Worsening Kidney Function Is the Major Mechanism of Heart Failure in Hypertension: The ALLHAT Study.
Pubmed ID: 33189627
Pubmed Central ID: PMC7855256
Journal: JACC. Heart failure
Publication Date: 02/01/2021
Affiliation: Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA. Electronic address: firstname.lastname@example.org.
MeSH Terms: Humans, Male, Female, Aged, Hypertension, Heart Failure, Treatment Outcome, Double-Blind Method, Myocardial Infarction, Kidney, Antihypertensive Agents, Amlodipine
Grants: R01 HL118277, N01HC35130, R56 HL118277
Authors: Davis BR, Oparil S, Tereshchenko LG, Khayyat-Kholghi M
Cite As: Khayyat-Kholghi M, Oparil S, Davis BR, Tereshchenko LG. Worsening Kidney Function Is the Major Mechanism of Heart Failure in Hypertension: The ALLHAT Study. JACC Heart Fail 2021 Feb;9(2):100-111. Epub 2020 Nov 11.
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).