Family History as a Risk Factor for Peripheral Arterial Disease (PAD) and Carotid Artery Stenosis (CAS)

In the first part of this thesis we investigated whether a family history of peripheral arterial disease (PAD) and coronary heart disease (CHD) was associated with presence of PAD in a large case-control study. Cases and controls were identified from non-invasive vascular and stress ECG laboratories, respectively. We also assessed whether sibling history of atherosclerotic vascular disease was more strongly associated with PAD than parental history. We hypothesized that: i) a family history of PAD is a stronger risk factor of PAD than family history of CHD; ii) that sibling history of these PAD/CHD is a stronger risk factor than parental family history because of greater sharing of environmental factors between siblings.;We accomplished this by conducting a large case-control study. The study cohort included 2296 patients (69+/-10 y, 63% men) with PAD and 4390 controls (66+/-11 y, 62% men) identified from non-invasive vascular and stress ECG laboratories, respectively, from October 2006 to June 2012. PAD was defined as a resting/post-exercise ankle-brachial index (ABI) ≤0.9, a history of lower extremity revascularization, or having poorly compressible leg arteries. Controls were patients with normal ABI or without history of PAD. Family history of PAD was obtained using a detailed questionnaire and defined as having at least one first-degree relative who had undergone revascularization or stent placement for PAD before age 65. Logistic regression analyses were used to evaluate whether family history of PAD was associated with presence of PAD. Family history of PAD was present more often in PAD patients than in controls (10.3% vs. 4.9%, respectively) with a resulting odds ratio (OR) (95% confidence interval) of 2.20 (1.81-2.66). The association remained significant after adjustment for conventional risk factors; OR: 1.96 (1.60-2.42). Adjusted ORs were similar for sibling and parental history of PAD; 1.86 (1.45-2.37) and 2.29 (1.56-3.38), respectively. The association was stronger in younger individuals (age <68 y); adjusted OR: 2.46 (1.79-3.38) than in older individuals; adjusted OR: 1.61 (1.22-2.12). A greater number of affected relatives with PAD was also associated with higher odds of presence of PAD; adjusted OR: 1.86 (1.48-2.33) and 2.56 (1.60-4.11) for patients with 1 and ≥2 affected relatives with PAD, respectively. In conclusion, family history of PAD was associated with presence of PAD independent of conventional risk factors. The association was stronger in younger individuals and in those with ≥2 affected relatives.;In the second part of this thesis, we investigate whether family history of stroke or CHD was associated with the presence of carotid artery stenosis (CAS). We also assessed whether number of affected relatives with stroke or CHD was associated with CAS. In addition, we assessed whether parental vs. sibling history of atherosclerotic vascular disease confer a different risk of CAS. We hypothesized that: i) a higher number of affected relatives with stroke or CHD is associated with higher odds of CAS, ii) that sibling history of ischemic stroke or CHD is a stronger risk factor than parental family history because of greater sharing of environmental factors between siblings.;We evaluated 864 patients (72+/-8 y, 68% men) with severe CAS and 1698 controls (61+/-11 y, 55% men) referred for non-invasive vascular evaluation. Severe CAS was defined as having ≥70% stenosis in the internal carotid artery on ultrasound or history of carotid artery revascularization. Controls were patients without severe CAS or history of cerebrovascular disease or CHD. Family history of stroke and CHD was obtained using a detailed questionnaire and defined as having at least one first-degree relative who had stroke or CHD before age 65. Logistic regression analyses were used to evaluate whether family history of stroke or CHD were associated with presence of CAS, independent of conventional risk factors. Family history of stroke and CHD were present more often in severe CAS patients than in controls (19.8% and 50.6% vs. 10.9% and 33.7% respectively) with a resulting odds ratios (OR) (95% confidence interval) of 2.02 (1.11-2.53) and 2.01 (1.70-2.37), respectively. The associations were weakened but remained significant after adjustment for age, sex, body mass index, smoking, diabetes, hypertension and dyslipidemia; ORs: 1.41 (1.06-1.90) and 1.69 (1.35-2.10), respectively. A greater number of affected relatives with stroke or CHD were associated with higher odds of CAS; adjusted ORs: 1.25 (0.91-17.2) and 1.46 (1.36-1.89) vs. 2.65 (1.35-5.40) and 2.13 (1.57-2.90) for patients with 1 and ≥2 affected relatives with stroke and CHD, respectively. In conclusion, family history of stroke and CHD are associated with presence of severe CAS independent of conventional risk factors. Further work is needed to assess the utility of screening carotid ultrasound for patients with such history.;The results of this study indicate that family history of atherosclerotic vascular disease is a significant risk factor for PAD and CAS, independent of conventional risk factors. In addition, we found that individuals with greater number of affected relatives are at higher risk. (Abstract shortened by UMI.).