Racial Differences in Characteristics and Outcomes of Patients With Heart Failure and Preserved Ejection Fraction in the Treatment of Preserved Cardiac Function Heart Failure Trial.

BACKGROUND: Black patients have been shown to have different baseline characteristics and outcomes compared with nonblack patients in cohort studies. However, few studies have focused on heart failure (HF) with preserved ejection fraction (HFpEF) patients. We aimed to determine the difference in cardiovascular outcomes in black and nonblack patients with HFpEF and to determine the relative efficacy and safety of spironolactone in black and nonblack patients. METHODS AND RESULTS: Patients with HFpEF, randomized to spironolactone versus placebo in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) in North and South America, were grouped according to self-described black and nonblack race. Black HFpEF patients (n=302) were younger and were more likely to have diabetes mellitus and hypertension than nonblack patients but had similar HFpEF severity. Black patients had higher risk for the primary outcome (hazard ratio [HR], 1.34; 95% confidence interval, 1.06-1.71; P=0.02) and first HF hospitalization (HR, 1.51; 95% confidence interval, 1.167-1.97; P=0.002)], but no significant difference in cardiovascular mortality risk (HR, 0.78; 95% confidence interval, 0.51-1.20; P=0.326). In black and nonblack patients, randomization to spironolactone conferred similar efficacy in the primary outcome (HR, 0.83 versus 0.79; P for interaction=0.49), HF hospitalization (HR, 0.67 versus 0.82; P for interaction=0.76), and cardiovascular mortality (P for interaction=0.19). The risk of hyperkalemia and worsening renal function with spironolactone and study drug adherence were also similar. CONCLUSIONS: Black patients with HFpEF have a higher HF hospitalization risk than nonblack patients, but spironolactone is similarly effective and safe in both groups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00094302.

Non-adherence in Hypertension Management Deficit in Information or Trust?

Hypertension, a leading cause of cardiovascular morbidity and mortality worldwide, continues to challenge health professionals. There are too many patients with uncontrolled hypertension who end up with life altering or life ending complications. Over the years so much hypertension research has been conducted; and numerous effective antihypertensive drugs have been discovered and yet the rate of blood pressure control remains unacceptably low. It is high time that we focused our attention on the optimal use of the available knowledge and medications. More emphasis on teaching the patients and the public at large is required and patients need to have full trust of their health care providers in order to adhere to the prescriptions provided. If patients take their medications as prescribed and follow therapeutic lifestyle changes like physical activity and calorie and salt restrictions, there would be very few patients with uncontrolled hypertension and its complications.

Should Antihypertensive Treatment Recommendations Differ in Patients With and Without Coronary Heart Disease? (from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]).

Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with preexisting CHD). This post hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n = 9048) or lisinopril (n = 9,054) with those assigned chlorthalidone (n = 15,255), stratified by CHD status. After 4 to 8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8 to 13 years. For most CVD outcomes, end-stage renal disease, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall hazard ratios [HRs] 1.10, p <0.001, and 1.38, p <0.001, respectively). During extended follow-up, significant outcomes according to CHD status interactions (p = 0.012) were noted in amlodipine versus chlorthalidone comparison for CVD and CHD mortality (HR 0.88, p = 0.04, and 0.84, p = 0.04, respectively) in those with CHD at baseline (HR 1.06, p = 0.15, and 1.08, p = 0.17) and in those without. The results of the overall increased stroke mortality in lisinopril compared with chlorthalidone (HR 1.2; p = 0.03) and hospitalized heart failure in amlodipine compared with chlorthalidone (HR 1.12; p = 0.01) during extended follow-up did not differ by baseline CHD status. In conclusion, these results provide no reason to alter our previous recommendation to include a properly dosed diuretic (such as chlorthalidone 12.5 to 25 mg/day) in the initial antihypertensive regimen for most hypertensive patients.

Obesity and Cardiovascular Diseases in a High-Risk Population: Evidence-Based Approach to CHD Risk Reduction.

BACKGROUND: Obesity is becoming a worldwide public health problem and it is expected to worsen as its prevalence is increasing in children and adolescents. This report examined the distribution of major cardiovascular disease (CVD) risk factors and the effect of life-style changes on coronary heart disease (CHD) risk prediction in a high risk obese African Americans. METHODS: We examined the baseline distribution of CVD risk factors in 515 obese African Americans, with mean BMI of 42.9 ± 6.8 kg/m2, and prospectively the effect of a 6-month low-salt, low-fat diet and aerobic-exercise intervention program on risk reduction. RESULTS: Prevalence of hypertension, dyslipidemia, and diabetes mellitus were 57%, 27% and 24% respectively. Metabolic syndrome was present in 36% and 39% met two features of the syndrome. The 10-year risk prediction for developing CHD ranged from 4% to 17% for women and 6% to 29% for men. After 6 months of life-style changes, many of the risk factors improved, and the CHD risk scores decreased from 6% to 4% in the women and 16% to 13% in the men. CONCLUSION: The high prevalence and increasing incidence of obesity and associated cardiovascular risk emphasizes the need to focus on obesity reduction in this high risk population.

Blood pressure control and cardiovascular outcomes in normal-weight, overweight, and obese hypertensive patients treated with three different antihypertensives in ALLHAT.

OBJECTIVE: Epidemiologically, there is a strong relationship between BMI and blood pressure (BP) levels. We prospectively examined randomization to first-step chlorthalidone, a thiazide-type diuretic; amlodipine, a calcium-channel blocker; and lisinopril, an angiotensin-converting enzyme inhibitor, on BP control and cardiovascular outcomes in a hypertensive cohort stratified by baseline BMI [kg/m(2); normal weight (BMI <25), overweight (BMI = 25-29.9), and obese (BMI >30)]. METHODS: In a randomized, double-blind, practice-based Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, 33,357 hypertensive participants, aged at least 55 years, were followed for an average of 4.9 years, for a primary outcome of fatal coronary heart disease or nonfatal myocardial infarction, and secondary outcomes of stroke, heart failure, combined cardiovascular disease, mortality, and renal failure. RESULTS: Of participants, 37.9% were overweight and 42.1% were obese at randomization. For each medication, BP control (<140/90 mmHg) was equivalent in each BMI stratum. At the fifth year, 66.1, 66.5, and 65.1% of normal-weight, overweight, and obese participants, respectively, were controlled. Those randomized to chlorthalidone had highest BP control (67.2, 68.3, and 68.4%, respectively) and to lisinopril the lowest (60.4, 63.2, and 59.6%, respectively) in each BMI stratum. A significant interaction (P = 0.004) suggests a lower coronary heart disease risk in the obese for lisinopril versus chlorthalidone (hazard ratio 0.85, 95% confidence interval 0.74-0.98) and a significant interaction (P = 0.011) suggests a higher risk of end-stage renal disease for amlodipine versus chlorthalidone in obese participants (hazard ratio 1.49, 95% confidence interval 1.06-2.08). However, these results were not consistent among other outcomes. CONCLUSION: BMI status does not modify the effects of antihypertensive medications on BP control or cardiovascular disease outcomes.

Long-term follow-up of participants with heart failure in the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT).

BACKGROUND: In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in high-risk hypertensive participants, risk of new-onset heart failure (HF) was higher in the amlodipine (2.5-10 mg/d) and lisinopril (10-40 mg/d) arms compared with the chlorthalidone (12.5-25 mg/d) arm. Similar to other studies, mortality rates following new-onset HF were very high (≥50% at 5 years), and were similar across randomized treatment arms. After the randomized phase of the trial ended in 2002, outcomes were determined from administrative databases. METHODS AND RESULTS: With the use of national databases, posttrial follow-up mortality through 2006 was obtained on participants who developed new-onset HF during the randomized (in-trial) phase of ALLHAT. Mean follow-up for the entire period was 8.9 years. Of 1761 participants with incident HF in-trial, 1348 died. Post-HF all-cause mortality was similar across treatment groups, with adjusted hazard ratios (95% confidence intervals) of 0.95 (0.81-1.12) and 1.05 (0.89-1.25), respectively, for amlodipine and lisinopril compared with chlorthalidone, and 10-year adjusted rates of 86%, 87%, and 83%, respectively. All-cause mortality rates were also similar among those with reduced ejection fractions (84%) and preserved ejection fractions (81%), with no significant differences by randomized treatment arm. CONCLUSIONS: Once HF develops, risk of death is high and consistent across randomized treatment groups. Measures to prevent the development of HF, especially blood pressure control, must be a priority if mortality associated with the development of HF is to be addressed. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Blood pressure control by drug group in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Blood pressure (BP) control rates and number of antihypertensive medications were compared (average follow-up, 4.9 years) by randomized groups: chlorthalidone, 12.5-25 mg/d (n=15,255), amlodipine 2.5-10 mg/d (n=9048), or lisinopril 10-40 mg/d (n=9054) in a randomized double-blind hypertension trial. Participants were hypertensives aged 55 or older with additional cardiovascular risk factor(s), recruited from 623 centers. Additional agents from other classes were added as needed to achieve BP control. BP was reduced from 145/83 mm Hg (27% control) to 134/76 mm Hg (chlorthalidone, 68% control), 135/75 mm Hg (amlodipine, 66% control), and 136/76 mm Hg (lisinopril, 61% control) by 5 years; the mean number of drugs prescribed was 1.9, 2.0, and 2.1, respectively. Only 28% (chlorthalidone), 24% (amlodipine), and 24% (lisinopril) were controlled on monotherapy. BP control was achieved in the majority of each randomized group-a greater proportion with chlorthalidone. Over time, providers and patients should expect multidrug therapy to achieve BP <140/90 mm Hg in a majority of patients.

Incidence and predictors of angioedema in elderly hypertensive patients at high risk for cardiovascular disease: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Angioedema is a rare, potentially life-threatening condition that has been associated with angiotensin-converting enzyme inhibitors since their introduction in the 1980s. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the largest antihypertensive study conducted to date, randomized 42,418 participants to a diuretic (chlorthalidone), a calcium channel blocker (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), or an alpha-blocker (doxazosin). Patients who developed angioedema were compared for baseline characteristics and changes in antihypertensive drug administration. Fifty-three participants developed angioedema during active follow-up: 55% were black, 60% men, and 70% were assigned to lisinopril (including 62% of black participants with angioedema), 15% to chlorthalidone, 9% to doxazosin, and 6% to amlodipine. Six percent occurred within a day of randomization and 23% within the first week. Over half did not have an increase in their assigned (blinded) antihypertensive drug before angioedema onset; 3 (6%) had a dose increase within a week before onset. One patient died following an angioedema episode. The occurrence of angioedema in the angiotensin-converting enzyme inhibitor arm corresponds with previously reported angioedema-angiotensin-converting enzyme inhibitor associations.

Obese African Americans: the prevalence of dyslipidemia, hypertension, and diabetes mellitus.

CONTEXT: The prevalence of the cardiovascular disease risk factors, dyslipidemia, hypertension, and diabetes mellitus, is increased in the setting of obesity. OBJECTIVE: To determine whether the prevalence of these risk factors increases with increasing body mass index in an obese cohort, or whether there is a threshold for their appearance. DESIGN AND SETTING: Individuals with body mass index > or = 30 kg/m2 joined a weight reduction program in the Howard University General Clinical Research Center. PARTICIPANTS: Five hundred fifteen African Americans (aged 12-74 years, mean body mass index of 42.8 +/- 8.5 kg/m2). OUTCOME MEASURES: The cohort was divided by incremental increases in body mass index of 4.99 kg/m2, and the prevalence rates of hypertension (blood pressure > or = 140/90 mm Hg), dyslipidemia (total cholesterol > 200 mg/dL, or low-density lipoprotein > 130 mg/dL, or elevated ratio of total or low-density to high-density lipoprotein cholesterol) and diabetes mellitus (fasting blood glucose > or = 126 mg/dL or random blood glucose > 200 mg/dL) were determined for each group. RESULTS: The cohort prevalence rates were: dyslipidemia, 27.0%; hypertension, 56.9%; and diabetes mellitus, 24.1%. These rates are higher than those found in the African-American population by the third National Health and Nutrition Examination Survey. After adjusting for age and sex, there were no significant differences in the prevalence rates of these risk factors according to increasing body mass index, suggesting a threshold of between 30 kg/m2-34.99 kg/m2 for maximal appearance of these risk factors. CONCLUSION: The incidence rates of dyslipidemia, hypertension, and diabetes mellitus do not increase with a greater degree of obesity above a body mass index of 34.99 kg/m2.

Hypertension and concomitant diseases: a guide for evidence-based therapy.

Hypertension remains one of the leading causes of morbidity and mortality in the United States. Numerous antihypertensive agents are available today, and most hypertensive patients suffer from concomitant diseases/conditions. Many of these diseases/conditions require appropriate selection of antihypertensive agents. It gets quite complex to pick the initial and additional antihypertensive agents that are simultaneously beneficial in the management of these comorbidities. The authors believe this guide will assist physicians in picking the right agent to achieve goal blood pressure recommended by the Joint National Committee (JNC). In this paper, the introduction section briefly outlines some aspects of the pathophysiology of hypertension. This is followed by subsections that identify commonly encountered diseases/conditions that coexist with hypertension, and a list of antihypertensive drugs to be used for these conditions in the order of preference. The suggested choices are based on evidence from clinical trials, for the most part, and in some cases based on mechanisms of action of the drugs. The list of choices is then followed by concise explanations or rationale, including citations for the clinical trials or other relevant sources. Such a systematic approach and use of a handy flow chart would enhance appropriate blood pressure control and patient compliance and, hopefully, make a little dent in the rate of hypertension-related cardiovascular morbidity and mortality.