Blood pressure stress reactivity and left ventricular mass in a random community sample of African-American and caucasian men and women

Exaggerated blood pressure (BP) reactivity to stress may contribute to left ventricular (LV) hypertrophy, a major risk factor for cardiovascular morbidity. This study examined the extent to which BP responses to acute stress are associated with LV mass and relative wall thickness in a community sample of African-American and white men and women. BP was measured at rest and in response to 2 acute challenges (mental arithmetic and handgrip). Systolic BP at rest was positively associated with LV mass and relative wall thickness (p < 0.001). The associations between the responses to the stressors and LV mass were not significant. African-American and white men who exhibited high BP responses to the arithmetic stressor had greater relative wall thickness than those with low reactivity (p < 0.05). In conclusion, BP reactivity is not related to LV mass, but may be related to concentric remodeling.     

Crystal structure of a human CD3-epsilon/delta dimer in complex with a UCHT1 single-chain antibody fragment

The alpha/beta T cell receptor complex transmits signals from MHC/peptide antigens through a set of constitutively associated signaling molecules, including CD3-epsilon/gamma and CD3-epsilon/delta. We report the crystal structure at 1.9-A resolution of a complex between a human CD3-epsilon/delta ectodomain heterodimer and a single-chain fragment of the UCHT1 antibody. CD3-epsilon/delta and CD3-epsilon/gamma share a conserved interface between the Ig-fold ectodomains, with parallel packing of the two G strands. CD3-delta has a more electronegative surface and a more compact Ig fold than CD3-gamma; thus, the two CD3 heterodimers have distinctly different molecular surfaces. The UCHT1 antibody binds near an acidic region of CD3-epsilon opposite the dimer interface, occluding this region from direct interaction with the TCR. This immunodominant epitope may be a uniquely accessible surface in the TCR/CD3 complex, because there is overlap between the binding site of the UCHT1 and OKT3 antibodies. Determination of the CD3-epsilon/delta structure completes the set of TCR/CD3 globular ectodomains and contributes information about exposed CD3 surfaces.     

Genome-wide linkage analyses for age at diagnosis of hypertension and early-onset hypertension in the HyperGEN study

A genome-wide scan was performed to identify chromosomal regions related to age at diagnosis of hypertension and to early-onset hypertension in white and African American families from the Hypertension Genetic Epidemiology Network (HyperGEN). Age at diagnosis of hypertension was reported by participants at recruitment and standardized residuals adjusted for sex, study center, and body mass index were created. Participants were classified as having early-onset hypertension if their reported age at diagnosis was before 45 years in whites or before 35 years in African Americans. Variance component linkage analysis was performed for age at diagnosis and an affected sibpair linkage analysis was performed for early-onset hypertension, both implemented in GENEHUNTER. In whites, the heritability of diagnosis age was estimated to be 35% and the maximum LOD score was found on chromosome 1 at 123 cM (LOD = 1.48). The maximum LOD score for early-onset hypertension was located on chromosome 18 at 69 cM (LOD = 1.21). In African Americans, the heritability of age of diagnosis was estimated to be 42% and the maximum LOD scores were found on chromosome 4 at 120 cM (LOD = 2.44) and on chromosome 15 at 60 cM (LOD = 2.31). The maximum LOD for early-onset hypertension in African Americans was also on chromosome 4 at 153 cM (LOD = 2.05) and overlies the mineralocorticoid receptor. Although these results report modest LOD scores, several of these loci have been previously reported to be linked to hypertension and blood pressure, lending further support that genes related to the risk of hypertension may be at these loci.     

Effect of influenza vaccine on markers of inflammation and lipid profile

Despite wide use of the influenza vaccine, relatively little is known about its effect on the measurement of inflammatory markers. Because inflammatory markers such as C-reactive protein (CRP) are increasingly being used in conjunction with lipids for the clinical assessment of cardiovascular disease and in epidemiologic studies, we evaluated the effect of influenza vaccination on markers of inflammation and plasma lipid concentrations. We drew blood from 22 healthy individuals 1 to 6 hours before they were given an influenza vaccination and 1, 3, and 7 days after the vaccination. Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. There was a significant increase in mean IL-6 (P < .01 absolute values, P < .001 normalized values) on day 1 after receiving the influenza vaccine. The mean increases in normalized high sensitivity CRP values were significant on day 1 (P < .01) and day 3 (P = .05), whereas the mean increase in normalized serum amyloid A was significant only on day 1 (P < .05). No significant changes were seen in mean concentrations of IL-2 soluble receptor alpha, monocyte chemotactic protein-1, or tumor necrosis factor-alpha. Of the lipids, significant decreases in mean concentrations of normalized triglyceride values were seen on days 1 (P < .05), 3 (P < .001), and 7 (P < .05) after vaccination. Our findings show that the influenza vaccination causes transient changes in select markers of inflammation and lipids. Consequently, clinical and epidemiologic interpretation of the biomarkers affected should take into account the possible effects of influenza vaccination.     

Arterial stiffness is greater in African Americans than in whites: evidence from the Forsyth County, North Carolina, ARIC cohort

BACKGROUND: Impairment of arterial dilation is thought to occur earlier than arterial wall thickening in the atherosclerotic process. In comparison with whites, African Americans reportedly have a generalized attenuation of their vasodilation mechanisms. We set out to evaluate arterial stiffness and its correlates by ethnicity, hypothesizing that African Americans would have stiffer common carotid arteries (ie, lower arterial distension for a given systolic pressure) than their white counterparts. METHODS: The study population included 268 African Americans and 2459 whites, who were aged 45 to 64 years at baseline examination in 1986 to 1989, free of coronary heart disease and stroke/transient ischemic attack, from Forsyth County, North Carolina. The beta stiffness index and pulsatile arterial diameter change were derived from brachial blood pressure and from echo-tracked systolic and diastolic carotid arterial diameters. RESULTS: African Americans had stiffer carotid arteries than their white counterparts, with a right shift of the beta stiffness index distribution. After adjustment for selected cardiovascular risk factors, the mean beta stiffness index was 9% higher for African Americans (mean +/- SEM: 11.3 +/- 0.3) than for whites (mean +/- SEM: 10.3 +/- 0.1) among participants not taking antihypertensive medication. Socioeconomic status and comorbidities were differentially associated with arterial stiffness by ethnicity. Specifically, the association between these correlates and beta stiffness index was stronger in African Americans than in whites. CONCLUSIONS: This report on arterial mechanics in African Americans suggests that large artery stiffening either occurs earlier, or is more accelerated in African Americans than in whites in our sample, perhaps as a result of earlier exposure to multiple risk factors. This finding may have implications for hypertension prevention, as arterial stiffness is associated with the development of hypertension.     

Influence of leisure time physical activity and television watching on atherosclerosis risk factors in the NHLBI Family Heart Study

Physical activity favorably influences atherosclerosis risk factors but only a few studies in adults considered the time watching television (TV) as a measure of physical inactivity. We therefore determined in a population-based sample of 1778 subjects from the NHLBI Family Heart Study (FHS) whether leisure time physical activity and TV watching have independent or interactive associations with cardiovascular disease risk factors and carotid artery intima-media wall thickness (IMT). Subjects were free from diabetes mellitus and clinically-ascertained coronary artery disease and did not take lipid-lowering or antihypertensive drugs. Only 0.7 and 1.3% of the variance in leisure time physical activity in women and men, respectively, was explained by the amount of TV watching. Leisure time physical activity had a clearly favorable, and TV watching an unfavorable association with anthropometric measurements (BMI (body mass index), waist girth, waist-hip ratio, subscapular and triceps skinfold thickness). The odds ratio (95% CI) of being overweight was 0.41 (0.28-0.62) in women and 0.69 (0.46-1.04) in men in the highest quartile of leisure time physical activity compared to the lowest quartile. The odds ratio increased for increasing quartiles of TV watching to 2.12 (1.45-3.10) in women and 1.61 (1.07-2.43) in men. Watching TV only 1 h per day in women with a BMI of 30 kg/m2 and doing about 75 min of moderate exercise per week was associated with a BMI 1.8 kg/m2 lower than in women watching TV 3 h per day and doing the same amount of exercise. Those with twice the amount of moderate exercise and watching TV 1 h per day had a BMI 0.45 kg/m2 lower. Furthermore, leisure time physical activity was negatively associated with concentrations of triglycerides and positively with HDL cholesterol in both genders. TV watching was significantly positively associated with triglycerides and slightly negatively with HDL cholesterol in men. The observed associations of leisure time physical activity and TV watching with atherosclerosis risk factors were independent from each other. Finally, we analyzed the relation between leisure time physical activity, TV watching and the degree of IMT of the carotid arteries. Neither of these two measures was significantly associated with IMT. In summary, TV watching, in addition to leisure time physical activity, shows an independent association with obesity-related anthropometric measurements, HDL and triglycerides. Decreasing the amount of TV watching might be effective as a first step in reducing atherosclerosis risk factors, especially overweight.     

Gender difference in diastolic function in hypertension (the HyperGEN study)

Although several studies indicate that there are gender differences in left ventricular (LV) systolic function, it remains unclear whether similar differences exist with regard to diastolic function. Accordingly, Doppler echocardiograms were analyzed in 515 male and 839 female, mostly treated (95%) hypertensive participants enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) study with no evidence of abnormal wall motion or significant valvular heart disease. There was no difference in age between genders, but after adjusting for age and race, men had lower body mass indexes (29.8 +/- 5.2 vs 32.3 +/- 7.6 kg/m(2)) and heart rates (67 +/- 12 vs 69 +/- 11 beats/min) and higher systolic and diastolic blood pressures (BP) than women (134 +/- 20 vs 130 +/- 21 and 80 +/- 11 vs 72 +/- 11 mm Hg, all p <0.001). LV mass/height(2.7) was slightly greater in women than in men (43 +/- 10 vs 42 +/- 9 g/m(2.7), p <0.05). After adjusting for age, race, systolic BP, body mass index, heart rate, and LV hypertrophy, both mitral E-wave (70 +/- 18 vs 77 +/- 19) and A-wave (74 +/- 15 vs 79 +/- 17, both p <0.001) velocities were lower in men than in women, but the mitral E/A ratio and atrial filling fraction were nearly identical in both genders. Deceleration time (221 +/- 55 vs 214 +/- 46 cm/s, p = 0.018) and isovolumic relaxation time (IVRT) were longer in men than in women (85 +/- 18 vs 81 +/- 17 cm/s, p <0.001). Prolonged IVRT was present in more men than women (14% vs 7%, p <0.05). In analyses of covariance, adjusting for age, race, systolic BP, body mass index, heart rate, and medications, male gender remained related to prolonged deceleration time and IVRT. Thus, in this population-based sample of hypertensive adults, men had evidence of slower early diastolic LV filling than women. This gender difference in diastolic function may provide insight into gender differences in congestive heart failure and other specific cardiovascular diseases.     

Hostility, social support, and carotid artery atherosclerosis in the National Heart, Lung, and Blood Institute Family Heart Study

This cross-sectional study investigates the association of hostility and social support (measured by standardized instruments) to carotid artery atherosclerosis in men and women with a high familial risk for coronary heart disease (CHD) and those with low to medium risk. The hypothesis was that high hostility and low social support would have a stronger association in subjects with a familial predisposition to CHD. There were 535 low- to medium-risk women, 491 low- to medium-risk men, 1,950 high-risk women, and 1,667 high-risk men in the study. The extent of carotid artery atherosclerosis was assessed by B-mode ultrasound imaging. A lesion was defined as an intimal-medial far wall thickness of 1 mm in the common, internal, or carotid bifurcation, or identification of plaque at any site. Odds ratios and their 95% confidence intervals were calculated using generalized estimating equations (GEE) for logistic regression. Family was specified as the clustering variable, and robust SEEs were obtained that account for dependence of the data within families. After controlling for age, education, body mass index, ever having smoked, ever drinking > 5 drinks a day, and metabolic index, hostility was significantly associated with increased odds of carotid lesions in only high-risk women. High-risk women showed a significantly reduced odds of carotid lesions with high social support, but the extent of this protection was reduced when age and education were included in the equation. A combination of high hostility and low social support was associated with higher odds than hostility alone in both high-risk men and women. These results suggest that women with a high familial predisposition for CHD may be more vulnerable to cardiovascular influences from hostility and social support than high-risk men or men and women with low to medium risk.     

Genome-wide linkage mapping for valve calcification susceptibility loci in hypertensive sibships: the Hypertension Genetic Epidemiology Network Study

It remains unclear whether genetic factors contribute to the susceptibility to valve calcification. Accordingly, echocardiograms and genotyping were performed in 1871 hypertensive siblings who participated in the Hypertension Genetic Epidemiology Network Study. Genome-wide affected sibpair nonparametric linkage analysis was conducted using the allele-sharing method implemented in the Merlin computer program. A total of 1014 sibships from 858 families were evaluated for aortic valve sclerosis or mitral annular calcification. Of these, 78 sibships from 68 families contained > or =2 affected siblings with > or =1 type of valve calcification (142 affected siblings). All 3 of the traits showed a modest degree of familial aggregation, with sibling recurrence risk (SD) and sibling recurrence risk ratio (95% CI) being 0.25 (0.035) and 2.31 (1.72 to 3.11) for aortic valve sclerosis, 0.25 (0.035) and 1.78 (1.36 to 2.33) for mitral annular calcification, and 0.31 (0.030) and 1.52 (1.24 to 1.85) for aortic valve sclerosis and mitral annular calcification, respectively. Affected sibpair linkage analysis revealed the highest logarithm of odds score (3.14) in chromosome 16 at 105.6 cM for aortic valve sclerosis. Other chromosomal regions with logarithm of odds score > or =1.9 were found in chromosomes 19 (2.88), 16 (2.63), 1 (2.12), and 2 (2.03) for aortic valve sclerosis and chromosome 13 (2.12) for any valve calcification. There was no logarithm of odds score > or =1.9 for mitral annular calcification. Our study shows strong linkage of aortic valve sclerosis to chromosome 16q22.1-q22.3 and suggestive linkage to chromosome 19p13.11-p11 and identifies several other promising genomic regions that may contain specific susceptibility loci for valve calcification.