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 (P_age² = 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.

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.

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. 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 (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)). 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.

Background: Experimental studies have demonstrated that lead and cadmium have direct toxic effects on the myocardium, but the few human studies are limited by design, assessment of exposure, and use of heart failure as a late‐stage endpoint. Methods and Results: In a prospective population study, we studied the association of left ventricular ( LV ) function with blood lead (BPb) and 24‐hour urinary cadmium (UCd). In 179 participants randomly recruited from a Flemish population (50.3% women; mean age 39.1 years), geometric mean BP b and UC d at enrollment (1985‐2000) were 0.20 μmol/L and 6.1 nmol, respectively. We assessed systolic and diastolic LV function 11.9 years (median) later (2005‐2010) by using Doppler imaging of the transmitral blood flow and the mitral annular movement and speckle tracking. In multivariable‐adjusted linear regression, LV systolic function decreased with BP b. For a doubling of exposure, estimates were −0.392% for global longitudinal strain ( P =0.034), −0.618% and −0.113 s ⁻¹ for regional longitudinal strain ( P =0.028) and strain rate ( P =0.008), and −0.056 s ⁻¹ for regional radial strain rate ( P =0.050). Regional longitudinal strain rate (−0.066 s ⁻¹ , P =0.009) and regional radial strain (−2.848%, P =0.015) also decreased with UC d. Models including both exposure indexes did not allow differentiating whether LV dysfunction was predominately related to BP b or UC d. Diastolic LV function was not associated with BP b or UC d ( P ≥0.159). Conclusions: Although effect sizes were small, our results suggest that environmental exposure to lead, cadmium, or both might be a risk factor for systolic LV dysfunction, a condition often proceeding to heart failure.

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 was a strong predictor of worsening of LVDF from normal/mild grade to more advanced grade (odds ratio, 3.22; P <0.0001). A doubling of baseline insulin was associated with a 184% increase in the odds of worsening of LVDF ( P <0.0001). Moreover, baseline diastolic blood pressure and the change in systolic blood pressure over time predicted worsening of LVDF ( P ≤0.014). Conclusions—: The key findings of this study are that LVDF tended to worsen over time and was associated with advanced age, higher baseline insulin level, and hemodynamic parameters, such as heart rate and blood pressure.

The cardio-renal interaction occurs via hemodynamic and humoral factors. Noninvasive assessment of renal hemodynamics is currently possible by assessment of renal resistive index (RRI) derived from intrarenal Doppler arterial waveforms as ((peak systolic velocity − end-diastolic velocity)/peak systolic velocity). Limited information is available regarding the relationship between RRI and cardiac hemodynamics. We investigated these associations in randomly recruited subjects from a general population. In 171 participants (48.5% women; mean age, 52.2 years), using pulsed wave Doppler, we measured RRI (mean, 0.60) and left ventricular outflow tract (LVOT) and transmitral (E and A) blood flow peak velocities and its velocity time integrals (VTI). Using carotid applanation tonometry, we measured central pulse pressure and arterial stiffness indexes such as augmentation pressure and carotid–femoral pulse wave velocity. In stepwise regression analysis, RRI independently and significantly increased with female sex, age, body weight, brachial pulse pressure, and use of β-blockers, whereas it decreased with body height and mean arterial pressure. In multivariable-adjusted models with central pulse pressure and arterial stiffness indexes as the explanatory variables, we observed a significant and positive correlation of RRI only with central pulse pressure (P < 0.0001). Among the Doppler indexes of left ventricular blood flow, RRI was significantly and positively associated with LVOT and E peak velocities (P ≤ 0.012) and VTIs (P ≤ 0.010). 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.