The prevalence and correlates of subclinical atherosclerosis among adults with low-density lipoprotein cholesterol <70 mg/dL: The Multi-Ethnic Study of Atherosclerosis (MESA) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND AND AIMS: The prevalence and correlates of subclinical atherosclerosis when low-density lipoprotein cholesterol (LDL-C) levels are low remain unclear. Therefore, we examined the association of cardiovascular risk factors and subclinical atherosclerosis among individuals with untreated LDL-C <70 mg/dL. METHODS: We included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohorts. To optimize accuracy, LDL-C was calculated by the validated Martin/Hopkins equation that uses an adjustable factor for the ratio of triglycerides to very low-density lipoprotein cholesterol. We defined subclinical atherosclerosis as a coronary artery calcium (CAC) score >0 in the combined cohort or common carotid intima media thickness (cIMT) in the 4th quartile, using cohort-specific cIMT distributions at baseline. Logistic regression models examined the cross-sectional associations of cardiovascular risk factors and subclinical atherosclerosis. RESULTS: Among 9411 participants not on lipid lowering therapy, 263 (3%) had LDL-C <70 mg/dL (MESA: 206, ELSA: 57). Mean age in this population was 58 (SD 12) years, with 43% men, and 41% Black. The prevalence of CAC >0 in those with untreated LDL-C<70 mg/dL was 30%, and 18% were in 4th quartile of cIMT. In demographically adjusted models, only ever smoking was significantly associated with both CAC and cIMT. Similar results were obtained in risk factor-adjusted models (smoking: OR, 2.29; 95% CI, 1.10-4.80 and OR, 3.44; 95% CI, 1.41-8.37 for CAC and cIMT, respectively). CONCLUSIONS: Among middle-aged to older individuals with untreated LDL-C <70 mg/dL, subclinical atherosclerosis remains moderately common and is associated with cigarette smoking.

Associations of Cigarette Smoking With Subclinical Inflammation and Atherosclerosis: ELSA-Brasil (The Brazilian Longitudinal Study of Adult Health).

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 [hsCRP]) 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 hsCRP (ß=0.24, 0.19-0.29 mg/L; P<0.001) and carotid intima-media thickness (ß=0.03, 0.02-0.04 mm; P<0.001) and odds of ankle-brachial index ≤1.0 (odds ratio: 2.52; 95% confidence interval, 2.06-3.08; P<0.001) and CAC >0 (odds ratio: 1.83; 95% confidence interval, 1.46-2.30; P<0.001). Among former and current smokers, pack-years of smoking (burden) were significantly associated with hsCRP (P<0.001 and P=0.006, respectively) and CAC (P<0.001 and P=0.002, respectively). Among former smokers, hsCRP 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<0.01). Among current smokers, number of cigarettes per day (intensity) was positively associated with hsCRP (P<0.001) and CAC >0 (P=0.03) after adjusting for duration of smoking. CONCLUSIONS: Strong associations were observed between smoking status, burden, and intensity with inflammation (hsCRP) 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.