Early Carotid Atherosclerosis and Family History of Vascular Disease

Abstract

Objective-Carotid artery intima-media thickness (IMT) is an intermediate phenotype for atherosclerosis. In a community population (nϭ5400), we determined whether a parental history of myocardial infarction (MI) or stroke is associated with increased IMT and whether associations differ at specific sites in the carotid arterial tree. Methods and Results-Using regression modeling, the proportion of IMT that remains unexplained after controlling for vascular risk factors was determined. A parental history of stroke was associated with both increased common carotid artery (CCA) and increased internal carotid artery (ICA)-IMT, but in young individuals (Յ60 years of age), the association was stronger with ICA-IMT, with an odds ratio (95% CI) for ICA-IMT in the highest quartile of 2. been widely used to study genetic and other novel risk factors for atherosclerosis is carotid artery intima-media thickness (IMT). This can be estimated noninvasively using ultrasound and seems to reflect subclinical atherosclerosis. Crosssectional studies have shown that increased common carotid IMT is both a marker of atherosclerosis elsewhere in the arterial system 3 and an independent predictor of future stroke and myocardial infarction (MI) risk. 4 -6 Carotid IMT measurements are increasingly being used as an intermediate phenotype for genetic studies of vascular disease. 7-9 Their use has several advantages. First, the number of genes involved in this intermediate phenotype are likely to be considerably less than those involved in ischemic stroke or MI. Second, the technique can be readily applied to large-scale community-based populations, reducing selection bias. Third, the use of a continuous index of risk rather than a dichotomous variable such as stroke and the related avoidance of nonpenetrance of asymptomatic disease markedly increase power.IMT measurements are strongly influenced by conventional risk factors. 10 This may complicate and reduce the power of studies to investigate genes that independently increase IMT rather than those that merely predispose to conventional risk factors. Spence et al 11 devised a novel method of combining quantitative measures of carotid plaque area measured by ultrasound and linear regression modeling to determine unexplained atherosclerosis, ie, the proportion of atherosclerosis that remains unexplained after controlling for conventional vascular risk factors. This approach was then used to identify subjects with novel risk factors for atherosclerosis, in this case, elevated homocysteine. 11 A drawback of this method is that measurements can only be obtained in subjects with established carotid plaque, and it is therefore not applicable to a general community population. We have applied this method to carotid IMT measurements instead of plaque area, using similar regression modeling, to determine the extent of IMT that remains unexplained by conventional

Intima-Media Thickness Side Differences Are Limited to the Common Carotid Artery

“…1 We do not completely agree with the interpretation of the reported findings. Based on an analyses of the Carotid Atherosclerosis Progression Study community-based sample of 6972 subjects (age 51.0Ϯ12.9 years, 50.8% female), 2,3 we confirm the finding of a significantly higher CCA-IMT on the left side (0.716Ϯ0.165 mm versus 0.688Ϯ0.147 mm; PϽ0.001). This was also the case in hypertensive patients (nϭ1399; 0.786Ϯ0.201 mm versus 0.751Ϯ0.169 mm; PϽ0.001).…”

Carotid Intima-Media Thickening Indicates a Higher Vascular Risk Across a Wide Age Range

“…9,10 All members of a German primary healthcare scheme (nϭ32 708), living within a 50 km radius of 5 study sites in Western Germany, were invited to participate. Within a predefined time limit, 6962 people (21.3%) agreed to take part.…”

“…Details of the risk-factor assessment protocol have already been published. 9,10 Follow-up events were identified from the primary healthcare scheme records. Every time medical care was sought, the healthcare scheme was notified of the date and corresponding ICD code.…”

Coronary artery calcification and family history of premature coronary heart disease. Sibling history is more strongly associated than parental history

“…19 To the best of our knowledge, none of the other published literature describing the relation of FH of premature CHD with subclinical atherosclerosis has shown a varied effect with the age of the participants. 8,20 In our study, a slightly higher association, although not statistically significant, of a FH of premature CHD with CAC was observed in the older individuals (men Ն55 years, women Ն65 years): First, the results may imply a time-dependent expression of genes, a gene-environment interaction, or a familial aggregation of environmental factors 19 ; second, survival and selection biases might have occurred as subjects with a positive FH might have clinically manifested CHD at early ages and thus were excluded from our study. 20 The risk of FH of premature CHD on the manifestation of subclinical atherosclerosis and clinical CHD with aging needs to be further evaluated in longitudinal studies.…”

“…the association of FH to be similar in both genders with CAC, and this is consistent with reports describing the association of FH with subclinical athersclerosis. 8,19,20 Finally, individuals with a positive FH may also be more susceptible to the deleterious effects of the traditional risk factors and may have greater atherosclerosis risk through smoking or dyslipidemia than individuals with similar risk factor exposure but without a family history. 34 Consistent with other reports, we found traditional risk factors to be equally predictive of CHD risk for persons with and without a FH of premature CHD.…”