{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:14:51Z","timestamp":1790352891293,"version":"4.1.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,4,16]]},"abstract":"\n Background<\/jats:title>\n \n Hypertension is a known risk factor for heart failure (\n HF<\/jats:styled-content>\n ), possibly via the mechanism of cardiac remodeling and left ventricular hypertrophy (\n LVH<\/jats:styled-content>\n ). We studied the extent to which blood pressure (\n BP<\/jats:styled-content>\n ) change and evolving\n LVH<\/jats:styled-content>\n contribute to the effect that lisinopril, doxazosin, and amlodipine have on\n HF<\/jats:styled-content>\n compared with chlorthalidone.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We conducted causal mediation analysis of\n ALLHAT<\/jats:styled-content>\n (Antihypertensive and Lipid\u2010Lowering Treatment to Prevent Heart Attack Trial) data (1994\u20102002; in\u2010trial follow\u2010up).\n ALLHAT<\/jats:styled-content>\n participants with available serial\n ECG<\/jats:styled-content>\n s and\n BP<\/jats:styled-content>\n measurements were included (n=29\u00a0892; mean age 67\u00b14\u00a0years; 32% black; 56% men): 11\u00a0008 were randomized to chlorthalidone, 5967 to doxazosin, 6593 to amlodipine, and 6324 to lisinopril. Evolving\n ECG LVH<\/jats:styled-content>\n and\n BP<\/jats:styled-content>\n lowering served as mediators. Incident symptomatic\n HF<\/jats:styled-content>\n was the primary outcome. Linear regression (for mediator) and logistic regression (for outcome) models were adjusted for mediator\u2010outcome confounders (demographic and clinical characteristics known to be associated both with both\n LVH<\/jats:styled-content>\n \/hypertension and\n HF<\/jats:styled-content>\n ). A large majority of participants (96%) had\n ECG LVH<\/jats:styled-content>\n status unchanged, but 4% developed evolving\n ECG LVH<\/jats:styled-content>\n . On average,\n BP<\/jats:styled-content>\n decreased by 11\/7\u00a0mm\u00a0Hg. In adjusted Cox regression analyses, progressing\n ECG LVH<\/jats:styled-content>\n (hazard ratio [\n HR<\/jats:styled-content>\n ] 1.78 [95% CI 1.43\u20102.22]), resolving\n ECG LVH<\/jats:styled-content>\n (\n HR<\/jats:styled-content>\n 1.33 [95% CI 1.03\u20101.70]), and baseline\n ECG LVH<\/jats:styled-content>\n (1.17 [95% CI 1.04\u20101.31]) carried risk of incident\n HF<\/jats:styled-content>\n . After full adjustment, evolving\n ECG LVH<\/jats:styled-content>\n mediated 4% of the effect of doxazosin on\n HF<\/jats:styled-content>\n . Systolic\n BP<\/jats:styled-content>\n lowering mediated 12% of the effect of doxazosin, and diastolic\n BP<\/jats:styled-content>\n lowering mediated 10% of the effect of doxazosin, 7% of the effect of amlodipine, and borderline 9% of the effect of lisinopril on\n HF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Evolving\n ECG LVH<\/jats:styled-content>\n and\n BP<\/jats:styled-content>\n change account for 4% to 13% of the mechanism by which antihypertensive medications prevent\n HF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n URL<\/jats:styled-content>\n :\n http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n . Unique identifier:\n NCT<\/jats:styled-content>\n 00000542.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.011961","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T05:03:52Z","timestamp":1554354232000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Prevention of Heart Failure in Hypertension\u2014Disentangling the Role of Evolving Left Ventricular Hypertrophy and Blood Pressure Lowering: The ALLHAT Study"],"prefix":"10.1161","volume":"8","author":[{"given":"Kyle","family":"Johnson","sequence":"first","affiliation":[{"name":"The Knight Cardiovascular Institute Oregon Health & Science University Portland OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Oparil","sequence":"additional","affiliation":[{"name":"Department of Medicine School of Medicine University of Alabama at Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry R.","family":"Davis","sequence":"additional","affiliation":[{"name":"University of Texas School of Public Health Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa G.","family":"Tereshchenko","sequence":"additional","affiliation":[{"name":"The Knight Cardiovascular Institute Oregon Health & Science University Portland 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