Hypertension
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Transgenic mice with endothelium-specific endothelin-1 (ET-1) overexpression exhibit endothelial dysfunction and vascular remodeling, oxidative stress, and inflammation. We previously observed that monocytes/macrophages play a role in angiotensin II, aldosterone, and deoxycorticosterone acetate/salt-induced vascular remodeling, oxidative stress, and inflammation using a model with reduced monocytes/macrophages, the osteopetrotic (Op) mouse, which has a mutation in the macrophage colony stimulating factor (Csf1) gene. However, it is unknown whether monocytes/macrophages are implicated in adverse vascular effects of ET-1. ⋯ ET-1-induced oxidative stress measured by dihydroethidium staining (P<0.05) and NADPH oxidase activity assessed with lucigenin chemiluminescence (P<0.05) were blunted by CSF1 deficiency. ET-1 caused a 2.5-fold increase in monocyte/macrophage infiltration compared with wild-type mice (P<0.001), which was blunted in the mice deficient in CSF1. Reduction of monocyte/macrophage-dependent inflammation in mice overexpressing ET-1 in endothelium results in reduced vascular remodeling and oxidative stress, providing evidence for a role of monocytes/macrophages and innate immunity in ET-1-induced vascular injury.
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Comparative Study
Body fat is associated with reduced aortic stiffness until middle age.
Obesity is a major risk factor for cardiometabolic disease, but the effect of body composition on vascular aging and arterial stiffness remains uncertain. We investigated relationships among body composition, blood pressure, age, and aortic pulse wave velocity in healthy individuals. Pulse wave velocity in the thoracic aorta, an indicator of central arterial stiffness, was measured in 221 volunteers (range, 18-72 years; mean, 40.3±13 years) who had no history of cardiovascular disease using cardiovascular MRI. ⋯ In multivariate analysis, after adjustment for age, sex, and mean arterial blood pressure, elevated body fat% was associated with reduced aortic stiffness until the age of 50 years, thereafter adiposity had an increasingly positive association with aortic stiffness (β=0.16; P<0.001). Body fat% was positively associated with cardiac output when age, sex, height, and absolute lean mass were adjusted for (β=0.23; P=0.002). These findings suggest that the cardiovascular system of young adults may be capable of adapting to the state of obesity and that an adverse association between body fat and aortic stiffness is only apparent in later life.
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Comparative Study
Four-limb blood pressure as predictors of mortality in elderly Chinese.
The predictive value of blood pressure (BP) for cardiovascular morbidity and mortality diminishes in the elderly, which may be confounded and compensated by the BP differences across the 4 limbs, markers of peripheral arterial disease. In a prospective elderly (≥60 years) Chinese study, we performed simultaneous 4-limb BP measurement using an oscillometric device in the supine position, and calculated BP differences between the 4 limbs. At baseline, the mean age of the 3133 participants (1383 men) was 69 years. ⋯ In categorical analyses, similar results were observed for a decreased ankle-brachial index (≤0.90, ≤0.95, or ≤1.00) or increased interarm or interankle difference (≥15 mm Hg or ≥10 mm Hg). In conclusion, in the elderly, above and beyond arm BP level and together with ankle-brachial index, the interarm and interankle BP differences improve prediction of mortality. Simultaneous 4-limb BP measurement has become feasible with current technology and might be useful in cardiovascular prevention.
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Comparative Study
Maternal cardiovascular risk profile after placental abruption.
The prevalence of premature cardiovascular diseases (CVD) is increased in women with a history of maternal placental syndromes, including pregnancy-associated hypertensive disorders (eg, preeclampsia), fetal growth restriction, and placental abruption. Whereas previous studies have shown a high prevalence of CVD risk factors after pregnancies complicated by preeclampsia, this has not been studied for women with a history of placental abruption. To explore the association of placental abruption with CVD risk factors after delivery, we compared 75 women with a history of placental abruption with a control group of 79 women with uneventful pregnancies at 6 to 9 months postpartum for the presence of common CVD risk factors. ⋯ Women with previous placental abruption had significantly higher mean systolic blood pressure, body-mass index, fasting blood glucose, C-reactive protein, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol as compared with controls with only uneventful pregnancies. In the subanalysis, all differences remained significant for women with a history of placental abruption only (ie, without concomitant gestational hypertension), except for the associations with low-density lipoprotein-cholesterol and diastolic and systolic blood pressure. Most likely, the identified CVD risk factors predispose to placental abruption and development of premature CVD later in life.
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Recent genome-wide association studies have identified genetic variants associated with blood pressure (BP). We investigated whether genetic risk scores (GRSs) constructed of these variants would predict incident cardiovascular disease (CVD) events. We genotyped 32 common single nucleotide polymorphisms in several Finnish cohorts, with up to 32,669 individuals after exclusion of prevalent CVD cases. ⋯ Hazard ratios comparing the highest quintiles of systolic BP and diastolic BP GRSs with the lowest quintiles after adjustment for age, age squared, and sex were 1.25 (1.07-1.46; P=0.006) and 1.23 (1.05-1.43; P=0.01), respectively, for incident coronary heart disease; 1.24 (1.01-1.53; P=0.04) and 1.35 (1.09-1.66; P=0.005), respectively, for incident stroke; and 1.23 (1.08-1.40; P=2 × 10(-6)) and 1.26 (1.11-1.44; P=5 × 10(-4)), respectively, for composite CVD. In conclusion, BP findings from genome-wide association studies are strongly replicated. GRSs comprising bona fide BP-single nucleotide polymorphisms predicted CVD risk, consistent with a lifelong effect on BP of these variants collectively.