高血压患者心血管危险因素与微血管功能及大动脉功能的关系

高血压是心血管疾病发生和死亡的主要危险因素,这可能与高血压所致动脉血管床功能及结构异常有关,高血压常引起微循环结构异常进而损害组织和靶器官,后者又反过来加重急/慢性缺血综合征及猝死.血管内皮功能障碍是高血压导致细小动脉和大动脉病变的共同特征.     

Biomarkers of left ventricular hypertrophy and remodeling in blacks

Left ventricular (LV) hypertrophy, a marker for adverse cardiovascular events, is more common in blacks than in non-Hispanic whites. Mechanisms leading to LV hypertrophy and mediating its clinical sequelae in blacks are not fully understood. We investigated the associations of 39 candidate biomarkers in distinct biological pathways with LV mass and geometry in blacks. Participants included 1193 blacks (63±9 years of age; 72% women; 78% hypertensive) belonging to hypertensive sibships. LV mass was measured by transthoracic echocardiography and indexed to height.(2.7) LV geometry was categorized as normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Generalized estimating equations were used to assess associations of the 39 biomarkers with LV mass index after adjustment for age, sex, and conventional risk factors. After adjustment for potential confounders, log-transformed levels of the following biomarkers were independently associated with LV mass index: N-terminal pro-brain natriuretic peptide (β±SE=0.07±0.01 pg/mL; P<0.0001), mid-regional pro-atrial natriuretic peptide (β±SE=0.08±0.02 pmol/L; P<0.0001), mid-regional pro-adrenomedullin (β±SE=0.09±0.03 nmol/L; P=0.0006), C-terminal pro-endothelin (β± SE=0.05±0.02 pmol/L; P=0.0009), and osteoprotegerin (β±SE=0.07±0.02 pg/mL; P=0.0005) (β is for 1 log increase in biomarker level). The associations of these biomarkers with LV mass index were mainly due to their association with eccentric hypertrophy. Higher circulating levels of natriuretic peptides, adrenomedullin, endothelin, and osteoprotegerin were associated with increased LV mass index, providing insights into the pathophysiology of LV hypertrophy in blacks.     

Relation of markers of inflammation (C-reactive protein, white blood cell count, and lipoprotein-associated phospholipase A2) to the ankle-brachial index

Markers of inflammation are predictive of cardiovascular events but their association with atherosclerotic burden remains poorly defined. We hypothesized that markers of inflammation, including C-reactive protein (CRP), white blood cell (WBC) count, and lipoprotein-associated phospholipase A2 (Lp-PLA2), would be associated with the ankle-brachial index (ABI), a marker of atherosclerotic burden. Subjects were 247 patients referred for lower extremity arterial evaluation to the non-invasive vascular laboratory excluding those with active infection or lower extremity revascularization within the previous year. ABI was measured at two sites in both legs and the lowest of four measurements was used in the analyses. CRP was measured by a high-sensitivity immunoturbidimetric assay and Lp-PLA2 was measured by ELISA. The mean patient age was 68+/-11 years, and 54% were men. Mean ABI was 0.84+/-0.31 and 49% had an ABI < 0.9. Age, hypertension, fasting plasma glucose, and 'ever' smoking were independently associated with the ABI. Spearman correlation coefficients of inflammatory markers with the ABI were: CRP (r = -0.15, p= 0.02), WBC count (r = -0.27, p = 0.001), and Lp-PLA2 (r = -0.09, p = 0.21). In a multiple regression model that included conventional risk factors and statin use, CRP and WBC count were no longer significantly associated with ABI, whereas Lp-PLA2 was a borderline-significant predictor of lower ABI (p = 0.05). These data indicate that CRP and WBC count are not independently associated with ABI, a marker of atherosclerotic burden in subjects referred for non-invasive lower extremity arterial evaluation. The association of Lp-PLA2 with ABI merits further study.     

Aortic augmentation index is inversely associated with cardiorespiratory fitness in men without known coronary heart disease

BACKGROUND: We investigated whether the aortic augmentation index (AIx), a measure of arterial wave reflection and stiffness, is associated with cardiorespiratory fitness in men without known coronary heart disease (CHD). METHODS: Asymptomatic men (n = 201, mean age 51 +/- 9.2 years) referred for a screening exercise electrocardiogram (ECG) underwent applanation tonometry to obtain radial artery pulse waveforms, and an ascending aortic pressure waveform was derived by a transfer function. The AIx is the difference between the first and second systolic peak of the ascending aortic pressure waveform, expressed as a percentage of the pulse pressure. Cardiorespiratory fitness was assessed by maximal oxygen consumption (VO2max mL/min/kg) during a symptom-limited graded exercise test. Multivariable regression analyses were used to identify significant independent determinants of AIx and of VO2 max. RESULTS: Diabetes was present in 2.5% of subjects, 34.8% had history of smoking, and 29% were hypertensive. Mean (+/- SD) AIx was 19.9% +/- 9.0% and mean VO(2 max) was 33.9 +/- 6.4 mL/min/kg. In a multivariable linear regression model, AIx was positively associated with age, hypertension, and history of smoking and inversely with heart rate, height, and body mass index (BMI). The VO2 max was significantly inversely related to AIx after adjustment for age, heart rate, height, and BMI (r = -0.22, P = .002), after further adjustment for CHD risk factors (total cholesterol, HDL-cholesterol, history of smoking, diabetes, hypertension) (P = .006), and after additional adjustment for behavioral factors (physical activity score, alcohol intake, and percent body fat) (P = .022). CONCLUSIONS: These findings indicate that AIx, a measure of arterial wave reflection and stiffness, is inversely associated with cardiorespiratory fitness in men without CHD.     

A novel quantitative trait locus on chromosome 1 with pleiotropic effects on HDL-cholesterol and LDL particle size in hypertensive sibships

BACKGROUND: High-density lipoprotein (HDL)-cholesterol, triglycerides, and LDL particle size are correlated lipid traits. Abnormal levels of these traits are frequent in hypertensive individuals and contribute to increased risk of coronary heart disease (CHD). We performed univariate and bivariate linkage analyses to identify genomic regions that influence levels of these traits and exert pleiotropic effects on the traits in hypertensive sibships. METHODS: Subjects included 691 non-Hispanic white individuals (mean age 63.1+/-8.5 years, 57% women, 78% hypertensive) ascertained through sibships with two or more individuals diagnosed with hypertension before age 60 years. The LDL particle size was measured by polyacrylamide gel electrophoresis and triglycerides were log-transformed to reduce skewness. Genotypes were measured at 366 microsatellite marker loci distributed across the 22 autosomes. Univariate and bivariate linkage analyses were performed using a variance components approach. RESULTS: Significant (P < .001) genetic correlations were confirmed for all pairwise combinations of the traits. Univariate linkage analyses demonstrated evidence of linkage (defined as multipoint LOD scores > or =1.3) for HDL-cholesterol on chromosomes 1p, 3p, 9q, and 18q; for log triglycerides on chromosome 10q; and for LDL particle size on chromosomes 2p and 8p. Pairwise bivariate linkage analyses of the three traits revealed a region with pleiotropic effects on HDL-cholesterol and LDL particle size on chromosome 1p (LOD score 4.48). CONCLUSIONS: These findings indicate the presence of a quantitative trait locus on chromosome 1 that has pleiotropic effects on HDL-cholesterol and LDL particle size and may therefore influence CHD susceptibility in hypertensive sibships.     

Mining peripheral arterial disease cases from narrative clinical notes using natural language processing

Objective

Lower extremity peripheral arterial disease (PAD) is highly prevalent and affects millions of individuals worldwide. We developed a natural language processing (NLP) system for automated ascertainment of PAD cases from clinical narrative notes and compared the performance of the NLP algorithm with billing code algorithms, using ankle-brachial index test results as the gold standard.

Methods for the selection of tagging SNPs: a comparison of tagging efficiency and performance

There is great interest in the use of tagging single nucleotide polymorphisms (tSNPs) to facilitate association studies of complex diseases. This is based on the premise that a minimum set of tSNPs may be sufficient to capture most of the variation in certain regions of the human genome. Several methods have been described to select tSNPs, based on either haplotype-block structure or independent of the underlying block structure. In this paper, we compare eight methods for choosing tSNPs in 10 representative resequenced candidate genes (a total of 194.2 kb) with different levels of linkage disequilibrium (LD) in a sample of European-Americans. We compared tagging efficiency (TE) and prediction accuracy of tSNPs identified by these methods, as a function of several factors, including LD level, minor allele frequency, and tagging criteria. We also assessed tagging consistency between each method. We found that tSNPs selected based on the methods Haplotype Diversity and Haplotype r2 provided the highest TE, whereas the prediction accuracy was comparable among different methods. Tagging consistency between different methods of tSNPs selection was poor. This work demonstrates that when tSNPs-based association studies are undertaken, the choice of method for selecting tSNPs requires careful consideration.