Few studies have examined the relationship between parental history of stroke and myocardial infarction (MI) and subclinical atherosclerosis, especially among young, asymptomatic individuals. This study investigates the association between coronary artery calcification (CAC) and parental history of stroke and MI in African-Americans and Caucasians from the CARDIA study.
Parental history of stroke and MI was determined by self-administered family history questionnaire at baseline and Year 5 examinations. Presence of coronary calcification was determined by computed tomography on 3041 individuals, age 32 to 47, including 1375 African-Americans and 1666 Caucasians. Analyses were restricted to individuals free of clinically manifest coronary heart disease (CHD) and stroke.
Parental history of stroke is associated with a two-fold greater risk of CAC in African-Americans, and this relationship is independent from established CHD risk factors (95% CI=1.14-3.43). There is no relationship between parental history of stroke and CAC status in Caucasians. Parental history of MI is associated with a two-fold greater risk of CAC in Caucasians (95% CI=1.38-2.92). The impact of parental history of MI in African-Americans is lower (OR=1.65; 95% CI=1.01-2.69) and no longer statistically significant after adjusting for known CHD risk factors.
The identification of individuals with a parental history of stroke and MI provides important information for clinicians by which to target primary prevention efforts. Further characterization of familial factors, especially genetic factors, contributing to increased risk of CAC will shed light on the basis of the observed associations.
"Several studies have found family history of stroke is a significant risk factor for coronary heart disease (Khaw et al., 1986; Vitullo et al., 1996; Wannamethee et al., 1996; Fornage et al., 2004; Scheuner et al., 2006). We found that a family history of stroke generally had no significant associations with the adjusted mean CACS estimates or with a positive CACS. "
[Show abstract][Hide abstract] ABSTRACT: To investigate the possibility that family history beyond early-onset coronary heart disease might contribute to coronary heart disease susceptibility, we studied associations between additional family history and the coronary artery calcium score.
Associations between coronary artery calcium score and self-reports of coronary heart disease, stroke, and diabetes in first-degree relatives of 5264 nondiabetic subjects were assessed using logistic and linear regression adjusting for risk factors; adjusted mean coronary artery calcium score estimates were determined by pooling results.
Family history of coronary heart disease alone and in combination with diabetes and/or stroke was significantly associated with a positive coronary artery calcium score compared with no family history with odds ratios ranging from 1.7 (95% CI: 1.3-2.3) to 1.9 (95% CI: 1.6-2.3) and adjusted mean coronary artery calcium score estimates ranging from 137 (95% CI: 101-173) to 184 (95% CI: 143-226). Associations between family history of coronary heart disease and coronary artery calcium score were significant regardless of age at onset, sex, lineage, or number of relatives with coronary heart disease. The association between family history of diabetes only and coronary artery calcium score was also significant (OR, 1.3; 95% CI: 1.1-1.7) with an adjusted mean coronary artery calcium score estimate of 122 (95% CI: 93-151). Generally, family history of stroke had nonsignificant associations with coronary artery calcium score.
Numerous family history variables in addition to early-onset coronary heart disease are associated with subclinical atherosclerosis. Our results have implications for improving coronary heart disease risk assessment.
Genetics in medicine: official journal of the American College of Medical Genetics 01/2009; 10(12):879-87. DOI:10.1097/GIM.0b013e31818e639b · 7.33 Impact Factor
"Our aim was to examine certain features of HUVECs isolated from healthy newborns with a strong family history of myocardial infarction, given that recent reports describe endothelial pro-atherogenic alterations already in early life    . We focused on the interplay of TNF-␣ and oxLDL with CD40 and CD40L, both molecules expressed on endothelial cells   and both, central to the inflammatory process in atherogenesis . "
[Show abstract][Hide abstract] ABSTRACT: Recent findings indicate that atherosclerosis, a chronic inflammatory process, might start during childhood. Nevertheless, the expression of inflammation-related molecules of endothelial cell isolated from healthy neonates with a strong family history of myocardial infarction (SFHMI) has been rarely analyzed.
Human umbilical vein endothelial cells (HUVECs) from children with SFHMI were assessed for the expression of CD40 and CD40L, in the presence of TNF-alpha and oxLDL. The intracellular content of CD80, CXCL8 and tissue factor by HUVECs stimulated with a CD40 agonist monoclonal antibody as well as monocytes/lymphocyte adhesion to TNF-alpha-stimulated HUVECs was also evaluated.
The basal expression of CD40 and CD40L was higher in SFHMI-positive HUVECs in comparison to controls. TNF-alpha and oxLDL upregulated the expression of CD40 and CD40L in SFHMI versus control HUVECs (p<0.001). The intracellular expression of CXCL8, tissue factor and CD80 was also higher than in controls, and the adhesion of lymphocyte- and monocyte-like cells augmented upon TNF-alpha stimulation.
It is possible that the modifications observed in the SFHMI-positive HUVECs, all of them relevant to the atherosclerosis process, may lead to early inflammatory reactions, thus contributing to the premature initiation of atherosclerotic lesions in these children.
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