Dataset Information

Worsening Kidney Function Is the Major Mechanism of Heart Failure in Hypertension: The ALLHAT Study.

ABSTRACT:

Objectives

The authors aimed to quantify the extent to which the effect of antihypertensive drugs on incident heart failure (HF) is mediated by their effect on kidney function.

Background

The authors hypothesized that the dynamic change in kidney function is the mechanism behind differences in the rate of incident HF in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) participants randomized to lisinopril and chlorthalidone, in comparison with those randomized to amlodipine and doxazosin.

Methods

Causal mediation analysis of ALLHAT data (1994 to 2002) included participants with available baseline and 24- to 48-month estimated glomerular filtration rate (eGFR) (N = 27,918; mean age 66 ± 7.4 years; 32.4% Black, 56.3% men). Change in eGFR was the mediator. Incident symptomatic HF was the primary outcome. Hospitalized/fatal HF was the secondary outcome. Linear regression (for mediator) and logistic regression (for outcome) analyses were adjusted for demographics, cardiovascular disease, and risk factors.

Results

There were 1,769 incident HF events, including 1,359 hospitalized/fatal HF events. In fully adjusted causal mediation analysis, the relative change in eGFR mediated 18% of the effect of chlorthalidone, and 33% of lisinopril on incident symptomatic HF, and 25% of the effect of chlorthalidone, and 41% of lisinopril on hospitalized/fatal HF. In participants with diabetes, the relative change in eGFR mediated nearly 50% of the effect of lisinopril on incident symptomatic HF, whereas in diabetes-free participants, only 17%.

Conclusions

On the risk difference scale, change in eGFR accounts for up to 50% of the mechanism by which antihypertensive medications affect HF. (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]; NCT00000542).

SUBMITTER: Khayyat-Kholghi M

PROVIDER: S-EPMC7855256 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background The relationship between intensive volume removal in acute decompensated heart failure patients with preexisting worsening renal function (WRF) and renal tubular injury, postdischarge renal function, and clinical outcomes is unknown. Methods and Results We used data from the multicenter CARRESS-HF trial (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) that randomized patients with acute decompensated heart failure and preexisting WRF to intensive volume removal with stepped pharmacological therapy or fixed rate ultrafiltration. Patients in the urinary renal tubular injury biomarker substudy (NAG [N-acetyl-b-D-glucosaminidase], KIM-1 [kidney injury molecule-1], and NGAL [neutrophil gelatinase-associated lipocalin]) were evaluated (N=105). The severity of prerandomization WRF was unrelated to baseline renal tubular injury biomarkers ( r=0.14; P=0.17). During randomized intensive volume removal, creatinine further worsened in 53% of patients. Despite a small to moderate magnitude increase in creatinine in most of these patients, postrandomization WRF was strongly associated with worsening in renal tubular injury biomarkers (odds ratio, 12.6; P=0.004). This observation did not differ by mode of volume removal (stepped pharmacological therapy versus ultrafiltration, Pinteraction=0.46). Increase in renal tubular injury biomarkers was associated with a higher incidence of hemoconcentration (odds ratio, 3.1; P=0.015), and paradoxically, better recovery of creatinine at 60 days ( P=0.01). Conclusions In acute decompensated heart failure patients with preexisting WRF, intensive volume removal resulted in a further worsening of creatinine approximately half of the time, a finding associated with a rise in tubular injury biomarkers. However, decongestion and renal function recovery at 60 days were superior in patients with increased tubular injury markers. These data suggest that the benefits of decongestion may outweigh any modest or transient increases in serum creatinine or tubular injury markers that occur during intensive volume removal. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00608491.