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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]

Objective: It was the aim of this study to document the risks of symptomatic patients with angina in placebo-controlled, anti-anginal drug development trials in which symptom-limited exercise testing was used as the primary endpoint. Patients and Methods: The original case report forms submitted to the United States Food and Drug Administration in support of approval of new or supplemental new drug applications between 1973 and 2001 were identified and subjected to a by-patient meta-analysis, utilizing both a maximum likelihood analysis and classical Mantel-Haenszel methods. Results: There were 63 placebo-controlled, clinical trials that randomized 10,865 patients, with 1,047 patient-years of observation time. The trials involved 21 different chemical entities from 4 different drug classes. The relative risk (RR) for withdrawal (placebo compared to drug-treated patients) was not increased [RR = 0.92, 95% confidence interval (CI) 0.78-1.08; p = 0.28]. Of interest, a RR of 0.54 (95% CI 0.26-1.04; p < 0.068) for irreversible harm (a combination of cerebrovascular accidents, myocardial infarction and death) and a RR of 0.89 (95% CI 0.61-1.30; p = 0.56) for serious cardiovascular events (myocardial infarction, congestive heart failure, cerebrovascular accidents) both non-statistically significantly favored being randomized to placebo. Conclusions: For the development of current or future drugs for the treatment of angina, there is no obvious contraindication to the use of placebo controls and exercise tolerance testing. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Context: Aspirin use may reduce the risk of stroke and coronary heart disease. Differential use for vascular prophylaxis may contribute to racial and geographic disparities in stroke and coronary heart disease morbidity or mortality. Objective: To assess the prevalence and predictors of aspirin use for primary prophylaxis of stroke in the general population free of clinically diagnosed stroke or coronary heart disease. Design and setting: Cross-sectional analysis of 16,908 participants (age 45 or greater), from a population-based national cohort study (REasons for Geographic And Racial Differences in Stroke) enrolled from February 2003–August 2006 with oversampling from the southeastern Stroke Belt and African Americans. Individuals with a prior stroke or coronary heart disease, or regular use of aspirin for pain relief were excluded from analyses. Main outcome measures: Aspirin use and reasons for use were assessed using a computer-assisted telephone interview. Results: Prophylactic aspirin use was substantially higher among whites (34.7%) than African Americans (27.2%; p <0.0001). There was a higher prevalence of aspirin use for prophylaxis in the Stroke Belt (32.1%) than in the rest of the nation (30.8%; p =0.07). After adjustment for measures of socio-economic status, the odds ratio of aspirin use in the rest of the nation compared to Stroke Belt was 0.90 (95% CI 0.84–0.97). There was a higher likelihood of prophylactic aspirin use among participants who were white, male, older, past cigarette smokers, or of higher socio-economic status (higher income or education). Conclusions: In this study, aspirin use to prevent stroke and coronary heart disease was higher among whites than African Americans, raising the possibility that differential aspirin use could contribute to the racial disparities in vascular disease mortality. Counter to our hypothesis, aspirin use was more common in the Stroke Belt than the rest of the country, so differential aspirin use in the Stroke Belt is unlikely to contribute to geographic disparities in stroke. [Copyright &y& Elsevier]

The new drug application database submitted to the US Food and Drug Administration for drug approval (phases I-III or phases 1-3) is limited both in scope and size. Although randomized controlled trials, the hallmark of phase III trials, are the gold standard for the drug-approval process, they invariably have a number of limitations, including relatively small sample sizes, selective populations, short follow-up, the use of intermediate (surrogate) endpoints (almost always), and limited generalizability. The challenges of monitoring drugs once approved are also numerous. After approval by the Food and Drug Administration, marketed drugs undergo continued scrutiny, and this scrutiny is increasing because of problems that have surfaced with some drugs after their approval. Postmarketing research includes a variety of study designs and the use of registries and self-reporting of drug side effects. Along with this has come great confusion about what postmarketing research is and what a phase IV study is. Among the important strengths of phase IV research are the exposure of a broader range of patients to the drug under study, resulting in more "real-world" information about the drug's safety and efficacy, and consideration of a broader range of clinical endpoints. As a result, phase IV or postmarketing research, has become an integral part of the drug evaluation process for a wide range of agents. The authors discuss the different types of study designs that are common under the phase IV terminology and provide some examples. They also discuss the use of registries and self-reporting of adverse events using the Med Watch System. [ABSTRACT FROM AUTHOR]

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.

Comments on the use of organic nitrates for the chronic treatment of ischaemic heart disease and congestive heart failure. Effect of nitrates on coronary circulation; Incidence of tolerance with the use of nitrate therapy; Mechanism for the development of nitrate tolerance; Strategies for avoidance of nitrate tolerance, including the use of an inhibitor of angiotensin-converting enzyme (ACE).

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.

The purpose of this investigation was to examine the associations between circulating markers of inflammation and arterial elasticity in healthy older women. Participants were 50 women older than 60 years of age, body mass index 27±4, and physically untrained. Large artery elasticity, small artery elasticity, systemic vascular resistance, total vascular impedance, estimated cardiac output, and estimated cardiac index were determined using pulse contour analysis. Serum concentrations of tumor necrosis factor-α, C-reactive protein (CRP), and interleukin 6 were assessed. Results from Pearson’s correlation revealed that tumor necrosis factor-α was inversely associated with large artery elasticity (−.426, p < .01) and estimated cardiac index (−.324, p < .05) and positively associated with systemic vascular resistance (.386, p < .01) and total vascular impedance (.416, p < .01). Additionally, C-reactive protein was inversely associated with large artery elasticity (−.308, p < .01). The overall implication was that tumor necrosis factor-α and C-reactive protein appear to be critical inflammatory cytokines associated with reductions in arterial elasticity in older women. [ABSTRACT FROM PUBLISHER]

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]

Presents a study to examine whether low-density lipoprotein (LDL) size is an independent predictor of recurrent coronary events in patients with known coronary heart disease (CHD), as opposed to a marker for other lipid abnormalities. Context; Objective; Design and setting; Participants; Main outcome measure; Results; Conclusions.

Markers of systemic inflammation are associated with increased risk of cognitive impairment, but it is unclear if they are associated with a faster rate of cognitive decline and whether this relationship differs by race. Our objective was to examine the association of baseline C-reaction protein (CRP) with cognitive decline among a large racially diverse cohort of older adults. Participants included 21,782 adults aged 45 and older (36% were Black, Mean age at baseline 64) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. CRP was measured at baseline and used as a continuous variable or a dichotomous grouping based on race-specific 90th percentile cutoffs. Cognitive measures of memory and verbal fluency were administered every 2 years for up to 12 years. Latent growth curve models evaluated the association of CRP on cognitive trajectories, adjusting for relevant demographic and health factors. We found that higher CRP was associated with worse memory (B = -.039, 95% CI [-.065,-.014]) and verbal fluency at baseline (B = -.195, 95% CI [-.219,-.170]), but not with rate of cognitive decline. After covariate adjustment, the association of CRP on memory was attenuated (B = -.005, 95% CI [-.031,-.021]). The association with verbal fluency at baseline, but not over time, remained (B = -.042, 95% CI [-.067,-.017]). Race did not modify the association between CRP and cognition. Findings suggest that levels of CRP at age 45+, are a marker of cognitive impairment but may not be suitable for risk prediction for cognitive decline. [ABSTRACT FROM AUTHOR]

It is unclear whether metabolic syndrome (MetS) is associated with atrial fibrillation (AF) in an older population with greater cardiovascular risk, including those with chronic kidney disease. The authors investigated the association between MetS and AF in participants in SPRINT (Systolic Blood Pressure Intervention Trial). MetS was defined based on the Modified Third National Cholesterol Education Program. The baseline prevalence rate for MetS was 55%, while 8.2% of the participants had AF. In multivariate regression analyses, AF was not associated with presence of MetS in either chronic kidney disease or non-chronic kidney disease subgroups. Age, race, history of cardiovascular diseases, decreased triglycerides, decreased pulse pressure, and albuminuria remained significantly associated with AF risk. In contrast to the general population, MetS was not associated with AF in the older population with increased cardiovascular risk studied in SPRINT. [ABSTRACT FROM AUTHOR]

Aerobic exercise transiently lowers blood pressure. However, limited research has concurrently evaluated blood pressure and small arterial elasticity (SAE), an index of endothelial function, among African American (AA) and European American (EA) women the morning after (i.e., ≈22 h later) acute bouts of moderate-intensity continuous (MIC) and highintensity interval (HII) exercise matched for total work. Because of greater gradients of shear stress, it was hypothesized that HII exercise would elicit a greater reduction in systolic blood pressure (SBP) compared to MIC exercise. After baseline, 22 AA and EA women initiated aerobic exercise training 3 times/week. Beginning at week 8, three follow-up assessments were conducted over the next 8 weeks at random to measure resting blood pressure and SAE. In total all participants completed 16 weeks of training. Follow-up evaluations were made: (i) in the trained state (TS; 8-16 weeks of aerobic training); (ii) ≈22 h after an acute bout of MIC exercise; and (iii) ≈22 h after an acute bout of HII exercise. Among AAs, the acute bout of HII exercise incited a significant increase in SBP (mm Hg) (TS, 121 ± 14 versus HII, 128 ± 14; p = 0.01) whereas responses (TS, 116 ± 12 versus HII, 113 ± 9; p = 0.34) did not differ in EAs. After adjusting for race, changes in SAE were associated (partial r = -0.533; p = 0.01) with changes in SBP following HII exercise. These data demonstrate an acute, unaccustomed bout of HII exercise produces physiological perturbations resulting in a significant increase in SBP that are independently associated with decreased SAE among AA women, but not EA women. [ABSTRACT FROM AUTHOR]

Background: The association between perceived stress and atrial fibrillation (AF) remains unclear.Purpose: The aim of this study was to examine the association between perceived stress and AF.Methods: A total of 25,530 participants (mean age 65 ± 9.4 years; 54 % women; 41 % blacks) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were included in this analysis. Logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for the association between the short version of the Cohen Perceived Stress Scale and AF.Results: In a multivariable analysis adjusted for demographics, cardiovascular risk factors, and potential confounders, the prevalence of AF was found to increase with higher levels of stress (none: OR = 1.0, referent; low stress: OR = 1.12, 95 % CI = 0.98, 1.27; moderate stress OR = 1.27, 95 % CI = 1.11, 1.47; high stress: OR = 1.60, 95 % CI = 1.39, 1.84).Conclusion: Increasing levels of perceived stress are associated with prevalent AF in REGARDS. [ABSTRACT FROM AUTHOR]

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]

Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin therapy on plasma CoQ10 concentrations through the meta-analysis of available RCTs. The literature search included selected databases up to April 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I 2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The data from 8 placebo-controlled treatment arms suggested a significant reduction in plasma CoQ10 concentrations following treatment with statins (WMD: −0.44 μmol/L, 95%CI: −0.52, −0.37, p < 0.001). The pooled effect size was robust and remained significant in the leave-one-out sensitivity analysis. Subgroup analysis suggested that the impact of statins on plasma CoQ10 concentrations is significant for all 4 types of statins studied i.e. atorvastatin (WMD: −0.41 μmol/L, 95%CI: −0.53, −0.29, p < 0.001), simvastatin (WMD: −0.47 μmol/L, 95% CI: −0.61, −0.33, p < 0.001), rosuvastatin (WMD: −0.49 μmol/L, 95%CI: −0.67, −0.31, p < 0.001) and pravastatin (WMD: −0.43 μmol/L, 95%CI: −0.69, −0.16, p = 0.001). Likewise, there was no differential effect of lipophilic (WMD: −0.43 μmol/L, 95%CI: −0.53, −0.34, p < 0.001) and hydrophilic statins (WMD: −0.47 μmol/L, 95%CI: −0.62, −0.32, p < 0.001). With respect to treatment duration, a significant effect was observed in both subsets of trials lasting <12 weeks (WMD: −0.51 μmol/L, 95%CI: −0.64, −0.39, p < 0.001) and ≥12 weeks (WMD: −0.40 μmol/L, 95%CI: −0.50, −0.30, p < 0.001). The meta-analysis showed a significant reduction in plasma CoQ10 concentrations following treatment with statins. Further well-designed trials are required to confirm our findings and elucidate their clinical relevance. [ABSTRACT FROM AUTHOR]

Objective: To identify approximately 500 cases of incident cognitive impairment (ICI) in a large, national sample adapting an existing cognitive test-based case definition and to examine relationships of vascular risk factors with ICI.Method: Participants were from the REGARDS study, a national sample of 30,239 African-American and White Americans. Participants included in this analysis had normal cognitive screening and no history of stroke at baseline, and at least one follow-up cognitive assessment with a three-test battery (TTB). Regression-based norms were applied to TTB scores to identify cases of ICI. Logistic regression was used to model associations with baseline vascular risk factors.Results: We identified 495 participants with ICI of 17,630 eligible participants. In multivariable modeling, income (OR 1.83 CI 1.27,2.62), stroke belt residence (OR 1.45 CI 1.18,1.78), history of transient ischemic attack (OR 1.90 CI 1.29,2.81), coronary artery disease(OR 1.32 CI 1.02,1.70), diabetes (OR 1.48 CI 1.17,1.87), obesity (OR 1.40 CI 1.05,1.86), and incident stroke (OR 2.73 CI 1.52,4.90) were associated with ICI.Conclusions:We adapted a previously validated cognitive test-based case definition to identify cases of ICI. Many previously identified risk factors were associated with ICI, supporting the criterion-related validity of our definition. [ABSTRACT FROM PUBLISHER]

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]

Objective To determine the association between objectively measured sleep and 10-year changes in estimated glomerular filtration rate (eGFR). Methods From 2003 to 2005, an ancillary sleep study was conducted at the Chicago site of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Community-based black and white adults (aged 32–51 years) wore a wrist actigraph for up to six nights to record sleep duration and fragmentation. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Participants without history of cardiovascular or chronic kidney diseases, proteinuria, or hypertension at the 2000–2001 CARDIA examination were followed over 10 years ( n  = 463). eGFR was estimated from serum creatinine (eGFR Cr ) at the 2000–2001, 2005–2006, and 2010–2011 CARDIA examinations, whereas cystatin-C-estimated eGFR (eGFR Cys ) was measured at the 2000–2001 and 2005–2006 examinations. Generalized estimating equation regression and linear models estimated the associations of each sleep parameter with changes in eGFR Cr and eGFR Cys , controlling for cardiovascular and renal risk. Results Sleep parameters were not related to 5-year change in eGFR Cys . However, each 1 h decrease in sleep duration was significantly associated with a 1.5 mL/min/1.73 m 2 higher eGFR Cr [95% confidence interval (CI), 0.2–2.7], and each one-point increase in PSQI was significantly associated with a 0.5 mL/min/1.73 m 2 higher eGFR Cr (95% CI, 0.04–0.9) over 10 years. Conclusion In this community-based sample, shorter sleep and poorer sleep quality were related to higher kidney filtration rates over 10 years. [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]

Arterial health may influence muscle function in older adults. Study purpose was to determine whether arterial elasticity is related to strength, central and peripheral fatigue, fatigue at rest, and treadmill endurance. Subjects were 91 healthy women aged >60. Treadmill endurance and maximal oxygen uptake (VO2 max) were measured. Peripheral and central fatigue for the knee extensors were evaluated using two isometric fatigue tests (one voluntary and one adding electrical stimulation). Arterial elasticity was determined using radial artery pulse wave analysis. Linear multiple regression was used in statistical analysis. Large artery elasticity was associated with central fatigue (ρ < 0.01) and treadmill endurance (ρ < 0.02) after adjusting for VO2 max and knee extension strength. Subjective fatigue at rest was related to large artery elasticity after adjusting for ethnic origin (<0.02). Strength was significantly related to small artery elasticity after adjusting for ethnic origin, leg lean tissue, age, and blood pressure. Arterial elasticity is independently related to strength and fatigue in older women, especially in the central nervous system where arterial elasticity is independently related to perceptions of fatigue at rest and central fatigue. These results suggest that arterial health may be involved with the ability of the central nervous system to activate muscle in older women. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Diabetes is often undiagnosed, resulting in incorrect risk stratification for lipid-lowering therapy. We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2005-2010 to determine the prevalence, awareness, treatment, and control of elevated LDL cholesterol (LDL-C) among U.S. adults with undiagnosed diabetes. RESEARCH DESIGN AND METHODS--Fasting NHANES participants 20 years of age or older who had 10-year Framingham coronary heart disease (CHD) risk scores,20%and were free of CHD or other CHD risk equivalents ( = 5,528) were categorized as having normal glucose, impaired fasting glucose, undiagnosed diabetes, or diagnosed diabetes. High LDL-C was defined by the 2004 Adult Treatment Panel (ATP) III guidelines. RESULTS--The prevalence of diagnosed and of undiagnosed diabetes was 8 and 4%, respectively. Mean LDL-C was 102 ± 2 mg/dL among those with diagnosed diabetes and 117 6 3m g / dL for those with undiagnosed diabetes (, 0.001). The prevalence of high LDL-C was similar among individuals with undiagnosed (81%) and diagnosed (77%) diabetes. Among individuals with undiagnosed diabetes and high LDL-C, 38% were aware, 27% were treated, and 16% met the ATP III LDL-C goal for diabetes. In contrast, among individuals with diagnosed diabetes and high LDL-C, 70% were aware, 61% were treated, and 36% met the ATP III goal. Subjects with undiagnosed diabetes remained less likely to have controlled LDL-C after multivariable adjustment (prevalence ratio, 0.42; 95% CI, 0.23-0.80). CONCLUSIONS--Improved screening for diabetes and reducing the prevalence of undiagnosed diabetes may identify individuals requiring more intensive LDL-C reduction. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend that the decision threshold for troponin should be the 99th percentile of a normal population, or, if the laboratory assay is not sufficiently precise at this low level, the level at which the assay achieves a 10% or better coefficient of variation (CV). Our objectives were to examine US hospital laboratory troponin reports to determine whether either the 99th percentile or the 10% CV level were clearly indicated, and whether nonconcordance with these guidelines was a potential barrier to detecting clinically important microscopic or 'microsize' myocardial infarctions (MIs). To confirm past reports of the clinical importance of microsize MIs, we also contrasted in-hospital, 28-day and 1-year mortality among those with microsize and nonmicrosize MI. Methods: In the REasons for Geographic And Racial Differences in Stroke national prospective cohort study (n=30,239), 1029 participants were hospitalized for acute coronary syndrome (ACS) between 2003-2009. For each case, we recorded all thresholds of abnormal troponin on the laboratory report and whether the 99th percentile or 10% CV value were clearly identified. All cases were expert adjudicated for presence of MI. Peak troponin values were used to classify MIs as microsize MI (< five times the lowest listed upper limit of normal) and nonmicrosize MI. Results: Participants were hospitalized at 649 acute care US hospitals, only 2% of whose lab reports clearly identified the 99th percentile or the 10% CV level; 52% of reports indicated an indeterminate range, a practice that is no longer recommended. There were 183 microsize MIs and 353 nonmicrosize MIs. In-hospital mortality tended to be lower in the microsize than in the nonmicrosize MI group (1.1 vs. 3.6%, p = 0.09), but 28-day and 1-year mortality were similar (2.5% vs. 2.7% [p = 0.93] and 5.2% vs. 4.3% [p = 0.64], respectively). Conclusions: Current practices in many US hospitals created barriers to the clinical recognition of microsize MI, which was common and clinically important in our study. Improved hospital troponin reporting is warranted. [ABSTRACT FROM AUTHOR]

Objective: To examine an intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) on 4-year change in fitness and physical activity (PA), and to examine the effect of change in fitness and PA, adjusting for potential confounders, on glycemic control in the Look AHEAD Trial.Research Design and Methods: Subjects were overweight/obese adults with type 2 diabetes mellitus (T2DM) with available fitness data at 4 years (n = 3,942).This clinical trial randomized subjects to DSE or ILI. DSE subjects received standard care plus information related to diet, PA, and social support three times per year. ILI subjects received weekly intervention contact for 6 months, which was reduced over the 4-year period, and were prescribed diet and PA. Measures included weight, fitness, PA, and HbA1c.Results: The difference in percent fitness change between ILI and DSE at 4 years was significant after adjustment for baseline fitness and change in weight (3.70 vs. 0.94%; P < 0.01). At 4 years, PA increased by 348 (1,562) kcal/week in ILI vs. 105 (1,309) kcal/week in DSE (P < 0.01). Fitness change at 4 years was inversely related to change in HbA1c after adjustment for clinical site, treatment, baseline HbA1c, prescribed diabetes medication, baseline fitness, and weight change (P < 0.01). Change in PA was not related to change in HbA1c.Conclusions: A 4-year ILI increased fitness and PA in overweight/obese individuals with T2DM. Change in fitness was associated with improvements in glycemic control, which provides support for interventions to improve fitness in adults with T2DM. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine an intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) on 4-year change in fitness and physical activity (PA), and to examine the effect of change in fitness and PA, adjusting for potential confounders, on glycemic control in the Look AHEAD Trial. RESEARCH DESIGN AND METHODS--Subjects were overweight/obese adults with type 2 diabetes mellitus (T2DM) with available fitness data at 4 years (n = 3,942). This clinical trial randomized subjects to DSE or ILI. DSE subjects received standard care plus information related to diet, PA, and social support three times per year. ILI subjects received weekly intervention contact for 6 months, which was reduced over the 4-year period, and were prescribed diet and PA. Measures included weight, fitness, PA, and HbA1c. RESULTS--The difference in percent fitness change between ILI and DSE at 4 years was significant after adjustment for baseline fitness and change in weight (3.70 vs. 0.94%; P < 0.01). At 4 years, PA increased by 348 (1,562) kcal/week in ILI vs. 105 (1,309) kcal/week in DSE (P < 0.01). Fitness change at 4 years was inversely related to change in HbA1c after adjustment for clinical site, treatment, baseline HbA1c, prescribed diabetes medication, baseline fitness, and weight change (P < 0.01). Change in PA was not related to change in HbA1c. CONCLUSIONS--A 4-year ILI increased fitness and PA in overweight/obese individuals with T2DM. Change in fitness was associated with improvements in glycemic control, which provides support for interventions to improve fitness in adults with T2DM. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether combined (aerobic and anaerobic) training decreases blood pressure (BP) and improves vascular properties. Seventy-nine postmenopausal women were randomly assigned to 3 groups that trained at different frequencies. Maximum oxygen uptake, body composition, BP, and arterial elasticity were evaluated prior to training and after 16 weeks of training. There was a significant time effect (decrease) for resting systolic BP (SBP) and rate pressure product. Exercise SBP, diastolic BP (DBP), heart rate, and RPP also decreased. Changes in total vascular impedance were related to SBP and changes in systemic vascular resistance were related to changes in DBP independent of body composition changes. Our findings suggest that combined training reduces SBP and improves vascular properties and that combined training 1 d/wk decreases BP similar to more frequent combined training. Training-induced changes in arterial resistance and impedance may be involved in inducing changes in BP. J Clin Hypertens (Greenwich). 2012;00:00-00 ©2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article presents a study that deals with racial differences in the impact of elevated blood pressure on stroke risk. The study shows that combined racial differences and previously documented higher prevalence of hypertension and poorer control of hypertension in African-Americans is linked to racial disparity in stroke risk. It focuses on stroke risk in 27,748 African American and American participants recruited between 2003 and 2007.

The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) found a higher risk of stroke after carotid artery stenting and a higher risk of myocardial infarction (MI) after carotid endarterectomy. Methods and Results-Cardiac biomarkers and ECGs were performed before and 6 to 8 hours after either procedure and if there was clinical evidence of ischemia. In CREST, MI was defined as biomarker elevation plus either chest pain or ECG evidence of ischemia. An additional category of biomarker elevation with neither chest pain nor ECG abnormality was prespecified (biomarker+ only). Crude mortality and risk-adjusted mortality for MI and biomarker+ only were assessed during follow-up. Among 2502 patients, 14 MIs occurred in carotid artery stenting and 28 MIs in carotid endarterectomy (hazard ratio, 0.50; 95% confidence interval, 0.26 to 0.94; P=0.032) with a median biomarker ratio of 40 times the upper limit of normal. An additional 8 carotid artery stenting and 12 carotid endarterectomy patients had biomarker+ only (hazard ratio, 0.66; 95% confidence interval, 0.27 to 1.61; P=0.36), and their median biomarker ratio was 14 times the upper limit of normal. Compared with patients without biomarker elevation, mortality was higher over 4 years for those with MI (hazard ratio, 3.40; 95% confidence interval, 1.67 to 6.92) or biomarker+ only (hazard ratio, 3.57; 95% confidence interval, 1.46 to 8.68). After adjustment for baseline risk factors, both MI and biomarker+ only remained independently associated with increased mortality. Conclusions-In patients randomized to carotid endarterectomy versus carotid artery stenting, both MI and biomarker+ only were more common with carotid endarterectomy. Although the levels of biomarker elevation were modest, both events were independently associated with increased future mortality and remain an important consideration in choosing the mode of carotid revascularization or medical therapy. Clinical Trial Registration-URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00004732. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To examine the effect of a lifestyle intervention to produce weight loss and increased physical fitness on use and cost of medications to treat cardiovascular disease (CVD) risk factors in people with type 2 diabetes. RESEARCH DESIGN AND METHODS- Look AHEAD is a multicenter randomized controlled trial of 5,145 overweight or obese individuals with type 2 diabetes, aged 45-76 years. An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition. Medications prescribed to treat diabetes, hypertension, and hyperlipidemia were compared at baseline and 1 year. Medication costs were conservatively estimated using prices from a national online pharmacy. RESULTS-- Participants randomized to an ILI had significantly greater improvements in CVD risk parameters and reduced medication use and cost compared with those assigned to DSE. At 1 year, average number of medications prescribed to treat CVD risk factors was 3.1 ± 1.8 for the ILI group and 3.6 ± 1.8 for the DSE group (P < 0.0001), with estimated total monthly medication costs of $143 and $173, respectively (P < 0.0001). DSE participants meeting optimal care goals at 1 year were taking an average of 3.8 ± 1.6 medications at an estimated cost of $194/month. ILI participants at optimal care required fewer medications (3.2 ± 1.7) at lower cost ($154/month) (P < 0.001). CONCLUSIONS-- At 1 year, ILI significantly improved CVD risk factors, while at the same time reduced medication use and cost. Continued intervention and follow-up will determine whether these changes are maintained and reduce cardiovascular risk. [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]

Background: Recent studies have suggested that there has been an increase in the number of 'warning letters' issued by the US Food and Drug Administration (FDA) despite the publication of the FDA advertising guidelines. However, limited information is available on the description of warning letters. The objective of this study was to analyse the frequency and content of FDA warning letters in relation to promotional claims and discuss the influence of regulatory and industry constraints on promotion. Methods: All warning letters published by the FDA between 5 May 1995 and 11 June 2007 were reviewed. Warning letters related to promotional issues were included and analysed. Information related to the identification number, date of the warning letter, FDA division that issued the letter, drug name, manufacturer, specific warning problem, type of promotional material and requested action was extracted. Two independent investigators reviewed and classified each PDF file, any differences were discussed until a consensus was reached. Results: Between May 1995 and June 2007 a total of 8692 warning letters were issued, of which 25% were related to drugs. Of these, 206 warning letters focused on drug promotion and were included in this study: 23% were issued in 2005, 15% in 2004 and 14% in 1998. In total, 47% of the warning letters were issued because of false or misleading unapproved doses and uses, 27% failed to disclose risks, 15% cited misleading promotion, 8% related to misleading labelling and 3% promoted false effectiveness claims. Discussion: There is an important variation in the number of warning letters issued in the last decade, probably because of the increasing number of drugs approved by the FDA, drug withdrawal scandals, and the publication of the FDA and the Pharmaceutical Research and Manufacturers of America (PhRMA) guidelines. Conclusion: We found that benefit-related claims, such as unapproved uses or doses of drugs, and failure to disclose risks, are the main causes of FDA issued warning letters for promotional claims related to medications. [ABSTRACT FROM AUTHOR]

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]

Introduction: Approximately 17.3 million adults have systolic blood pressure (SBP) between 130 and 139 mmHg in the USA, and they have increased risk of cardiovascular disease (CVD). Hypothesis: In this post-hoc analysis in the SPRINT, we assessed whether targeting an intensive SBP goal of <120 mmHg compared to the standard SBP goal of <140 mmHg reduced the risk of CVD events in adults with SBP between 130 and 139 mmHg with or without the use of antihypertensive medications at screening. Methods: We used Cox models to estimate the effect of the target SBP goal on the risk of CVD outcomes. The primary CVD outcome was the composite of first occurrence of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, congestive heart failure or CVD mortality. The main secondary outcome was the composite of all-cause mortality or CVD events. Results: Patients were predominantly males (72%) of Caucasian ancestry (59%) with a median age of 67 years and high prevalence of CVD history (22.6%) and chronic kidney disease (30.5%). Patients in the intensive group (N=1724) and the standard group (N=1760) had similar baseline characteristics. Compared with the standard goal, targeting an intensive SBP goal significantly reduced the risk of the primary CVD outcome after adjusting for baseline age, ancestry, gender, CVD history, smoking, use of statin, use of aspirin, glucose value and diastolic blood pressure value (aHR 0.76, [95% CI 0.58-0.98]; 1.78 vs. 2.37 events/100 pt-ys). Targeting an intensive SBP goal tended to reduce the risk of the main secondary outcome (aHR 0.80, [0.64-1.00]; 2.54 vs. 3.20 events/100 pt-ys). Conclusions: In the SPRINT, targeting a SBP goal <120 mmHg significantly reduced the risk of CVD events by 24% in patients with mild elevation of SBP.The views expressed in this presentation are those of the authors and do not necessarily represent the official position of the National Institutes of Health (NIH), the Department of Veterans Affairs, the U.S. Government or the SPRINT Research Group. This presentation was approved by the SPRINT Publications and Presentations Committee. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend that the decision threshold for troponin should be the 99th percentile of a normal population, or, if the laboratory assay is not sufficiently precise at this low level, the level at which the assay achieves a 10% or better coefficient of variation (CV). Our objectives were to examine US hospital laboratory troponin reports to determine whether either the 99th percentile or the 10% CV level were clearly indicated, and whether nonconcordance with these guidelines was a potential barrier to detecting clinically important microscopic or 'microsize' myocardial infarctions (MIs). To confirm past reports of the clinical importance of microsize MIs, we also contrasted in-hospital, 28-day and 1-year mortality among those with microsize and nonmicrosize MI.Methods: In the REasons for Geographic And Racial Differences in Stroke national prospective cohort study (n=30,239), 1029 participants were hospitalized for acute coronary syndrome (ACS) between 2003-2009. For each case, we recorded all thresholds of abnormal troponin on the laboratory report and whether the 99th percentile or 10% CV value were clearly identified. All cases were expert adjudicated for presence of MI. Peak troponin values were used to classify MIs as microsize MI (< five times the lowest listed upper limit of normal) and nonmicrosize MI.Results: Participants were hospitalized at 649 acute care US hospitals, only 2% of whose lab reports clearly identified the 99th percentile or the 10% CV level; 52% of reports indicated an indeterminate range, a practice that is no longer recommended. There were 183 microsize MIs and 353 nonmicrosize MIs. In-hospital mortality tended to be lower in the microsize than in the nonmicrosize MI group (1.1 vs. 3.6%, p = 0.09), but 28-day and 1-year mortality were similar (2.5% vs. 2.7% [p = 0.93] and 5.2% vs. 4.3% [p = 0.64], respectively).Conclusions: Current practices in many US hospitals created barriers to the clinical recognition of microsize MI, which was common and clinically important in our study. Improved hospital troponin reporting is warranted. [ABSTRACT FROM AUTHOR]