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Randomized Controlled Trial
. 2022 Oct 18;80(16):1516-1525.
doi: 10.1016/j.jacc.2022.08.735.

Intensive Blood Pressure Lowering in Patients With Malignant Left Ventricular Hypertrophy

Simon B Ascher  1 , James A de Lemos  2 , MinJae Lee  3 , Elaine Wu  2 , Elsayed Z Soliman  4 , Ian J Neeland  5 , Dalane W Kitzman  6 , Christie M Ballantyne  7 , Vijay Nambi  8 , Anthony A Killeen  9 , Joachim H Ix  10 , Michael G Shlipak  11 , Jarett D Berry  12
Affiliations
Randomized Controlled Trial

Intensive Blood Pressure Lowering in Patients With Malignant Left Ventricular Hypertrophy

Simon B Ascher et al. J Am Coll Cardiol. .

Abstract

Background: Left ventricular hypertrophy (LVH) combined with elevations in cardiac biomarkers reflecting myocardial injury and neurohormonal stress (malignant LVH) is associated with a high risk for heart failure and death.

Objectives: The aim of this study was to determine the impact of intensive systolic blood pressure (SBP) control on the prevention of malignant LVH and its consequences.

Methods: A total of 8,820 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were classified into groups based on the presence or absence of LVH assessed by 12-lead ECG, and elevations in biomarker levels (high-sensitivity cardiac troponin T ≥14 ng/L or N-terminal pro-B-type natriuretic peptide ≥125 pg/mL) at baseline. The effects of intensive vs standard SBP lowering on rates of acute decompensated heart failure (ADHF) events and death and on the incidence and regression of malignant LVH were determined.

Results: Randomization to intensive SBP lowering led to similar relative reductions in ADHF events and death across the combined LVH/biomarker groups (P for interaction = 0.68). The absolute risk reduction over 4 years in ADHF events and death was 4.4% (95% CI: -5.2% to 13.9%) among participants with baseline malignant LVH (n = 449) and 1.2% (95% CI: 0.0%-2.5%) for those without LVH and nonelevated biomarkers (n = 4,361). Intensive SBP lowering also reduced the incidence of malignant LVH over 2 years (2.5% vs 1.1%; OR: 0.44; 95% CI: 0.30-0.63).

Conclusions: Intensive SBP lowering prevented malignant LVH and may provide substantial absolute risk reduction in the composite of ADHF events and death among SPRINT participants with baseline malignant LVH.

Keywords: heart failure; hypertension; malignant LVH; natriuretic peptide; troponin.

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Conflict of interest statement

Funding Support and Author Disclosures This ancillary study was supported by the National Heart, Lung, and Blood Institute (1R01HL144112-01 for Dr Berry). Analytical reagents for hs-cTnT and NT-proBNP measurements were donated by Roche. SPRINT was sponsored by the National Institutes of Health, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under Contract Numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, HHSN268200900049C, and Inter-Agency Agreement Number A-HL-13–002-001. It was also supported in part with resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the U.S. Department of Veterans Affairs, or the United States Government. Support was also received from the following CTSAs funded by the National Center for Advancing Translational Sciences: CWRU: UL1TR000439, OSU: UL1RR025755, U Penn: UL1RR024134 and UL1TR000003, Boston: UL1RR025771, Stanford: UL1TR000093, Tufts: UL1RR025752, UL1TR000073 and UL1TR001064, University of Illinois: UL1TR000050, University of Pittsburgh: UL1TR000005, UT Southwestern: 9U54TR000017–06, University of Utah: UL1TR000105–05, Vanderbilt University: UL1 TR000445, George Washington University: UL1TR000075, University of California, Davis: UL1 TR000002, University of Florida: UL1 TR000064, University of Michigan: UL1TR000433, Tulane University: P30GM103337 COBRE Award NIGMS, Wake Forest University: UL1TR001420. Dr de Lemos has received grant support from Roche Diagnostics and Abbott Diagnostics; has received consulting fees from Roche Diagnostics, Abbott Diagnostics, Ortho Clinical Diagnostics, Quidel Cardiovascular, Inc, and Siemen’s Health Care Diagnostics; and has been named a co-owner on a patent awarded to the University of Maryland (US Patent Application Number: 15/309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure.” Dr Kitzman has received honoraria as a consultant outside the present study from Bayer, Merck, Pfizer, Corvia Medical, Boehringer Ingelheim, Ketyo, Rivus, Novo Nordisk, AstraZeneca, and Novartis; has received grant funding from Novartis, Bayer, Pfizer, Novo Nordisk, and AstraZeneca; and has stock ownership in Gilead Sciences. Dr Berry has received grant support from the National Institutes of Health, Roche Diagnostics, and Abbott Diagnostics; and has received consulting fees from Roche Diagnostics and the Cooper Institute. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Figure 1.
Figure 1.. Associations between LVH/biomarker categories and incident ADHF events and mortality.
Hazard ratios with 95% confidence intervals obtained from multivariable Cox proportional hazards models that included demographics (age, sex, race, site), treatment assignment, and clinical characteristics (body mass index, smoking status, prevalent CVD, systolic blood pressure, estimated glomerular filtration rate, and low density lipoprotein cholesterol). Combined LVH and biomarker categories include: 1) no LVH and non-elevated cardiac biomarkers (LVH− biomarker−), 2) no LVH and elevated cardiac biomarkers (LVH− biomarker+), 3) LVH and non-elevated cardiac biomarkers (LVH+ biomarker−), and 4) LVH and elevated cardiac biomarkers (LVH+ biomarker+). Elevated cardiac biomarkers defined as hs-cTnT ≥ 14 ng/L or NT-proBNP ≥ 125 pg/mL. Abbreviations: ADHF, acute decompensated heart failure; CVD, cardiovascular disease; HR, hazard ratio; hs-cTnT, high-sensitivity cardiac troponin T; LVH, left ventricular hypertrophy; NT-proBNP, N-terminal pro-B-type natriuretic peptide; SPRINT, Systolic Blood Pressure Intervention Trial.
Figure 2.
Figure 2.. Intensive SBP lowering effects on incident LVH and malignant LVH.
Odds ratios with 95% confidence intervals obtained from logistic regression models. Panel A displays proportion without LVH at baseline who developed LVH during follow-up stratified by randomized treatment assignment and baseline cardiac biomarker levels. Biomarker+ indicates hs-cTnT ≥14 ng/L or NT-proBNP ≥125 pg/mL. Panel B displays proportion without malignant LVH at baseline who developed malignant LVH during follow-up stratified by randomized treatment assignment. Abbreviations: hs-cTnT, high-sensitivity cardiac troponin T; LVH, left ventricular hypertrophy; NT-proBNP, N-terminal pro-B-type natriuretic peptide; OR, odds ratio; SBP, systolic blood pressure; SPRINT, Systolic Blood Pressure Intervention Trial.
Central Illustration:
Central Illustration:. Intensive SBP lowering and the natural history of malignant LVH.
Randomization to intensive SBP lowering (SBP <120 mm Hg) versus standard SBP lowering (SBP <140 mm Hg) not only prevents the development of malignant LVH (LVH with hs-cTnT ≥14 ng/L or NT-proBNP ≥125 pg/mL), but may also lead to substantial absolute risk reductions in the composite of ADHF events and all-cause mortality when malignant LVH is present. Abbreviations: ADHF, acute decompensated heart failure; hs-cTnT, high-sensitivity cardiac troponin T; LVH, left ventricular hypertrophy; NT-proBNP, N-terminal pro-B-type natriuretic peptide; SBP, systolic blood pressure; SPRINT, Systolic Blood Pressure Intervention Trial.
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Comment in

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