Background-Techniques of 2-dimensional speckle tracking enable the measurement of myocardial deformation (strain) during systole. Recent clinical studies explored the prognostic role of left ventricular global longitudinal strain (GLS). However, there are few data on the association between cardiovascular outcome and GLS in the community. Therefore, we hypothesized that GLS contains additive prognostic information over and beyond traditional cardiovascular risk factors in a large, population-based cohort. Methods and Results-We measured GLS by 2-dimensional speckle tracking in the apical 4-chamber view in 791 participants (mean age 50.9 years). We calculated multivariable adjusted hazard ratios for midwall, endocardial, and epicardial GLS, while accounting for family cluster and cardiovascular risk factors. Median follow-up was 7.9 years (5th to 95th percentile, 3.7-9.6). In continuous analysis, with adjustments applied for covariables, midwall, endocardial, and epicardial GLS were significant predictors of fatal and nonfatal cardiovascular (n=96; P<0.0001) and cardiac events (n=68; P≤0.001). In the sex-specific low quartile of midwall GLS (<18.8% in women and <17.4% in men), the risk was significantly higher than the average population risk for cardiovascular (128%, P<0.0001) and cardiac (94%, P=0.0007) events. We also noticed that the risk for cardiovascular events increased with increasing number of left ventricular abnormalities, such as low GLS, diastolic dysfunction, and hypertrophy (log-rank P<0.0001). Conclusions-Low GLS measured by 2-dimensional speckle tracking predicts future cardiovascular events independent of conventional risk factors. Left ventricular midwall strain represents a simple echocardiographic measure, which might be used for assessing cardiovascular risk in a population-based cohort. Methods Study ParticipantsThe Ethics Committee of the University of Leuven approved the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO), a large family-based population resource on the genetic epidemiology of cardiovascular phenotypes. 13,14 From August 1985 to December 2005, we identified a random population sample stratified by sex and age from a geographically defined area in northern Belgium as described in the Data Supplement.13,14 From 2005 to 2009, we invited 1031 former participants for a technical examination at our field center, including echocardiography. We obtained informed written consent from 828 subjects (participation rate, 80%). To study the incidence of mortality and morbidity in relation to baseline LV systolic dysfunction, we collected outcome data on average 7.9 years after their first echocardiographic examination. For the current analysis, we further excluded 37 subjects because of atrial fibrillation (n=8), the presence of an artificial pacemaker (n=3), or because of GLS (n=22) or diastolic function (n=4) could not be reliably determined. Thus, the outcome cohort included 791 participants. EchocardiographyEchocardiographic methods are detailed in Methods sectio...

Accumulation of mitochondrial DNA (mtDNA) mutations leads to alterations of mitochondrial biogenesis and function that might produce a decrease in mtDNA content within cells. This implies that mtDNA content might be a potential biomarker associated with oxidative stress and inflammation. However, data on correlates of mtDNA content in a general population are sparse. Our goal in the present study was to describe in a randomly recruited population sample the distribution and determinants of peripheral blood mtDNA content. From 2009 to 2013, we examined 689 persons (50.4% women; mean age = 54.4 years) randomly selected from a Flemish population (Flemish Study on Environment, Genes, and Health Outcomes). Relative mtDNA copy number as compared with nuclear DNA was measured by quantitative real-time polymerase chain reaction in peripheral blood. There was a curvilinear relationship between relative mtDNA copy number and age. mtDNA content slightly increased until the fifth decade of life and declined in older subjects (Page2 = 0.0002). mtDNA content was significantly higher in women (P = 0.007) and increased with platelet count (P < 0.0001), whereas it was inversely associated with white blood cell count (P < 0.0001). We also observed lower mtDNA content in women using estroprogestogens (P = 0.044). This study demonstrated in a general population that peripheral blood mtDNA content is significantly associated with sex and age. Blood mtDNA content is also influenced by platelet and white blood cell counts and estroprogestogen intake. Further studies are required to clarify the impact of chronic inflammation and hormone therapy on mitochondrial function.

Because life expectancy and the prevalence of risk factors, such as hypertension, obesity, insulin resistance and diabetes mellitus are rising globally, heart failure is growing into a major health problem. Impairment of left ventricular diastolic function (LVDF) appears early in the course of heart disease. Recent heart failure guidelines, therefore, place special emphasis on the detection of subclinical LV dysfunction and the timely identification of risk factors for progression to symptomatic heart failure.1 Conventional echocardiography combined with new imaging techniques such as tissue Doppler imaging (TDI) is a sensitive tool to detect early subclinical deterioration of LV function.2 Recent community-based studies revealed a higher than hitherto expected prevalence of LV diastolic dysfunction, using comprehensive conventional and TDI echocardiographic imaging. [3][4][5][6] For instance, in the Flemish Study on Environment, Genes, and Health Outcomes (FLEMENGHO), the frequency was 27.3%.5 LV diastolic dysfunction is also associated with increased risk for various cardiovascular diseases. 4,7,8 See Editorial by Fitzgibbons and Aurigemma See Clinical PerspectiveCommunity-based studies have identified cross-sectionally that age, body mass index, heart rate (HR), and diastolic blood pressure (DBP) are important correlates of echocardiographic LVDF indexes. 5,6 However, data on the longitudinal tracking of LVDF over time are sparse. To our knowledge, 2 community-based studies 9,10 explored the factors predictive of the development of subclinical LV diastolic dysfunction. In the clinical setting, Aljaroudi et al 11 reported that in patients with normal baseline LV ejection fraction, worsening of diastolic function grade was an independent predictor of mortality. However, serial imaging studies are also needed to clarify the clinical correlates of change in LVDF indexes. These data are currently lacking. We, therefore, investigated Background-Data on changes in left ventricular diastolic function (LVDF) over time in the general population are sparse.We, therefore, investigated in the population cohort clinical correlates of longitudinal changes in Doppler diastolic indexes analyzed as continuous measures and assessed factors predictive of the changes in LVDF grades over time. Methods and Results-We measured early and late diastolic peak velocities of mitral inflow (E and A) by conventional Doppler, and the mitral annular velocities (e′ and a′) by tissue Doppler imaging in 650 participants (mean age, 50.7 years) at baseline and after 4.7 years (5th to 95th percentile, 3.7-5.4). In stepwise regression, the multivariable-adjusted correlates of the change in the transmitral and tissue Doppler imaging diastolic indexes included sex, age, baseline serum insulin, blood pressure, and heart rate. During follow-up, LVDF grades remained unchanged in 87.2% (95% confidence interval, 84.6%-89.8%), improved in 3.7% (95% confidence interval, 2.25%-5.15%), and worsened in 9.1% (95% confidence interval, 6.9%-11.3%). Baseline age ...

Aims The association between peak systolic blood pressure (SBP) during exercise testing and outcome remains controversial, possibly due to the confounding effect of external workload (metabolic equivalents of task (METs)) on peak SBP as well as on survival. Indexing the increase in SBP to the increase in workload (SBP/MET-slope) could provide a more clinically relevant measure of the SBP response to exercise. We aimed to characterize the SBP/MET-slope in a large cohort referred for clinical exercise testing and to determine its relation to all-cause mortality. Methods and results Survival status for male Veterans who underwent a maximal treadmill exercise test between the years 1987 and 2007 were retrieved in 2018. We defined a subgroup of non-smoking 10-year survivors with fewer risk factors as a lower-risk reference group. Survival analyses for all-cause mortality were performed using Kaplan–Meier curves and Cox proportional hazard ratios (HRs (95% confidence interval)) adjusted for baseline age, test year, cardiovascular risk factors, medications and comorbidities. A total of 7542 subjects were followed over 18.4 (interquartile range 16.3) years. In lower-risk subjects ( n = 709), the median (95th percentile) of the SBP/MET-slope was 4.9 (10.0) mmHg/MET. Lower peak SBP (<210 mmHg) and higher SBP/MET-slope (>10 mmHg/MET) were both associated with 20% higher mortality (adjusted HRs 1.20 (1.08–1.32) and 1.20 (1.10–1.31), respectively). In subjects with high fitness, a SBP/MET-slope > 6.2 mmHg/MET was associated with a 27% higher risk of mortality (adjusted HR 1.27 (1.12–1.45)). Conclusion In contrast to peak SBP, having a higher SBP/MET-slope was associated with increased risk of mortality. This simple, novel metric can be considered in clinical exercise testing reports.

We demonstrated that in unselected subjects RRI was significantly associated with central pulse pressure and left ventricular systolic and diastolic Doppler blood flow indexes. Our findings imply that in addition to the anthropometric characteristics, cardiac hemodynamic factors influence the intrarenal arterial Doppler waveform patterns.

BackgroundPopulation data on the longitudinal changes of left ventricular (LV) structure and function in relation to insulin resistance are sparse. Therefore, we assessed in a general population whether hyperinsulinemia predicts longitudinal changes in LV and arterial characteristics.Methods and ResultsIn 627 participants (mean age 50.7 years, 51.4% women), we assessed echocardiographic indexes of LV structure and function and carotid‐femoral pulse wave velocity by applanation tonometry at baseline and after 4.7 years. We regressed longitudinal changes in these indexes on baseline insulin and its change during follow‐up, and reported standardized effect sizes as a percentage of the SD of LV changes associated with a doubling of insulin. After adjustment, higher baseline insulin predicted a greater temporal increase in LV mass index (effect size: +15.1%) and E/e′ ratio (+22.1%), and a greater decrease in e′ peak and longitudinal strain (−11.2% to −17.1%). A greater increase in insulin during follow‐up related to a greater increase in LV mass index (+10.7%) and decline in ejection fraction and longitudinal strain (−11.4% to −15.7%). Participants who became or remained insulin resistant during follow‐up experienced worse changes in longitudinal strain, E/e′, and LV mass index as compared with participants who did not develop or had improved insulin resistance over time (P≤0.033). Moreover, multivariable‐adjusted increase in pulse wave velocity was higher in participants with diabetes mellitus than in participants without diabetes mellitus (+1.46 m/s versus +0.71 m/s; P=0.039).ConclusionsHyperinsulinemia at baseline and during follow‐up predicted worsening of LV function and remodeling over time. Our findings underline the importance of management of insulin resistance.

Systolic ABP is a significant predictor of incident AF in a population-based cohort. We also observed that participants with a daytime systolic BP load >38% had significantly increased risk of incident AF.

Background: The noninvasive assessment of renal hemodynamics is currently possible by assessing the renal resistive index (RRI) derived from intrarenal Doppler arterial waveforms as (peak systolic velocity - end-diastolic velocity)/peak systolic velocity. In this review, we outline the important determinants of the RRI to clarify the true identity of the RRI and highlight its potential diagnostic and prognostic value in renal and cardiovascular pathology. Summary: Although the RRI was initially considered to reflect intrarenal vascular pathological processes, this index is actually a product of a complex interaction between renal and systemic vascular wall properties and hemodynamic factors. Indeed, studies in patients and general populations consistently demonstrated a significant and direct association between the RRI and central or peripheral pulse pressure independent of other covariables. Moreover, studies in renal transplant patients also showed that the RRI mainly reflects characteristics of the recipient but not those of the graft. Thus, the major influence of the systemic hemodynamics on the intrarenal arterial waveforms excludes RRI as a specific marker of renal vascular pathology. On the other hand, because the RRI reflects pulsatility in renal arteries, it might be useful for the early detection of renal microvascular damage. Future longitudinal studies are still needed to clarify whether the detection of Doppler changes in intrarenal arteries might yield an improvement in the adverse cardiovascular and renal outcome. Conclusion: Published studies on RRI imply that the interaction between the systemic hemodynamics and peripheral circulation in the kidney is a complex physiological phenomenon. In addition to renal vascular properties, the central hemodynamic factors significantly influence the intrarenal arterial Doppler waveform patterns. Previous research also suggested an important role of the RRI for the evaluation of renal target organ damage, particularly in patients with increased pulsatility of the intrarenal blood flow.