Otelio S. Randall

Intensive blood-pressure control in hypertensive chronic kidney disease.

BACKGROUND In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P=0.27). However, the effects differed according to the baseline level of proteinuria (P=0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P=0.01). CONCLUSIONS In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.)

Design and baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study

Hypertension and end-stage renal disease (ESRD) are major causes of morbidity and mortality in the United States, especially among African Americans. The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of conducting a long-term clinical trial to compare the effects of two levels of blood pressure control and three different antihypertensive drug regimens on the rate of decline in glomerular filtration rate (GFR) in African Americans with clinically diagnosed hypertensive renal disease. African American men and women aged 18-70 years with a GFR of 25-70 ml/min/ 1.73m2 and hypertension were randomized in a 3 x 2 factorial design to initial treatment with either an angiotensin-converting enzyme inhibitor (enalapril), a calcium channel blocker (amlodipine), or a beta blocker (atenolol) and to a mean arterial blood pressure (goal MAP) of either 102-107 mm Hg or < or = 92 mm Hg. Furosemide, doxazosin, clonidine, hydralazine, and minoxidil were added sequentially until goal MAP was achieved. To compare the pathologic diagnosis with the clinical diagnosis of renal disease, study participants without contraindication were also asked to undergo a renal biopsy. The goals of the AASK Pilot Study were to evaluate recruitment techniques, adherence to prescribed antihypertensive drug regimens, ability of the antihypertensive regimens to achieve blood pressure goals, rates of participation in scheduled clinic visits and procedures, and variability of GFR measurements. A further goal was to obtain renal biopsy data in at least 75% of the randomized study participants. Compared to the ESRD patient population whose renal disease is caused by hypertension, women were underrepresented in the AASK Pilot Study. AASK Pilot Study participants had higher unemployment rates and lower income levels than African Americans in the general U.S. population.

Validation of heart failure events in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants assigned to doxazosin and chlorthalidone

BackgroundThe Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, double-blind, active-controlled trial designed to compare the rate of coronary heart disease events in high-risk hypertensive participants initially randomized to a diuretic (chlorthalidone) versus each of three alternative antihypertensive drugs: alpha-adrenergic blocker (doxazosin), ACE-inhibitor (lisinopril), and calcium-channel blocker (amlodipine). Combined cardiovascular disease risk was significantly increased in the doxazosin arm compared to the chlorthalidone arm (RR 1.25; 95% CI, 1.17–1.33; P < .001), with a doubling of heart failure (fatal, hospitalized, or non-hospitalized but treated) (RR 2.04; 95% CI, 1.79–2.32; P < .001). Questions about heart failure diagnostic criteria led to steps to validate these events further.Methods and ResultsBaseline characteristics (age, race, sex, blood pressure) did not differ significantly between treatment groups (P < .05) for participants with heart failure events. Post-event pharmacologic management was similar in both groups and generally conformed to accepted heart failure therapy. Central review of a small sample of cases showed high adherence to ALLHAT heart failure criteria. Of 105 participants with quantitative ejection fraction measurements provided, (67% by echocardiogram, 31% by catheterization), 29/46 (63%) from the chlorthalidone group and 41/59 (70%) from the doxazosin group were at or below 40%. Two-year heart failure case-fatalities (22% and 19% in the doxazosin and chlorthalidone groups, respectively) were as expected and did not differ significantly (RR 0.96; 95% CI, 0.67–1.38; P = 0.83).ConclusionResults of the validation process supported findings of increased heart failure in the ALLHAT doxazosin treatment arm compared to the chlorthalidone treatment arm.

Metabolic syndrome, proteinuria, and the risk of progressive CKD in hypertensive African Americans.

BACKGROUND Chronic kidney disease (CKD) is more likely to progress to kidney failure (end-stage renal disease) in African Americans, although the reasons for this are unclear. Metabolic syndrome is a risk factor for the development of diabetes and cardiovascular disease and recently was linked to incident CKD. The purpose of this study is to examine whether metabolic syndrome is associated with kidney disease progression in hypertensive African Americans. DESIGN & PARTICIPANTS The current study design is a secondary analysis of the African-American Study of Hypertension and Kidney Disease, a randomized controlled trial of blood pressure goal and agents in hypertensive African Americans with CKD. PREDICTORS Metabolic syndrome was defined according to the modified National Cholesterol Education Program guidelines. OUTCOMES Decrease in glomerular filtration rate of 50% or 25 mL/min/1.73 m(2), end-stage renal disease (initiation of dialysis therapy or transplantation), death, or a composite outcome of all 3. RESULTS 842 subjects were included in this analysis, and 41.7% met criteria for metabolic syndrome. Subjects meeting criteria for metabolic syndrome had greater levels of proteinuria. Cox regression analyses adjusted for age, sex, glomerular filtration rate, and other significant covariates except for proteinuria indicated a 31% increased risk, with a 95% confidence interval of 1.03 to 1.7 (P = 0.03) for time to reach the composite outcome in those with metabolic syndrome. Adjusting for proteinuria, the effect was abated to 16% (95% confidence interval, 0.9 to 1.5), no longer remained significant (P = 0.2), and was unchanged by adjusting randomized treatment group (blood pressure goal or antihypertensive drug). LIMITATIONS Lack of waist circumference as a better surrogate of abdominal obesity. CONCLUSIONS In summary, metabolic syndrome is associated with proteinuria in hypertensive African Americans, but is not independently associated with CKD progression.

Ethnic differences in electrocardiographic criteria for left ventricular hypertrophy: the LIFE study

BACKGROUND African Americans have greater precordial QRS voltages than whites, with concomitant higher prevalences of electrocardiographic (ECG) left ventricular hypertrophy (LVH) and lower specificity of ECG LVH criteria for the identification of anatomic hypertrophy. However, the high mortality associated with LVH in African American patients makes more accurate ECG detection of LVH in these patients a clinical priority. METHODS Electrocardiograms and echocardiograms were obtained at study baseline in 120 African American and 751 white hypertensive patients enrolled in the Losartan Intervention For Endpoint (LIFE) echocardiographic substudy. The ECG LVH was determined using Sokolow-Lyon, 12-lead sum, and Cornell voltage criteria. Echocardiographic LVH was defined by LV mass indexed to height(2.7) >46.7 g/m(2.7) in women and >49.1 g/m(2.7) in men. RESULTS After adjusting for ethnic differences in LV mass, body mass index, sex, and prevalence of diabetes, mean Sokolow-Lyon and 12-lead sum of voltage were significantly higher, but Cornell voltage was lower, in African Americans than in whites. As a consequence of these differences, when identical partition values were used in both ethnic groups, Sokolow-Lyon and 12-lead voltage criteria had lower specificity in African Americans than whites (44% v 69%, P = .007 and 44% v 59%, P = .10) but had greater sensitivity in African Americans (51% v 27%, P < .001 and 62% v 45%, P = .003). In contrast, Cornell voltage specificity was higher (78% v 62%, P = .09) but sensitivity was slightly lower (49% v 57%, P = 0.16) in African Americans. However, when overall test performance was compared using receiver operating curve analyses that were independent of partition value selection, ethnic differences in test performance disappeared, with no differences in accuracy of any of the ECG voltage criteria for the identification of LVH between African American and white hypertensive individuals. CONCLUSIONS When standard, non-ethnicity-specific thresholds for the identification of LVH are used, Sokolow-Lyon and 12-lead voltage overestimate and Cornell voltage underestimates the presence and severity of LVH in African American relative to white individuals. However, these apparent ethnic differences in test performance disappear when ethnic differences in the distribution of ECG LVH criteria are taken into account. These findings demonstrate that ethnicity-specific ECG criteria can equalize detection of anatomic LVH in African American and white patients.

Design and Statistical Aspects of the African American Study of Kidney Disease and Hypertension (AASK)

The African American Study of Kidney Disease and Hypertension (AASK) is a multicenter randomized clinical trial designed to test the effectiveness of three anti-hypertensive drug regimens and two levels of BP control on the progression of hypertensive kidney disease. Participants include African-American men and women aged 18 to 70 yr who have hypertensive kidney disease and GFR between 20 and 65 ml/min per 1.73 m(2). The three anti-hypertensive drug regimens include an angiotensin converting enzyme inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine) or a beta-blocker (metoprolol) as initial therapy. The BP control levels are a lower goal (mean arterial pressure, </=92 mmHg) and a usual goal (mean arterial pressure, 102 to 107 mmHg inclusive). The primary outcome is rate of change in renal function as measured by GFR, assessed by (125) I-iothalamate clearance. The main secondary patient outcome is a composite including the following events: (1) reduction in GFR by 50%, (2) end-stage renal disease, or (3) death.

Malnutrition-Inflammation Modifies the Relationship of Cholesterol with Cardiovascular Disease

In moderate and severe CKD, the association of cholesterol with subsequent cardiovascular disease (CVD) is weak. We examined whether malnutrition or inflammation (M-I) modifies the risk relationship between cholesterol levels and CVD events in African Americans with hypertensive CKD and a GFR between 20 and 65 ml/min per 1.73 m². We stratified 990 participants by the presence or absence of M-I, defined as body mass index <23 kg/m² or C-reactive protein >10 mg/L at baseline. The primary composite outcome included cardiovascular death or first hospitalization for coronary artery disease, stroke, or congestive heart failure occurring during a median follow-up of 77 months. Baseline total cholesterol (212 ± 48 versus 212 ± 44 mg/dl) and overall incidence of the primary CVD outcome (19 versus 21%) were similar in participants with (n = 304) and without (n = 686) M-I. In adjusted analyses, the CVD composite outcome exhibited a significantly stronger relationship with total cholesterol for participants without M-I than for participants with M-I at baseline (P < 0.02). In the non-M-I group, the cholesterol-adjusted hazard ratio (HR) for CVD increased progressively across cholesterol levels: HR = 1.19 [95% CI; 0.77, 1.84] and 2.18 [1.43, 3.33] in participants with cholesterol 200 to 239 and ≥240 mg/dl, respectively (reference: cholesterol <200). In the M-I group, the corresponding HRs did not vary significantly by cholesterol level. In conclusion, the presence of M-I modifies the risk relationship between cholesterol level and CVD in African Americans with hypertensive CKD.

Posttraumatic Stress Disorder and Nocturnal Blood Pressure Dipping in Young Adult African Americans

Objective: To evaluate the relationship between posttraumatic stress disorder (PTSD) and nocturnal blood pressure (BP) dipping in young adult African Americans (AAs). PTSD is associated with physical illnesses including cardiovascular conditions. Sleep disturbances related to heightened arousal likely contribute to physical health risk; however, this possibility has not been studied. The studies that have found a relationship between PTSD and hypertension (HTN) have substantial representation of AAs. AAs have elevated rates of HTN and are more likely to exhibit an absence of the normal “dip” of BP at night. Nocturnal BP “nondipping” is an established risk factor for HTN and its cardiovascular complications. Nocturnal BP nondipping and sleep disturbances of PTSD have both been linked to sympathetic nervous system function. Methods: Thirty healthy young adult AAs (60% female; mean age = 20.0 years; 17 with lifetime full or subthreshold PTSD, 4 with current symptoms) received 24-hour BP and actigraphy monitoring, filled out sleep diaries, and had structured clinical assessment of PTSD. Results: There were significant associations of lifetime full and subthreshold PTSD and BP nondipping, and the degree of nocturnal dipping correlated with lifetime and current PTSD severity. Conclusion: Elevated nocturnal BP may be a link between PTSD and cardiovascular morbidity in AAs that can be targeted in prevention. PTSD = posttraumatic stress disorder; AA = African American; HTN = hypertension; BP = blood pressure; SNS = sympathetic nervous system; MAP = mean arterial pressure; CAPS = Clinician Administered PTSD Scale.

The impact of body mass index on pulse pressure in obesity.

Objective Pulse pressure, a marker of arterial vascular properties, has been linked to cardiovascular diseases and complications. This study examined the impact of excess body mass and cardiovascular disease risk factors on pulse pressure (PP). Design Cross-sectional and prospective study. Methods Baseline data consist of 219 obese African Americans, with mean ± SD age of 46.8 ± 10.9 years enrolled in a diet and exercise program of weight reduction. A non-invasive monitoring device was used to acquire 24 hourly ambulatory blood pressures. Pulse pressure was calculated as the difference between the average 24-h systolic and diastolic blood pressure and studied as a continuous variable and according to quartiles. The cross-sectional association of pulse pressure with body mass index (BMI) was examined using multivariate linear regression and proportional odds models that controlled for cardiovascular disease risk factors. In addition, we examined prospectively, in 36 participants, the effect of weight loss on pulse pressure, using the Wilcoxon signed ranked test. Results At baseline, a 5 kg/m2 increase in BMI was independently associated with a 35% risk [relative risk (RR) = 1.35, confidence interval (CI) = 1.10–1.65, P < 0.01] in the general study population and 19% (RR = 1.19, CI = 1.07–1.56, P = 0.04) in obese normotensives for increasing PP by one quartile after adjustment for other significant variables. After 3 months of diet and exercise intervention, BMI decreased by an average of 10.6% (P < 0.01) and resulted in an 8.8% (P < 0.01) reduction in PP. Conclusions In the context of obesity, increasing BMI is independently associated with decreasing arterial compliance, as reflected in PP. This association highlights the potential value to cardiovascular health of any reduction in body weight in obese individuals.

The Metabolically Healthy But Obese Phenotype in African Americans

J Clin Hypertens (Greenwich).