useful information for AF risk among postmenopausal women.

Abstract P152: The Association Between Menopause Age And Carotid Plaque In The Multi-Ethnic Study Of Atherosclerosis (MESA)

Background: The menopause transition is associated with an accelerated rise in cardiovascular disease (CVD) risk among women. Early-onset menopause is associated with incident CVD events. Detection of subclinical atherosclerosis may be an opportunity to institute preventive efforts before the onset of clinical CVD. We assessed whether menopause age was associated with carotid plaque, a marker of subclinical atherosclerosis, in a multiethnic cohort. Methods: We studied post-menopausal women in MESA free of CVD who had age of menopause onset ascertained by questionnaire and carotid plaque measured by B-mode ultrasound at baseline. Menopause age was categorized as &lt;45, 45-&lt;50, 50-&lt;55 (ref) and ≥55 yrs. Multivariable logistic and linear regression models were performed to evaluate the association of menopause age with carotid plaque presence (yes/no) and extent (carotid plaque score (CPS)), respectively. Results: Of the 2,297 women included, 38% were White, 28% Black, 12% Chinese, and 22% Hispanic with a mean age (SD) of 64 (9) yrs. The distribution of menopause age was 22.7% at age &lt;45, 28.8% at age 45-49, 36.1% at age 50-54, 12.5% at age ≥55. Overall, carotid plaque was present in 52%. The association of carotid plaque presence/absence and CPS are shown in the Table . There was no statistically significant association of menopause age with carotid plaque presence. Compared to women with menopause age 50-55, menopause before age 45 was significantly associated with a 9% greater CPS [percent difference 9 (95% CI 2, 17) after adjusting for demographics. This was attenuated and no longer statistically significant after further adjustment for CVD risk factors. Conclusion: In a multiethnic cohort of women, a younger age of onset of menopause was associated with a greater extent of carotid plaque, which appears to be mediated through traditional CVD risk factors. Further studies are needed to evaluate the association between the age of onset of menopause and atherosclerotic risk.

Association of Net Worth and Ambulatory Blood Pressure in Early Middle-aged African American Women

Low socioeconomic status (SES) in the form of educational level and income has been linked to greater cardiovascular risk across cohorts; however, associations have been inconsistent for African American individuals. Net worth, a measure of overall assets, may be a more relevant metric, especially for African American women, because it captures longer-term financial stability and economic reserve. To examine whether net worth is associated with increased ambulatory blood pressure (ABP), a marker of cardiovascular disease (CVD) risk, independent of educational level and income, in young to middle-aged African American women. A cross-sectional, community-based study conducted in the southeastern US was performed using 48-hour ambulatory BP monitoring. Participants included 384 African American women aged 30 to 46 years without clinical CVD recruited between December 16, 2016, and March 21, 2019; data analysis was performed from September 2020 to December 2021. Self-reported net worth (total financial assets minus debts), self-reported educational level, and self-reported income. Mean daytime and nighttime BP levels, assessed via 48-hour ABP monitoring and sustained hypertension (ABP daytime and clinic BP ≥130/80 mm Hg). The 384 African American women in this study represented a range of SES backgrounds; mean (SD) age was 38.0 (4.3) years. Excluding 66 women who were not receiving antihypertensive medications, in linear regression models adjusted for age, marital status, educational level, family income, and family size, women reporting a negative net worth (debt) had higher levels of daytime (β = 6.7; SE = 1.5; P < .001) and nighttime (β = 6.4; SE = 1.4; P < .001) systolic BP, compared with women reporting a positive net worth. Similar associations were observed with sustained hypertension: women reporting a negative net worth had 150% higher odds (odds ratio, 2.5; 95% CI, 1.3-4.7) of sustained hypertension than those reporting a positive net worth. Associations remained significant after additional adjustments for smoking, body mass index, psychosocial stress due to debt, and depressive symptoms and were similar, although attenuated, when women receiving antihypertensive medications were included and treatment was controlled for in all analyses. In this cross-sectional study, having a negative net worth (ie, debt) was associated with elevated BP in African American women, independent of traditional indicators of SES. This finding suggests that limited assets or a lack of economic reserve may be associated with poor CVD outcomes in this at-risk group.

Psychosocial Well-Being and Progression of Coronary Artery Calcification in Midlife Women.

BackgroundPrevention of cardiovascular disease (CVD) is a public health priority. The combination of physical activity, a healthy diet, and abstaining from tobacco plays an important role in prevention whereas aspects of psychosocial well‐being have largely been examined separately with conflicting results. This study evaluated whether the combination of indices of psychosocial well‐being was associated with less progression of coronary artery calcium (CAC).Methods and ResultsParticipants were 312 women (mean age 50.8) from the SWAN (Study of Women’s Health Across the Nation) ancillary Heart Study, free of clinical CVD at baseline. A composite psychosocial well‐being score was created from 6 validated psychosocial questionnaires assessing optimism, vitality, life engagement, life satisfaction, rewarding multiple roles, and positive affect. Subclinical CAC progression was defined as an increase of ≥10 Agatston units over 2.3 years measured using electron beam tomography. Relative risk (RR) regression models examined the effect of well‐being on CAC progression, progressively adjusting for sociodemographic factors, depression, healthy lifestyle behaviors, and standard CVD risk factors. At baseline, 42.9% had a CAC score >0, and progression was observed in 17.6%. Well‐being was associated with less progression (RR, 0.909; 95% CI, 0.843−0.979; P=0.012), which remained significant with adjustment for potential confounders, depression, and health behaviors. Further adjustment for standard CVD risk factors weakened the association for the total sample (RR, 0.943; 95% CI, 0.871−1.020; P=0.142) but remained significant for the 134 women with baseline CAC>0 (RR, 0.921; 95% CI, 0.852−0.995; P=0.037).ConclusionsOptimum early prevention of CVD in women may result from including the mind side of the mind‐heart‐body continuum.