Late systolic central hypertension as a predictor of incident heart failure: the Multi-ethnic Study of Atherosclerosis

Abstract

Background: Experimental studies demonstrate that high aortic pressure in late systole relative to early systole causes greater myocardial remodeling and dysfunction, for any given absolute peak systolic pressure.

Methods and results: We tested the hypothesis that late systolic hypertension, defined as the ratio of late (last one third of systole) to early (first two thirds of systole) pressure-time integrals (PTI) of the aortic pressure waveform, independently predicts incident heart failure (HF) in the general population. Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 6124 adults. The late/early systolic PTI ratio (L/E(SPTI)) was assessed as a predictor of incident HF during median 8.5 years of follow-up. The L/E(SPTI) was predictive of incident HF (hazard ratio per 1% increase=1.22; 95% CI=1.15 to 1.29; P<0.0001) even after adjustment for established risk factors for HF (HR=1.23; 95% CI=1.14 to 1.32: P<0.0001). In a multivariate model that included brachial systolic and diastolic blood pressure and other standard risk factors of HF, L/E(SPTI) was the modifiable factor associated with the greatest improvements in model performance. A high L/E(SPTI) (>58.38%) was more predictive of HF than the presence of hypertension. After adjustment for each other and various predictors of HF, the HR associated with hypertension was 1.39 (95% CI=0.86 to 2.23; P=0.18), whereas the HR associated with a high L/E was 2.31 (95% CI=1.52 to 3.49; P<0.0001).

Conclusions: Independently of the absolute level of peak pressure, late systolic hypertension is strongly associated with incident HF in the general population.

Keywords: arterial hemodynamics; heart failure; late systolic load; left ventricular afterload.

© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1.

Assessment of early vs late aortic systolic pressure. The tonometric radial pressure waveform (left) is used to derive an aortic pressure waveform (right). The duration of the systolic portion of the aortic pressure waveform was then split in 3 equal tertiles to compute the area under the curve (pressure–time integral [PTI]) corresponding to each tertile (PTI1, PTI2, and PTI3). The late/early systolic PTI (L/ESPTI) was then computed as PTI3/(PTI1+PTI2). AIx indicates augmentation index; P1, first systolic peak; P2, second systolic peak; 1, 2 and 3, 1st, 2nd and 3rd pressure‐time integrals of systole, respectively.

Figure 2.

Examples of central pressure waveforms demonstrating a high (top row) and low (bottom row) late/early systolic pressure–time integral (L/ESPTI). AIx indicates Augmentation index.

Figure 3.

Hazard ratio associated with hypertension or a high L/ESPTI in various Cox models. All models include the presence of hypertension and a high L/ESPTI as predictors of HF. Model 1 (n=6124) includes no additional covariables. Model 2 (n=6124) is adjusted for age, ethnicity, gender, and heart rate. Model 3 (n=6107) is additionally adjusted for diabetes mellitus and body mass index. Model 4 (n=6098) is additionally adjusted for antihypertensive medication use, total cholesterol, HDL cholesterol, current smoking, estimated glomerular filtration rate, aortic augmentation index, and aortic‐to‐radial pulse pressure amplification. HDL indicates high‐density lipoprotein; HF, heart failure; L/ESPTI, late/early systolic pressure–time integral; SBP, systolic blood pressure.

Figure 4.

Cumulative hazard curves for HF among participants stratified according to the presence or absence of hypertension (prevalence=45%) or a high L/ESPTI (set empirically to an identical prevalence of 45% based on E/LSPTI). Curves are adjusted for age, ethnicity, gender, heart rate, diabetes mellitus, body mass index, antihypertensive medication use, total cholesterol, HDL cholesterol, current smoking, and estimated glomerular filtration rate. The numbers of participants in each stratum are as follows: No HTN/Low L/ESPTI=2214; HTN/Low L/ESPTI=1155; No HTN/High L/ESPTI=1182; HTN/High L/ESPTI=1574. HDL indicates high‐density lipoprotein; HF, heart failure; L/ESPTI, late/early systolic pressure time integral; HTN, hypertension; CHF, congestive heart failure.