Inclisiran: A New Strategy for LDL-C Lowering and Prevention of Atherosclerotic Cardiovascular Disease.

Multiple lines of evidence confirm that the cumulative burden of low-density lipoprotein cholesterol (LDL-C) is causally related to the development of atherosclerotic cardiovascular disease (ASCVD). As such, lowering LDL-C is a central tenet in all ASCVD prevention guidelines, which recommend matching the intensity of LDL-C lowering with the absolute risk of the patient. Unfortunately, issues such as difficulty with long-term adherence to statin therapy and inability to achieve desired LDL-C thresholds with statins alone results in residual elevated ASCVD risk. Non-statin therapies generally provide similar risk reduction per mmol/L of LDL-C reduction and are included by major society guidelines as part of the treatment algorithm for managing LDL-C. Per the 2022 American College of Cardiology Expert Consensus Decision Pathway, patients with ASCVD are recommended to achieve both an LDL-C reduction ≥50% and an LDL-C threshold of <55 mg/dL in patients at very high-risk and <70 mg/dL in those not at very high risk. Patients with familial hypercholesterolemia (FH) but without ASCVD should lower LDL-C to <100 mg/dL. For patients who remain above LDL-C thresholds with maximally tolerated statin therapy plus lifestyle changes, non-statin therapy warrants strong consideration. While several non-statin therapies have been granted FDA approval for managing hypercholesterolemia (eg, ezetimibe, Proprotein Convertase Subtilisin/Kexin 9 [PCSK9] monoclonal antibodies, and bempedoic acid), the focus of the current review is on inclisiran, a novel small interfering RNA therapy that inhibits the production of the PCSK9 protein. Inclisiran is currently FDA approved as an adjunct to statin therapy in patients with clinical ASCVD or heterozygous FH who require additional LDL-lowering. The drug is administered by subcutaneous injection twice a year, after an initial baseline and 3 month dose. In this review, we sought to provide an overview of the use of inclisiran, review current trial data, and outline an approach to potential patient selection.

Association of Depression and Poor Mental Health With Cardiovascular Disease and Suboptimal Cardiovascular Health Among Young Adults in the United States.

Background Depression is a nontraditional risk factor for cardiovascular disease (CVD). Data on the association of depression and poor mental health with CVD and suboptimal cardiovascular health (CVH) among young adults are limited. Methods and Results We used data from 593 616 young adults (aged 18-49 years) from the 2017 to 2020 Behavioral Risk Factor Surveillance System, a nationally representative survey of noninstitutionalized US adults. Exposures were self-reported depression and poor mental health days (PMHDs; categorized as 0, 1-13, and 14-30 days of poor mental health in the past 30 days). Outcomes were self-reported CVD (composite of myocardial infarction, angina, or stroke) and suboptimal CVH (≥2 cardiovascular risk factors: hypertension, hypercholesterolemia, overweight/obesity, smoking, diabetes, physical inactivity, and inadequate fruit and vegetable intake). Using logistic regression, we investigated the association of depression and PMHDs with CVD and suboptimal CVH, adjusting for sociodemographic factors (and cardiovascular risk factors for the CVD outcome). Of the 593 616 participants (mean age, 34.7±9.0 years), the weighted prevalence of depression was 19.6% (95% CI, 19.4-19.8), and the weighted prevalence of CVD was 2.5% (95% CI, 2.4-2.6). People with depression had higher odds of CVD than those without depression (odds ratio [OR], 2.32 [95% CI, 2.13-2.51]). There was a graded association of PMHDs with CVD. Compared with individuals with 0 PMHDs, the odds of CVD in those with 1 to 13 PMHDs and 14 to 30 PHMDs were 1.48 (95% CI, 1.34-1.62) and 2.29 (95% CI, 2.08-2.51), respectively, after adjusting for sociodemographic and cardiovascular risk factors. The associations did not differ significantly by sex or urban/rural status. Individuals with depression had higher odds of suboptimal CVH (OR, 1.79 [95% CI, 1.65-1.95]) compared with those without depression, with a similar graded relationship between PMHDs and suboptimal CVH. Conclusions Depression and poor mental health are associated with premature CVD and suboptimal CVH among young adults. Although this association is likely bidirectional, prioritizing mental health may help reduce CVD risk and improve CVH in young adults.

THE ABCDE'S OF PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE.

The growing burden of obesity, smoking, elevated cholesterol, diabetes, hypertension, sedentary lifestyle, and unhealthy dietary habits fuels cardiovascular disease. In 2015, the rates of cardiovascular disease in the United States rose for the first time after decades of steady decline. To combat this rising trend, there is a great need to emphasize primary cardiovascular prevention. In this review, we provide a summary of the current primary prevention recommendations using a simplified ABCDE approach. The aim is to help clinicians utilize an easy-to-use, structured approach to primary atherosclerotic cardiovascular disease prevention.

Association between hypercholesterolemia and mortality risk among patients referred for cardiac imaging test: Evidence of a "cholesterol paradox?"

AIM: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Comparing eligibility for statin therapy for primary prevention under 2022 USPSTF recommendations and the 2018 AHA/ACC/ multi-society guideline recommendations: From National Health and Nutrition Examination Survey.

INTRODUCTION: The United States Preventive Services Taskforce (USPSTF) recently released recommendations for statin therapy eligibility for the primary prevention of cardiovascular disease (CVD). We report the proportion and the absolute number of US adults who would be eligible for statin therapy under these recommendations and compare them with the previously published 2018 American Heart Association (AHA)/ American College of Cardiology (ACC)/ Multisociety (MS) Cholesterol guidelines. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 of adults aged 40-75 years without prevalent self-reported atherosclerotic CVD (ASCVD) and low-density lipoprotein-cholesterol <190 mg/dL. The 2022 USPSTF recommends statin therapy for primary prevention in those with a 10-year ASCVD risk of ≥10% and ≥ 1 CVD risk factor (diabetes mellitus, dyslipidemia, hypertension, or smoking). The 2018 AHA/ ACC/ MS Cholesterol guideline recommends considering statin therapy for primary prevention for those with diabetes mellitus, or 10-year ASCVD risk ≥20% or 10-year ASCVD risk 7.5 to <20% after accounting for risk-enhancers and shared decision making. Survey recommended weights were used to project these proportions to national estimates. RESULTS: Among 1799 participants eligible for this study, the weighted mean age was 56.0 ± 0.5 years, with 53.0% women (95% confidence interval [CI] 49.7, 56.3), and 10.6% self-reported NH Black individuals (95% CI 7.7, 14.3). The weighted mean 10-year ASCVD risk was 9.6 ± 0.3%. The 2022 USPSTF recommendations and the 2018 AHA/ ACC/ MS Cholesterol guidelines indicated eligibility for statin therapy in 31.8% (95% CI 28.6, 35.1) and 46.8% (95% CI 43.0, 50.5) adults, respectively. These represent 33.7 million (95% CI 30.4, 37.2) and 49.7 million (95% CI 45.7, 53.7) adults, respectively. For those with diabetes mellitus, 2022 USPSTF recommended statin therapy in 63.0% (95% CI 52.1, 72.7) adults as compared with all adults with diabetes aged 40-75 years under the 2018 AHA/ ACC/ MS Cholesterol guidelines. CONCLUSION: In this analysis of the nationally representative US population from 2017 to 2020, approximately 15% (~16.0 million) fewer adults were eligible for statin therapy for primary prevention under the 2022 USPSTF recommendations as compared to the 2018 AHA/ ACC/ MS Cholesterol guideline.

A Simple Approach to the Identification of Guideline-Based Coronary Artery Calcium Score Percentiles (From the Multi-Ethnic Study of Atherosclerosis).

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, >300) will place a patient above the 75th percentile. Also, we derived gender-specific age cutoffs by which 95% of participants with any (>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 CAC >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 (>100) place nearly all men <60 years and all women <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 (men <50 years and women <60 years with any CAC, men <60 years and women <70 years with CAC >100) for identifying CAC >75th percentile that might be readily adopted in clinical practice.

Racial Disparities in Prevalence of Gestational Diabetes by Maternal Nativity and Length of US Residence in an Urban Low-Income Population in the United States.

Background: 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. Methods: 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. Results: Foreign-born NHB, NHW, and Hispanic women with a duration of US residence of < 10 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 of < 10 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 of < 10 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. Conclusions: 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.

Introduction: 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. Méthodes: 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. (< 10 vs ≥ 10 ans), et le DSG dans chaque groupe racial/ethnique. Résultats: Les femmes NNH, BNH et hispaniques nées à l'étranger qui avaient une durée de résidence aux É.-U. de < 10 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 % vs 3,1 %; BNH : 5,7 % vs 8,1 %; hispaniques : 0,4 % vs 2,6 %); l'obésité (NNH : 17,1 % vs 23,4 %; BNH : 3,8 % vs 15,6 %; hispaniques : 10,9 % vs 22,7 %); le stress important (NNH : 8,7 % vs 11,9 %; BNH : 5,7 % vs 28,1 %; hispaniques : 3,8 % vs 7,3 %). Lors de l'ajustement des caractéristiques sociodémographiques et des facteurs de risque de MCV, les femmes NNH nées à l'étranger qui avaient une durée de résidence aux É.-U. de < 10 ans montraient une plus grande probabilité d'avoir le DSG (rapport de cotes ajusté : 1,60, intervalle de confiance à 95 % : 0,99-2,60) que leurs homologues nées aux É.-U., alors que les femmes hispaniques nées à l'étranger qui avaient une durée de résidence aux É.-U. de < 10 ans montraient une plus faible probabilité d'avoir le DSG (rapport de cotes ajusté : 0,54, intervalle de confiance à 95 % : 0,32-0,91). La probabilité que les femmes hispaniques et NNH qui avaient une durée de résidence aux É.-U. de ≥ 10 ans aient le DSG n'était pas significativement différente de celles de leurs homologues nées aux É.-U. Conclusions: L'« effet de l'immigrant en bonne santé ¼ 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.

Lipoprotein(a) and Subclinical Vascular and Valvular Calcification on Cardiac Computed Tomography: The Atherosclerosis Risk in Communities Study.

Background Lipoprotein(a) (Lp(a)) is a potent causal risk factor for cardiovascular events and mortality. However, its relationship with subclinical atherosclerosis, as defined by arterial calcification, remains unclear. This study uses the ARIC (Atherosclerosis Risk in Communities Study) to evaluate the relationship between Lp(a) in middle age and measures of vascular and valvular calcification in older age. Methods and Results Lp(a) was measured at ARIC visit 4 (1996-1998), and coronary artery calcium (CAC), together with extracoronary calcification (including aortic valve calcium, aortic valve ring calcium, mitral valve calcification, and thoracic aortic calcification), was measured at visit 7 (2018-2019). Lp(a) was defined as elevated if >50 mg/dL and CAC/extracoronary calcification were defined as elevated if >100. Logistic and linear regression models were used to evaluate the association between Lp(a) and CAC/extracoronary calcification, with further stratification by race. The mean age of participants at visit 4 was 59.2 (SD 4.3) years, with 62.2% women. In multivariable adjusted analyses, elevated Lp(a) was associated with higher odds of elevated aortic valve calcium (adjusted odds ratio [aOR], 1.82; 95% CI, 1.34-2.47), CAC (aOR, 1.40; 95% CI, 1.08-1.81), aortic valve ring calcium (aOR, 1.36; 95% CI, 1.07-1.73), mitral valve calcification (aOR, 1.37; 95% CI, 1.06-1.78), and thoracic aortic calcification (aOR, 1.36; 95% CI, 1.05-1.77). Similar results were obtained when Lp(a) and CAC/extracoronary calcification were examined on continuous logarithmic scales. There was no significant difference in the association between Lp(a) and each measure of calcification by race or sex. Conclusions Elevated Lp(a) at middle age is significantly associated with vascular and valvular calcification in older age, represented by elevated CAC, aortic valve calcium, aortic valve ring calcium, mitral valve calcification, thoracic aortic calcification. Our findings encourage assessing Lp(a) levels in individuals with increased cardiovascular disease risk, with subsequent comprehensive vascular and valvular assessment where elevated.

Cardiovascular Disease Risk Among Cancer Survivors: The Atherosclerosis Risk In Communities (ARIC) Study.

BACKGROUND: More than 80% of adult patients diagnosed with cancer survive long term. Long-term complications of cancer and its therapies may increase the risk of cardiovascular disease (CVD), but prospective studies using adjudicated cancer and CVD events are lacking. OBJECTIVES: The aim of this study was to assess the risk of CVD in cancer survivors in a prospective community-based study. METHODS: We included 12,414 ARIC (Atherosclerosis Risk In Communities) study participants. Cancer diagnoses were ascertained via linkage with state registries supplemented with medical records. Incident CVD outcomes were coronary heart disease (CHD), heart failure (HF), stroke, and a composite of these. We used multivariable Poisson and Cox regressions to estimate the association of cancer with incident CVD. RESULTS: Mean age was 54 years, 55% were female, and 25% were Black. A total of 3,250 participants (25%) had incident cancer over a median 13.6 years of follow-up. Age-adjusted incidence rates of CVD (per 1,000 person-years) were 23.1 (95% CI: 24.7-29.1) for cancer survivors and 12.0 (95% CI: 11.5-12.4) for subjects without cancer. After adjustment for cardiovascular risk factors, cancer survivors had significantly higher risks of CVD (HR: 1.37; 95% CI: 1.26-1.50), HF (HR: 1.52; 95% CI: 1.38-1.68), and stroke (HR: 1.22; 95% CI: 1.03-1.44), but not CHD (HR: 1.11; 95% CI: 0.97-1.28). Breast, lung, colorectal, and hematologic/lymphatic cancers, but not prostate cancer, were significantly associated with CVD risk. CONCLUSIONS: Compared with persons without cancer, adult cancer survivors have significantly higher risk of CVD, especially HF, independent of traditional cardiovascular risk factors. There is an unmet need to define strategies for CVD prevention in this high-risk population.

Hepatocyte growth factor is associated with greater risk of extracoronary calcification: results from the multiethnic study of atherosclerosis.

BACKGROUND: Hepatocyte growth factor (HGF) is a biomarker with potential for use in the diagnosis, treatment and prognostication of cardiovascular disease (CVD). Elevated HGF is associated with calcification in the coronary arteries. However, knowledge is limited on the role HGF may play in extracoronary calcification (ECC). This study examined whether HGF is associated with ECC in the aortic valve (AVC), mitral annulus (MAC), ascending thoracic aorta and descending thoracic aortic (DTAC). METHODS: At baseline, adults aged 45-84 years, free of CVD, in the Multi-Ethnic Study of Atherosclerosis had HGF and ECC measured by ELISA and cardiac CT scan, respectively. ECC measurements were repeated after an average of 2.4 years of follow-up. Prevalent ECC was defined as Agatston score >0 at baseline. Incident ECC was defined as Agatston score >0 at follow-up among participants with Agatston score=0 at baseline. We used Poisson and linear mixed-effects regression models to estimate the association between HGF and ECC, adjusted for sociodemographic and CVD risk factors. RESULTS: Of 6648 participants, 53% were women. Mean (SD) age was 62 (10) years. Median (IQR) of HGF was 905 (757-1087) pg/mL. After adjustment for CVD risk factors, the highest HGF levels (tertile 3) were associated with greater prevalence and extent of AVC, MAC and DTAC at baseline compared with the lowest tertile (tertile 1). Additionally, the risk of incident AVC and MAC increased by 62% and 45%, respectively, in demographic-adjusted models. However, the associations were not statistically significant in fully adjusted models. The highest HGF levels were also associated with 10% and 13% increase in MAC and DTAC progression, respectively, even after adjustment for CVD risk factors. CONCLUSION: Higher HGF levels were significantly associated with a greater risk of calcification at some extracoronary sites, suggesting an alternate biological pathway that could be targeted to reduce CVD risk.

Nativity-Related Disparities in Preterm Birth and Cardiovascular Risk in a Multiracial U.S. Cohort.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Association of Preterm Birth With Maternal Nativity and Length of Residence Among Non-Hispanic Black Women.

Background: Preterm birth (PTB) is associated with future cardiovascular disease (CVD) risk and disproportionally affects non-Hispanic Black (NHB) women. Limited data exist on the influence of length of US residence on nativity-related disparities in PTB. We examined PTB by maternal nativity (US born vs foreign born) and length of US residence among NHB women. Methods: We analyzed data from 2699 NHB women (1607 US born; 1092 foreign born) in the Boston Birth Cohort, originally designed as a case-control study. Using multivariable logistic regression, we investigated the association of PTB with maternal nativity and length of US residence. Results: In the total sample, 29.1% of women delivered preterm (31.4% and 25.6% among US born and foreign born, respectively). Compared with foreign born, US-born women were younger (25.8 vs 29.5 years), had higher prevalence of obesity (27.6% vs 19.6%), smoking (20.5% vs 4.9%), alcohol use (13.2% vs 7.4%), and moderate to severe stress (73.5% vs 59.4%) (all P < 0.001). Compared with US-born women, foreign-born women had lower odds of PTB after adjusting for sociodemographic characteristics, alcohol use, stress, parity, smoking, body mass index, chronic hypertension, and diabetes (adjusted odds ratio [aOR], 0.79; 95% confidence interval [CI], 0.65-0.97). Foreign-born NHB women with < 10 years of US residence had 43% lower odds of PTB compared with US-born (aOR, 0.57; 95% CI, 0.43-0.75), whereas those with ≥ 10 years of US residence did not differ significantly from US-born women in their odds of PTB (aOR, 0.76; 95% CI, 0.54-1.07). Conclusions: The prevalence of CVD risk factors and proportion of women delivering preterm were lower in foreign-born than US-born NHB women. The "foreign-born advantage" was not observed with ≥ 10 years of US residence. Our study highlights the need to intensify public health efforts in exploring and addressing nativity-related disparities in PTB.

Introduction: L'accouchement avant terme (AAT) est associé à un risque futur de maladie cardiovasculaire (MCV) et touche disproportionnellement les femmes noires non hispaniques (NNH). Les données sur l'influence de la durée de résidence aux É.-U. sur les disparités de l'AAT liées au lieu de naissance sont limitées. Nous avons examiné l'AAT en fonction du lieu de naissance de la mère (née aux É.-U. vs née à l'étranger) et la durée de résidence aux É.-U. chez les femmes NNH. Méthodes: Nous avons analysé les données de 2 699 femmes NNH (1 607 nées aux É.-U.; 1 092 nées à l'étranger) de la Boston Birth Cohort, conçue à l'origine comme une étude cas-témoins. À l'aide de la régression logistique multivariée, nous avons examiné l'association de l'AAT au lieu de naissance de la mère et à la durée de résidence aux É.-U. Résultats: Dans l'échantillon total, 29,1 % des femmes qui avaient accouché avant terme (soit 31,4 % des femmes nées aux É.-U. et 25,6 % des femmes nées à l'étranger). Comparativement aux femmes nées à l'étranger, les femmes nées aux É.-U. étaient plus jeunes (25,8 vs 29,5 ans), montraient une prévalence plus élevée d'obésité (27,6 % vs 19,6 %), du tabagisme (20,5 % vs 4,9 %), de la consommation d'alcool (13,2 % vs 7,4 %) et de stress modéré à important (73,5 % vs 59,4 %) (toutes les valeurs P < 0,001). Comparativement aux femmes nées aux É.-U., les femmes nées à l'étranger avaient un risque inférieur d'AAT après l'ajustement des caractéristiques sociodémographiques, de la consommation d'alcool, du stress, de la parité, du tabagisme, de l'indice de masse corporelle, de l'hypertension chronique et du diabète (ratio d'incidence approché ajusté [RIAa], 0,79; intervalle de confiance [IC] à 95 %, 0,65-0,97). Les femmes NNH nées à l'étranger de < 10 ans de résidence aux É.-U. avaient une probabilité 43 % plus faible d'AAT que les femmes nées aux É.-U. (RIAa, 0,57; IC à 95 %, 0,43-0,75), tandis que les femmes de ≥ 10 ans de résidence aux É.-U. ne montraient pas de différence significative dans leur probabilité d'AAT par rapport aux femmes nées aux É.-U. (RIAa, 0,76; IC à 95 %, 0,54-1,07). Conclusions: La prévalence des facteurs de risque de MCV et la proportion de femmes qui accouchent avant terme étaient plus faibles chez les femmes NNH nées à l'étranger que chez les femmes NNH nées aux É.-U. L'« avantage d'être nées à l'étranger ¼ n'était pas observé lors de ≥ 10 ans de résidence aux É.-U. Notre étude illustre la nécessité d'intensifier les efforts de santé publique pour explorer et remédier aux disparités liées au lieu de naissance dans l'AAT.

Favorable Cardiovascular Health Is Associated With Lower Prevalence, Incidence, Extent, and Progression of Extracoronary Calcification: MESA.

BACKGROUND: Ideal cardiovascular health (CVH) is associated with a lower incidence of cardiovascular disease. Extracoronary calcification (ECC)-measured at the aortic valve, mitral annulus, ascending thoracic aorta, and descending thoracic aorta-is an indicator of systemic atherosclerosis. This study examined whether favorable CVH was associated with a lower risk of ECC. METHODS: We analyzed data from MESA (Multi-Ethnic Study of Atherosclerosis) participants aged 45 to 84 years without cardiovascular disease at baseline. ECC was measured by noncontrast cardiac computed tomography scan at baseline and after an average of 2.4 years. Prevalent ECC was defined as an Agatston score >0 at the baseline scan. Incident ECC was defined as Agatston score >0 at the follow-up scan among participants with Agatston score of 0 at the baseline scan. Each CVH metric (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose) was scored 0 to 2 points, with 2 indicating ideal; 1, intermediate; and 0, poor. The aggregated CVH score was 0 to 14 points (0-8, inadequate; 9-10, average; 11-14, optimal). We used Poisson and linear mixed-effects regression models to examine the association between CVH and ECC adjusted for sociodemographic factors. RESULTS: Of 6504 participants, 53% were women with a mean age (SD) of 62 (10) years. Optimal and average CVH scores were associated with lower ECC prevalence, incidence, and extent. For example, optimal CVH scores were associated with 57%, 56%, 70%, and 54% lower risk of incident aortic valve calcification, mitral annulus calcification, ascending thoracic aorta calcification, and descending thoracic aorta calcification, respectively. In addition, optimal and average CVH scores were associated with lower ECC progression at 2 years, although these associations were only significant for mitral annulus calcification and descending thoracic aorta calcification. CONCLUSIONS: In this multiethnic cohort, favorable CVH was associated with a lower risk of extracoronary atherosclerosis. These findings emphasize the importance of primordial prevention as an intervention to reduce the burden of cardiovascular disease.

Social Determinants of Suboptimal Cardiovascular Health Among Pregnant Women in the United States.

Background Suboptimal cardiovascular health (CVH) and social determinants of health (SDOH) have a significant impact on maternal morbidity and mortality. We aimed to evaluate the association of SDOH with suboptimal CVH among pregnant women in the United States. Methods and Results We examined cross-sectional data of pregnant women aged 18 to 49 years from the National Health Interview Survey (2013-2017). We ascertained optimal and suboptimal CVH based on the presence of 0 to 1 and ≥2 risk factors (hypertension, diabetes, hyperlipidemia, current smoking, obesity, and insufficient physical activity), respectively. We calculated an aggregate SDOH score representing 38 variables from 6 domains (economic stability; neighborhood, physical environment, and social cohesion; community and social context; food; education; and healthcare system) and divided into quartiles. We used Poisson regression model to evaluate the association of SDOH with suboptimal CVH and risk factors. Our study included 1433 pregnant women (28.8±5.5 years, 13% non-Hispanic Black). Overall, 38.4% (95% CI, 33.9-43.0) had suboptimal CVH versus 51.7% (95% CI, 47.0-56.3) among those in the fourth SDOH quartile. Risk ratios of suboptimal CVH, smoking, obesity, and insufficient physical activity were 2.05 (95% CI, 1.46-2.88), 8.37 (95% CI, 3.00-23.43), 1.54 (95% CI, 1.17-2.03), and 1.19 (95% CI, 1.01-1.42), respectively among those in the fourth SDOH quartile compared with the first quartile. Conclusions Over 50% of pregnant women with the highest SDOH burden had suboptimal CVH, highlighting the public health urgency for interventions in socially disadvantaged pregnant women with renewed strategies toward improving modifiable risk factors, especially smoking and insufficient physical activity.

Coronary artery calcium is associated with increased risk for lung and colorectal cancer in men and women: the Multi-Ethnic Study of Atherosclerosis (MESA).

AIMS: This study explored the association of coronary artery calcium (CAC) with incident cancer subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA). CAC is an established predictor of cardiovascular disease (CVD), with emerging data also supporting independent predictive value for cancer. The association of CAC with risk for individual cancer subtypes is unknown. METHODS AND RESULTS: We included 6271 MESA participants, aged 45-84 and without known CVD or self-reported history of cancer. There were 777 incident cancer cases during mean follow-up of 12.9 ± 3.1 years. Lung and colorectal cancer (186 cases) were grouped based on their strong overlap with CVD risk profile; prostate (men) and ovarian, uterine, and breast cancer (women) were considered as sex-specific cancers (in total 250 cases). Incidence rates and Fine and Gray competing risks models were used to assess relative risk of cancer-specific outcomes stratified by CAC groups or Log(CAC+1). The mean age was 61.7 ± 10.2 years, 52.7% were women, and 36.5% were White. Overall, all-cause cancer incidence increased with CAC scores, with rates per 1000 person-years of 13.1 [95% confidence interval (CI): 11.7-14.7] for CAC = 0 and 35.8 (95% CI: 30.2-42.4) for CAC ≥400. Compared with CAC = 0, hazards for those with CAC ≥400 were increased for lung and colorectal cancer in men [subdistribution hazard ratio (SHR): 2.2 (95% CI: 1.1-4.7)] and women [SHR: 2.2 (95% CI: 1.0-4.6)], but not significantly for sex-specific cancers across sexes. CONCLUSION: CAC scores were associated with cancer risk in both sexes; however, this was stronger for lung and colorectal when compared with sex-specific cancers. Our data support potential synergistic use of CAC scores in the identification of both CVD and lung and colorectal cancer risk.

Efficacy and safety for the achievement of guideline-recommended lower low-density lipoprotein cholesterol levels: a systematic review and meta-analysis.

AIM: The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors). METHODS AND RESULTS: Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD -1.56; RR 0.94 (0.89-1.00)], cardiovascular mortality [ARD -1.49; RR 0.90 (0.81-1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. CONCLUSION: This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.

Determinants of Incident Atherosclerotic Cardiovascular Disease Events Among Those With Absent Coronary Artery Calcium: Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The 2018 American Heart Association/American College of Cardiology/Multisociety cholesterol guideline states that statin therapy may be withheld or delayed among intermediate-risk individuals in the absence of coronary artery calcium (CAC=0). We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) events among individuals with CAC=0 over long-term follow-up. METHODS: We included participants with CAC=0 at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of clinical ASCVD at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors (cigarette smoking, diabetes, hypertension, preventive medication use [aspirin and statin], family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers) and adjudicated incident ASCVD outcomes. RESULTS: We studied 3416 individuals (mean [SD] age 58 [9] years; 63% were female, 33% White, 31% Black, 12% Chinese American, and 24% Hispanic). Over a median follow-up of 16 years, there were 189 ASCVD events (composite of coronary heart disease and stroke) of which 91 were coronary heart disease, 88 were stroke, and 10 were both coronary heart disease and stroke events. The unadjusted event rates of ASCVD were ≤5 per 1000 person-years among individuals with CAC=0 for most risk factors with the exception of current cigarette smoking (7.3), diabetes (8.9), hypertension (5.4), and chronic kidney disease (6.8). After multivariable adjustment, risk factors that were significantly associated with ASCVD included current cigarette smoking: hazard ratio, 2.12 (95% CI, 1.32-3.42); diabetes: hazard ratio, 1.68 (95% CI, 1.01-2.80); and hypertension: hazard ratio, 1.57 (95% CI, 1.06-2.33). CONCLUSIONS: Current cigarette smoking, diabetes, and hypertension are independently associated with incident ASCVD over a 16-year follow-up among those with CAC=0.

Nativity-Related Disparities in Preeclampsia and Cardiovascular Disease Risk Among a Racially Diverse Cohort of US Women.

Importance: Preeclampsia is an independent risk factor for future cardiovascular disease and disproportionally affects non-Hispanic Black women. The association of maternal nativity and duration of US residence with preeclampsia and other cardiovascular risk factors is well described among non-Hispanic Black women but not among women of other racial and ethnic groups. Objective: To examine differences in cardiovascular risk factors and preeclampsia prevalence by race and ethnicity, nativity, and duration of US residence among Hispanic, non-Hispanic Black, and non-Hispanic White women. Design, Setting, and Participants: This cross-sectional analysis of the Boston Birth Cohort included a racially diverse cohort of women who had singleton deliveries at the Boston Medical Center from October 1, 1998, to February 15, 2016. Participants self-identified as Hispanic, non-Hispanic Black, or non-Hispanic White. Data were analyzed from March 1 to March 31, 2021. Exposures: Maternal nativity and duration of US residence (<10 vs ≥10 years) were self-reported. Main Outcome and Measures: Diagnosis of preeclampsia, the outcome of interest, was retrieved from maternal medical records. Results: A total of 6096 women (2400 Hispanic, 2699 non-Hispanic Black, and 997 non-Hispanic White) with a mean (SD) age of 27.5 (6.3) years were included in the study sample. Compared with Hispanic and non-Hispanic White women, non-Hispanic Black women had the highest prevalence of chronic hypertension (204 of 2699 [7.5%] vs 65 of 2400 [2.7%] and 28 of 997 [2.8%], respectively), obesity (658 of 2699 [24.4%] vs 380 of 2400 [15.8%] and 152 of 997 [15.2%], respectively), and preeclampsia (297 of 2699 [11.0%] vs 212 of 2400 [8.8%] and 71 of 997 [7.1%], respectively). Compared with their counterparts born outside the US, US-born women in all 3 racial and ethnic groups had a significantly higher prevalence of obesity (Hispanic women, 132 of 556 [23.7%] vs 248 of 1844 [13.4%]; non-Hispanic Black women, 444 of 1607 [27.6%] vs 214 of 1092 [19.6%]; non-Hispanic White women, 132 of 776 [17.0%] vs 20 of 221 [9.0%]), smoking (Hispanic women, 98 of 556 [17.6%] vs 30 of 1844 [1.6%]; non-Hispanic Black women, 330 of 1607 [20.5%] vs 53 of 1092 [4.9%]; non-Hispanic White women, 382 of 776 [49.2%] vs 42 of 221 [19.0%]), and severe stress (Hispanic women, 76 of 556 [13.7%] vs 85 of 1844 [4.6%]; non-Hispanic Black women, 231 of 1607 [14.4%] vs 120 of 1092 [11.0%]; non-Hispanic White women, 164 of 776 [21.1%] vs 26 of 221 [11.8%]). After adjusting for sociodemographic and cardiovascular risk factors, birth status outside the US (adjusted odds ratio [aOR], 0.74 [95% CI, 0.55-1.00]) and shorter duration of US residence (aOR, 0.62 [95% CI, 0.41-0.93]) were associated with lower odds of preeclampsia among non-Hispanic Black women. However, among Hispanic and non-Hispanic White women, maternal nativity (aOR for Hispanic women, 1.07 [95% CI, 0.72-1.60]; aOR for non-Hispanic White women, 0.98 [95% CI, 0.49-1.96]) and duration of US residence (aOR for Hispanic women <10 years, 1.04 [95% CI, 0.67-1.59]; aOR for non-Hispanic White women <10 years, 1.20 [95% CI, 0.48-3.02]) were not associated with preeclampsia. Conclusions and Relevance: Nativity-related disparities in preeclampsia persisted among non-Hispanic Black women but not among Hispanic and non-Hispanic White women after adjusting for sociodemographic and cardiovascular risk factors. Further research is needed to explore the interplay of factors contributing to nativity-related disparities in preeclampsia, particularly among non-Hispanic Black women.

Exercise-Induced Ventricular Ectopy and Cardiovascular Mortality in Asymptomatic Individuals.

BACKGROUND: The prognosis of exercise-induced premature ventricular contractions (PVCs) in asymptomatic individuals is unclear. OBJECTIVES: This study sought to investigate whether high-grade PVCs during stress testing predict mortality in asymptomatic individuals. METHODS: A cohort of 5,486 asymptomatic individuals who took part in the Lipid Research Clinics prospective cohort had baseline interview, physical examination, blood tests, and underwent Bruce protocol treadmill testing. Adjusted Cox survival models evaluated the association of exercise-induced high-grade PVCs (defined as either frequent (>10 per minute), multifocal, R-on-T type, or ≥2 PVCs in a row) with all-cause and cardiovascular mortality. RESULTS: Mean baseline age was 45.4 ± 10.8 years; 42% were women. During a mean follow-up of 20.2 ± 3.9 years, 840 deaths occurred, including 311 cardiovascular deaths. High-grade PVCs occurred during exercise in 1.8% of individuals, during recovery in 2.4%, and during both in 0.8%. After adjusting for age, sex, diabetes, hypertension, lipids, smoking, body mass index, and family history of premature coronary disease, high-grade PVCs during recovery were associated with cardiovascular mortality (hazard ratio [HR]: 1.82; 95% CI: 1.19-2.79; P = 0.006), which remained significant after further adjusting for exercise duration, heart rate recovery, achieving target heart rate, and ST-segment depression (HR: 1.68; 95% CI: 1.09-2.60; P = 0.020). Results were similar by clinical subgroups. High-grade PVCs occurring during the exercise phase were not associated with increased risk. Recovery PVCs did not improve 20-year cardiovascular mortality risk discrimination beyond clinical variables. CONCLUSIONS: High-grade PVCs occurring during recovery were associated with long-term risk of cardiovascular mortality in asymptomatic individuals, whereas PVCs occurring only during exercise were not associated with increased risk.