Intensive Blood Pressure Reduction Benefits Malignant LVH

October 13, 2022

Intensive blood pressure lowering has substantial benefits for both the prevention and treatment of malignant left ventricular hypertrophy (LVH), a new analysis of the SPRINT trial shows.

The analysis found that compared with lowering systolic blood pressure to under 140 mm Hg, more intensive lowering to a target of less than 120 mm Hg reduced both the occurrence of malignant LVH and the development of heart failure or death in persons with malignant LVH.

The authors note that until now, no therapies have been established for the specific prevention or treatment of malignant LVH, so these findings have important clinical implications.

"Multiple previous observational studies have shown that patients with malignant LVH are a high-risk group at increased risk of heart failure and death, but it has not been shown before that this condition is modifiable," senior author of the new analysis, Jarett D. Berry, MD, University of Texas at Tyler Health Science Center, told | Medscape Cardiology.

"We have observed for the first time that the risk related to malignant LVH is modifiable. That is a very important point for those healthcare providers who take care of patients with hypertension."

Lead author of the paper, Simon B. Ascher, MD, University of California, San Francisco, added, "We know these patients with malignant LVH are at very high risk of adverse outcomes, but now we know that risk is modifiable, and specifically, it is modifiable by intensive blood pressure lowering."

The new analysis is published in the October 18 issue of the Journal of the American College of Cardiology, which was available online on October 10.

The authors explain that LVH, characterized by thickening of the left ventricle and identified on ECG, is a common complication of hypertension and has strong associations with incident heart failure and death. Recent observational data demonstrate that different LVH phenotypes exist, with markedly different risks for heart failure and death.

Patients who have LVH accompanied by biomarker evidence of chronic myocardial injury, as measured by high-sensitivity cardiac troponin T (hs-cTnT) or I, and neurohormonal activation, as measured by N-terminal pro–B-type natriuretic peptide (NT-proBNP) — a subgroup known as malignant LVH — are at particularly high risk for heart failure and death.

The authors note that although several trials have shown that intensive blood pressure lowering is associated with prevention and regression of LVH, it is not known whether such treatment can prevent or reverse malignant LVH, or affect the risk for heart failure events and death when malignant LVH is present.

In the current study, the authors aimed to address these questions by analyzing data from the landmark SPRINT trial, which compared a strategy of intensive blood pressure lowering (to a systolic target below 120 mm Hg) with a strategy of standard blood pressure lowering (to a systolic target below 140 mm Hg) in 9361 patients with hypertension and at high risk for cardiovascular disease.

The current analysis included 8820 patients (94.2% of the SPRINT cohort) who had a baseline standard 12-lead ECG and baseline measures of hs-cTnT and NT-proBNP. Of these, 5% were categorized as having malignant LVH. Older age, African American race, female sex, and a higher burden of comorbidities were associated with baseline malignant LVH.

Patients with baseline malignant LVH had an increased risk for heart failure/death during the study, occurring in 13.6% compared with 8.2% of those who were LVH negative but biomarker positive, 5.6% of those with LVH but without raised biomarkers, and 1.9% of those without LVH or raised biomarkers. These findings persisted in multivariable-adjusted analyses, in which patients with malignant LVH had a 4fourfold higher risk for heart failure or death compared with those without LVH.

Results showed that randomization to intensive vs standard blood pressure lowering was associated with a similar relative risk reduction for heart failure or death across all LVH categories. However, because of the much higher event rate in the malignant LVH group, these patients had a greater 4-year absolute risk reduction — 4.4%, compared with 2% in patients with LVH without raised biomarkers and 1.2% in patients without LVH or raised biomarkers.

The number needed to treat to prevent one heart failure event or death was 23 in patients with malignant LVH, 50 in patients with LVH without raised biomarkers, and 82 for those without LVH or raised biomarkers.

Intensive blood pressure lowering also seemed to prevent the development of malignant LVH.

Among 7431 participants without malignant LVH at baseline, 1.8% developed malignant LVH. Compared with standard blood pressure lowering, intensive blood pressure lowering led to a significant reduction in the incidence of malignant LVH (2.5% vs 1.1%).

Intensive blood pressure lowering was also associated with regression of malignant LVH, which occurred in 61.8% of patients in the intensive blood pressure lowering group vs 53.4% in the standard group.

Among patients without LVH at baseline, intensive blood pressure lowering reduced the risk of developing incident LVH, and in those with LVH without raised biomarkers at baseline, intensive blood pressure was associated with LVH regression.

Berry noted that intensive blood pressure lowering slowed each stage of LVH progression.

"In the natural history, patients with hypertension go from having a normal heart to LVH, where the heart muscle has thickened; then the next step is the development of malignant LVH, where in addition to this heart muscle thickening, there is an elevation of biomarkers; and then ultimately patients can progress to heart failure and death. There is a transition process that happens over time," he explained.

"We have shown that in the SPRINT trial, intensive blood pressure reduction modified each of those stages. It prevented the development of LVH, the transition from LVH to malignant LVH, and then among those who already had malignant LVH, it prevented the transition to heart failure and death. So, it appears that intensive blood pressure reduction affects the natural history of malignant LVH from its beginning all the way to its final consequences," Berry said.

Ascher added, "It was already known that lowering blood pressure is beneficial for preventing and treating LVH. But this study now shows that it also has benefits for the prevention and treatment of malignant LVH."

"Our take-home message is that intensive blood pressure lowering is particularly important in this high-risk group of patients with malignant LVH as a primary prevention strategy to reduce heart failure risk," Ascher commented.

The authors suggest that greater efforts need to be made to identify these high-risk patients.

"Our findings suggest that ECG surveillance augmented by cardiac biomarkers to detect malignant LVH could be considered as an efficient strategy to identify those who may derive substantial absolute heart failure and mortality benefits from intensive blood pressure lowering," they write.

Focus Efforts on This High-Risk Group

In an accompanying editorial, Christopher R. deFilippi, MD, Inova Heart and Vascular Institute, Virginia, and Stephen Seliger, MD, University of Maryland School of Medicine, Baltimore, note that this new SPRINT analysis has shown that malignant LVH is modifiable.

"Often, as clinicians, we think of progressions through preclinical stages to symptomatic disease as unidirectional; to this end, Ascher et al have provided important information with respect to the incident rate of malignant LVH and its regression with intensive versus standard blood pressure control," they write.

The editorialists point out that although there was no treatment interaction between persons with and those without malignant LVH, "the larger absolute risk reduction and resulting fewer number needed to treat in those with malignant LVH might focus efforts on these higher-risk stage B pre-heart failure patients."

But they add that more information on the incidence and duration of malignant LVH as a risk factor for heart failure is needed to determine if its presence could ultimately be used to initiate and determine the efficacy of treatments to prevent heart failure and death.

This study was supported by the National Heart, Lung, and Blood Institute. 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. deFilippi has served as a consultant for Abbott Diagnostics, FujiRebio, Quidell/Ortho Diagnostics, Roche Diagnostics, and Siemens Healthineers; and adjudicates endpoints for Siemens Healthineers. Seliger and deFilippi are co-owners on a patent awarded to the University of Maryland, titled "Methods for Assessing Differential Risk for Developing Heart Failure."

J Am Coll Cardiol. Published online October 10, 2022. Abstract; Editorial

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