Background and Aim: Prehypertension is an increasingly highly prevalent condition in the general population, and is associated with an increased risk for coronary heart disease and stroke. However, evidence from population-based studies of the risk factors for prehypertension is scant. We sought to examine the predictors of progression from normotension to prehypertension in a community-based population from Western New York.Methods and Results: A longitudinal analysis, over 6 years of follow-up, among 569 men and women (mean age 51.8 years) who were free of prehypertension, hypertension, cardiovascular disease and diabetes at the baseline examination, in the Western New York Health Study (WNYHS). Incident prehypertension at follow-up was defined as systolic blood pressure of 120-139 mm Hg and/or diastolic blood pressure of 80-89 mm Hg.The cumulative six year incidence of prehypertension was 33.5% (189/564). In bivariate analyses, there were several correlates of incident prehypertension, including age, BMI and waist circumference, impaired fasting glucose (IFG), uric acid, and baseline blood pressure levels. After multivariate adjustment, IFG at baseline [odds ratio (OR): 1.70, 95% CI: 1.07-2.69) and weight gain since age 25 (OR: 1.12, 1.04-1.21 per 10 lb increase)] were the strongest significant predictors of prehypertension at follow-up. Neither baseline waist circumference nor change in BMI were predictor variables in models when they were substituted for weight gain.Conclusions: Results from this study suggest early dysregulation of glucose metabolism and weight gain over the lifespan may represent important risk factors for prehypertension in the general population. (C) 2013 Elsevier B.V. All rights reserved.

Background and aims: Glycoprotein 6 (GP6) is a platelet-specific collagen receptor implicated in the thrombotic pathway to acute myocardial infarction (AMI), but a possible genetic relationship between GP6 and AMI is poorly understood. We tested for the genetic association between AMI and single nucleotide polymorphisms (SNPs) in 24 loci, including GP6.Methods and results: We conducted a case-control study of AMI and GP6 in a community-based population (n = 652 cases, 625 controls). We also examined men and women separately and stratified the latter by use of hormone replacement therapy (HRT). Among both sexes, the strongest association was for a protective missense polymorphism (rs1163662) in the GP6 gene (OR = 0.70; Bonferroni-adjusted p < 0.05). SNPs in GP6 were also strongly associated with AMI among women who reported ever taking HRT, but not among women who never took HRT. Haplotype analyses were consistent with the single-SNP findings.Conclusions: In this sample of white non-Hispanic men and women, several SNPs in GP6 were significantly related to risk of AMI. Development of pharmacologic therapy directed towards platelet activity and thrombosis may reduce the incidence of AMI among at-risk groups. (c) 2009 Elsevier B.V. All rights reserved.

P>Objective: The exposure of tissue factor (TF) to blood flow is the initial step in the coagulation process and plays an important role in thrombogenesis. We investigated the role of genetic polymorphisms and haplotypes of the TF gene in the risk of ischemic vascular disease. Methods: Four hundred and twenty-two Italian patients with juvenile myocardial infarction (MI) and 434 controls, 808 US cases with MI and 1005 controls, 267 Italian cases with juvenile ischemic stroke and 209 controls and 148 German cases with juvenile ischemic stroke and 191 controls were studied. rs1361600, rs3917629 (rs3354 in the US population), rs1324214 and rs3917639 Tag single nucleotide polymorphisms were genotyped. Additionally, a meta-analysis of all previous studies on TF loci and the risk of ischemic coronary disease (ICD) was performed. Results: After multivariable analysis none of the SNPs, major SNP haplotypes or haplotype-pairs showed any consistent association with MI. Pooled meta-analysis of six studies also suggested that TF polymorphisms are not associated with CHD. A significant, independent association between SNP rs1324214 (C/T) and juvenile stroke was found in Italian and German populations (OR for TT homozygotes = 0.47, 95% CI 0.24-0.92, in combined analysis). Pooled analysis also showed a significant association for haplotype H3 (OR = 0.76, 95% CI 0.57-1.00) and haplotype-pair H3-H3 (OR = 0.43, 95% CI 0.20-0.92). Conclusions: TF genetic variations were associated with the risk of ischemic stroke at young age, but did not affect ischemic coronary disease.

We consider methods for estimating the maximum from a sequence of measurements of flow-mediated diameter of the brachial artery. Flow-mediated vasodilation (FMD) is represented using the maximum change from a baseline diameter measurement after the release of a blood pressure cuff that has been inflated to reduce flow in the brachial artery. The influence of the measurement error on the maximum diameter from raw data can lead to overestimation of the average maximum change from the baseline for a sample of individuals. Nonparametric regression models provide a potential means for dealing with this problem. When using this approach, it is necessary to make a judicious choice of regression methods and smoothing parameters to avoid overestimation or underestimation of FMD. This study presents results from simulation studies using kernel-based local linear regression methods that characterize the relationship between the measurement error, smoothing and bias in estimates of FMD. Comparisons between fixed or constant smoothing and automated smoothing parameter selection using the generalized cross validation (GCV) statistic are made, and it is shown that GCV-optimized smoothing may over-smooth or under-smooth depending on the heart rate, measurement error and measurement frequency. We also present an example using measured data from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) pilot study. In this example, smoothing resulted in lower estimates of FMD and there was no clear evidence of an optimal smoothing level. The choice to use smoothing and the appropriate smoothing level to use may depend on the application.

PURPOSE: The Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) study is one of the first population-based studies to integrate psychological, physiological, and subclinical measures of stress, disease, and mental dysfunction. This pilot study was undertaken to establish a methodology and descriptive results for a larger police study.METHODS: A stratified sample of 100 officers was randomly selected from the Buffalo, NY Police Department. Salivary cortisol served as a stress biomarker. Flow mediated dilation (FMD) and carotid intima-media thickness (IMT) were performed with ultrasound. Dual Energy X-Ray Absorptiometry (DEXA) and anthropometric measures assessed body composition. Self-report measures of depression and posttraumatic stress disorder (PTSD) were obtained.RESULTS: Recruitment attained for the study was 100%. Seventy-five percent showed a cortisol increase upon awakening, 90% a negative diurnal slope, and 77% an increased cortisol response after a high protein lunch challenge. Dexamethasone suppression was evident. FMD showed an increase in mean brachial artery diameter of 3.2% in men and 3.9% in women, and mean IMT was lower (male = 0.67 mm; female = 0.62. mm) compared to populations of similar age. For males, the mean body-mass index (BMI) was 29.8 kg/ in 2 and total body fat 23.4%. For females, the mean BMI was 26.7 kg/m(2) and total body fat 31.5%. For all officers, 16% met criteria for depression; 36% reported elevated PTSD symptoms.CONCLUSIONS: Compared to populations of similar age, police officers had slightly lower FMD, lower carotid IMT, elevated BMI, and higher reported rates of depression and PTSD. Standardized physiological and psychological data collection and descriptive results confirmed that the methodology of the study is feasible in a working police population.

To determine if nHDL (total (cid:2) HDL cholesterol) is a more useful predictor of CHD risk than LDL, using data from the Framingham Heart Study: N ¼ 5,794 (men ¼ 2,693; women ¼ 3,101). All Persons were age (cid:1) 30 yrs and free of CHD at baseline. Incident CHD was the endpoint. The risk of CHD was assessed based on the joint distribution of LDL & nHDL (mg/dl). The reference group included persons with LDL < 130 & nHDL < 160. The group LDL (cid:1) 160 & nHDL < 160 was excluded from the analyses due to a limited number. Cox-proportional hazards models were used to estimate the relative risk (RR) of CHD risk and the 95% confidence intervals (CI). A total of 990 incident CHD events (men ¼ 618, women ¼ 372) were recorded during 15 yr (average) of follow-up. After multivariate adjust- ment, within nHDL level no association was found between LDL and the risk of CHD; while within LDL level, a strong positive and graded association between nHDL and risk of CHD was observed [(group): RR (95% CI); (LDL 130–159 & nHDL < 160): 1.2 (0.88–1.51); (LDL < 130 & nHDL 160–189): 1.5 (1.02–2.09); (LDL 130–159 & nHDL 160– 189): 1.5 (1.23–1.85); (LDL (cid:1) 160 & nHDL 160–189): 1.7 (1.29–2.31); (LDL < 130 & nHDL (cid:1) 190): 2.4 (1.55–3.73); (LDL 130–159 & nHDL (cid:1) 190): 2.3 (1.72–3.01); (LDL (cid:1) 160 & nHDL (cid:1) 190): 2.3 (1.90–2.69)]. This analysis was repeated within TG level (TG: < 200 vs. (cid:1) 200 mg/dl) and the risk pattern did not change much. These results suggest that nHDL level is a stronger predictor of CHD risk than LDL, indicating that VLDL may play a critical role in the development of CHD. Purpose: To assess the reason for the relative high risk of women for local complications following cardiac catheterization by evaluating the associa-tions between gender, sheath size, and local adverse outcomes following cardiac catheterization. Methods: The data used in this study was obtained from a portion of the American College of Cardiology-National Cardiovas- cular Data Registry (cid:1) (ACC-NCDR (cid:1) ), which included 13,878 patients who underwent cardiac catheterization at one of 59 participating cardiac catheterization institutions throughout the United States during late 2003. Rates of serious local vascular adverse events were calculated by gender following cardiac catheterization, by type of vascular hemostasis used, stratified by arterial sheath size. Results: Serious local vascular events were reported in 3.54% of patients, most commonly hematoma (2.00%). The relative risk for women of any vascular complication was 1.40 [95% CI ¼ 1.17, 1.67, p ¼ .0002]. A statisticallysignificant relative riskfor woman was evident when collagen plug devices or manual compression alonewere used as the first method for hemostasis. The rate of vascular complications in-creased progressively with increasing sheath size, more so in women than in men. Conclusions: High relative risk for women of local vascular complications following cardiac catheterization was demonstrated with use of manual compression, as well as with collagen plug devices to control fem-oral artery bleeding. Large sheath size is associated with both a relatively high absolute risk and a high relative risk for women. Knowledge of this information should be considered by interventional cardiologists in making decisions on how to achieve hemostasis following cardiac catheterization. We examined the racial/ethnic disparities in the association of IR with LV dysfunction. Methods: The Multi-Ethnic Study of Atherosclerosis includes 6,814 men and women, aged 45–85 years of four race/ethnic groups: Whites, Blacks, Hispanics, and Chinese. Race/ethnicity was self-designated. The ho-meostasis model assessment (HOMA), an index of IR, was calculated using fasting glucose and insulin levels at baseline. Global LV function (left ventricular ejection fraction (LVEF), LV mass, and stroke volume) was measured by MRI. Regional LV dysfunction (systolic strain in four segments)was determined by tagged MRI. Linear regression models were used for the analysis. Results: The highest median IR (calculated using HOMA score) was observed in Hispanics (41.6%), followed by Blacks (33.1%), Chinese (19.0%), and Whites (10.6%). The differences between non-white ethnic groups and Whites remained significant after adjusting for age, gender, BMI, income, and education (p-values < 0.01).The magnitude of the negative association between IR and LVEF (co-efficient: (cid:2) 0.58, p: 0.02), the positive association between IR and LV mass (coefficient: 6.23, p < 0.01), and the negative association between IR and stroke volume (coefficient: (cid:2) 4.61, p < 0.01) were diminished in minority ethnic groups, although none of the interaction terms were statistically significant. IR was significantly associated with lower systolic strain in posterior, lateral, and septal segments in Whites and Hispanics but not in Blacks or Chinese. There were no differences among racial/ethnic groups in terms of the association of IR with systolic strain in anterior segment. Conclusion: There are significant disparities in IR among ethnic groups and these disparities are not fully explained by other covariates. IR is associated with global and regional LV function and this association is stronger in Whites and Hispanics than in Blacks and Chinese. and no-AMD, the corresponding prevalence of hypertension was 33%, 27% and 25%, and of diabetes was 5.0%, 4.7% and 4.5%. The 2-year incidence of stroke was 8.14%, 7.41%, and 6.35% among persons with wet-AMD, dry-AMD, and no-AMD. Ad- justing for age, sex, race, hypertension, and diabetes, the incident odds ratios (95% CI) of ischemic stroke were 1.20 (1.18, 1.23), 1.31 (1.26, 1.37), and 1.18 (1.15, 1.21), respectively, for the AMD, wet-AMD, and dry-AMD groups compared to the no-AMD group. These findings, if con- firmed by studies that control for smoking and other lifestyle factors, suggest that AMD is associated with higher risk of incident ischemic stroke, indicating the possibility of their shared etiological antecedents.

Periodontal disease has been associated with cardiovascular disease (CVD), and inflammation may represent a common pathophysiology. Oral health screening in the context of CVD risk assessment represents a potential opportunity to identify individuals at risk for CVD. The purposes of this study were to determine if self-reported oral health status is independently associated with inflammatory markers and if oral health assessment as part of CVD risk screening can identify at-risk individuals without traditional CVD risk factors. A baseline analysis was conducted among participants in the National Heart, Lung, and Blood Institute's Family Intervention Trial for Heart Health (FIT Heart; n = 421, mean age 48 ± 13.5 years, 36% nonwhite) without CVD or diabetes who underwent standardized assessment of oral health, lifestyle, CVD risk factors, and the inflammatory markers high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2. Statistical associations between oral health, risk factors, and inflammatory markers were assessed, and logistic regression was used to adjust for effects of lifestyle and potential confounders. Periodontal disease was independently associated with being in the top quartile of lipoprotein-associated phospholipase A2 compared with the lower 3 quartiles (odds ratio 1.9, 95% confidence interval 1.1 to 3.2) after adjustment for lifestyle and risk factors. Histories of periodontal disease were reported by 24% of nonoverweight, nonhypertensive, nonhypercholesterolemic participants, and of these participants, 37% had elevated high-sensitivity C-reactive protein (≥3 mg/L) or lipoprotein-associated phospholipase A2 (≥215 ng/ml) levels. In conclusion, self-reported periodontal disease is independently associated with inflammation and common in individuals without traditional CVD risk factors.

OBJECTIVE:To assess coronary heart disease (CHD) risk within levels of the joint distribution of non-HDL and LDL cholesterol among individuals with and without diabetes. RESEARCH DESIGN AND METHODS:We used four publicly available data sets for this pooled post hoc analysis and confined the eligible subjects to white individuals aged > or = 30 years and free of CHD at baseline (12,660 men and 6,721 women). Diabetes status was defined as either "reported by physician-diagnosed and on medication" or having a fasting glucose level > or = 126 mg/dl at the baseline examination. The primary end point was CHD death. Within diabetes categories, risk was assessed based on lipid levels (in mg/dl): non-HDL <130 and LDL <100 (group 1); non-HDL <130 and LDL > or = 100 (group 2); non-HDL > or = 130 and LDL <100 (group 3); and non-HDL > or = 130 and LDL > or = 100 (group 4). Group 1 within those without diabetes was the overall reference group. RESULTS:Of the subjects studied, approximately 6% of men and 4% of women were defined as having diabetes. A total of 773 CHD deaths occurred during the average 13 years of follow-up time. A Cox proportional hazard model was used to estimate the relative risk (RR) of CHD death. Those with diabetes had a 200% higher RR than those without diabetes. In a multivariate model, CHD risk in those with diabetes did not increase with increasing LDL, whereas it did increase with increasing non-HDL: RR (95% confidence interval) for group 1: 5.7 (2.0-16.8); group 2: 5.7 (1.6-20.7); group 3: 7.2 (2.6-19.8); and group 4: 7.1 (3.7-13.6). CONCLUSIONS:Non-HDL is a stronger predictor of CHD death among those with diabetes than LDL and should be given more consideration in the clinical approach to risk reduction among diabetic patients.

AIMS:Alcohol consumption has been associated with a reduced risk of heart disease incidence and mortality. However, most studies have focused on an average volume per specific time period and have paid little attention to the pattern of drinking. The aim of this study was to examine the association between various drinking patterns and myocardial infarction (MI).DESIGN:A population-based case-control study.METHODS:Participants were 427 white males with incident MI and 905 healthy white male controls (age 35-69 years) selected randomly from two Western New York counties. During computer-assisted interviews detailed information was collected regarding patterns of alcohol consumption during the 12-24 months prior to interview (controls) or MI (cases).FINDINGS:Compared to life-time abstainers, adjusted odds ratios (ORs) and 95% confidence interval (CI) for non-current and current drinkers were 0.66 (0.31-1.39) and 0.50 (0.24-1.02), respectively. Daily drinkers exhibited a significantly lower OR (0.41) compared to life-time abstainers. Participants who drank mainly without food had an OR of 1.49 (0.96-2.31) compared to those who drank mainly with food and 0.62 (0.28-1.37) compared to life-time abstainers. Men who reported drinking only at weekends had a significantly greater MI risk [1.91; (1.21-3.01)] compared to men who drank less than once/week, but not compared to life-time abstainers [0.91 (0.40-2.07)].CONCLUSIONS:Our results indicate that patterns of alcohol use have important cardiovascular health implications.

OBJECTIVES:To examine the relationship between markers of oxidative status and glucose on a population basis.STUDY DESIGN AND SETTING:We report here on a population-based sample of 1315 women and 981 men, aged 35-79 years, randomly selected from residents of Erie and Niagara Counties in western New York between 1996 and 1999. Thiobarbituric reactive substances (TBARS), erythrocyte glutathione (GSH) and plasma glutathione peroxidase (GSH-Px) were measured as markers of oxidative status. Study sample was categorized by quartiles of glucose, degree of abnormality of fasting glucose, and level of metabolic control in patients with diabetes.RESULTS:Men and women in the uppermost quartiles of glucose had higher levels of TBARS (men: Quartile 4 = 1.55 +/- 0.03, Quartile 1 = 1.36 +/- 0.03, women: 1.49 +/- 0.02, 1.30 +/- 0.02 nmol/ml) and lower levels of GSH (men: Quartile 4 = 1.57 +/- 0.03, Quartile 1 = 1.69 +/- 0.03, women: 1.71 +/- 0.03, 1.97 +/- 0.0 mmol/l packed RBCs). In women, compared with normal fasting glucose, impaired fasting glucose was associated with higher levels of TBARS (1.29 +/- 0.01 vs. 1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.85 +/- 0.02 vs. 1.76 +/- 0.05 mmol/l packed RBCs), and higher GSH-Px activity (618.94 +/- 2.64 vs. 644.77 +/- 8.90 IU/l). In women, abnormal fasting glucose was associated with higher levels of TBARS (1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.68 +/- 0.06 mmol/l packed RBCs), and higher levels of GSH-Px (647.72 +/- 9.87 IU/l) than normal or impaired fasting glucose. In men, abnormal fasting glucose was associated with higher TBARS (1.76 +/- 0.04 vs. 1.37 +/- 0.07 nmol/ml), and lower GSH (1.62 +/- 0.05 vs. 2.78 +/- 0.02 mmol/l packed RBCs), than normal fasting glucose. Poor metabolic control was associated with higher TBARS (men: 2.07 +/- 0.08 vs. 1.33 +/- 0.14 nmol/l, women: 2.02 +/- 0.09 vs. 1.35 +/- 0.18 nmol/l) and GSH-Px activity (men: 654.34 +/- 13.45 vs. 599.86 +/- 24.76, women: 660.61 +/- 13.25 vs. 579.42 +/- 27.42 IU/l).CONCLUSIONS:Glucose levels play a role in determining oxidative status in a population sample. The balance between oxidative and antioxidant processes appears to be sensitive to glucose levels with moderate elevations of glucose affecting the oxidative status.