Abstract
Background and Objectives:
Subclinical atherosclerotic plaque is an important marker of increased vascular risk. Traditional risk factors explain less than 50% of the variance in atherosclerotic carotid plaque (ACP). Identifying factors underlying unexplained ACP, either deleterious or protective, may help targeting preventive strategies with significant scientific impact and health relevance. We aimed to identify individuals with unexplained subclinical ACP or unexplained protection against ACP using 2-D high-resolution B-mode carotid ultrasound.
Methods:
As a part of the NINDS carotid imaging project of the Northern Manhattan Study, 1,790 stroke-free individuals (mean age 69±9; 60% women; 61% Hispanic, 19% black, 18% white) were assessed for total ACP burden (TACP), the sum of plaque areas in all carotid arteries (mm
2
) within an individual and transformed using a cube root function (x
1/3
) for normality. Multiple linear regression models were conducted: (1) including pre-specified traditional risk factors (age, sex, LDL-cholesterol, diabetes, pack-years of smoking, blood pressure (BP), and treatment for BP); and (2) the best-fit model with addition of socioeconomic and less traditional factors including inflammation biomarkers and homocysteine. The standardized TACP residual scores were constructed from the best-fit regression model to select individuals with unexplained TACP.
Results:
Prevalence of carotid plaque was 58%. Mean TACP was 12.1±mm
2
before the x
1/3
transformation. Traditional model (model 1) explained 21% of the variance in TACP (
R
2
=
0.21). Age (15%), smoking (3%), systolic BP (1.2%), and diabetes (1%) were most contributing factors. The best-fit model (model 2) explained 23% of TACP, with most contribution by age (14%), smoking (3%), systolic BP (1%), fasting glucose (1%), LDL:HDL ratio (1%), diastolic BP (1%), homocysteine (1%) and white blood cell count (1%).
Conclusion:
Variation in subclinical carotid plaque is largely unexplained by traditional and novel risk cardiovascular risk factors. Identification of genetic and environmental factors underlying unexplained subclinical atherosclerosis is of utmost importance for successful prevention of cardiovascular disease and stroke.