Search

Background: Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC. Methods: The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute –funded Multi-Ethnic Study of Atherosclerosis. Results: During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04–1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06–1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87–1.18]). Similarly, a very high LDL-C level ( > 193 mg/dL) versus LDL-C 0 (aHR, 2.42 [95% CI, 1.59–3.67]) but not in those without CAC (aHR, 0.92 [0.48–1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis. Conclusions: LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis.

Machine learning (ML) models of risk prediction with coronary artery calcium (CAC) and CAC characteristics exhibit high performance, but are not inherently interpretable.To determine the direction and magnitude of impact of CAC characteristics on 10-year all-cause mortality (ACM) with explainable ML.We analyzed asymptomatic subjects in the CAC consortium. We trained ML models on 80% and tested on 20% of the data with XGBoost, using clinical characteristics ​+ ​CAC (ML 1) and additional CAC characteristics of CAC density and number of calcified vessels (ML 2). We applied SHAP, an explainable ML tool, to explore the relationship of CAC and CAC characteristics with 10-year all-cause and CV mortality.2376 deaths occurred among 63,215 patients [68% male, median age 54 (IQR 47-61), CAC 3 (IQR 0-94.3)]. ML2 was similar to ML1 to predict all-cause mortality (Area Under the Curve (AUC) 0.819 vs 0.821, p ​= ​0.23), but superior for CV mortality (0.847 vs 0.845, p ​= ​0.03). Low CAC density increased mortality impact, particularly ≤0.75. Very low CAC density ≤0.75 was present in only 4.3% of the patients with measurable density, and 75% occurred in CAC1-100. The number of diseased vessels did not increase mortality overall when simultaneously accounting for CAC and CAC density.CAC density contributes to mortality risk primarily when it is very low ≤0.75, which is primarily observed in CAC 1-100. CAC and CAC density are more important for mortality prediction than the number of diseased vessels, and improve prediction of CV but not all-cause mortality. Explainable ML techniques are useful to describe granular relationships in otherwise opaque prediction models.

Exercise capacity (EC) is inversely related to the risk of cardiovascular disease and incident heart failure (HF) in healthy subjects. However, there are no present studies that exclusively evaluate EC and the risk of incident HF in patients with known coronary heart disease (CHD). We aimed to determine the relation between EC and incident HF in patients with an established clinical diagnosis of CHD. We retrospectively identified 8,387 patients (age 61 ± 12 years; 30% women; 33% non-White) with a history of myocardial infarction (MI) or coronary revascularization procedure and no history of HF at the time of a clinically indicated exercise stress test completed between 1991 and 2009. EC was quantified in metabolic equivalents of task (METs) estimated from treadmill testing. Incident HF was identified through June 2010 from administrative databases based on ≥3 encounters with International Classification of Diseases, Ninth Revision 428.x. Cox regression analysis was used to evaluate the risk of incident HF associated with METs. Covariates included age; gender; race; hypertension, diabetes, hyperlipidemia, smoking, and MI; medications for CHD and lung diseases; and clinical indication for treadmill testing. During a median follow-up of 8.2 years (interquartile range 4.7 to 12.4 years) after the exercise test, 23% of the cohort experienced a new HF diagnosis. Lower EC categories were associated with higher HF incidence compared with METs ≥12, with nearly fourfold greater adjusted risk among patients with METslt;6. Per unit increase in METs of EC was associated with a 12% lower adjusted risk for HF. There was no significant interaction based on race (p = 0.06), gender (p = 0.88), age ≤61 years (p = 0.60), history of MI (p = 0.31), or diabetes (p = 0.38). This study reveals that among men and women with CHD and no history of HF, EC is independently and inversely related to the risk of future HF.

Absolute coronary artery calcium (CAC) scores and CAC percentiles can identify different patient groups, which could be confusing in clinical practice. We aimed to create a simple "rule of thumb" for identifying the American College of Cardiology/American Heart Association endorsed 75th CAC percentile based on age, gender, and the absolute CAC score. Using the Multi-Ethnic Study of Atherosclerosis, we calculated the age and gender-specific percent likelihood that a guideline-based absolute CAC score group (1 to 100, 100 to 300,gt;300) will place a patient above the 75th percentile. Also, we derived gender-specific age cutoffs by which 95% of participants with any (gt;0), moderate (≥100), or severe (≥300) CAC score would be over the 75th percentile. We repeated the analysis using the 90th percentile threshold and also conducted sensitivity analyses stratified by race. Any CACgt;0 places 95% of women younger than 60 years and over 90% of men younger than 50 years over the 75th percentile. Moderate absolute CAC scores (gt;100) place nearly all menlt;60 years and all womenlt;70 years over the 75th percentile. Confirmatory analysis for age cutoffs was consistent with primary analysis, with cutoffs of 48 years for men and 59 years for women indicating a 95% likelihood that any CAC would place patients over the 75th percentile. In conclusion, our study provides a simple rule of thumb (menlt;50 years and womenlt;60 years with any CAC, menlt;60 years and womenlt;70 years with CACgt;100) for identifying CACgt;75th percentile that might be readily adopted in clinical practice.

Some observational studies have observed a lower, rather than higher, mortality rate in association with hypercholesterolemia during follow-up of patients after cardiac stress testing. We aim to assess the relationship of hypercholesterolemia and other CAD risk factors to mortality across a wide spectrum of patients referred for various cardiac tests.We identified four cardiac cohorts: 64,357 patients undergoing coronary artery calcium (CAC) scanning, 10,814 patients undergoing coronary CT angiography (CCTA), 31,411 patients without known CAD undergoing stress/rest single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and 5051 patients with known CAD undergoing stress/rest SPECT-MPI. Each cohort was followed for all-cause mortality using risk-adjusted Cox models. We pooled the hazard ratios between cohorts with a random effects model. Baseline risk varied markedly among cohorts, from an annualized mortality rate of 0.31%/year in CAC patients to 3.63%/year among SPECT-MPI patients with known CAD. Hypertension, diabetes, and smoking were each associated with increased mortality in each patient cohort (pooled hazard ratio[95% CI]: 1.38[1.33-1.44], 1.88[1.76-2.00], and 1.67[1.48-1.86], respectively). By contrast, hypercholesterolemia was associated with decreased rather than increased mortality (pooled hazard ratio[95% CI]: 0.71[0.58-0.84]). Analysis of serum lipids among 7744 patients undergoing CAC or CCTA scanning revealed an inverse relationship between LDL cholesterol and mortality.Among a broad spectrum of patients referred for a variety of cardiac tests and ranging from low to high clinical risk, hypercholesterolemia was not associated with increased mortality risk. Our findings suggest that hypercholesterolemia may be sensitive to confounding by other clinical factors and post-test treatment changes in patient populations.

Background: Current guidelines recommend coronary artery calcium (CAC) scoring for stratification of atherosclerotic cardiovascular disease risk only in patients with borderline to intermediate risk score by the pooled cohort equation with low-density lipoprotein-cholesterol (LDL-C) of 70 to 190 mg/dL. It remains unknown if CAC or thoracic aorta calcification (TAC), detected on routine chest computed tomography, can provide further risk stratification in patients with LDL-C≥190 mg/dL. Methods: From a multisite medical center, we retrospectively identified all patients from March 2005 to June 2021 age ≥40 years, without established atherosclerotic cardiovascular disease and LDL-C≥190 mg/dL who had non-gated non-contrast chest computed tomography within 3 years of LDL-C measurement. Ordinal CAC and TAC scores were measured by visual inspection. Kaplan-Meier curves and multivariable Cox-regression models were built to ascertain the association of CAC and TAC scores with all-cause mortality. Results: We included 811 patients with median age 59 (53–68) years, 262 (32.3%) were male, and LDL-C median level was 203 (194–217) mg/dL. Patients were followed for 6.2 (3.29–9.81) years, and 109 (13.4%) died. Overall, 376 (46.4%) of patients had CAC=0 and 226 (27.9%) had TAC=0. All-cause mortality increased with any CAC and moderate to severe TAC. In a multivariate model, patients with CAC had a significantly higher mortality compared with those without CAC: mild hazard ratio (HR), 1.71 (1.03–2.83), moderate HR, 2.12 (1.14–3.94), and severe HR, 3.49 (1.94–6.27). Patients with moderate TAC (HR, 2.34 [1.19–4.59]) and those with severe TAC (HR, 3.02 [1.36–6.74]) had higher mortality than those without TAC. Conclusions: In patients without history of atherosclerotic cardiovascular disease and LDL-C≥190 mg/dL, the presence and severity of CAC and TAC are independently associated with all-cause mortality.

ObjectiveThe association of sex-specific hormones with coronary computed tomography angiography(CCTA)-based plaque characteristics in women without cardiovascular disease is not well understood. We investigated the association of sex-specific hormones with coronary artery plaque characteristics in a contemporary multiracial cohort with no clinical coronary artery disease (CAD).MethodsIn this cross-sectional analysis, we utilized data from 2,325 individuals with no clinical CAD from the Miami Heart (MiHeart) study. Multivariable logistic regression models were used to investigate the association of sex hormones: sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), free and total testosterone, estradiol, with plaque characteristics among women and men.ResultsOf the 1,155 women, 34.2% had any plaque and 3.4% had any high-risk plaque features (HRP) while among men (n=1170), 63.1% had any plaque and 10.4% had HRP. Among women, estradiol and SHBG were associated with lower odds of any plaque after adjusting for age and race-ethnicity (estradiol OR per SD increase: 0.87, 95%CI: 0.76-0.98; SHBG OR per SD increase: 0.82, 95%CI: 0.72-0.93) but the significance did not persist after adjustment of cardiovascular risk factors. High free testosterone was associated with higher odds of HRP (aOR:3.48, 95%CI:1.07-11.26) but null associations for the other sex hormones with HRP, in the context of limited sample size. Among men, there were no significant associations between sex-specific hormones and plaque or HRP.ConclusionAmong young to middle-aged women with no clinical CAD, increasing estradiol and SHBG were associated with lower odds of any plaque and higher free testosterone was associated with HRP. Larger cohorts may be needed to validate this.

INTRODUCTION: Factors predisposing asymptomatic individuals within the community to venous thromboembolism (VTE) are not fully understood. This study characterizes the incidence and determinants of VTE among the Multi-Ethnic Study of Atherosclerosis cohort with a focus on race/ethnicity and obesity. METHODS: This study (analyzed in 2020–2021) used the Multi-Ethnic Study of Atherosclerosis cohort (2000–2017), which includes participants with diverse ethnic/racial backgrounds aged 45–84 years without cardiovascular disease at baseline. The primary endpoint was time to diagnosis of VTE defined using ICD codes (415, 451, 453, 126, 180, and 182). Multivariable adjusted hazard ratios of the predictors of VTE were calculated with a focus on the interaction between obesity and race/ethnicity categories. RESULTS: Over a median follow-up period of 14 years, 233 individuals developed VTE. Incidence rates (per 1,000 person-years) varied across racial/ethnic groups with the highest incidence among Black (4.02) followed by White (2.98), Hispanic (2.08), and Chinese (0.79) participants. There was a stepwise increase in the incidence rate of VTE with increasing BMI regardless of race/ethnicity: normal (1.95), overweight (2.52), obese (3.63), and morbidly obese (4.55). The association between BMI and VTE was strongest among non-White women with the highest incidence rate for obese (4.8) compared with non-obese (1.6). The interaction for obesity, gender, and race was statistically significant (p=0.01) in non-White obese women. Risk of VTE increased with age for all race/ethnicities. Other significant predictors of VTE were cancer at baseline and follow-up, long-term warfarin use, smoking, and D-dimer levels, whereas statin use was associated with lower VTE events. CONCLUSIONS: This study finds that obesity may confer an increased risk for VTE among non-White women as compared with other groups—White men, White women, and non-White men.

Both E-cigarette use and the prevalence of prediabetes have risen dramatically in the past decade. It is crucial to understand whether E-cigarette use is associated with the risk of prediabetes.Participants who completed the prediabetes and E-cigarette modules of the Behavioral Risk Factor Surveillance System survey (2016-2018) were included in this study. E-cigarette use information was collected by asking: Have you ever used an e-cigarette or other electronic "vaping" product, even just one time, in your entire life? We defined sole E-cigarette users as current E-cigarette users who are never combustible-cigarette users, and dual users were defined as both current E-cigarette and combustible-cigarette users. Participants with prediabetes were identified by asking: Ever been told by a doctor or other health professional that you have prediabetes or borderline diabetes? Multivariable logistic regression was used to determine the association between E-cigarette use and prediabetes.Among the 600,046 respondents, 28.6% of respondents were aged35 years. The prevalence of prediabetes among current E-cigarette, sole E-cigarette users, and dual users was 9.0% (95% CI=8.6, 9.4), 5.9% (95% CI=5.3, 6.5), and 10.2% (95% CI=9.8, 10.7), respectively. In the fully adjusted model, the ORs for prediabetes were 1.22 (95% CI=1.10, 1.37) for current E-cigarette users and 1.12 (95% CI=1.05, 1.19) for former E-cigarette users compared with that of never E-cigarette users. The ORs for prediabetes were 1.54 (95% CI=1.17, 2.04) for sole E-cigarette users and 1.14 (95% CI=0.97, 1.34) for dual users.In this representative sample of U.S. adults, E-cigarette use was associated with greater odds of prediabetes. The results were consistent in sole E-cigarette users.

Gestational diabetes mellitus (GDM) is associated with increased risk of cardiovascular disease (CVD). Racial/ethnic differences in GDM prevalence have been described, but disparities by nativity and duration of US residence are not well studied.We analyzed data from 6088 women (mean age: 27.5 years [standard deviation: 6.3 years]) from the Boston Birth Cohort who self-identified as non-Hispanic Black (NHB; n = 2697), Hispanic (n = 2395), or non-Hispanic White (NHW; n = 996). Using multivariable logistic regression, we examined the cross-sectional association of nativity and duration of US residence (10 vs ≥ 10 years) with GDM within each race/ethnicity group.Foreign-born NHB, NHW, and Hispanic women with a duration of US residence of10 years had a lower prevalence of CVD risk factors than those with US residence of ≥ 10 years, respectively, as follows: smoking (NHB: 1.7% vs 3.1%; NHW: 5.7% vs 8.1%; Hispanic: 0.4% vs 2.6%); obesity (NHB: 17.1% vs 23.4%; NHW: 3.8% vs 15.6%; Hispanic: 10.9% vs 22.7%); and severe stress (NHB: 8.7% vs 11.9%; NHW: 5.7% vs 28.1%; Hispanic: 3.8% vs 7.3%). In analyses adjusting for sociodemographic characteristics and CVD risk factors, foreign-born NHB women with a duration of US residence of10 years had higher odds of having GDM (adjusted odds ratio: 1.60, 95% confidence interval: 0.99-2.60), compared with their US-born counterparts, whereas foreign-born Hispanic women with a duration of US residence of10 years had lower odds of having GDM (adjusted odds ratio: 0.54, 95% confidence interval: 0.32-0.91). The odds of having GDM in Hispanic and NHB women with a duration of US residence of ≥ 10 years were not significantly different from those of their US-born counterparts.The "healthy immigrant effect" and its waning with longer duration of US residence apply to the prevalence of GDM among Hispanic women but not NHB women. Further research on the intersectionality of race and nativity-based disparities is needed.Le diabète sucré gestationnel (DSG) est associé à l’augmentation du risque de maladies cardiovasculaires (MCV). Les différences raciales/ethniques dans la prévalence du DSG ont été décrites, mais les disparités selon le lieu de naissance et la durée de résidence aux É.-U font l’objet de peu d’études.Nous avons analysé les données de 6 088 femmes (âge moyen : 27,5 ans [écart type : 6,3 ans]) de la Boston Birth Cohort qui ont déclaré être noires non hispaniques (NNH; n = 2 697), hispaniques (n = 2 395) ou blanches non hispaniques (BNH; n = 996). À l’aide de la régression logistique multivariée, nous avons examiné l’association transversale entre le lieu de naissance et la durée de résidence aux É.-U. (10Les femmes NNH, BNH et hispaniques nées à l’étranger qui avaient une durée de résidence aux É.-U. de10 ans avaient une prévalence plus faible des facteurs de risque de MCV que celles qui avaient une résidence aux É.-U. de ≥ 10 ans, et ce, de façon respective comme suit : le tabagisme (NNH : 1,7 %L’« effet de l’immigrant en bonne santé » et son déclin associé à la plus longue durée de résidence aux É.-U. s’appliquent à la prévalence du DSG chez les femmes hispaniques, mais non chez les femmes NNH. D’autres recherches sur l’intersectionnalité entre la race et les disparités selon le lieu de naissance sont nécessaires.

Smoking is well-recognized as a risk factor for heart failure (HF). However, few studies have evaluated the prospective association of cigarette smoking and smoking cessation with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) as distinct phenotypes.The aim of this study was to quantify the association of cigarette smoking and smoking cessation with the incidence of HFpEF and HFrEF.In 9,345 ARIC (Atherosclerosis Risk In Communities) study White and Black participants without history of HF at baseline in 2005 (age range 61-81 years), we quantified the associations of several established cigarette smoking parameters (smoking status, pack-years, intensity, duration, and years since cessation) with physician-adjudicated incident acute decompensated HF using multivariable Cox models.Over a median follow-up of 13.0 years, there were 1,215 incident HF cases. Compared with never smokers, current cigarette smoking was similarly associated with HFpEF and HFrEF, with adjusted HRs ∼2. There was a dose-response relationship for pack-years of smoking and HF. A more extended period of smoking cessation was associated with a lower risk of HF, but significantly elevated risk persisted up to a few decades for HFpEF and HFrEF.All cigarette smoking parameters consistently showed significant and similar associations with HFpEF and HFrEF. Smoking cessation significantly reduced the risk of HF, but excess HF risk persisted for a few decades. Our results strengthened the evidence that smoking is an important modifiable risk factor for HF and highlighted the importance of smoking prevention and cessation for the prevention of HF, including HFpEF.

Having a preterm birth is associated with future cardiovascular risk. Non-Hispanic Black women have higher rates of preterm birth than non-Hispanic White and Hispanic women, but nativity-related disparities in preterm birth are not well understood.Data from 6,096 women in the Boston Birth Cohort: non-Hispanic Black (2,699), non-Hispanic White (997), or Hispanic (2,400), were analyzed in June 2021. Differences in cardiovascular risk factors were assessed. The association of preterm birth with nativity and duration of U.S. residence were investigated using multivariable logistic regression.U.S.-born women in all 3 racial-ethnic groups had a higher prevalence of obesity, smoking, and severe stress than foreign-born women. Foreign-born non-Hispanic Black and Hispanic women had lower odds of preterm birth than U.S.-born counterparts (non-Hispanic Black: AOR=0.79, 95% CI=0.65, 0.97; Hispanic: AOR=0.72, 95% CI=0.56, 0.93). In all the 3 groups, foreign-born women with shorter (10 years) duration of U.S. residence had lower odds of preterm birth than the U.S.-born women (non-Hispanic Black: AOR=0.57, 95% CI=0.43, 0.75; Hispanic: AOR=0.72, 95% CI=0.55, 0.94; non-Hispanic White: AOR=0.46, 95% CI=0.25, 0.85), whereas the odds of preterm birth in foreign-born women with ≥10 years of residence were not significantly different.Foreign-born women had better cardiovascular risk profiles in all groups and lower odds of preterm birth in non-Hispanic Black and Hispanic groups. In all the 3 groups, a shorter duration of U.S. residence was associated with lower odds of preterm birth. Further studies are needed to understand the biological and social determinants underlying these nativity-related disparities and the impact of acculturation.

Introduction Educational attainment is an important social determinant of health (SDOH) for cardiovascular disease (CVD). However, the association between educational attainment and all-cause and CVD mortality has not been longitudinally evaluated on a population-level in the US, especially in individuals with atherosclerotic cardiovascular disease (ASCVD). In this nationally representative study, we assessed the association between educational attainment and the risk of all-cause and cardiovascular (CVD) mortality in the general adult population and in adults with ASCVD in the US. Methods We used data from the 2006–2014 National Death Index-linked National Health Interview Survey for adults ≥ 18 years. We generated age-adjusted mortality rates (AAMR) by levels of educational attainment ( Results The sample comprised 210,853 participants (mean age 46.3), representing ~ 189 million adults annually, of which 8% had ASCVD. Overall, 14.7%, 27%, 20.3%, and 38% of the population had educational attainment Conclusions Lower educational attainment is independently associated with increased risk of all-cause and CVD mortality in both the total and ASCVD populations, with the highest risk observed for individuals with

Background Although there is research on the impact of social determinants of health (SDOHs) on cardiovascular health, most existing evidence is based on individual SDOH components. We evaluated the impact of cumulative SDOH burden on cardiovascular risk factors, subclinical atherosclerosis, and incident cardiovascular disease events. Methods and Results We included 6479 participants from the MESA (Multi‐Ethnic Study of Atherosclerosis). A weighted aggregate SDOH score representing the cumulative number of unfavorable SDOHs, identified from 14 components across 5 domains (economic stability, neighborhood and physical environment, community and social context, education, and health care system access) was calculated and divided into quartiles (quartile 4 being the least favorable). The impact of cumulative SDOH burden on cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, and obesity), systemic inflammation, subclinical atherosclerosis, and incident cardiovascular disease was evaluated. Increasing social disadvantage was associated with increased odds of all cardiovascular risk factors except dyslipidemia. Smoking was the risk factor most strongly associated with worse SDOH (odds ratio [OR], 2.67 for quartile 4 versus quartile 1 [95% CI, 2.13–3.34]). Participants within SDOH quartile 4 had 33% higher odds of increased high‐sensitivity C‐reactive protein (OR, 1.33 [95% CI, 1.11–1.60]) and 31% higher risk of all cardiovascular disease (hazard ratio, 1.31 [95% CI, 1.03–1.67]), yet no greater burden of subclinical atherosclerosis (OR, 1.01 [95% CI, 0.79–1.29]), when compared with those in quartile 1. Conclusions Increasing social disadvantage was associated with more prevalent cardiovascular risk factors, inflammation, and incident cardiovascular disease. These findings call for better identification of SDOHs in clinical practice and stronger measures to mitigate the higher SDOH burden among the socially disadvantaged to improve cardiovascular outcomes.

Aims Lipoprotein(a) [Lp(a)] levels are generally constant throughout an individual’s lifetime, and current guidelines recommend that a single measurement is sufficient to assess the risk of coronary artery disease (CAD). However, it is unclear whether a single measurement of Lp(a) in individuals with acute myocardial infarction (MI) is indicative of the Lp(a) level six months following the event. Methods and results Lp(a) levels were obtained from individuals with non–ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI) (n = 99) within 24 h of hospital admission and after six months, who were enrolled in two randomized trials of evolocumab and placebo, and in individuals with NSTEMI or STEMI (n = 9) who enrolled in a small observation arm of the two protocols and did not receive study drug, but whose levels were obtained at the same time points. Median Lp(a) levels increased from 53.5 nmol/L (19, 165) during hospital admission to 58.0 nmol/L (14.8, 176.8) six months after the acute infarction (P = 0.02). Subgroup analysis demonstrated no difference in the baseline, six-month, or change between the baseline and six-month Lp(a) values between the STEMI and NSTEMI groups and between the group which received evolocumab and the group that did not. Conclusion This study demonstrated that Lp(a) levels in individuals with acute MI are significantly higher six months after the initial event. Therefore, a single measurement of Lp(a) in the peri-infarction setting is not sufficient to predict the Lp(a)-associated CAD risk in the post-infarction period. Registration Evolocumab in Acute Coronary Syndrome Trial [EVACS I] NCT03515304, Evolocumab in Patients with Acute Myocardial Infarction [EVACS II], NCT04082442

Lipoprotein(a), or Lp(a), levels and the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on Lp(a) during the peri-infarction and early postinfarction period are not well characterized. This study aimed to describe the trajectory of Lp(a), as well as the effect of PCSK9 inhibition on that trajectory during the peri-infarction and early postinfarction period. Lp(a) levels were obtained within 24 hours of hospital admission as well as within 24 hours of hospital discharge and at 30 days from 74 participants who presented with a NSTEMI (troponin I5 ng/ml) or with a STEMI and were enrolled in 2 randomized, double-blind trials of evolocumab and placebo (Evolocumab in Acute Coronary Syndrome [EVACS I]; ClinicalTrials.gov, NCT03515304 and Evolocumab in Patients With STEMI [EVACS II]; ClinicalTrials.gov Identifier: NCT04082442). There was a significant increase from the pretreatment level in the placebo-treated patients, from 64 (41,187) nmol/L to 80 (47, 172) nmol/L at hospital discharge and to 82 (37, 265) at 30 days. This was primarily driven by the results from participants with high Lp(a) at hospital admission (75 nmol/L) in whom the median increase was 28% as compared with a 10% increase in those with pretreatment Lp(a) of75 nmol/L. In contrast, there was no significant change from the pretreatment level in the evolocumab-treated patients regardless of pretreatment Lp(a) levels. In conclusion, Lp(a) rises during the peri-infarction and early postinfarction period in patients with acute myocardial infarction. The increase was prevented by a single dose of subcutaneous evolocumab given within 24 hours of hospital admission.

BACKGROUND AND AIMS: Coronary artery calcium (CAC) burden displays a stepwise association with atherosclerotic cardiovascular disease (ASCVD) risk. Among primary prevention patients, we sought to determine the CAC scores equivalent to ASCVD mortality rates observed in the FOURIER trial, a modern secondary prevention cohort.METHODS AND RESULTS: For the main analysis, we included participants from the CAC Consortium ≥50 years old with a 10-year ASCVD risk ≥7.5% (n = 20,207). Poisson regression was used to define the relationship between CAC and annual ASCVD mortality. Equations generated from the regression models were then used to derive CAC scores associated with equivalent annual ASCVD mortality as observed in FOURIER placebo participants from the overall trial and in key trial subgroups. The CAC Consortium participants had a similar age (65.5 versus 62.5 years) and sex (22% versus 24% female) distribution as FOURIER. The annualized ASCVD mortality rate in FOURIER participants (0.766 per 100 person-years) corresponded to a CAC score of 781 (418-1467). A CAC score of 255 (162-394) corresponded to an ASCVD mortality rate equivalent to the lowest risk FOURIER subgroup (presence of myocardial infarction >2 years prior to trial enrollment). No CAC score produced a risk equivalent to high-risk FOURIER subgroups, particularly those with symptomatic peripheral arterial disease and/or multivessel coronary heart disease.CONCLUSIONS: Primary prevention individuals with increased CAC burden may have annualized ASCVD mortality rates equivalent to persons with stable secondary prevention-level risk. These findings argue for a risk continuum between higher risk primary prevention and stable secondary prevention patients, as their ASCVD risks may overlap.

Objectives This study sought to assess the relationship between mean vs peak calcified plaque density and their impact on calculating coronary artery calcium (CAC) scores and to compare the corresponding differential prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) mortality. Background The Agatston CAC score is quantified per lesion as the product of plaque area and a 4-level categorical peak calcium density factor. However, mean calcium density may more accurately measure the heterogenous mixture of lipid-rich, fibrous, and calcified plaque reflective of ASCVD risk. Methods We included 10,373 individuals from the CAC Consortium who had CAC >0 and per-vessel measurements of peak calcium density factor and mean calcium density. Area under the curve and continuous net reclassification improvement analyses were performed for CHD and ASCVD mortality to compare the predictive abilities of mean calcium density vs peak calcium density factor when calculating the Agatston CAC score. Results Participants were on average 53.4 years of age, 24.4% were women, and the median CAC score was 68 Agatston units. The average values for mean calcium density and peak calcium density factor were 210 ± 50 Hounsfield units and 3.1 ± 0.5, respectively. Individuals younger than 50 years of age and/or those with a total plaque area 100. Conclusion Mean and peak calcium density may differentially describe plaque composition early in the atherosclerotic process. Mean calcium density performs better than peak calcium density factor when combined with plaque area for ASCVD mortality prediction among persons with Agatston CAC 1-99.

Background The inverse association between ideal cardiovascular health (CVH) as measured by the American Heart Association’s Life Simple 7 (LS7) and cardiovascular disease (CVD) incidence is well documented. However, research exploring the association between CVH and specific risk factors for cardiometabolic disease is sparse in diverse cohorts. Methods This study included 7717 participants from the Mediators of Atherosclerosis in South Asians Living in America and the Multi-Ethnic Study of Atherosclerosis cohorts. We assigned each LS7 component a 0, 1, and 2 and summed these scores to derive an overall CVH score. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and hepatic fat attenuation were measured using noncontrast computed tomography. Multivariable linear regression was used to examine associations between CVH categories and each log-transformed ectopic fat depot, as well as the homeostatic assessment for insulin resistance (HOMA-IR). Results In adjusted analysis, compared to those with ideal CVH, participants with poor CVH demonstrated 63.4% (95% CI, 54.3-73.0) higher visceral fat area, 84.0% (95% CI, 76.5-92.1) higher pericardial fat volume, 61.6% (95% CI, 50.7-73.2) higher subcutaneous fat area, and 40.6% (95% CI, 30.2-52.0) higher intermuscular fat area, and 15.1% (95% CI, 13.1-17.2) higher hepatic fat (all Ps Conclusion Poor and intermediate CVH, as defined by LS7 metrics, were associated with significantly higher measures of ectopic fat and insulin resistance among individuals from 5 racial/ethnic groups.

To examine the association of social determinants of health (SDOH) on prevalence of stroke in non-elderly adults (65 years of age).We used the National Health Interview Survey (2013-2017) database. The study population was stratified into younger (45 years of age) and middle age (45 to 64 years of age) adults. For each individual, an SDOH aggregate score was calculated representing the cumulative number of individual unfavorable SDOH (present vs absent), identified from 39 subcomponents across five domains (economic stability, neighborhood, community and social context, food, education, and health care system access) and divided into quartiles (quartile 1, most favorable; quartile 4, most unfavorable). Multivariable models tested the association between SDOH score quartiles and stroke.The age-adjusted prevalence of stroke was 1.4% in the study population (n=123,631; 58.2% (n=71,956) in patients45 years of age). Young adults reported approximately 20% of all strokes. Participants with stroke had unfavorable responses to 36 of 39 SDOH; nearly half (48%) of all strokes were reported by participants in the highest SDOH score quartile. A stepwise increase in age-adjusted stroke prevalence was observed across increasing quartiles of SDOH (first, 0.6%; second, 0.9%; third, 1.4%; and fourth, 2.9%). After accounting for demographics and cardiovascular disease risk factors, participants in the fourth vs first quartile had higher odds of stroke (odds ratio, 2.78; 95% CI, 2.25 to 3.45).Nearly half of all non-elderly individuals with stroke have an unfavorable SDOH profile. Standardized assessment of SDOH risk burden may inform targeted strategies to mitigate disparities in stroke burden and outcomes in this population.