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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2004.08.002 Byline: Stephen P. Glasser (a), Theophilus J. Gana (b), Luz G. Pascual (b), Kenneth S. Albert (b) Abstract: The efficacy and safety of a once-daily graded-release diltiazem hydrochloride (GRD) formulation dosed at 10 pm in doses of 180, 360, and 420 mg were compared with placebo and with GRD 360 mg dosed once daily at 8 am in patients (n = 311) with chronic stable angina pectoris. Author Affiliation: (a) Department of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Ala (b) Clinical Development Department, Biovail Corporation, Chantilly, Va Article History: Received 31 December 2003; Accepted 4 August 2004

Orthostatic changes in systolic blood pressure (SBP) impact cardiovascular outcomes. In this study, we aimed to determine the pattern of orthostatic systolic pressure changes in participants enrolled in the SBP Intervention Trial (SPRINT) at their baseline visit before randomization and sought to understand clinical factors predictive of these changes. Of the 9323 participants enrolled in SPRINT, 8662 had complete data for these analyses. The SBP after 1 minute of standing was subtracted from the mean value of the three preceding seated SBP values. At the baseline visit, medical history, medications, anthropometric measures, and standard laboratory testing were undertaken. The mean age of SPRINT participants was 68 years, two-thirds were male, with 30% black, 11% Hispanic, and 55% Caucasian. The spectrum of SBP changes on standing demonstrated that increases in SBP were as common as declines, and about 5% of participants had an increase, and 5% had a decrease of >20 mm Hg in SBP upon standing. Female sex, taller height, more advanced kidney disease, current smoking, and several drug classes were associated with larger declines in BP upon standing, while black race, higher blood levels of glucose and sodium, and heavier weight were associated with more positive values of the change in BP upon standing. Our cross-sectional results show a significant spectrum of orthostatic SBP changes, reflecting known (eg, age) and less well-known (eg, kidney function) relationships that may be important considerations in determining the optimal target blood pressure in long-term outcomes of older hypertensive patients. [ABSTRACT FROM AUTHOR]

Background The association between lipid levels and stroke rates is less than lipid levels and coronary heart disease (CHD). Objective. To assess if there are geographic, racial, and ethnic differences in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride levels with incident stroke. Methods From the RE asons for G eographic A nd R acial D ifferences in S troke (REGARDS) study we evaluated baseline levels of LDL-C, HCL-C, TC, Non-HDL-C (Total-HDL-C) and triglycerides in participants free of prevalent stroke at baseline. Cox Proportional-Hazard models were the main analytical tool used to examine the association between incident stroke and lipids. For each adjusted lipid measure (LDL-C, HDL-C, triglycerides, TC, and non-HDL-C) we calculated a series of incremental models. Results The analysis cohort was 23,867 participants with a mean follow-up time of 7.5 ± 2.9 years, and 1031 centrally adjudicated strokes (874 ischemic and 77 hemorrhagic strokes). HDL-C baseline level was associated with an overall unadjusted 13% risk reduction (HR 0.87, 95% confidence interval [CI]: 0.81–0.93; p < 0.05; 14% for ischemic and 16% for hemorrhagic strokes), and TC with an 8% (HR 0.92, 95%CI: 0.87–0.99; p < 0.05) risk reduction of all strokes. When the results were fully adjusted a significant association was observed only for LDL-C and non-HDL-C and ischemic stroke. There were no significant differences in these associations when adjusted for age, race, age ∗ race, gender, education, region, or income. Conclusion In a disease free population, LDL-C and non-HDL-C baseline levels are significantly associated with the risk of ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that aspirin used for secondary prevention significantly reduces cardiovascular and stroke risk. The data for aspirin and primary prevention of cardiovascular disease, and in particular stroke, are less clear, especially among blacks. Objective: To evaluate prophylactic aspirin use and incident stroke in a large cohort of black and white participants. Methods: The Reasons for Geographic and Racial Differences in Stroke study is a national, population-based, longitudinal study of 30,239 African Americans and whites, older than 45 years. Participants with stroke at baseline were excluded, reducing the cohort to 27,219. Proportional hazard models were used to estimate the association of incident stroke with prophylactic aspirin use, adjusted for confounding factors. Separate analyses were performed for subjects who self-reported baseline aspirin use for primary prevention of vascular disease compared with those using aspirin use for other indications. Results: In all, 10,177 participants taking prophylactic aspirin were followed for a mean of 4.6 years. Univariate analysis showed an increased stroke risk for prophylactic aspirin use (hazard ratio [HR]: 1.37; 95% confidence interval: 1.16-1.62), but the association was attenuated (HR: 1.06; 95% CI: .86-1.32) with multivariable adjustment, adjusting for demographic factors (age, race, sex, and region), socioeconomic factors (income and education), perceived general health, cardiovascular disease (CVD) risk factors (hypertension, diabetes, dyslipidemia, cigarette smoking, and alcohol use), and finally the Framingham Stroke Risk Score (in a separate model). No racial, sex, or regional differences in the association were demonstrated. Conclusions: In this observational study, prophylactic aspirin use was not associated with risk of first stroke, and there were no sex, race, or regional differences. [Copyright &y& Elsevier]

Abstract: The morning blood pressure surge (MBPS) has been shown to be an independent predictor of cardiovascular events. There is insufficient evidence on the effect of nebivolol, a vasodilating β1-receptor blocker, on the MBPS when given in the morning or the evening. This is a prospective, randomized, double-blind, crossover study designed to test morning vs. evening dosing of nebivolol in nondiabetic, hypertensive patients. Patients received nebivolol 5 mg/day (force-titrated to 10 mg/day after 1 week) in the morning or evening and corresponding placebos. Patients underwent ambulatory BP monitoring at baseline and after each treatment phase. Forty-two patients were randomized, of whom 38 completed both study periods. Both morning and evening dosed nebivolol significantly lowered daytime, nighttime, and 24-hour BP after 3 weeks of treatment. Evening (but not morning) dosing significantly reduced prewaking systolic BP from baseline (8.64 ± 26.46 mm Hg, P = .048). Nebivolol given in the morning or the evening significantly reduces 24-hour BP parameters. Evening dosed nebivolol may confer some advantage over morning dosing in reducing prewaking systolic BP. [Copyright &y& Elsevier]

Abstract: Reduced arterial elasticity and endothelial dysfunction both may indicate early cardiovascular (CV) disease in young adults. Pulse waveform analysis estimates large (LAE) and small (SAE) artery elasticity noninvasively. We assessed the associations between LAE and SAE and markers of endothelial dysfunction and CV risk factors. The Coronary Artery Risk Development in Young Adults (CARDIA) assessed arterial elasticity and other characteristics cross-sectionally in 389 men and 381 women age 27 to 42 years in 1995 (CARDIA year 10) and circulating levels of P-selectin and soluble intercellular adhesion molecule 1 (sICAM1) in 2000. We adjusted for variables included in the estimation of arterial elasticity (year 10 height, body mass index, age, heart rate, and blood pressure) and other year 10 characteristics. Mean adjusted SAE was 8.5 vs. 7.6 mL/mm Hg × 100 in those with urine albumin/creatinine ratio ≤4 vs. microalbuminuria (ratio >25; P trend = .008). Mean LAE was 25.6 vs. 24.2 mL/mm Hg × 10 in the lowest vs. highest quintile of P-selectin (P trend = .004). sICAM1 was unrelated to either LAE or SAE. Plasma triglycerides were inversely related to LAE (P trend = .029). Cigarette smokers had lower SAE than nonsmokers (P trend = .009). In addition to smoking and triglycerides, biomarkers for endothelial dysfunction were associated with impaired LAE and SAE in young adults. [Copyright &y& Elsevier]

Examines the clinical functions of nitrates. Use of nitrates in the therapy of coronary artery disease and congestive heart failure; Basic mechanisms of nitrate action include vasodilation as well as antiplatelet and antithrombotic activity; Analysis of nitrate tolerance; Recommendations for clinical practice.

Examines the effects of zatebradine, a sinus node inhibitor, on heart rate (HR) and exercise duration in stable angina pectoris. Exercise parameters at baseline and after four weeks of treatment with zatebradine; Assessment on the efficacy and safety of zatebradine; Relation of HR reduction in the improvement of anti-ischemic effects.

We evaluated the prevalence of major and minor electrocardiographic (ECG) abnormalities based on blood pressure (BP) control and hypertension (HTN) treatment resistance. We analyzed data from the Reasons for Geographic and Racial Differences in Stroke study of 20,932 participants who were divided into presence of major (n = 3782), only minor (n = 8944), or no (n = 8206) ECG abnormalities. The cohort was stratified into normotension (n = 3373), pre-HTN (n = 4142), controlled HTN (n = 8619), uncontrolled HTN (n = 3544), controlled apparent treatment-resistant HTN (aTRH, n = 400), and uncontrolled aTRH (n = 854) groups, and the prevalence ratios (PRs) of major and minor ECG abnormalities were assessed separately for each BP group. The full multivariable adjustment included demographics, risk factors, and HTN duration. Compared with normotension, the PRs of major ECG abnormalities for pre-HTN, controlled HTN, uncontrolled HTN, controlled aTRH, and uncontrolled aTRH groups were 1.01 (0.90–1.14), 1.30 (1.16–1.45), 1.37 (1.23–1.54), 1.42 (1.22–1.64), and 1.44 (1.26–1.65), respectively ( P < .001), whereas the PRs of minor ECG abnormalities among each of the above BP groups were similar. Detection of major ECG abnormalities among hypertensive persons with poor control and treatment resistance may help improve their cardiovascular risk stratification and early intervention. [ABSTRACT FROM AUTHOR]

Pulse pressure (PP) has been associated with atrial fibrillation (AF) independent of other measures of arterial pressure and other AF risk factors. However, the impact of gender, race, age, and geographic region on the association between PP and AF is unclear. A cross-sectional study of data from 25,109 participants (65 ± 9 years, 54% women, 40% black) from the Reasons for Geographic and Racial Differences in Stroke study recruited between 2003 and 2007 were analyzed. AF was defined as a self-reported history of a previous physician diagnosis or presence of AF on ECG. Multivariable logistic regression models were used to calculate the odds ratio for AF. Interactions for age (<75 years and ≥75 years), gender, race, and region were examined in the multivariable adjusted model. The prevalence of AF increased with widening PP (7.9%, 7.9%, 8.4%, and 11.6%, for PP < 45, 45–54.9, 55–64.9, and ≥65 mm Hg, respectively, [ P for trend <.001]) but attenuated with adjustment. No differences by gender, race, and region were observed. However, there was evidence of significant effect modification by age (interaction P = .0002). For those <75 years, PP ≥ 65 mm Hg compared to PP < 45 mm Hg was significantly associated with higher risk of AF in both the unadjusted and multivariable adjusted models (odds ratio = 1.66 [95% CI = 1.42–1.94] and 1.32 [95% CI = 1.03–1.70], respectively). In contrast, higher PP (55–64.9 mm Hg) among those ≥75 years was significantly associated with a lower risk of AF. The relationship between PP and AF may differ for older versus younger individuals. [ABSTRACT FROM AUTHOR]

The association of atrial fibrillation (AF) with the severity and control of hypertension (HTN) remains unclear. We analyzed data from the national biracial cohort of REasons for Geographic And Racial Differences in Stroke study. The AF prevalence ratios were estimated and full multivariable adjustment included demographics, risk factors, medication adherence, HTN duration, and antihypertensive medication classes. Of the 30,018 study participants (8.6% with AF), 4386 had normotension (4.3% with AF), 5916 had prehypertension (4.3 with AF%), 12,294 had controlled HTN (11.2% with AF), 5587 had uncontrolled HTN (8.1% with AF), 547 had controlled apparent treatment-resistant hypertension (aTRH) (19.2% with AF), and 1288 had uncontrolled aTRH (15.5% with AF). Compared with normotension, the AF prevalence ratios for prehypertension, controlled HTN, uncontrolled HTN, controlled aTRH, and uncontrolled aTRH groups in fully adjusted model were 1.01 (95% confidence interval: 0.84, 1.21), 1.42 (1.18, 1.71), 1.37 (1.14, 1.65), 1.17 (0.86, 1.58), and 1.42 (1.10, 1.84), respectively ( P < .001). The prevalence of AF was similar among persons with HTN regardless of blood pressure level and antihypertensive treatment resistance. [ABSTRACT FROM AUTHOR]

Discusses myocardial infarction (MI) as a leading cause of heart failure. Correlation of MI with left ventricular dysfunction; Structural changes in the residual normal myocardium; Effectiveness of the use of angiotensin-converting enzyme inhibitors for the treatment of MI; Time-dependence of the left ventricular remodeling following MI.

Abstract: Hypertension is a common disorder associated with increased cardiovascular morbidity and mortality. Unfortunately, in the US only about one-third of those who are aware of their hypertensive status have their blood pressure adequately controlled. One reason for this is the variable and unpredictable response individuals have to pharmacologic treatment. Clinicians often resort to “trial-and-error” to match patients with effective drug treatment. Hypertension pharmacogenetics seeks to find genetic predictors of drug response. To date, more than forty studies have investigated associations between genetic polymorphisms and response to antihypertensive drugs. Angiotensin-converting enzyme inhibitors and beta blockers have been most frequently studied, followed by angiotensin II blockers, diuretics, adrenergic alpha-agonists, and calcium channel blockers. Renin–angiotensin–aldosterone system genes have been the most widely studied, with the angiotensin-converting enzyme I/D variant being typed in about one-half of all hypertension pharmacogenetic studies. In total, 160 possible gene polymorphism–drug interactions have been explored, with about one-quarter of these showing that genes predict drug response. However, disparate and conflicting findings have been the rule rather than the exception, and the discovery of clinically relevant antihypertensive drug-response genes remains elusive. While there is a growing enthusiasm that pharmacogenetics of hypertension is important, the translation of pharmacogenetic findings to clinical practice in the future will depend on additional studies to enhance our pharmacogenetics knowledge base, the availability of pharmacogenetic screening tests that are affordable and easy to implement in clinical practice, a cohort of clinicians who are trained to interpret genetic test results, and health care systems that pay for them. Caution regarding the future of hypertension pharmacogenetics is warranted. [Copyright &y& Elsevier]

Background: Nonstatin lipid-lowering therapy is adjunctive therapy for high-risk individuals on statins or monotherapy among those who cannot tolerate statins. Objectives: This study determined time trends between 2007 and 2011 for statin and nonstatin lipid-lowering therapy (niacin, fibrates, bile acid sequestrants, and ezetimibe) use among Medicare beneficiaries with coronary heart disease (CHD) in light of emerging clinical trial evidence. Methods: We conducted a retrospective cohort study using the national 5% random sample of Medicare beneficiaries (n = 310,091). We created 20 cohorts of individuals with CHD, representing calendar quarters from 2007 through 2011, to assess trends in use of statins and nonstatin lipid-lowering medications. Results: Statin use increased from 53.1% to 58.8% between 2007 and 2011. Ezetimibe use peaked at 12.1% and declined to 4.6% by the end of 2011, declining among both patients on statins (18.4% to 6.2%) and not on statins (5.0% to 2.4%). Fibrate use increased from 4.2% to 5.0%, bile acid sequestrants did not change significantly, and niacin use increased from 1.5% to 2.4% and then declined in late 2011. Use of nonstatin lipid-lowering therapy was less common at older age, among African Americans, patients with heart failure, and patients with a higher Charlson comorbidity score. Nonstatin lipid-lowering therapy use was more common among men and patients with diabetes, those who had cardiologist visits, and among those taking statins. Conclusions: Declining ezetimibe and niacin use but not fibrate therapy among Medicare beneficiaries with CHD coincides with negative clinical trial results for these agents. [ABSTRACT FROM AUTHOR]

Background Lipid management is less aggressive in blacks than whites and women than men. Purpose To examine whether differences in lipid management for race–sex groups compared to white men are due to factors influencing health services utilization or physician prescribing patterns. Methods Because coronary heart disease (CHD) risk influences physician prescribing, Adult Treatment Panel III CHD risk categories were constructed using baseline data from REasons for Geographic And Racial Differences in Stroke study participants (recruited 2003–2007). Prevalence, awareness, treatment, and control of hyperlipidemia were examined for race–sex groups across CHD risk categories. Multivariable models conducted in 2013 estimated prevalence ratios adjusted for predisposing, enabling, and need factors influencing health services utilization. Results The analytic sample included 7,809 WM; 7,712 white women; 4,096 black men; and 6,594 black women. Except in the lowest risk group, black men were less aware of hyperlipidemia than others. A higher percentage of white men in the highest risk group was treated (83.2%) and controlled (72.8%) than others (treatment, 68.6%–72.1%; control, 52.2%–65.5%), with black women treated and controlled the least. These differences remained significant after adjustment for predisposing, enabling, and need factors. Stratified analyses demonstrated that treatment and control were lower for other race–sex groups relative to white men only in the highest risk category. Conclusions Hyperlipidemia was more aggressively treated and controlled among white men compared with white women, black men, and especially black women among those at highest risk for CHD. These differences were not attributable to factors influencing health services utilization. [ABSTRACT FROM AUTHOR]

Purpose The purpose of the study was to investigate secular changes in coronary heart disease (CHD) incidence and mortality among adults with and without diabetes and to determine the effect of increased lipid-lowering medication use and reductions in low-density lipoprotein cholesterol (LDL-C) levels on these changes. Methods We analyzed data on participants aged 45 to 64 years from the Atherosclerosis Risk in Communities Study in 1987-1996 (early period) and the Reasons for Geographic and Racial Differences in Stroke Study in 2003-2009 (late period). Hazard ratios (HRs) for the association of diabetes and period with incident CHD and CHD mortality were obtained after adjustment for sociodemographics cardiovascular risk factors, lipid-lowering medication use, and LDL-C. Results After multivariable adjustment, diabetes was associated with an increased CHD risk during the early (HR = 1.99, 95% confidence interval = 1.59-2.49) and late (HR = 2.39, 95% confidence interval = 1.69-3.35) periods. CHD incidence and mortality declined between the early and late periods for individuals with and without diabetes. Increased use of lipid-lowering medication and lower LDL-C explained 33.6% and 27.2% of the decline in CHD incidence and CHD mortality, respectively, for those with diabetes. Conclusions Although rates have declined, diabetes remains associated with an increased risk of CHD incidence and mortality, highlighting the need for continuing diabetes prevention and cardiovascular risk factor management. [ABSTRACT FROM AUTHOR]

Abstract: Background: Smoking is associated with increased postprandial hypertriglyceridemia (PPT). Inflammation and insulin resistance are potential “drivers” for this phenomenon. We tested whether inflammatory patterns and/or insulin resistance explain the effect of smoking on PPT. Methods and results: Men and women in the NHLBI Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) study (n =1036, age 49±16y) were included. Each participant was asked to suspend use of lipid-lowering drugs for 3 weeks and was given a high-fat milkshake (83% fat and 700kcal/m2). Triglyceride concentrations at 0, 3.5 and 6h after the fat load were measured. Inflammatory markers were measured at baseline. Principal component analysis was used to derive inflammatory patterns from individual inflammatory markers (hsCRP, IL2 soluble receptor-α, IL6, TNF-α and MCP1). Insulin resistance (IR) was estimated using the HOMA equation. Repeated measures-ANOVA was used for analyses. Two inflammatory patterns, namely CRP-IL6 pattern and MCP1-TNF-α pattern, were derived. We found significant main (smoking and time) and interaction (smoking×time) effects (P <0.01) for triglycerides. The multivariate-adjusted triglyceride (mg/dL) concentrations (mean±S.E.M.) for never, past and current smokers were 127.38±1.04, 119.82±1.05 and 134.92±1.08 at 0h; 229.42±1.04, 238.39±1.05 and 293.94±1.08 at 3.5h; and 194.63±1.04, 208.38±1.05 and 248.27±1.08 at 6h after the fat load, respectively. Smoking remained significant after adjusting for HOMA-IR and/or inflammatory patterns which showed independent associations with PPT (P <0.05). Conclusions: These data confirm impaired metabolism of fat among smokers and suggest that mechanisms other than inflammation or insulin resistance may explain the observed hypertriglyceridemia among smokers. [Copyright &y& Elsevier]

Purpose: Children with acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, have a 5-year survival rate of better than 80%. Long-term survivors of childhood ALL, however, carry an elevated risk of early mortality from cardiac events and stroke and a disproportionately high prevalence of dyslipidemia and obesity, presumably as an adverse effect of treatment. Methods: As part of a clinical follow-up study of 70 young adult survivors of childhood ALL, we evaluated the degree to which this high-risk group differed in knowledge about symptoms of heart attack and stroke from that of a population-based comparison group frequency-matched by age, sex, and body mass index. Questions from the Behavioral Risk Factor Surveillance System were used to assess health knowledge. Results: Survivors of ALL scored considerably worse on symptom knowledge than did their population counterparts. The strongest association was observed for chest pain as a symptom of heart attack: ALL survivors were 14-fold more likely than the comparison group to answer the question incorrectly. Seventy-seven percent of survivors failed to identify pain in the jaw, neck, or back as a heart attack symptom. Conclusions: These results indicate an important gap in knowledge and underscore the need for health education among survivors of childhood leukemia that includes information about symptoms of myocardial infarction and stroke. [Copyright &y& Elsevier]