Intensive SBP lowering reduces incident malignant left ventricular hypertrophy
Intensive Blood Pressure Lowering in Patients With Malignant Left Ventricular Hypertrophy
Introduction and methods
Left ventricular hypertrophy (LVH) is associated with incident HF and death. This risk is particularly high in the subgroup with malignant LVH, which is defined as LVH in combination with high hs-cTnT or NT-proBNP [1-5]. The SPRINT trial previously showed that targeting a SBP <120 mmHg compared with <140 mmHg resulted in lower rates of ADHF and death, among patients with hypertension and at high CVD risk . Moreover, SPRINT and other clinical trials showed that intensive blood pressure lowering prevents and may lead to the regression of malignant LVH [7-9]. However, it is unclear whether intensive blood pressure lowering can reduce the risk of acute decompensated HF (ADHF) events and death when malignant LVH is present.
Aim of the study
This ancillary analysis of SPRINT investigated whether intensive versus standard SBP lowering would reduce ADHF events and death in patients with malignant LVH present at baseline. Whether intensive SBP lowering could prevent the development of malignant LVH was assessed as well .
In the open-label SPRINT trial individuals aged ≥50 years with SBP 130 to 180 mmHg and at high CVD risk were assigned to a SBP target of either <140 mm Hg (standard-treatment group) or < 120 mm Hg (intensive-treatment group).
In this ancillary analysis, participants (n=8,820) from SPRINT were divided into 4 groups based on the presence or absence of LVH assessed by ECG, and elevations in biomarker levels; either hs-cTnT ≥14 ng/L or NT-proBNP ≥125 pg/mL at baseline: 1) no LVH and no elevated cardiac biomarkers (LVH -, biomarker -), n=4361; 2) no LVH with elevated cardiac biomarkers (LVH -, biomarker +), n=3761; 3) LVH with non-elevated cardiac biomarkers (LVH +, biomarker -), n=249; and 4) LVH with elevated cardiac biomarkers (LVH +, biomarker +), n=449. The effects of intensive versus standard SBP lowering on rates of ADHF events and death (over 4 years) and the incidence and regression of LVH and malignant LVH (over 2 years) were determined in the 4 groups.
The primary outcome of this analysis was the composite of incident ADHF events and all-cause mortality. Secondary outcomes were all-cause mortality, the incidence and regression of malignant LVH, and the incidence and regression of LVH.
Associations between LVH/biomarker categories and incident ADHF events and mortality
- The proportion of participants who experienced the composite of ADHF events and all-cause mortality was highest (13.9%) in the group with malignant LVH and lowest (1.9%) in participants with no LVH, non-elevated biomarkers. 8.2% of participants with no LVH, elevated biomarkers, and 5.6% with LVH, non-elevated biomarkers experienced the primary endpoint.
- Participants with malignant LVH had a 4-fold higher risk of the composite of incident ADHF events and all-cause mortality compared with participants with no LVH, non-elevated biomarkers. Malignant LVH was associated with increased risk of the composite of incidence ADHF events and all-cause mortality (HR 3.88, 95%CI: 2.44-6.18) and all-cause mortality (HR 3.69, 95%CI: 2.18-6.24) when compared to no LVH, non- elevated biomarkers.
Effects of intensive versus standard SBP lowering on ADHF events and all-cause mortality
- Intensive SBP lowering led to similar risk reductions in ADHF and death across all 4 combined LVH/biomarker groups (P for interaction=0.68). However, because of the difference in event rates across the subgroups, differences in absolute risk reductions were observed.
- At 4 years, the absolute risk reduction among patients with malignant LVH was 4.4% (95%CI: –5.2% to 13.9%, NNT 23) compared with 1.2% (95%CI: 0.0%-2.5%, NNT 82) in those with no LVH, non-elevated biomarkers; 2.5% (95%CI: –0.3% to 5.3%, NNT 41) in participants with no LVH and elevated biomarkers, and 2.0% (95%CI: –6.6% to 10.7%, NNT 50) in those with LVH, non-elevated biomarkers.
Effects of intensive vs standard SBP lowering on LVH outcomes
- At 2 years, intensive SBP lowering, compared with standard SBP lowering led to a significant reduction in the incidence of malignant LVH (2.5% vs 1.1%; OR: 0.44; 95%CI: 0.30-0.63).
- At 2 years, intensive SBP lowering, compared with standard SBP lowering reduced the risk of incident LVH similarly among participants with non-elevated (OR: 0.51; 95% CI: 0.37- 0.69) and elevated biomarkers (OR: 0.61; 95% CI:0.43-0.88; P for interaction=0.43).
- 61.8% of patients in the intensive SBP lowering group experienced malignant LVH regression over 2 years, compared with 53.4% in the standard SBP lowering group (OR 1.41, 95%CI 0.94-2.13).
- Intensive vs. standard SBD treatment led to more LVH regression and this was comparable between participants with non-elevated (OR: 2.29; 95%CI: 1.29-4.06) and elevated biomarkers (OR: 1.71; 95%CI: 1.12- 2.59, P for interaction = 0.42).
In this analysis of the SPRINT trial, intensive SBP lowering compared with standard SBP lowering reduced the risk of incident malignant LVH among patients with hypertension and at high CVD risk. Intensive SBP lowering led to similar risk reductions in ADHF and death across the 4 LVH/biomarker groups. Relative and absolute risk reductions with intensive SBP lowering in the malignant LVH group did not reach statistical significance.