N-terminal pro-B-type natriuretic peptide and microsize myocardial infarction risk in the reasons for geographic and racial differences in stroke study.

BACKGROUND: N-terminal pro B-type peptide (NT-proBNP) has been associated with risk of myocardial infarction (MI), but less is known about the relationship between NT-proBNP and very small non ST-elevation MI, also known as microsize MI. These events are now routinely detectable with modern troponin assays and are emerging as a large proportion of all MI. Here, we sought to compare the association of NT-proBNP with risk of incident typical MI and microsize MI in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. METHODS: The REGARDS Study is a national cohort of 30,239 US community-dwelling black and white adults aged ≥ 45 years recruited from 2003 to 2007. Expert-adjudicated outcomes included incident typical MI (definite/probable MI with peak troponin ≥ 0.5 µg/L), incident microsize MI (definite/probable MI with peak troponin < 0.5 µg/L), and incident fatal CHD. Using a case-cohort design, we estimated the hazard ratio of the outcomes as a function of baseline NT-proBNP. Competing risk analyses tested whether the associations of NT-proBNP differed between the risk of incident microsize MI and incident typical MI as well as if the association of NT-proBNP differed between incident non-fatal microsize MI and incident non-fatal typical MI, while accounting for incident fatal coronary heart disease (CHD) as well as heart failure (HF). RESULTS: Over a median of 5 years of follow-up, there were 315 typical MI, 139 microsize MI, and 195 incident fatal CHD. NT-proBNP was independently and strongly associated with all CHD endpoints, with significantly greater risk observed for incident microsize MI, even after removing individuals with suspected HF prior to or coincident with their incident CHD event. CONCLUSION: NT-proBNP is associated with all MIs, but is a more powerful risk factor for microsize than typical MI.

Antidepressant Medication Use and Its Association With Cardiovascular Disease and All-Cause Mortality in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

BACKGROUND: Mixed evidence suggests that second-generation antidepressants may increase the risk of cardiovascular and cerebrovascular events. OBJECTIVE: To assess whether antidepressant use is associated with acute coronary heart disease (CHD), stroke, cardiovascular disease (CVD) death, and all-cause mortality. METHODS: Secondary analyses of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) longitudinal cohort study were conducted. Use of selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, bupropion, nefazodone, and trazodone was measured during the baseline (2003-2007) in-home visit. Outcomes of CHD, stroke, CVD death, and all-cause mortality were assessed every 6 months and adjudicated by medical record review. Cox proportional hazards time-to-event analysis followed patients until their first event on or before December 31, 2011, iteratively adjusting for covariates. RESULTS: Among 29 616 participants, 3458 (11.7%) used an antidepressant of interest. Intermediate models adjusting for everything but physical and mental health found an increased risk of acute CHD (hazard ratio [HR] = 1.21; 95% CI = 1.04-1.41), stroke (HR = 1.28; 95% CI = 1.02-1.60), CVD death (HR = 1.29; 95% CI = 1.09-1.53), and all-cause mortality (HR = 1.27; 95% CI = 1.15-1.41) for antidepressant users. Risk estimates trended in this direction for all outcomes in the fully adjusted model but only remained statistically associated with increased risk of all-cause mortality (HR = 1.12; 95% CI = 1.01-1.24). This risk was attenuated in sensitivity analyses censoring follow-up time at 2 years (HR = 1.37; 95% CI = 1.11-1.68). CONCLUSIONS: In fully adjusted models, antidepressant use was associated with a small increase in all-cause mortality.

Burden of Coronary Heart Disease Rehospitalizations Following Acute Myocardial Infarction in Older Adults.

PURPOSE: Studies of prognosis following acute myocardial infarction (AMI) conventionally examine the first recurrent coronary heart disease (CHD) event which may not adequately characterize the full burden of CHD hospitalizations. We therefore examined the cumulative number of CHD rehospitalizations following AMI among older adults in the United States. METHODS: We conducted a retrospective cohort study of 78,085 Medicare beneficiaries aged ≥66 years without recent CHD history who were hospitalized for AMI in 2000-2010. Counts of CHD rehospitalizations over a maximum of 10 years of follow-up were calculated. Characteristics were assessed through claims and enrollment information and associations with CHD rehospitalizations were evaluated using Poisson models. RESULTS: Over 25 % of beneficiaries were aged ≥85 years, 55 % were women, and 89 % were white. Comorbidities were common, including diabetes (22.9 %), hypertension (46.7 %), heart failure (10.3 %), and chronic obstructive pulmonary disease (19.2 %). Following AMI, 16,078 beneficiaries (20.6 %) were hospitalized for CHD a total of 23,132 times. Among those who experienced at least one CHD rehospitalization, 35.9 % had ≥2 CHD rehospitalizations (n = 5773, 7.4 % of all beneficiaries with AMI) in the ensuing decade. Associations of demographics, comorbidities, and index hospitalization characteristics with rates of first and total CHD rehospitalizations were largely similar. Age ≥85 years versus 66-69 years was more strongly associated with first (rate ratio [RR] 1.43) than total (RR 1.35) CHD rehospitalization (p < 0.05), as was male versus female sex (RR 1.13 and 1.07). CONCLUSIONS: Emphasizing the first recurrent CHD rehospitalization underestimates the burden of disease experienced among older adults with AMI.

Statin therapy and plasma coenzyme Q10 concentrations--A systematic review and meta-analysis of placebo-controlled trials.

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.

Perceived Stress and Atrial Fibrillation: The REasons for Geographic and Racial Differences in Stroke Study.

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.

Assessment tools for unrecognized myocardial infarction: a cross-sectional analysis of the REasons for Geographic and Racial Differences in Stroke population.

BACKGROUND: Routine electrocardiograms (ECGs) are not recommended for asymptomatic patients because the potential harms are thought to outweigh any benefits. Assessment tools to identify high risk individuals may improve the harm versus benefit profile of screening ECGs. In particular, people with unrecognized myocardial infarction (UMI) have elevated risk for cardiovascular events and death. METHODS: Using logistic regression, we developed a basic assessment tool among 16,653 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study using demographics, self-reported medical history, blood pressure, and body mass index and an expanded assessment tool using information on 51 potential variables. UMI was defined as electrocardiogram evidence of myocardial infarction without a self-reported history (n = 740). RESULTS: The basic assessment tool had a c-statistic of 0.638 (95% confidence interval 0.617-0.659) and included age, race, smoking status, body mass index, systolic blood pressure, and self-reported history of transient ischemic attack, deep vein thrombosis, falls, diabetes, and hypertension. A predicted probability of UMI > 3% provided a sensitivity of 80% and a specificity of 30%. The expanded assessment tool had a c-statistic of 0.654 (95% confidence interval 0.634-0.674). Because of the poor performance of these assessment tools, external validation was not pursued. CONCLUSIONS: Despite examining a large number of potential correlates of UMI, the assessment tools did not provide a high level of discrimination. These data suggest defining groups with high prevalence of UMI for targeted screening will be difficult.

Hospital laboratory reporting may be a barrier to detection of 'microsize' myocardial infarction in the US: an observational study.

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.

Primary prophylactic aspirin use and incident stroke: reasons for geographic and racial differences in stroke study.

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.

Myocardial infarction after carotid stenting and endarterectomy: results from the carotid revascularization endarterectomy versus stenting trial.

BACKGROUND: 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.

Is Medication Adherence Predictive of Cardiovascular Outcomes and Blood Pressure Control? The Systolic Blood Pressure Intervention Trial (SPRINT).

BACKGROUND: Adherence to study medications is crucial to evaluating treatment effects in clinical trials. To assess whether in the SPRINT trial, adherence and cardiovascular outcomes are associated regardless of intervention assignment. METHODS: This study included 9,361 participants aged ≥50 years, recruited from 102 clinics. Participants were randomized to a Standard Treatment Group (targeted systolic blood pressure [SBP] <140 mm Hg) or an Intensive Treatment Group (targeted SBP <120 mm Hg) and followed for incident cardiovascular events until the study was halted early for benefit. The 8-item Morisky Medication Adherence Scale (MMAS-8) was administered at baseline, and at the 12- and 48-month (or close out) visit. RESULTS: Adjusting for covariates, there was no association between the baseline 8-item MMAS-8 and the likelihood of the primary composite endpoint, any of the secondary endpoints, or blood pressure (BP) control. Low adherence was associated with a higher body mass index, SBP, diastolic BP, and Patient Health Questionnaire, and high adherence was associated with a higher Montreal Cognitive Assessment. There was no difference in the MMAS-8 over time by treatment arm assignment. For the primary outcome (a composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes), baseline odds ratios (95% confidence intervals) for the Low vs. Medium and vs. High; and, for Medium vs. High MMAS-8 were 1.02 (0.82-1.28), 1.07 (0.85-1.34), and 1.05 (0.88-1.250). CONCLUSIONS: In SPRINT, medication adherence as measured using the MMAS-8 was not associated with outcomes or BP control.

Is randomization to placebo safe? Risk in placebo-controlled angina trials: angina risk meta-analysis.

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.

High-fat meal effect on LDL, HDL, and VLDL particle size and number in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN): an interventional study.

BACKGROUND: Postprandial lipemia (PPL) is likely a risk factor for cardiovascular disease but these changes have not been well described and characterized in a large cohort. We assessed acute changes in the size and concentration of total and subclasses of LDL, HDL, and VLDL particles in response to a high-fat meal. Participants (n = 1048) from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study who ingested a high-fat meal were included in this analysis. Lipids were measured at 0 hr (fasting), 3.5 hr, and 6 hr after a standardized fat meal. Particle size distributions were determined using nuclear magnetic resonance spectroscopy. Analyses were stratified by baseline triglycerides (normal vs. elevated) and gender. The effect of PPL on changes in lipoprotein subclasses was assessed using repeated measures ANOVA. RESULTS: Postprandially, LDL-C, HDL-C, VLDL-C, and triglycerides increased regardless of baseline triglyceride status, with the largest increases in VLDL-C and TG; however, those with elevated triglycerides demonstrated larger magnitude of response. Total LDL particle number decreased over the 6-hour time interval, mostly from a decrease in the number of small LDL particles. Similarly, total VLDL particle number decreased due to reductions in medium and small VLDL particles. Large VLDL particles and chylomicrons demonstrated the largest increase in concentration. HDL particles demonstrated minimal overall changes in total particle number. CONCLUSIONS: We have characterized the changes in LDL and VLDL particle number, and their subclass patterns following a high-fat meal.

Trust in physicians and blood pressure control in blacks and whites being treated for hypertension in the REGARDS study.

OBJECTIVES: Among persons treated for hypertension, Blacks are more likely to have uncontrolled blood pressure compared to Whites. Few studies have focused on trust in physicians as a potential contributor to this disparity in blood pressure (BP) control. The primary objective of this study was to assess the relationship between trust in physicians and blood pressure control among Blacks and Whites being treated for hypertension. DESIGN: Cross-sectional analysis of baseline data collected from the REasons for Geographic And Racial Differences in Stroke cohort, a US national, population-based cohort study. Participants were recruited by telephone from 2003-2007, completed a telephone survey, and had BP measured during an in-home visit. PARTICIPANTS: 2843 Black and White adults aged > 45 years with treated hypertension. MAIN OUTCOME MEASURES: Uncontrolled blood pressure was defined as systolic blood pressure > 140 mm Hg or diastolic blood pressure > 90 mm Hg. For participants with diabetes, renal disease, or self-reported previous myocardial infarction, uncontrolled blood pressure was defined as systolic blood pressure > 130 mm Hg or diastolic blood pressure > 80 mm Hg. RESULTS: Trust in physicians was not associated with uncontrolled blood pressure in either unadjusted (odd ratio [OR] 1.07; 95% confidence interval [CI) 0.92, 1.25) or adjusted analyses (OR 0.97; 0.83, 1.14). Both Black race (OR 1.58; 1.36, 1.84) and imperfect medication adherence (OR 1.56; 1.31,1.86) were associated with higher odds of uncontrolled blood pressure. CONCLUSIONS: Trust in physicians was not related to blood pressure control among Blacks and Whites with treated hypertension in this sample. The racial disparity in blood pressure control was not completely explained by trust in physicians or medication adherence, and a better understanding of the mechanisms leading to this disparity is needed.

C-reactive protein and risk of cognitive decline: The REGARDS study.

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.

Outcomes in adults with systolic blood pressure between 130 and 139 mmHg in Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial and Systolic Blood Pressure Intervention Trial.

BACKGROUND: Patients with stage 1 systolic hypertension have increased risk of cardiovascular disease (CVD) events. METHODS: Using Cox models, we assess the effect of targeting an intensive SBP goal of less than 120 mmHg compared with standard SBP goal of less than 140 mmHg on the risk of CVD events in adults with stage 1 systolic hypertension with diabetes mellitus enrolled in Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) (n = 1901) and without diabetes mellitus enrolled in Systolic Blood Pressure Intervention Trial (SPRINT) (n = 3484) that used identical SBP goal interventions. OUTCOMES: In ACCORD BP, the primary composite CVD outcome was the first occurrence of myocardial infarction, stroke, or CVD mortality. In SPRINT, the primary composite CVD outcome was the first occurrence of myocardial infarction, other acute coronary syndrome, stroke, heart failure, or CVD mortality. RESULTS: In SPRINT, targeting an intensive SBP goal significantly reduced the risk of the primary CVD outcome [hazard ratio 0.75 (95% confidence interval, 0.58-0.98); events 1.78 vs. 2.37%/year]. In ACCORD BP, the relationships of SBP goal with the primary CVD outcome was modified by the glycemia goal intervention (interaction P = 0.039). In the standard glycemia subgroup (A1c target 7-7.9%), intensive SBP goal significantly reduced the risk of the primary CVD outcome [hazard ratio 0.61 (0.40-0.94); events 1.63 vs. 2.56%/year]. In the intensive glycemia subgroup (A1c target <6%), the risk of the primary CVD outcome was not significantly different between groups [hazard ratio 1.20 (0.76-1.89); events 1.91 vs. 1.60%/year]. CONCLUSION: Targeting an intensive SBP goal significantly reduced the risk of CVD events in patients with stage 1 systolic hypertension without diabetes and with diabetes on standard glycemia goal.

History of Cardiovascular Disease, Intensive Lifestyle Intervention, and Cardiovascular Outcomes in the Look AHEAD Trial.

OBJECTIVE: To examine the effects of an intensive lifestyle intervention (ILI) on cardiovascular disease (CVD), the Action for Health in Diabetes (Look AHEAD) trial randomized 5,145 participants with type 2 diabetes and overweight/obesity to a ILI or diabetes support and education. Although the primary outcome did not differ between the groups, there was suggestive evidence of heterogeneity for prespecified baseline CVD history subgroups (interaction P = 0.063). Event rates were higher in the ILI group among those with a CVD history (hazard ratio 1.13 [95% CI: 0.90-1.41]) and lower among those without CVD (hazard ratio 0.86 [95% CI: 0.72-1.02]). METHODS: This study conducted post hoc analyses of the rates of the primary composite outcome and components, adjudicated cardiovascular death, nonfatal myocardial infarction (MI), stroke, and hospitalization for angina, as well as three secondary composite cardiovascular outcomes. RESULTS: Interaction P values for the primary and two secondary composites were similar (0.060-0.064). Of components, the interaction was significant for nonfatal MI (P = 0.035). This interaction was not due to confounding by baseline variables, different intervention responses for weight loss and physical fitness, or hypoglycemic events. In those with a CVD history, statin use was high and similar by group. In those without a CVD history, low-density lipoprotein cholesterol levels were higher (P = 0.003) and statin use was lower (P ≤ 0.001) in the ILI group. CONCLUSIONS: Intervention response heterogeneity was significant for nonfatal MI. Response heterogeneity may need consideration in a CVD-outcome trial design.

Effect of Intensive and Standard Clinic-Based Hypertension Management on the Concordance Between Clinic and Ambulatory Blood Pressure and Blood Pressure Variability in SPRINT.

Background Blood pressure ( BP ) varies over time within individual patients and across different BP measurement techniques. The effect of different BP targets on concordance between BP measurements is unknown. The goals of this analysis are to evaluate concordance between (1) clinic and ambulatory BP , (2) clinic visit-to-visit variability and ambulatory BP variability, and (3) first and second ambulatory BP and to evaluate whether different clinic targets affect these relationships. Methods and Results The SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP monitoring ancillary study obtained ambulatory BP readings in 897 participants at the 27-month follow-up visit and obtained a second reading in 203 participants 293±84 days afterward. There was considerable lack of agreement between clinic and daytime ambulatory systolic BP with wide limits of agreement in Bland-Altman plots of -21 to 34 mm Hg in the intensive-treatment group and -26 to 32 mm Hg in the standard-treatment group. Overall, there was poor agreement between clinic visit-to-visit variability and ambulatory BP variability with correlation coefficients for systolic and diastolic BP all <0.16. We observed a high correlation between first and second ambulatory BP ; however, the limits of agreement were wide in both the intensive group (-27 to 21 mm Hg) and the standard group (-23 to 20 mm Hg). Conclusions We found low concordance in BP and BP variability between clinic and ambulatory BP and second ambulatory BP . Results did not differ by treatment arm. These results reinforce the need for multiple BP measurements before clinical decision making.

Does differential prophylactic aspirin use contribute to racial and geographic disparities in stroke and coronary heart disease (CHD)?

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.

Race, Sex, Age, and Regional Differences in the Association of Obstructive Sleep Apnea With Atrial Fibrillation: Reasons for Geographic and Racial Differences in Stroke Study.

STUDY OBJECTIVES: To examine the cross-sectional association between obstructive sleep apnea (OSA) risk and atrial fibrillation (AF) in the REasons for Geographic And Racial Differences in Stroke (REGARDS), a cohort of black and white adults. METHODS: Using REGARDS data from subjects recruited between 2003-2007, we assessed 20,351 participants for OSA status. High OSA risk was determined if the participant met at least two criteria from the Berlin Sleep Questionnaire (persistent snoring, frequent sleepiness, high blood pressure, or obesity). AF was defined as a self-reported history of a previous physician diagnosis or presence of AF on electrocardiogram. Logistic regression was used to determine odds ratio and 95% confidence interval for the association between OSA status and AF with subgroup analysis to examine effect modification by age, race, sex, and geographical region. RESULTS: The prevalence of AF was 7% (n = 1,079/14,992) and 9% (n = 482/5,359) in participants at low and high risk of OSA, respectively (P < .0001). Persons at high risk of OSA had greater prevalence of diabetes and stroke history, and were more likely to be obese and taking sleep medications. In a multivariable analysis adjusted for demographics, cardiovascular risk factors, and potential confounders, high risk for OSA was associated with an increased odds of AF compared to low risk for OSA (odds ratio = 1.27, 95% confidence interval = 1.13, 1.44). This association differed significantly only by race (P for interaction = .0003). For blacks, there was a significant 58% increase in odds of AF in participants at high risk versus low risk of OSA, compared to a nonsignificant 12% increase in odds in whites. We were limited by self-reported variables, inability to adjust for obesity, and the cross-sectional nature of our study. CONCLUSIONS: High risk of OSA is associated with prevalent AF among blacks but not whites. COMMENTARY: A commentary on this article appears in this issue on page 1459.

Serum Tumor Necrosis Factor-alpha associates with Myocardial Oxygen Demand and Exercise Tolerance in Postmenopausal Women.

The functional implications of serum tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic parameters at rest and during physical exertion are unclear. The aims of this investigation were to examine the independent associations of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the association of TNF-α on exercise tolerance. Forty, postmenopausal women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake (VO2max). Large artery compliance was measured by pulse contour analyses while rate-pressure product (RPP), an index of myocardial oxygen demand, was measured at rest and during two submaximal workloads (i.e., ≈55% and ≈75% VO2max). RPP was calculated by dividing the product of heart rate and systolic blood pressure (via auscultation) by 100. Exercise tolerance corresponded with the cessation of the graded exercise test. During higher-intensity exertion, ≈75% VO2max, multiple linear regression revealed a positive association (r = 0.43; p = 0.015) between TNF-α and RPP while adjusting for maximal heart rate, VO2max, large artery compliance, and percent body fat. Path analyses revealed a significant indirect effect of large artery compliance on exercise tolerance through TNF-α, ß = 0.13, CI [0.03, 0.35], indicating greater levels of TNF-α associated with poorer exercise tolerance. These data suggest TNF-α independently associates with myocardial oxygen demand during physical exertion, thus highlighting the utility of higher-intensity efforts to expose important phenomena not apparent at rest. TNF-α also appears to be indirectly associated with the link between large artery compliance and exercise tolerance.