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Objectives: This study aimed to evaluate the risk of all-cause mortality and incident cardiovascular disease associated with peak systolic blood pressure (PeakSBP) at clinical exercise testing., Methods: Data from 10 096 clinical exercise tests (54% men, age 18-85 years) was cross-linked with outcome data from national registries. PeakSBP was compared with recently published reference percentiles as well as expressed as percentage predicted PeakSBP using reference equations.Natural cubic spline modelling and Cox regression were used to analyse data stratified by sex and baseline cardiovascular risk profile., Results: Median [IQR] follow-up times were 7.9 [5.7] years (all-cause mortality) and 5.6 [5.9] years (incident cardiovascular disease), respectively. The adjusted risk of all-cause mortality [hazard ratio, 95% confidence interval (95% CI)] for individuals with PeakSBP below the 10th percentile was 2.00 (1.59-2.52) in men and 2.60 (1.97-3.44) in women, compared with individuals within the 10th--90th percentile. The corresponding risk for incident cardiovascular disease was 1.55 (1.28-1.89, men) and 1.34 (1.05-1.71, women). For males in the upper 90th percentile, compared with individuals within the 10th--90th percentile, the adjusted risks of all-cause death and incident cardiovascular disease were 0.35 (0.22-0.54) and 0.72 (0.57-0.92), respectively, while not statistically significant in women. Spline modelling revealed a continuous increase in risk with PeakSBP values less than 100% of predicted in both sexes, with no increase in risk more than 100% of predicted., Conclusion: Low, but not high, PeakSBP was associated with an increased risk of mortality and future cardiovascular disease. Using reference standards for PeakSBP could facilitate clinical risk stratification across patients of varying sex, age and exercise capacity., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Echocardiographic definitions of subclinical left atrial dysfunction based on epidemiological data remain scarce. In this population study, we derived outcome-driven thresholds for echocardiographic left atrial function parameters discriminating between normal and abnormal values., Methods: In 1306 individuals (mean age, 50.7 years; 51.6% women), we echocardiographically assessed left atrial function and LV global longitudinal strain. We derived cut-off values for left atrial emptying fraction (LAEF), left atrial function index (LAFI) and left atrial reservoir strain (LARS) to define left atrial dysfunction using receiver-operating curve threshold analysis. Main outcome was the incidence of cardiac events and atrial fibrillation (AFib) on average 8.5 years later., Results: For prediction of new-onset AFib, left atrial cut-offs yielding the best balance between sensitivity and specificity (highest Youden index) were: LAEF less than 55%, LAFI less than 40.5 and LARS less than 23%. Applying these cut-offs, abnormal LAEF, LAFI and LARS were, respectively, present in 27, 37.1 and 18.1% of the cohort. Abnormal LARS (<23%) was independently associated with higher risk for cardiac events and new-onset AFib (P ≤ 0.012). Participants with both abnormal LAEF and LARS presented a significantly higher risk to develop cardiac events (hazard ratio: 2.10; P = 0.014) and AFib (hazard ratio: 6.45; P = 0.0036) than normal counterparts. The concomitant presence of an impaired LARS and LV global longitudinal strain improved prognostic accuracy beyond a clinical risk model for cardiac events and the CHARGE-AF Risk Score for AFib., Conclusion: Left atrial dysfunction based on outcome-driven thresholds predicted cardiac events and AFib independent of conventional risk factors. Screening for subclinical left atrial and LV systolic dysfunction may enhance cardiac disease prediction in the community.

Background: The contribution of central pulsatility to left ventricular (LV) dysfunction might be mediated by the haemodynamic loads of forward (Pf) and backward (Pb) pulse waves. We investigated the relation between echocardiographic indexes of LV function and pulsatile loads derived by wave separation analysis (WSA)., Methods: In 755 participants, we assessed LV dimensions, transmitral blood flow and mitral annular tissue velocities. We derived central pulse pressure (cPP) from radial tonometric recordings and calculated Pf, Pb and their ratio (reflection magnitude) using an automated, pressure-based WSA algorithm. Despite good quality recordings, WSA failed to derive Pf and Pb in 139 participants (18.4%), in particular in older women with unfavourable haemodynamics. Thus, our analysis included 616 participants (46.1% women; mean age, 49.2 years)., Results: Age and age explained most of the variance in cPP (36.9%), Pf (18.6%), Pb (41.5%) and reflection magnitude (36.7%; P < 0.0001) and altered the direct correlation between Pf and Pb (Pint < 0.0001). Haemodynamic loads were independently associated with sex, BMI, heart rate, mean arterial pressure, history of diabetes and use of antihypertensive drugs. In multivariable-adjusted analyses, transmitral velocities and E/e' ratio increased with higher cPP, Pf and Pb in men and women. We also observed an age-dependent association of LV radial strain with cPP, Pf and Pb., Conclusion: The commercial WSA algorithm holds limited clinical utility given its low feasibility in older participants with unfavourable haemodynamics. LV function indexes were similarly associated with Pf and Pb, favouring the use of the composite cPP for prediction of LV dysfunction.

Background: Late-systolic loading of the left ventricular (LV) is determined by arterial wave reflections and central vascular stiffening. We, therefore, investigated the relationship between various Doppler indexes reflecting LV systolic and diastolic function and arterial stiffness in the framework of a large population study of randomly recruited study participants., Methods: In 1233 study participants (51.7% women; mean age, 48 years; 41.5% hypertensive), using conventional and tissue Doppler imaging, we measured: the transmitral early (E) and late (A) diastolic velocities; tissue Doppler imaging systolic and early (e') and late diastolic mitral annular velocities; and end-systolic longitudinal and radial strain. Using applanation tonometry, we assessed central pulse pressure (cPP), augmentation pressure and carotid-femoral pulse wave velocity., Results: After full adjustment, transmitral E and A peaks increased with augmentation pressure and cPP (P less than 0.0001) and e' was positively associated with cPP (P = 0.013). The E/e' ratio increased significantly with augmentation pressure (P less than 0.0001), cPP (P less than 0.0001) and pulse wave velocity (P = 0.048). Although accounting for covariables, all arterial indexes were on average significantly higher in the diastolic dysfunction group with elevated filling pressure (n = 171) when compared to participants with normal diastolic function (n = 961; P ≤ 0.0004) or with impaired relaxation (n = 101; P ≤ 0.008). Longitudinal strain decreased independently with mean arterial pressure (P = 0.03). The correlation between radial strain and the arterial indexes shifted from positive at middle age (50-60 years) to negative at older (P less than 0.0001 for interaction)., Conclusion: Our study underscored the importance of arterial characteristics as a mediator of LV systolic and diastolic dysfunction. We demonstrated an age-dependent relationship between radial strain and indexes of arterial stiffness.