Powell Jose

Renal Function and Effectiveness of Angiotensin-Converting Enzyme Inhibitor Therapy in Patients With Chronic Stable Coronary Disease in the Prevention of Events with ACE inhibition (PEACE) Trial

Background— Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post–myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function. Methods and Results— We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6±19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg · mL−1 · 1.73 m−2). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13). Conclusions— Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.

Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial

Abstract Objectives To determine whether data on proteinuria are useful for refining estimates of risk based on kidney function alone, and whether the results of kidney function tests can be a useful adjunct to data on proteinuria. Design Analysis of data from a randomised trial. Impaired kidney function was defined as low glomerular filtration rate (< 60 ml/min/1.73 m2) and proteinuria ( 1+ protein) on dipstick urinalysis. Setting Study of cholesterol and recurrent events: a randomised trial of pravastatin 40 mg daily versus placebo. Participants 4098 men and women with previous myocardial infarction. Main outcome measures All cause mortality and cardiovascular events. Results 371 participants died in nearly 60 months of follow-up. Compared with participants without proteinuria or impaired kidney function, patients with both characteristics were at high risk (hazard ratio 2.39, 95% confidence interval 1.72 to 3.30), and those with only proteinuria or only impaired kidney function were at intermediate risk (1.69, 1.32 to 2.16; 1.41, 1.12 to 1.79, respectively) of dying from any cause. The results were similar for cardiovascular outcomes, including new cases of heart failure, stroke, and coronary death or non-fatal myocardial infarction. A graded increase in the risk of all cause mortality was seen for severity of renal impairment and degree of proteinuria by dipstick. Conclusions The presence or absence of proteinuria on dipstick urinalysis may be used to refine estimates of risk based on kidney function alone.

Increase in Creatinine and Cardiovascular Risk in Patients with Systolic Dysfunction after Myocardial Infarction

Baseline renal function is a potent independent risk factor for adverse events after acute myocardial infarction (MI). Worsening renal function (WRF) has been shown to influence outcomes in the heart failure population, but its impact on cardiovascular risk in the post-MI period has not been well defined. For assessment of the prognostic importance of WRF, 2231 patients who had left ventricular dysfunction and were enrolled in the Survival and Ventricular Enlargement (SAVE) trial were studied. Patients were randomly assigned between 3 and 16 d (average 11 d) after acute MI to receive captopril or placebo; those with a serum creatinine of >2.5 mg/dl were excluded from SAVE. WRF was defined as an increase in creatinine of >0.3 mg/dl measured from baseline to 2 wk after randomization. The predictive value of WRF on cardiovascular morbidity and mortality was examined during 42 mo of follow-up. Paired serum creatinine measurements at baseline and 2 wk were available in 1854 patients. WRF occurred in 223 (12.0%) patients and was a stronger predictor of death (hazard ratio [HR] 1.46; 95% confidence interval [CI] 1.05 to 2.02) than baseline creatinine (HR 1.31; 95% CI 1.01 to 1.70). WRF also showed an increased risk for cardiovascular death (HR 1.62; 95% CI 1.14 to 2.30) and the composite end point (HR 1.32; 95% CI 1.03 to 1.70). When stratified by treatment, 104 (5.7%) and 116 (6.4%) patients with WRF in the placebo and captopril groups had no significant association between treatment group and WRF (P = 0.38). The risk for death associated with WRF was HR 1.63 (95% CI 1.05 to 2.52) in the placebo group compared with HR 1.33 (95% CI 0.81 to 2.21) in the captopril group (P = 0.49 for interaction). WRF as early as 2 wk after MI was not uncommon (12.0%) and was associated with increased mortality in patients without renal dysfunction at baseline. Patients who received captopril did not demonstrate more WRF than patients who received placebo. Monitoring serum creatinine in patients during the first few weeks after MI may help to identify those who are at highest risk and guide effective long-term therapeutic choices.

Cardiovascular disease mortality in Asian Americans.

BACKGROUND Asian Americans are a rapidly growing racial/ethnic group in the United States. Our current understanding of Asian-American cardiovascular disease mortality patterns is distorted by the aggregation of distinct subgroups. OBJECTIVES The purpose of the study was to examine heart disease and stroke mortality rates in Asian-American subgroups to determine racial/ethnic differences in cardiovascular disease mortality within the United States. METHODS We examined heart disease and stroke mortality rates for the 6 largest Asian-American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) from 2003 to 2010. U.S. death records were used to identify race/ethnicity and cause of death by International Classification of Diseases-10th revision coding. Using both U.S. Census data and death record data, standardized mortality ratios (SMRs), relative SMRs (rSMRs), and proportional mortality ratios were calculated for each sex and ethnic group relative to non-Hispanic whites (NHWs). RESULTS In this study, 10,442,034 death records were examined. Whereas NHW men and women had the highest overall mortality rates, Asian Indian men and women and Filipino men had greater proportionate mortality burden from ischemic heart disease. The proportionate mortality burden of hypertensive heart disease and cerebrovascular disease, especially hemorrhagic stroke, was higher in every Asian-American subgroup compared with NHWs. CONCLUSIONS The heterogeneity in cardiovascular disease mortality patterns among diverse Asian-American subgroups calls attention to the need for more research to help direct more specific treatment and prevention efforts, in particular with hypertension and stroke, to reduce health disparities for this growing population.

Racial/Ethnic Differences in Dyslipidemia Patterns

Background— No studies have comprehensively examined the prevalence of dyslipidemia, a major risk factor for cardiovascular disease, among diverse racial/ethnic minority groups. The primary aim of this study was to identify racial/ethnic differences in dyslipidemia among minorities including Asian Americans (Asian Indian, Chinese, Filipino, Japanese, Korean, or Vietnamese), Mexican Americans, and blacks compared with non-Hispanic whites. Methods and Results— Using a 3-year cross section (2008–2011), we identified 169 430 active primary care patients (35 years or older) from an outpatient healthcare organization in northern California. Age-standardized prevalence rates were calculated for 3 dyslipidemia subtypes: high triglycerides (fasting laboratory value ≥150 mg/dL), low levels of high-density lipoprotein cholesterol (fasting laboratory value <40 mg/dL [men] and <50 mg/dL [women]), and high levels of low-density lipoprotein cholesterol (fasting laboratory value ≥130 mg/dL or taking low-density lipoprotein–lowering agents). Odds ratios were calculated by multivariable logistic regression, with adjustment for patient characteristics (age, measured body mass index, smoking). Compared with non-Hispanic whites, every minority subgroup had an increased prevalence of high triglycerides except blacks. Most minority groups had an increased prevalence of low high-density lipoprotein cholesterol, except for Japanese and blacks. The prevalence of high low-density lipoprotein cholesterol was increased among Asian Indians, Filipinos, Japanese, and Vietnamese compared with non-Hispanic whites. Conclusions— Minority groups, except for blacks, were more likely to have high triglyceride/low high-density lipoprotein cholesterol dyslipidemia. Further research is needed to determine how racial/ethnic differences in dyslipidemia affect racial/ethnic differences in cardiovascular disease rates.

Leading Causes of Death among Asian American Subgroups (2003–2011)

Background Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups. Methods and Findings We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer’s disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs. Conclusions Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.

Racial/Ethnic Differences in Hypertension Prevalence, Treatment, and Control for Outpatients in Northern California 2010–2012

BACKGROUND Hypertension (HTN) is a known major cardiovascular disease risk factor, but prevalence, treatment, and control of HTN among rapidly growing minority groups such as Asian Americans and Hispanics are unknown largely due to either underrepresentation in epidemiologic studies or aggregation of Asian American subgroups. METHODS A three-year cross-section (2010-2012) of patients from a large ambulatory care setting in northern California was examined in the following subgroups: Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Mexicans, non-Hispanic Blacks (NHBs), and non-Hispanic Whites (NHWs). We defined HTN as two separate nonemergent office visit blood pressure measurements ≥140/90 mm Hg, physician diagnosis of HTN, or use of antihypertensive medications. RESULTS A total of 208,985 patients were included in the study. Age-adjusted HTN prevalence ranged from 30.0% in Chinese women to 59.9% in Filipino men. Most minority subgroups had lower or similar odds of having HTN compared with NHWs, except for Filipinos and NHBs whose odds were significantly higher after adjusting for patient demographic and clinical characteristics. Asian Americans and NHBs were more likely to be treated for HTN compared with NHWs. Achievement of blood pressure control was lower among Filipino women (odds ratio = 0.82, 99% confidence interval 0.70-0.96) and NHB men (odds ratio = 0.73, 99% confidence interval 0.58-0.91), compared with NHW women and men. CONCLUSIONS Substantial racial/ethnic variation in HTN prevalence, treatment, and control was found in our study population. Filipino and NHB women and men are at especially high risk for HTN and may have more difficulty in achieving adequate blood pressure control.

Autonomic dysfunction independently predicts poor cardiovascular outcomes in asymptomatic individuals with type 2 diabetes in the DIAD study

Objective: The primary aim of this secondary analysis was to determine whether cardiac autonomic neuropathy independently predicted adverse cardiac outcomes in asymptomatic individuals with type 2 diabetes. Additional aims include the determination of the correlation of standard autonomic testing measures and power spectral analysis of heart rate variability, and the association of diabetes-related and cardiac risk factors with cardiac autonomic neuropathy measures. Methods: Cardiac autonomic neuropathy was assessed at the study entry into the Detection of Ischemia in Asymptomatic Diabetics study, using autonomic heart rate and blood pressure testing, and power spectral analysis of heart rate variability. All participants were prospectively followed for the composite clinical outcome of cardiac death, acute coronary syndromes, heart failure, or coronary revascularization. Results: Over 5 years of follow-up, 94 of 1119 (8.4%) subjects developed symptomatic cardiac disease. In unadjusted bivariate analyses, abnormalities in several cardiac autonomic neuropathy tests, including lower Valsalva and Standing Heart Rate Ratios, higher resting Heart Rate, greater systolic blood pressure decrease on standing, and lower low-frequency power, were predictive of symptomatic disease. Independent predictors of poor cardiac outcome were a lower Valsalva Heart Rate Ratio, non-Black ethnicity, longer diabetes duration, higher glycated hemoglobin (HbA1c), insulin use, reported numbness in the extremities, higher pulse pressure, family history of coronary artery disease, and higher waist-to-hip ratio. Clinical factors independently associated with a lower Valsalva Heart Rate Ratio were insulin use, clinical proteinuria, higher pulse pressure, use of angiotensin-converting enzyme inhibitor and non-Black ethnicity. Conclusion: Cardiac autonomic neuropathy predicted adverse cardiac outcomes in asymptomatic type 2 diabetes without known cardiac disease. Clinical variables may help to identify patients who might have cardiac autonomic neuropathy and warrant consideration for autonomic testing.

Geographic Variations in Cardiovascular Disease Mortality Among Asian American Subgroups, 2003–2011

Background There are well‐documented geographical differences in cardiovascular disease (CVD) mortality for non‐Hispanic whites. However, it remains unknown whether similar geographical variation in CVD mortality exists for Asian American subgroups. This study aims to examine geographical differences in CVD mortality among Asian American subgroups living in the United States and whether they are consistent with geographical differences observed among non‐Hispanic whites. Methods and Results Using US death records from 2003 to 2011 (n=3 897 040 CVD deaths), age‐adjusted CVD mortality rates per 100 000 population and age‐adjusted mortality rate ratios were calculated for the 6 largest Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) and compared with non‐Hispanic whites. There were consistently lower mortality rates for all Asian American subgroups compared with non‐Hispanic whites across divisions for CVD mortality and ischemic heart disease mortality. However, cerebrovascular disease mortality demonstrated substantial geographical differences by Asian American subgroup. There were a number of regional divisions where certain Asian American subgroups (Filipino and Japanese men, Korean and Vietnamese men and women) possessed no mortality advantage compared with non‐Hispanic whites. The most striking geographical variation was with Filipino men (age‐adjusted mortality rate ratio=1.18; 95% CI, 1.14–1.24) and Japanese men (age‐adjusted mortality rate ratio=1.05; 95% CI: 1.00–1.11) in the Pacific division who had significantly higher cerebrovascular mortality than non‐Hispanic whites. Conclusions There was substantial geographical variation in Asian American subgroup mortality for cerebrovascular disease when compared with non‐Hispanic whites. It deserves increased attention to prioritize prevention and treatment in the Pacific division where approximately 80% of Filipinos CVD deaths and 90% of Japanese CVD deaths occur in the United States.