Sustained SBP control and long-term nursing home admission among Medicare beneficiaries.

OBJECTIVES: Sustaining SBP control reduces the risk for cardiovascular events that impair function but its association with nursing home admission has not been well studied. METHODS: We conducted an analysis of sustained SBP control and long-term nursing home admissions using data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims restricted to participants with fee-for-service coverage, at least eight study visits with SBP measurements, who were not living in a nursing home during a 48-month baseline BP assessment period (n = 6557). Sustained SBP control was defined as less than 140 mmHg at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits. Nursing home admissions were identified using the Medicare Long Term Care Minimum Data Set. RESULTS: The mean age of participants was 73.8 years and 44.3% were men. Over a median follow-up of 9.2 years, 844 participants (12.8%) had a nursing home admission. Rates of nursing home admission per 100 person-years were 16.3 for participants with SBP control at less than 50%, 14.1 at 50% to less than 75%, 7.8 at 75% to less than 100%, and 5.3 at 100% of visits. Compared with those with sustained SBP control at less than 50% of visits, hazard ratios (95% confidence intervals) for nursing home admission were 0.79 (0.66-0.93), 0.70 (0.58-0.84), and 0.57 (0.44-0.74) among participants with SBP control at 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively. CONCLUSION: Among Medicare beneficiaries in ALLHAT, sustained SBP control was associated with a lower risk of long-term nursing home admission.

Association of Sustained Blood Pressure Control with Lower Risk for High-Cost Multimorbidities Among Medicare Beneficiaries in ALLHAT.

BACKGROUND: Clustering of chronic conditions is associated with high healthcare costs. Sustaining blood pressure (BP) control could be a strategy to prevent high-cost multimorbidity clusters. OBJECTIVE: To determine the association between sustained systolic BP (SBP) control and incident multimorbidity cluster dyads and triads. DESIGN: Cohort study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims. PARTICIPANTS: ALLHAT included adults with hypertension and ≥1 coronary heart disease risk factor. This analysis was restricted to 5234 participants with ≥ 8 SBP measurements during a 48-month BP assessment period. MAIN MEASURES: SBP control was defined as <140 mm Hg at <50%, 50 to <75%, 75 to <100%, and 100% of study visits during the BP assessment period. High-cost multimorbidity clusters included dyads (stroke/chronic kidney disease [CKD], stroke/chronic obstructive pulmonary disease [COPD], stroke/heart failure [HF], stroke/asthma, COPD/CKD) and triads (stroke/CKD/asthma, stroke/CKD/COPD, stroke/CKD/depression, stroke/CKD/HF, stroke/HF/asthma) identified during follow-up. KEY RESULTS: Incident dyads occurred in 1334 (26%) participants and triads occurred in 481 (9%) participants over a median follow-up of 9.2 years. Among participants with SBP control at <50%, 50 to <75%, 75 to <100%, and 100% of visits, 32%, 23%, 23%, and 19% of participants developed high-cost dyads, respectively, and 13%, 9%, 8%, and 5% of participants developed high-cost triads, respectively. Compared to those with sustained BP control at <50% of visits, adjusted HRs (95% CI) for incident dyads were 0.66 (0.57, 0.75), 0.67 (0.59, 0.77), and 0.51 (0.42, 0.62) for SBP control at 50 to <75%, 75 to <100%, and 100% of visits, respectively. The corresponding HRs (95% CI) for incident triads were 0.69 (0.55, 0.85), 0.56 (0.44, 0.71), and 0.32 (0.22, 0.47). CONCLUSIONS: Among Medicare beneficiaries in ALLHAT, sustained SBP was associated with a lower risk of developing high-cost multimorbidity dyads and triads.

Association of Sustained Blood Pressure Control with Multimorbidity Progression Among Older Adults.

BACKGROUND/OBJECTIVES: Due to the high costs and excess mortality associated with multimorbidity, there is a need to develop approaches for delaying its progression. High blood pressure (BP) is a common chronic condition and a risk factor for many additional chronic conditions, making it an ideal target for intervention. The purpose of this analysis was to determine the association between the level of sustained BP control and the progression of multimorbidity. DESIGN: Retrospective cohort study. SETTING: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims. PARTICIPANTS: A total of 6,591 ALLHAT participants with Medicare who had systolic BP (SBP) measurements at eight or more study visits. MEASUREMENTS: SBP control was categorized as lower than 140 mm Hg at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits. Multimorbidity progression was defined by the number of incident chronic conditions, including arthritis, asthma, atrial fibrillation, cancer, chronic kidney disease, chronic obstructive pulmonary disease, coronary heart disease, dementia, depression, diabetes mellitus, heart failure, hyperlipidemia, osteoporosis, and stroke. Recurrent event survival analysis was used to calculate rate ratios (RRs) for the association of sustained SBP control with progression of multimorbidity. RESULTS: Rates of incident conditions per 10 person-years (95% CIs) were 5.2 (5.1-5.4), 4.7 (4.5-4.8), 4.4 (4.2-4.5), and 4.0 (3.8-4.2) for participants with SBP control at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively, over a median follow-up of 9.0 years. Compared with participants with SBP control at less than 50% of visits, adjusted RRs (95% CIs) for multimorbidity progression were 0.90 (0.86-0.95), 0.85 (0.81-0.89), and 0.77 (0.72-0.82) for those with SBP control at 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively. CONCLUSIONS: Sustaining BP control may be an effective approach to slow multimorbidity progression and may reduce the population burden of multimorbidity.

Sustained blood pressure control and coronary heart disease, stroke, heart failure, and mortality: An observational analysis of ALLHAT.

Achieving blood pressure (BP) control is associated with lower cardiovascular disease (CVD) risk, but less is known about CVD risk associated with sustained BP control over time. This observational analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was restricted to participants with four to seven visits with systolic BP (SBP) measurements during a 22-month period (n = 24 309). The authors categorized participants as having sustained BP control (SBP < 140 mm Hg) at 100%, 75% to <100%, 50% to <75%, and <50% of visits during this period. Outcomes included fatal coronary heart disease (CHD)/nonfatal myocardial infarction (MI), stroke, heart failure (HF), a composite CVD outcome (fatal CHD/nonfatal MI, stroke, or HF), and mortality. Hazard ratios (HRs) for the association of category of sustained BP control for each outcome were obtained using proportional hazards models. SBP control was present among 20.0% of participants at 100%, 16.4% at 75% to less than 100%, 27.0% at 50% to less than 75%, and 36.6% at less than 50% of visits. Compared to those with SBP control at 100% visits, adjusted HR (95% CI) among those with SBP control at <50% of visits was 1.16 (0.93-1.44) for fatal CHD/nonfatal MI, 1.71 (1.26-2.32) for stroke, 1.63 (1.30-2.06) for HF, 1.39 (1.20-1.62) for the composite CVD outcome, and 1.14 (0.99-1.30) for mortality. Sustained SBP control may be beneficial for preventing stroke, HF, and CVD outcomes in adults taking antihypertensive medication.

Blood Pressure Assessment in Adults in Clinical Practice and Clinic-Based Research: JACC Scientific Expert Panel.

The accurate measurement of blood pressure (BP) is essential for the diagnosis and management of hypertension. Restricted use of mercury devices, increased use of oscillometric devices, discrepancies between clinic and out-of-clinic BP, and concerns about measurement error with manual BP measurement techniques have resulted in uncertainty for clinicians and researchers. The National Heart, Lung, and Blood Institute of the U.S. National Institutes of Health convened a working group of clinicians and researchers in October 2017 to review data on BP assessment among adults in clinical practice and clinic-based research. In this report, the authors review the topics discussed during a 2-day meeting including the current state of knowledge on BP assessment in clinical practice and clinic-based research, knowledge gaps pertaining to current BP assessment methods, research and clinical needs to improve BP assessment, and the strengths and limitations of using BP obtained in clinical practice for research and quality improvement activities.

Risk Factors Influencing Outcomes of Atrial Fibrillation in ALLHAT.

BACKGROUND AND AIMS: ALLHAT, a randomized, double-blind, active-controlled, multicenter clinical trial of high risk hypertensive participants, compared treatment with an ACE-inhibitor (lisinopril) or calcium channel blocker (amlodipine) with a diuretic (chlorthalidone). Primary outcome was the occurrence of fatal coronary heart disease or nonfatal myocardial infarction. For this report, post-hoc analyses were conducted to determine the contribution of baseline characteristics of participants with or without baseline or incident atrial fibrillation (AF) and atrial flutter (AFL) to stroke, heart failure (HF), coronary heart disease (CHD), and mortality outcomes. METHODS AND RESULTS: Minnesota Coding of baseline and biennial in-trial ECGs was used to determine the 334 baseline and 537 incident AF/AFL cases, respectively participants with AF/AFL: Cox regression was used to estimate hazard ratios of presence versus absence of either baseline or incident AF/AFL (as time-dependent covariate) for occurrence of stroke, CHD, HF, or mortality, while adjusting for selected baseline characteristics. Adjusted Cox regression was used to obtain hazard ratios (HRs) for presence versus absence of selected baseline characteristics among those with and without either baseline or incident AF/AFL. After adjusting for baseline characteristics, baseline AF/AFL was associated with stroke, HF, and mortality (HRs [95% CIs] 3.18, [2.34-4.33]; 2.65 [2.02-3.49]; and 2.10 [CI, 1.73-2.55], respectively, P < 0.05). Incident AF/AFL was a significant risk factor for HF and mortality (HRs 2.80 and 2.06, respectively, P < 0.05). Risk factor profiles for clinical outcomes for those with and without baseline or incident AF/AFL were largely similar. CONCLUSIONS: AF/AFL is a significant risk factor for stroke, HF, and mortality. Additional risk factors for these outcomes were generally similar for participants with and without baseline or incident AF/AFL.

Rapid eGFR change as a determinant of cardiovascular and renal disease outcomes and of mortality in hypertensive adults with and without type 2 diabetes.

A rapid decline in estimated glomerular filtration rate over 2 years in a large hypertensive cohort was associated with similar risks for overall cardiovascular disease in people with or without diabetes mellitus, but with higher all-cause mortality, heart failure, and end stage renal disease risk in people with diabetes.

The Effects of eGFR Change on CVD, Renal, and Mortality Outcomes in a Hypertensive Cohort Treated With 3 Different Antihypertensive Medications.

BACKGROUND: Impaired renal function is a risk factor for cardiovascular disease, end-stage renal disease (ESRD), and mortality. The impact of short-term renal function decline on outcomes is less well studied. The association of antihypertensive medications with the impact of short-term estimated glomerular filtration rate (eGFR) decline is not known. METHODS: We examined 20,207 hypertensive participants with baseline and 2-year creatinine levels from which eGFR changes were estimated. The associations between eGFR change with incident coronary heart disease (CHD), stroke, heart failure (HF), all-cause mortality, and ESRD during 2.9 years of in-trial follow up, and with mortality during in-trial and post-trial follow-up (7.6 years), were studied. Results were assessed by primary hypertension (HTN) treatment (chlorthalidone, lisinopril, and amlodipine) and adjusted for baseline eGFR levels. RESULTS: In the short run, an eGFR decline below the cohort median (-1.28 ml/minute/1.73 m2/2 years) vs. above the median, or a 5 ml/min/1.73 m2/year decline vs. no decline, was associated with significant hazard risk for CHD (1.06-1.28), HF (1.24-1.91), ESRD (2.84-6.01), and mortality (1.08-1.19), but not with stroke risk. In the long term, there was a significant association with mortality (1.11-1.34). Interaction terms for outcomes by antihypertensive treatments were not statistically significant except for ESRD between amlodipine vs. chlorthalidone (hazard ratio: 3.17 [2.59, 3.88] vs. 2.41 [1.98, 2.97]; P interaction = 0.005) for a 5 ml/min/1.73 m2/year eGFR decline. CONCLUSION: Decline in eGFR over 2 years is associated with increased risk of clinical outcomes beyond the effects of baseline eGFR. These risks were the same irrespective of the primary medication used to treat HTN.

Baseline Quality of Life and Risk of Stroke in the ALLHAT Study (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

BACKGROUND AND PURPOSE: The visual analogue scale is a self-reported, validated tool to measure quality of life (QoL). Our purpose was to determine whether baseline QoL predicted strokes in the ALLHAT study (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) and evaluate determinants of poststroke change in QoL. In the ALLHAT study, among the 33 357 patients randomized to treatment arms, 1525 experienced strokes; 1202 (79%) strokes were nonfatal. This study cohort includes 32 318 (97%) subjects who completed the baseline visual analogue scale QoL estimate. METHODS: QoL was measured on a visual analogue scale and adjusted using a Torrance transformation (transformed QoL [TQoL]). Kaplan-Meier curves and adjusted proportional hazards analyses were used to estimate the effect of TQoL on the risk of stroke, on a continuous scale (0-1) and by quartiles (≤0.81, >0.81≤0.89, >0.89≤0.95, >0.95). We analyzed the change from baseline to first poststroke TQoL using adjusted linear regression. RESULTS: After adjusting for multiple stroke risk factors, the hazard ratio for stroke events for baseline TQoL was 0.93 (95% confidence interval, 0.89-0.98) per 0.1 U increase. The lowest baseline TQoL quartile had a 20% increased stroke risk (hazard ratio=1.20 [95% confidence interval, 1.00-1.44]) compared with the reference highest quartile TQoL. Poststroke TQoL change was significant within all treatment groups (P≤0.001). Multivariate regression analysis revealed that baseline TQoL was the strongest predictor of poststroke TQoL with similar results for the untransformed QoL. CONCLUSIONS: The lowest baseline TQoL quartile had a 20% higher stroke risk than the highest quartile. Baseline TQoL was the only factor that predicted poststroke change in TQoL. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Association of 3 Different Antihypertensive Medications With Hip and Pelvic Fracture Risk in Older Adults: Secondary Analysis of a Randomized Clinical Trial.

IMPORTANCE: On the basis of observational studies, the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. Data from randomized clinical trials are lacking. OBJECTIVE: To examine whether the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. DESIGN, SETTING, AND PARTICIPANTS: Using Veterans Affairs and Medicare claims data, this study examined hip and pelvic fracture hospitalizations in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to first-step therapy with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), or an angiotensin-converting enzyme inhibitor (lisinopril). Recruitment was from February 1994 to January 1998; in-trial follow-up ended in March 2002. The mean follow-up was 4.9 years. Posttrial follow-up was conducted through the end of 2006, using passive surveillance via national databases. For this secondary analysis, which used an intention-to-treat approach, data were analyzed from February 1, 1994, through December 31, 2006. MAIN OUTCOMES AND MEASURES: Hip and pelvic fracture hospitalizations. RESULTS: A total of 22 180 participants (mean [SD] age, 70.4 [6.7] years; 43.0% female; and 49.9% white non-Hispanic, 31.2% African American, and 19.1% other ethnic groups) were followed for up to 8 years (mean [SD], 4.9 [1.5] years) during masked therapy. After trial completion, 16 622 participants for whom claims data were available were followed for up to 5 additional years (mean [SD] total follow-up, 7.8 [3.1] years). During the trial, 338 fractures occurred. Participants randomized to receive chlorthalidone vs amlodipine or lisinopril had a lower risk of fracture on adjusted analyses (hazards ratio [HR], 0.79; 95% CI, 0.63-0.98; P = .04). Risk of fracture was significantly lower in participants randomized to receive chlorthalidone vs lisinopril (HR, 0.75; 95% CI, 0.58-0.98; P = .04) but not significantly different compared with those randomized to receive amlodipine (HR, 0.82; 95% CI, 0.63-1.08; P = .17). During the entire trial and posttrial period of follow-up, the cumulative incidence of fractures was nonsignificantly lower in participants randomized to receive chlorthalidone vs lisinopril or amlodipine (HR, 0.87; 95% CI, 0.74-1.03; P = .10) and vs each medication separately. In sensitivity analyses, when 1 year after randomization was used as the baseline (to allow for the effects of medications on bone to take effect), similar results were obtained for in-trial and in-trial plus posttrial follow-up. CONCLUSIONS AND RELEVANCE: These findings from a large randomized clinical trial provide evidence of a beneficial effect of thiazide-type diuretic therapy in reducing hip and pelvic fracture risk compared with treatment with other antihypertensive medications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000542.

Conditional moving linear regression: modeling the recruitment process for ALLHAT.

Effective recruitment is a prerequisite for successful execution of a clinical trial. ALLHAT, a large hypertension treatment trial (N = 42, 418), provided an opportunity to evaluate adaptive modeling of recruitment processes using conditional moving linear regression. Our statistical modeling of recruitment, comparing Brownian and fractional Brownian motion, indicates that fractional Brownian motion combined with moving linear regression is better than classic Brownian motion in terms of higher conditional probability of achieving a global recruitment goal in four week ahead projections. Further research is needed to evaluate how recruitment modeling can assist clinical trialists in planning and executing clinical trials. Clinical Trial Registration: www.clinicaltrials.gov NCT00000542.

Electrocardiographic measures of left ventricular hypertrophy in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up electrocardiographies in 26,376 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH was examined using continuous and categorical classifications of Cornell voltage. At 2 and 4 years, prevalence of LVH in the C group (5.57%; 6.14%) was not statistically different from A group (2 years: 5.47%; P = .806, 4 years: 6.54%; P = .857) or L group (2 years: 5.64%; P = .857, 4 years: 6.50%; P = .430). Incident LVH followed similarly, with no difference at 2 years for C (2.99%) compared to A (2.57%; P = .173) or L (3.16%; P = .605) and at 4 years (C = 3.52%, A = 3.29%, L = 3.71%; P = .521 C vs. A, P = .618 C vs. L). Mean Cornell voltage decreased comparably across treatment groups (Δ baseline, 2 years = +3 to -27 µV, analysis of variance P = .8612; 4 years = +10 to -17 µV, analysis of variance P = .9692). We conclude that risk reductions associated with C treatment in secondary end points of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial cannot be attributed to differential improvements in electrocardiography LVH.

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.

Visit-to-Visit Variability of Blood Pressure and Coronary Heart Disease, Stroke, Heart Failure, and Mortality: A Cohort Study.

BACKGROUND: Variability of blood pressure (BP) across outpatient visits is frequently dismissed as random fluctuation around a patient's underlying BP. OBJECTIVE: To examine the association of visit-to-visit variability (VVV) of systolic BP (SBP) and diastolic BP with cardiovascular disease (CVD) and mortality outcomes. DESIGN: Prospective cohort study. SETTING: Post hoc analysis of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial). PARTICIPANTS: 25 814 ALLHAT participants. MEASUREMENTS: The VVV of SBP was defined as the SD across SBP measurements obtained at 7 visits conducted from 6 to 28 months after ALLHAT enrollment. Participants without CVD events during the first 28 months of follow-up were followed from the 28-month visit through the end of active ALLHAT follow-up. Outcomes included fatal coronary heart disease (CHD) or nonfatal myocardial infarction, all-cause mortality, stroke, and heart failure. RESULTS: During follow-up, 1194 fatal CHD or nonfatal MI events, 1948 deaths, 606 strokes, and 921 heart failure events occurred. After multivariable adjustment, including for mean SBP, the hazard ratio comparing participants in the highest versus lowest quintile of SD of SBP (≥14.4 mm Hg vs. <6.5 mm Hg) was 1.30 (95% CI, 1.06 to 1.59) for fatal CHD or nonfatal MI, 1.58 (CI, 1.32 to 1.90) for all-cause mortality, 1.46 (CI, 1.06 to 2.01) for stroke, and 1.25 (CI, 0.97 to 1.61) for heart failure. Higher VVV of diastolic BP was also associated with CVD events and mortality. LIMITATION: Long-term outcomes were not available. CONCLUSION: Higher VVV of SBP is associated with an increased risk for CVD and mortality. Future studies should examine whether reducing VVV of BP lowers this risk. PRIMARY FUNDING SOURCE: National Institutes of Health.

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.

Impaired fasting glucose and body mass index as determinants of mortality in ALLHAT: is the obesity paradox real?

Emerging literature suggests that obesity may be "protective" against mortality and cardiovascular outcomes, while dysglycemia may worsen outcomes regardless of obesity. The authors measured the association of weight, smoking, and glycemia with mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Among 5423 ALLHAT participants without established diabetes or cardiovascular disease, 3980 (73%) had normal fasting glucose and 1443 (27%) had impaired fasting glucose (IFG) levels at study entry. After a median of 4.9 years follow-up, 554 (10%) had died (37% cardiovascular). IFG was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02-1.50), while obesity was associated with lower all-cause mortality (adjusted HR, 0.76; 95% CI, 0.60-0.96). However, after excluding underweight individuals (body mass index [BMI] <22 kg/m(2) ) and smokers, neither obesity nor IFG was associated with all-cause mortality [corrected]. Although obesity appeared protective against mortality, this association was not significant in never-smokers or after exclusion of BMI <22 kg/m(2) . The obesity paradox may result from confounding by a sicker, underweight referent population and smoking.