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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.

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.

Background Periodontitis is a chronic inflammatory disease common among adults. It has been suggested that periodontal disease (PD) may be a contributing risk factor for cardiovascular disease; however, pathways underlying such a relationship require further investigation. Methods and Results A total of 665 men (mean age 68±9 years) and 611 women (mean age 67±9 years) enrolled in the MESA (Multiethnic Study of Atherosclerosis) underwent PD assessment using a 2‐item questionnaire at baseline (2000–2002) and had cardiovascular magnetic resonance 10 years later. PD was defined when participants reported either a history of periodontitis or gum disease or lost teeth caused by periodontitis or gum disease. Multivariable linear regression models were constructed to assess the associations of baseline self‐reported PD with cardiovascular magnetic resonance–obtained measures of interstitial myocardial fibrosis (IMF), including extracellular volume and native T1 time. Men with a self‐reported history of PD had greater extracellular volume percent (ß=0.6%±0.2, P =0.01). This association was independent of age, left ventricular mass, traditional cardiovascular risk factors, and history of myocardial infarction. In a subsequent model, substituting myocardial infarction for coronary artery calcium score, the association of PD with IMF remained significant (ß=0.6%±0.3, P =0.03). In women, a self‐reported history of PD was not linked to higher IMF. Importantly, a self‐reported history of PD was not found to be associated with myocardial scar independent of sex (odds ratio, 1.01 [95% CI, 0.62–1.65]; P =0.9). Conclusions In a community‐based setting, men but not women with a self‐reported PD history at baseline were found to be associated with increased measures of IMF. These findings support a plausible link between PD, a proinflammatory condition, and subclinical IMF.

Background Mobile health (mHealth) has an emerging role in the prevention of cardiovascular disease. This study evaluated possible inequities in mHealth access in older adults. Methods and Results mHealth access was assessed from 2019 to 2020 in MESA (Multi‐Ethnic Study of Atherosclerosis) telephone surveys of 2796 participants aged 62 to 102 years. A multivariable logistic regression model adjusted for general health status assessed associations of mHealth access measures with relevant demographic, socioeconomic, and cognitive characteristics. There were lower odds of all access measures with older age (odds ratios [ORs], 0.37–0.59 per 10 years) and annual income Conclusions Among older‐age adults, mHealth access varied by major demographic, socioeconomic, and cognitive characteristics, suggesting a digital divide. Novel mHealth interventions should consider individual access barriers. Registration URL: https://www.clinicaltrials.gov/ ; Unique identifier: NCT00005487.

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.

Background Atherosclerotic cardiovascular disease (ASCVD) results in high out‐of‐pocket healthcare expenditures predisposing to food insecurity. However, the burden and determinants of food insecurity in this population are unknown. Methods and Results Using 2013 to 2018 National Health Interview Survey data, we evaluated the prevalence and sociodemographic determinants of food insecurity among adults with ASCVD in the United States. ASCVD was defined as self‐reported diagnosis of coronary heart disease or stroke. Food security was measured using the 10‐item US Adult Food Security Survey Module. Of the 190 113 study participants aged 18 years or older, 18 442 (adjusted prevalence 8.2%) had ASCVD, representing ≈20 million US adults annually. Among adults with ASCVD, 2968 or 14.6% (weighted ≈2.9 million US adults annually) reported food insecurity compared with 9.1% among those without ASCVD ( P Conclusion About 1 in 7 US adults with ASCVD experience food insecurity, with more than 1 in 2 adults reporting food insecurity among the most vulnerable sociodemographic subgroups. There is an urgent need to address the barriers related to food security in this population.

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Influenza infection is associated with an increased risk of cardiovascular events (myocardial infarction, stroke, and heart failure exacerbation) and mortality, and all‐cause mortality in patients with CVD. Infection with influenza leads to a systemic inflammatory and thrombogenic response in the host body, which further causes destabilization of atherosclerotic plaques. Influenza vaccination has been shown to be protective against cardiovascular and cerebrovascular events in several observational and prospective studies of at‐risk populations. Hence, many international guidelines recommend influenza vaccination for adults of all ages, especially for individuals with high‐risk conditions such as CVD. Despite these long‐standing recommendations, influenza vaccine uptake among US adults with CVD remains suboptimal. Specifically, vaccination uptake is strikingly low among patients aged

Background Although Black adults are more likely to die from coronary heart disease (CHD) compared with White adults, few studies have examined the relationship between cigarette smoking and CHD risk among Black adults. We evaluated the relationship between cigarette smoking, incident CHD, and coronary artery calcification in the JHS (Jackson Heart Study). Methods and Results We classified JHS participants without a history of CHD (n=4432) by self‐reported baseline smoking status into current, former (smoked at least 400 cigarettes/life) or never smokers at baseline (2000–2004). We further classified current smokers by smoking intensity (number of cigarettes smoked per day [1–19 or ≥20]) and followed for incident CHD (through 2016). Hazard ratios (HR) for incident CHD for each smoking group compared with never smokers were estimated with adjusted Cox proportional hazard regression models. At baseline, there were 548 (12.4%) current, 782 (17.6%) former, and 3102 (70%) never smokers. During follow‐up (median, 13.8 years), 254 participants developed CHD. After risk factor adjustment, CHD risk was significantly higher in current smokers compared with never smokers (HR, 2.11; 95% CI, 1.39–3.18); the difference between former smokers and never smokers (HR, 1.37; 95% CI, 1.0–1.90) did not achieve statistical significance. Among current smokers, we did not observe a dose‐response effect for CHD risk. Additionally, in multivariable logistic regression models with a subset of our analytic cohort, current smokers had greater odds of coronary artery calcification score >0 compared with never smokers (odds ratio, 2.63; 95% CI, 1.88–3.68). Conclusions In a large prospective cohort of Black adults, current smoking was associated with a >2‐fold increased risk of CHD over a median follow‐up of greater than a decade.

Background The optimal method for communicating coronary heart disease (CHD) risk to individual patients is not yet clear. Recent research supports the concept of "coronary age" for more effective risk communication. We defined an individual's coronary age as the age at which an average healthy individual would have an equivalent estimated CHD risk as that calculated for the index individual, building on our previously validated MESA (Multi‐Ethnic Study of Atherosclerosis) 10‐year CHD Risk Score equations with and without coronary artery calcium (CAC). Methods and Results We derived a coronary age by (1) calculating the MESA 10‐year CHD risk; (2) mathematically setting this equal to an equation describing risk of an average healthy MESA participant, as a function of age; and (3) solving for age. The risk discrimination of the resultant coronary age was compared with that of chronological age, the MESA CHD Risk Score, and CAC alone. Approximately 95% of coronary age values ranged from 30 years less to 30 years higher than chronological age. Although the mean chronological age of individuals experiencing CHD events compared with those free of events was 67.4 versus 61.8 years, the difference in coronary age including CAC was larger (80.6 versus 62.8 years). Coronary age with CAC had identical predictive ability to that of MESA CHD Risk Score and outperformed chronological age and CAC alone. Conclusions The newly derived coronary age is a convenient transformation of MESA CHD Risk, retaining very good risk discrimination. This easy‐to‐communicate tool will be available for patients and clinicians, potentially facilitating risk communication in routine care.

Background Current strategies for cardiovascular disease (CVD) risk assessment focus on 10‐year or longer timeframes. Shorter‐term CVD risk is also clinically relevant, particularly for high‐risk occupations, but is under‐investigated. Methods and Results We pooled data from participants in the ARIC (Atherosclerosis Risk in Communities study), MESA (Multi‐Ethnic Study of Atherosclerosis), and DHS (Dallas Heart Study), free from CVD at baseline (N=16 581). Measurements included N‐terminal pro‐B‐type natriuretic peptide (>100 pg/mL prospectively defined as abnormal); high‐sensitivity cardiac troponin T (abnormal >5 ng/L); high‐sensitivity C‐reactive protein (abnormal >3 mg/L); left ventricular hypertrophy by ECG (abnormal if present); carotid intima‐media thickness, and plaque (abnormal >75th percentile for age and sex or presence of plaque); and coronary artery calcium (abnormal >10 Agatston U). Each abnormal test result except left ventricular hypertrophy by ECG was independently associated with increased 3‐year risk of global CVD (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation), even after adjustment for traditional CVD risk factors and the other test results. When a simple integer score counting the number of abnormal tests was used, 3‐year multivariable‐adjusted global CVD risk was increased among participants with integer scores of 1, 2, 3, and 4, by ≈2‐, 3‐, 4.5‐ and 8‐fold, respectively, when compared with those with a score of 0. Qualitatively similar results were obtained for atherosclerotic CVD (fatal or non‐fatal myocardial infarction or stroke). Conclusions A strategy incorporating multiple biomarkers and atherosclerosis imaging improved assessment of 3‐year global and atherosclerotic CVD risk compared with a standard approach using traditional risk factors.

Background Blacks are disproportionately affected by stroke compared with whites; however, less is known about the relationship between stroke and cigarette smoking in blacks. Therefore, we evaluated the relationship between cigarette smoking and all incident stroke in the JHS (Jackson Heart Study). Methods and Results JHS participants without a history of stroke (n=4410) were classified by self‐reported baseline smoking status into current, past (smoked at least 400 cigarettes/life), or never smokers at baseline (2000–2004). Current smokers were further classified by smoking intensity (number of cigarettes smoked per day [1–19 and ≥20]) and followed up for incident stroke (through 2015). Hazard ratios (HRs) for incident stroke for current and past smoking compared with never smoking were estimated with adjusted Cox proportional hazard regression models. After adjusting for cardiovascular risk factors, the risk for stroke in current smokers was significantly higher compared with never smokers (HR, 2.48; 95% CI, 1.60–3.83) but there was no significant difference between past smokers and never smokers (HR, 1.10; 95% CI, 0.74–1.64). There was a dose‐dependent increased risk of stroke with smoking intensity (HR, 2.28 [95% CI, 1.38–3.86] and HR, 2.78 [95% CI, 1.47–5.28] for current smokers smoking 1–19 and ≥20 cigarettes/day, respectively). Conclusions In a large cohort of blacks, current cigarette smoking was associated with a dose‐dependent higher risk of all stroke. In addition, past smokers did not have a significantly increased risk of all stroke compared with never smokers, which suggests that smoking cessation may have potential benefits in reducing the incidence of stroke in blacks.

Background Atherosclerotic cardiovascular disease ( ASCVD ) has a strong association with diabetes mellitus ( DM ), accounting for approximately two thirds of deaths in this patient population. Many individuals with ASCVD and DM are vulnerable to financial hardship associated with treatment‐related expenses. Therefore, we examined the burden of financial hardship from medical bills across the spectrum of ASCVD status with and without DM . Methods and Results Using data from the National Health Interview Survey from 2013 to 2017, we used logistic regression analysis to examine the association of ASCVD and DM status with financial hardship and an inability to pay medical bills from a representative sample of non‐elderly adults in the United States. Our study population consisted of 121 672 individuals. Approximately 3.1% of the weighted population had ASCVD , 5.6% had DM , and 1.3% had both ASCVD and DM . Nearly 50% of individuals with ASCVD and DM reported financial hardship from medical bills (23% being unable to pay medical bills at all), whereas ≈28% of those with neither ASCVD nor DM reported financial hardship from medical bills (8% being unable to pay medical bills at all). Individuals with concurrent ASCVD and DM had the highest relative odds of expressing an inability to pay at all when compared with those with neither condition (odds ratio, 2.69; 95% CI , 2.21–3.28). Conclusions Individuals with concurrent ASCVD and DM are at a disproportionately high risk of being unable to pay their medical bills. The findings provide strong evidence for developing more effective public health policies that protect vulnerable populations from financial hardship.

BackgroundCoronary artery calcium (CAC) is a predictor for the development of cardiovascular disease (CVD) and to a lesser extent cancer. The age‐ and sex‐specific relationship ofCACwithCVDand cancer mortality is unknown.Methods and ResultsAsymptomatic patients aged 40 to 75 years old without knownCVDwere included from theCACConsortium. We calculated sex‐specific mortality rates per 1000 person‐years’ follow‐up. Using parametric survival regression modeling, we determined the age‐ and sex‐specificCACscore at which the risk of death fromCVDand cancer were equal. Among the 59 502 patients included in this analysis, the mean age was 54.9 (±8.5) years, 34% were women, and 89% were white. There were 671 deaths attributable toCVDand 954 deaths attributable to cancer over a mean follow‐up of 12±3 years. Among patients withCAC=0, cancer was the leading cause of death, the total mortality rate was low (women, 1.8; men, 1.5), and theCVDmortality rate was exceedingly low for women (0.3) and men (0.3). The age‐specificCACscore at which the risk ofCVDand cancer mortality were equal had a U‐shaped relationship for women, while the relationship was exponential for men.ConclusionsThe age‐ and sex‐specific relationship ofCACwithCVDand cancer mortality differed significantly for women and men. Our age‐ and sex‐specificCACscore provides a more precise estimate and further facilitates the use ofCACas a synergistic tool in strategies for the prediction and prevention ofCVDand cancer mortality.

Background Arsenic‐related cardiovascular effects at exposure levels below the US Environmental Protection Agency's standard of 10 μg/L are unclear. For these populations, food, especially rice, is a major source of exposure. We investigated associations of rice intake, a marker of arsenic exposure, with subclinical cardiovascular disease (CVD) markers in a multiethnic population. Methods and Results Between 2000 and 2002, MESA (Multi‐Ethnic Study of Atherosclerosis) enrolled 6814 adults without clinical CVD . We included 5050 participants with baseline data on rice intake and markers of 3 CVD domains: inflammation (hsCRP [high‐sensitivity C‐reactive protein], interleukin‐6, and fibrinogen), vascular function (aortic distensibility, carotid distensibility, and brachial flow‐mediated dilation), and subclinical atherosclerosis at 3 vascular sites (carotid intima‐media thickness, coronary artery calcification, and ankle‐brachial index). We also evaluated endothelial‐related biomarkers previously associated with arsenic. Rice intake was assessed by food frequency questionnaire. Urinary arsenic was measured in 310 participants. A total of 13% of participants consumed ≥1 serving of rice/day. Compared with individuals consuming CVD risk factor adjustment (eg, geometric mean ratio [95% CI ] for hs CRP , 0.98 [0.86–1.11]; aortic distensibility, 0.99 [0.91–1.07]; and carotid intima‐media thickness, 0.98 [0.91–1.06]). Associations with urinary arsenic were similar to those for rice intake. Conclusions Rice intake was not associated with subclinical CVD markers in a multiethnic US population. Research using urinary arsenic is needed to assess potential CVD effects of low‐level arsenic exposure. Understanding the role of low‐level arsenic as it relates to subclinical CVD may contribute to CVD prevention and control.

Background Low gait speed has been linked with impaired mood, cognition, and quality of life ( QOL ) in older adults. We examined whether low gait speed was associated with impaired mood, cognition, and QOL among older adults with atrial fibrillation ( AF ). Methods and Results Participants (n=1185) had a diagnosis of AF , aged ≥65 years, CHA 2 DS 2 VAS c ≥2 and had no contraindications to anticoagulation. Participants completed a 15‐foot walk test, and low gait speed was categorized using cutoffs from the Fried Frailty Index. Participants self‐reported measures of depressive symptoms (Patient Health Questionnaire 9 ≥10), anxiety symptoms (Generalized Anxiety Disorder 7 ≥10), cognitive impairment (Montreal Cognitive Assessment ≤23), and potentially impaired Atrial Fibrillation Effect Quality‐of‐Life Questionnaire SD : 7.0) years, 48.0% were women, and 85.5% were non‐Hispanic white; 85.6% were taking an oral anticoagulant, 26.1% had low gait speed, 8.4% had elevated depressive symptoms, 5.7% had elevated anxiety symptoms, 41.1% were cognitively impaired, and 41.6% had potentially impaired AF ‐related QOL . Participants with low gait speed were significantly more likely to have elevated depressive symptoms (adjusted odds ratio: 2.1, 95% CI : 1.3–3.4), elevated anxiety symptoms (adjusted odds ratio: 2.2, 95% CI : 1.2–3.9), and cognitive impairment (adjusted odds ratio: 1.5, 95% CI : 1.1–2.1). Impaired AF ‐related QOL did not differ by gait speed after adjustment for clinical characteristics (adjusted odds ratio: 1.1, 95% CI : 0.8–1.5). Conclusions Twenty‐six percent of older adults with AF had low gait speed, and low gait speed was associated with impaired mood and cognition. Further research is needed to determine whether declines in gait speed lead to impaired mood and cognition or whether these conditions develop concurrently.

Background The relationship between lowering LDL (low‐density lipoprotein) cholesterol with contemporary lipid‐lowering therapies and incident diabetes mellitus ( DM ) remains uncertain. Methods and Results Thirty‐three randomized controlled trials (21 of statins, 12 of PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors, and 0 of ezetimibe) were selected using Medline , Embase, and the Cochrane Central Register of Controlled Trials (inception through November 15, 2018). A total of 163 688 nondiabetic patients were randomly assigned to more intensive (83 123 patients) or less intensive (80 565 patients) lipid‐lowering therapy. More intensive lipid‐lowering therapy was defined as the more potent pharmacological strategy ( PCSK 9 inhibitors, higher intensity statins, or statins), whereas less intensive therapy corresponded to active control group or placebo/usual care of the trial. Metaregression and meta‐analyses were conducted using a random‐effects model. No significant association was noted between 1‐mmol/L reduction in LDL cholesterol and incident DM for more intensive lipid‐lowering therapy (risk ratio: 0.95; 95% CI , 0.87–1.04; P =0.30; R 2 =14%) or for statins or PCSK 9 inhibitors. More intensive lipid‐lowering therapy was associated with a higher risk of incident DM compared with less intensive therapy (risk ratio: 1.07; 95% CI , 1.03–1.11; P 2 =0%). These results were driven by higher risk of incident DM with statins (risk ratio: 1.10; 95% CI , 1.05–1.15; P 2 =0%), whereas PCSK 9 inhibitors were not associated with incident DM (risk ratio: 1.00; 95% CI , 0.93–1.07; P =0.96; I 2 =0%; P =0.02 for interaction). Conclusions Among intensive lipid‐lowering therapies, there was no independent association between reduction in LDL cholesterol and incident DM . The risk of incident DM was higher with statins, whereas PCSK 9 inhibitors had no association with risk of incident DM .

Background Prevalence of peripheral artery disease ( PAD ) is significantly higher among blacks as compared with non‐Hispanic whites, but the role of cigarette smoking in PAD is understudied in blacks. We aimed to evaluate the relationship between cigarette smoking and PAD in blacks in the (JHS) Jackson Heart Study. Methods and Results JHS participants (n=5306) were classified by self‐reported baseline smoking status into current, past (smoked at least 400 cigarettes/life), or never smokers. We examined multivariable logistic and robust linear regression models to estimate the associations between baseline smoking status, smoking intensity, and measures of subclinical PAD (ankle‐brachial index [visit 1] and aortic calcium by computed tomography [visit 2]) to yield odds ratios and β‐coefficients (estimated adjusted difference) to compare each smoking status with never smokers (reference group). There were 3579 (68%) never smokers, 986 (19%) past smokers, and 693 (13%) current smokers self‐identified at baseline. After adjustment for covariates, current smokers had increased risk of ankle‐brachial index PAD by all of these measures compared with lower‐intensity use, suggesting a dose‐dependent relationship. Conclusions In a large black cohort, cigarette smoking was associated with measures of subclinical PAD in a dose‐dependent manner. These findings highlight the association between smoking and PAD in blacks and support further research exploring the impact of interventions on smoking cessation to reduce PAD in this population.

Background To examine the prevalence and patterns of recent electronic cigarette (e‐cigarette) use in a nationally representative sample of US adults and adolescents. Methods and Results Using tobacco information from NHANES (National Health and Nutrition Examination Survey) 2013–2014, 5423 adults and 895 adolescents (aged 13–17 years) were included in this analysis. Demographic, tobacco use, and drug use information were self‐reported. Recent e‐cigarette use (within the previous 5 days) was stratified by smoking status. Of 125 e‐cigarette users, 116 participants were aged ≥18 years, corresponding to 2.6% (95% confidence interval [ CI ], 2.0–3.1) and 1.21% (95% CI , 0.3–2.1) prevalence of e‐cigarette use among US adults and adolescents, respectively. E‐cigarette adult users were current smokers (68.1%), former smokers (23.7%), and never smokers (8.2%). The highest prevalence of e‐cigarette use was among current smokers (8.2%; 95% CI , 6.3–10.1), followed by former smokers (2.7%; 95% CI , 1.4–4.1), and then never smokers (0.4%; 95% CI , 0.2–0.6). After adjusting for age, sex, and ethnicity, e‐cigarette users had higher odds of being exposed to secondhand smoke (odds ratio: 6.3; 95% CI , 3.6–11.1) and drinking alcohol (odds ratio: 4.2; 95% CI, 1.8–10.0) and lower odds of having at least a college education or a higher income, compared with tobacco nonusers. Conclusions Between 2013 and 2014, e‐cigarette use in the United States was more common among younger people, those with low socioeconomic status, and current and former smokers. These findings will help inform future research as well as public policy and regulatory actions.

Background Evidence supporting nonstatin lipid‐lowering therapy in atherosclerotic cardiovascular disease risk reduction is variable. We aim to examine nonstatin utilization and expenditures in the United States between 2002 and 2013. Methods and Results We used the Medical Expenditure Panel Survey database to estimate national trends in nonstatin use and cost (total and out‐of‐pocket, adjusted to 2013 US dollars using a gross domestic product deflator) among adults 40 years or older. Nonstatin users increased from 3 million (2.5%) in 2002‐2003 (20.1 million prescriptions) to 8 million (5.6%) in 2012‐2013 (45.8 million prescriptions). Among adults with atherosclerotic cardiovascular disease, nonstatin use increased from 7.5% in 2002‐2003 to 13.9% in 2012‐2013 after peaking at 20.3% in 2006‐2007. In 2012‐2013, 15.9% of high‐intensity statin users also used nonstatins, versus 9.7% of low/moderate‐intensity users and 3.6% of statin nonusers. Nonstatin use was significantly lower among women (odds ratio 0.80; 95% confidence interval 0.75‐0.86), racial/ethnic minorities (odds ratio 0.41; 95% confidence interval 0.36‐0.47), and the uninsured (odds ratio 0.47; 95% confidence interval 0.40‐0.56). Total nonstatin expenditures increased from $1.7 billion (out‐of‐pocket cost, $0.7 billion) in 2002‐2003 to $7.9 billion (out‐of‐pocket cost $1.6 billion) in 2012‐2013, as per‐user nonstatin expenditure increased from $550 to $992. Nonstatin expenditure as a proportion of all lipid‐lowering therapy expenditure increased 4‐fold from 8% to 32%. Conclusions Between 2002 and 2013, nonstatin use increased by 124%, resulting in a 364% increase in nonstatin‐associated expenditures.

Background Previous reports on whether smoking is associated with insulin resistance and diabetes mellitus have yielded inconsistent findings. We aimed to evaluate the relationship between cigarette smoking and incident diabetes mellitus in the Jackson Heart Study. Methods and Results Jackson Heart Study participants enrolled at baseline without prevalent diabetes mellitus (n=2991) were classified by self‐report as current smokers, past smokers (smoked ≥400 cigarettes/life and no longer smoking), or never smokers. We quantified smoking intensity by number of cigarettes smoked daily; we considered ≥20 cigarettes per day (1 pack) “high‐intensity.” We defined diabetes mellitus as fasting glucose ≥126 mg/dL, hemoglobin A1c ≥6.5% or International Federation of Clinical Chemistry units HbA1c 48 mmol/mol, or use of diabetes mellitus medication. We estimated the adjusted associations of smoking status, intensity, and dose (pack‐years) with incident diabetes mellitus using Poisson regression models. At baseline there were 361 baseline current (1–10 cigarettes per day [n=242]; ≥20 [n=119]), 502 past, and 2128 never smokers. From Visit 1 to Visit 3 (mean 8.0±0.9 years), 479 participants developed incident diabetes mellitus. After adjustment for covariates, baseline current smokers who smoked less than a pack/d and past smokers had similar rates of incident diabetes mellitus compared with never smokers (incidence rate ratios 1.04, 95% confidence interval, 0.69–1.58 and 1.08, 95% confidence interval, 0.82–1.42, respectively). Baseline current high‐intensity smokers had a 79% (95% confidence interval, 1.14–2.81) higher incidence of diabetes mellitus compared with never smokers. Smoking dose (per 10 pack‐years) was also associated with a higher incidence of diabetes mellitus (incidence rate ratios 1.10, 95% confidence interval, 1.03–1.19) in adjusted models. Conclusions High‐intensity cigarette smoking and smoking pack‐years are associated with an increased risk of developing diabetes mellitus in blacks.

Background Few data exist on the association between strength training and mortality rates. We sought to examine the association between strength training and all‐cause, cardiovascular disease, and cancer mortality. Methods and Results Beginning in 2001 to 2005, 28 879 women throughout the United States (average baseline age, 62.2 years) from the Women's Health Study who were free of cardiovascular disease, diabetes mellitus, and cancer reported their physical activities, including strength training. During follow‐up (average, 12.0 years) through 2015, investigators documented 3055 deaths (411 from cardiovascular disease and 748 from cancer). After adjusting for covariables, including aerobic activity, time in strength training showed a quadratic association with all‐cause mortality (P=0.36 for linear trend; P1.00 for ≥146 min/wk of strength training. However, confidence intervals were wide at higher levels of strength training. Conclusions Time in strength training showed a J‐shaped association with all‐cause mortality in older women. A moderate amount of time in strength training seemed beneficial for longevity, independent of aerobic activity; however, any potential risk with more time (≈≥150 min/wk) should be further investigated.

Background Atherosclerotic cardiovascular disease ( ASCVD ) causes most deaths in the United States and accounts for the highest healthcare spending. The association between the modifiable risk factors ( MRF s) of ASCVD and pharmaceutical expenditures are largely unknown. Methods and Results We examined the association between MRF s and pharmaceutical expenditures among adults with ASCVD using the 2012 and 2013 Medical Expenditure Panel Survey. A 2‐part model was used while accounting for the survey's complex design to obtain nationally representative results. All costs were adjusted to 2013 US dollars using the gross domestic product deflator. The annual total pharmaceutical expenditure among those with ASCVD was $71.6 billion, 33% of which was for medications for cardiovascular disease and 14% medications for diabetes mellitus. The adjusted relationship between MRF s and pharmaceutical expenditures showed significant marginal increase in average annual pharmaceutical expenditure associated with inadequate physical activity ($519 [95% confidence interval ( CI ), $12–918; P =0.011]), dyslipidemia ($631 [95% CI , $168–1094; P =0.008]), hypertension: ($1078 [95% CI , $697–1460; P CI , $1470–2542]). Compared with those with optimal MRFs (0–1), those with average MRFs (2–3) spent an average of $1184 (95% CI , $805–1564; P MRFs (≥4) spent $2823 (95% CI , $2338–3307; P Conclusions Worsening MRFs were proportionally associated with higher annual pharmaceutical expenditures among patients with established ASCVD regardless of non‐ ASCVD comorbidity. In‐depth studies of the roles played by other factors in this association can help reduce medication‐related expenditures among ASCVD patients.

Background Inflammation is suggested to be a central feature of atherosclerosis, particularly among smokers. We studied whether inflammatory biomarkers GlycA and high‐sensitivity C‐reactive protein are associated with cigarette smoking. Methods and Results A total of 11 509 participants, 6774 from the MESA (Multi‐Ethnic Study of Atherosclerosis) and 4735 from ELSA ‐Brasil (The Brazilian Longitudinal Study of Adult Health) were included. We evaluated the cross‐sectional association between multiple measures of smoking behavior and the inflammatory biomarkers, GlycA and high‐sensitivity C‐reactive protein, using regression models adjusted for demographic, anthropometric, and clinical characteristics. Participants were 57.7±11.1 years old and 46.4% were men. Never, former, and current smokers comprised 51.7%, 34.0%, and 14.3% of the population, respectively. Multivariable‐adjusted mean absolute difference in GlycA levels (μmol/L) with 95% confidence interval (CI) were higher for former (4.1, 95% CI, 1.7–6.6 μmol/L) and current smokers (19.9, 95% CI, 16.6–23.2 μmol/L), compared with never smokers. Each 5‐unit increase in pack‐years of smoking was associated with higher GlycA levels among former (0.7, 95% CI, 0.3–1.1 μmol/L) and current smokers (1.6, 95% CI, 0.8–2.4 μmol/L). Among former smokers, each 5‐year increase in time since quitting smoking was associated with lower GlycA levels (−1.6, 95% CI, −2.4 to −0.8 μmol/L) and each 10‐unit increase in number of cigarettes/day was associated with higher GlycA among current smokers (2.8, 95% CI, 0.5–5.2 μmol/L). There were similar significant associations between all measures of smoking behavior, and both log‐transformed GlycA and high‐sensitivity C‐reactive protein. Conclusions Acute and chronic exposure to tobacco smoking is associated with inflammation, as quantified by both GlycA and high‐sensitivity C‐reactive protein. These biomarkers may have utility for the study and regulation of novel and traditional tobacco products.

Background There is a need to identify sensitive biomarkers of early tobacco‐related cardiovascular disease. We examined the association of smoking status, burden, time since quitting, and intensity, with markers of inflammation and subclinical atherosclerosis. Methods and Results We studied 14 103 participants without clinical cardiovascular disease in ELSA‐Brasil (Brazilian Longitudinal Study of Adult Health). We evaluated baseline cross‐sectional associations between smoking parameters and inflammation (high‐sensitivity C‐reactive protein [hs CRP ]) and measures of subclinical atherosclerosis (carotid intima–media thickness, ankle‐brachial index, and coronary artery calcium [ CAC ]). The cohort included 1844 current smokers, 4121 former smokers, and 8138 never smokers. Mean age was 51.7±8.9 years; 44.8% were male. After multivariable adjustment, compared with never smokers, current smokers had significantly higher levels of hs CRP (β=0.24, 0.19–0.29 mg/L; P P P CAC >0 (odds ratio: 1.83; 95% confidence interval, 1.46–2.30; P CRP ( P P =0.006, respectively) and CAC ( P P =0.002, respectively). Among former smokers, hs CRP and carotid intima–media thickness levels and odds of ankle‐brachial index ≤1.0 and CAC >0 were lower with increasing time since quitting ( P CRP ( P CAC >0 ( P =0.03) after adjusting for duration of smoking. Conclusions Strong associations were observed between smoking status, burden, and intensity with inflammation (hs CRP ) and subclinical atherosclerosis (carotid intima–media thickness, ankle‐brachial index, CAC ). These markers of early cardiovascular disease injury may be used for the further study and regulation of traditional and novel tobacco products.

Background Few studies have evaluated the association between secondhand smoke ( SHS ) and subclinical cardiovascular disease among ethnically diverse populations. This study assesses the impact of SHS on inflammation and atherosclerosis (carotid intima‐media thickness, coronary artery calcification, and peripheral arterial disease). Methods and Results We examined 5032 nonsmoking adults aged 45 to 84 years without prior cardiovascular disease participating in the Multi‐Ethnic Study of Atherosclerosis ( MESA ) from 2000 to 2002. SHS exposure was determined by self‐report, and urinary cotinine was measured in a representative subset (n=2893). The multi‐adjusted geometric mean ratios (95% CIs) for high‐sensitivity C‐reactive protein and interleukin‐6 comparing 407 participants with SHS ≥12 h/wk versus 3035 unexposed participants were 1.13 (1.02–1.26) and 1.04 (0.98–1.11), respectively. The multi‐adjusted geometric mean ratio for carotid intima‐media thickness was 1.02 (0.97–1.07). Fibrinogen and coronary artery calcification were not associated with SHS . The prevalence of peripheral arterial disease (ankle‐brachial index ≤0.9 or ≥1.4) was associated with detectable urinary cotinine (odds ratio, 2.10; 95% CI, 1.09–4.04) but not with self‐reported SHS . Urinary cotinine was not associated with inflammation or carotid intima‐media thickness. Conclusions Despite limited exposure assessment, this study supports the association of SHS exposure with inflammation and peripheral arterial disease.

Background The American Heart Association introduced the Life's Simple 7 ( LS 7) metrics to assess and promote cardiovascular health. We examined the association between the LS 7 metrics and noncardiovascular disease. Methods and Results We studied 6506 men and women aged between 45 and 84 years, enrolled in the Multi‐Ethnic Study of Atherosclerosis. Median follow‐up time was 10.2 years. Each component of the LS 7 metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and blood glucose) was assigned points, 0 indicates “poor” category; 1, “intermediate,” and 2, “ideal.” The LS 7 score, ranged from 0 to 14, was created from the points and categorized as optimal (11–14), average (9–10), and inadequate (0–8). Hazard ratios and event rates per 1000 person‐years were calculated for outcomes based on self‐reported hospitalizations with the International Classification of Diseases, 9th Revision, diagnoses of cancer, chronic kidney disease, pneumonia, deep venous thromboembolism/pulmonary embolism, chronic obstructive pulmonary disease, dementia, and hip fracture. Analyses were adjusted for age, sex, race/ethnicity, income, and education. Overall, noncardiovascular disease event rates were lower with increasing LS 7 scores. With the inadequate LS 7 score as reference, an optimal score was associated with a decreased risk for noncardiovascular disease events. The hazard ratio for cancer was, 0.80 (0.64–0.98); chronic kidney disease, 0.38 (0.27–0.54); pneumonia, 0.57 (0.40–0.80); deep venous thromboembolism/pulmonary embolism, 0.52 (0.33–0.82), and chronic obstructive pulmonary disease, 0.51 (0.31–0.83). Conclusions The American Heart Association's LS 7 score identified individuals who were vulnerable to multiple chronic nonvascular conditions. These results suggest that improving cardiovascular health will also reduce the burden of cancer and other chronic diseases.

Background Remnant lipoproteins (RLPs), the triglyceride‐enriched precursors to low‐density lipoprotein, are an emerging risk factor for coronary heart disease ( CHD ). We sought to determine the association of RLP cholesterol ( RLP ‐C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts. Methods and Results We analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable‐adjusted hazard ratios ( HRs ) for RLP ‐C (the sum of very low‐density lipoprotein 3 cholesterol and intermediate‐density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid‐lowering therapy for the combined population, RLP ‐C ( HR 1.23 per 1‐ SD increase, 95% CI 1.06–1.42, P HR 1.26 per 1‐ SD increase, 95% CI 1.08–1.47, P CHD during an 8‐year follow‐up. Associations were attenuated by high‐density lipoprotein cholesterol and ultimately lost significance with inclusion of real low‐density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort. Conclusion RLP ‐C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP ‐C to prevent CHD warrant further intensive investigation. Clinical Trial Registration URL : http://www.ClinicalTrials.gov . Unique identifier: NCT 00415415.

Background Coronary artery calcium ( CAC ) detected by noncontrast cardiac computed tomography scanning is a measure of coronary atherosclerosis burden. Increasing CAC levels have been strongly associated with increased coronary events. Prior studies of cardiovascular disease risk factors and CAC progression have been limited by short follow‐up or restricted to patients with advanced disease. Methods and Results We examined cardiovascular disease risk factors and CAC progression in a prospective multiethnic cohort study. CAC was measured 1 to 4 times (mean 2.5 scans) over 10 years in 6810 adults without preexisting cardiovascular disease . Mean CAC progression was 23.9 Agatston units/year. An innovative application of mixed‐effects models investigated associations between cardiovascular disease risk factors and CAC progression. This approach adjusted for time‐varying factors, was flexible with respect to follow‐up time and number of observations per participant, and allowed simultaneous control of factors associated with both baseline CAC and CAC progression. Models included age, sex, study site, scanner type, and race/ethnicity. Associations were observed between CAC progression and age (14.2 Agatston units/year per 10 years [95% CI 13.0 to 15.5]), male sex (17.8 Agatston units/year [95% CI 15.3 to 20.3]), hypertension (13.8 Agatston units/year [95% CI 11.2 to 16.5]), diabetes (31.3 Agatston units/year [95% CI 27.4 to 35.3]), and other factors. Conclusions CAC progression analyzed over 10 years of follow‐up, with a novel analytical approach, demonstrated strong relationships with risk factors for incident cardiovascular events. Longitudinal CAC progression analyzed in this framework can be used to evaluate novel cardiovascular risk factors.

Background The prognostic significance of modest elevations in exercise systolic blood pressure response has not been extensively examined. Methods and Results We examined the association between systolic blood pressure response and all‐cause death and incident myocardial infarction (MI) in 44 089 (mean age 53±13 years, 45% female, 26% black) patients who underwent exercise treadmill stress testing from the Henry Ford ExercIse Testing (FIT) Project (1991–2010). Exercise systolic blood pressure response was examined as a categorical variable (>20 mm Hg: referent; 1 to 20 mm Hg, and ≤0 mm Hg) and per 1 SD decrease. Cox regression was used to compute hazard ratios (HR) and 95% CI for the association between systolic blood pressure response and all‐cause death and incident MI. Over a median follow‐up of 10 years, a total of 4782 (11%) deaths occurred and over 5.2 years, a total of 1188 (2.7%) MIs occurred. In a Cox regression analysis adjusted for demographics, physical fitness, and cardiovascular risk factors, an increased risk of death was observed with decreasing systolic blood pressure response (>20 mm Hg: HR=1.0, referent; 1 to 20 mm Hg: HR=1.13, 95% CI=1.05, 1.22; ≤0 mm Hg: HR=1.21, 95% CI=1.09, 1.34). A trend for increased MI risk was observed (>20 mm Hg: HR=1.0, referent; 1 to 20 mm Hg: HR=1.09, 95% CI=0.93, 1.27; ≤0 mm Hg: HR=1.19, 95% CI=0.95, 1.50). Decreases in systolic blood pressure response per 1 SD were associated with an increased risk for all‐cause death (HR=1.08, 95% CI=1.05, 1.11) and incident MI (HR=1.09, 95% CI=1.03, 1.16). Conclusions Our results suggest that modest increases in exercise systolic blood pressure response are associated with adverse outcomes.