Echocardiographic estimates of RV and pulmonary vascular function are feasible during exercise and identify pathology with reasonable accuracy. They represent valid screening tools for the identification of pulmonary vascular disease in routine clinical practice.

Matrix Gla-protein is a vitamin K–dependent protein that strongly inhibits arterial calcification. Vitamin K deficiency leads to production of inactive nonphosphorylated and uncarboxylated matrix Gla protein (dp–ucMGP). The risk associated with dp–ucMGP in the population is unknown. In a Flemish population study, we measured circulating dp–ucMGP at baseline (1996–2011), genotyped MGP , recorded adverse health outcomes until December 31, 2012, and assessed the multivariable-adjusted associations of adverse health outcomes with dp–ucMGP. We applied a Mendelian randomization analysis using MGP genotypes as instrumental variables. Among 2318 participants, baseline dp–ucMGP averaged 3.61 μg/L. Over 14.1 years (median), 197 deaths occurred, 58 from cancer and 70 from cardiovascular disease; 85 participants experienced a coronary event. The risk of death and non-cancer mortality curvilinearly increased ( P ≤0.008) by 15.0% (95% confidence interval, 6.9–25.3) and by 21.5% (11.1–32.9) for a doubling of the nadir (1.43 and 0.97 μg/L, respectively). With higher dp–ucMGP, cardiovascular mortality log-linearly increased (hazard ratio for dp–ucMGP doubling, 1.14 [1.01–1.28]; P =0.027), but coronary events log-linearly decreased (0.93 [0.88–0.99]; P =0.021). dp–ucMGP levels were associated ( P ≤0.001) with MGP variants rs2098435 , rs4236 , and rs2430692. For non-cancer mortality and coronary events ( P ≤0.022), but not for total and cardiovascular mortality ( P ≥0.13), the Mendelian randomization analysis suggested causality. Higher dp–ucMGP predicts total, non-cancer and cardiovascular mortality, but lower coronary risk. For non-cancer mortality and coronary events, these associations are likely causal.

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 ...

CTED represents an intermediate clinical phenotype. Exercise imaging unmasks cardiovascular dysfunction not evident at rest and identifies hemodynamically significant disease that results from reduced contractile reserve or increased vascular load.

Abstract-In a previous cross-sectional study, we identified a multidimensional urinary classifier (HF1), which was associated with left ventricular dysfunction. We investigated whether HF1 predicts cardiovascular end points over and beyond traditional risk factors.

The Study for Promotion of Health in Recycling Lead (SPHERL) will enroll 500 newly hired workers, whose blood lead during 2 years of follow-up is expected to increase from levels less than 2 μg/dl, as currently observed in the US population, to 20-30 μg/dl. The main outcome variables to be studied are (i) blood pressure (BP) analyzed as a continuous or categorical variable, both cross-sectionally and longitudinally, and using conventional and ambulatory BP measurement; (ii) indexes of glomerular and tubular renal function, (iii) heart rate variability analyzed in the frequency domain as measure of autonomous sympathetic modulation, (iv) peripheral nerve conductivity velocity, (v) neurocognitive performance, and (vi) quality of life. Expected outcomes. Assuming a 10-fold increase in blood lead, SPHERL will have sufficient statistical power to detect over 2 years a steepening of the age-related rise in systolic BP from 1 to 5 mmHg and a doubling of the age-related decline in the estimated glomerular filtration rate from 3.5 to 7.0 ml/min/1.73 m(2). The longitudinal design of our study complies with the temporality principle of the Bradford-Hill criteria for assessing possible causality between outcomes and exposure. SPHERL will attempt to resolve the apparent contradiction between general population studies showing associations between adverse health effects and low lead exposure with blood lead levels below 5 μg/dl and studies conducted in occupational cohorts indicating that adverse effects of lead exposure occur at much higher blood lead levels.

Conclusions: Significant Bra-Rad-SBP Amp exists during light-moderate exercise. This will result in underestimation of central SBP unless Bra-Rad-SBP Amp is considered and is influenced by variation in peak blood flow velocity magnitude between the brachial and radial arteries.Abstracts 125

Current knowledge on the pathogenesis of diastolic heart failure predominantly rests on case-control studies involving symptomatic patients with preserved ejection fraction and relying on invasive diagnostic procedures including endomyocardial biopsy. Our objective was to gain insight in serum and urinary biomarkers reflecting collagen turnover and associated with asymptomatic diastolic LV dysfunction. We randomly recruited 782 Flemish (51.3% women; 50.5 years). We assessed diastolic LV function from the early and late diastolic peak velocities of the transmitral blood flow and of the mitral annulus. By sequencing urinary peptides, we identified 70 urinary collagen fragments. In serum, we measured carboxyterminal propeptide of procollagen type 1 (PICP) as marker of collagen I synthesis and tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1), an inhibitor of collagen-degrading enzymes. In multivariable-adjusted analyses with Bonferroni correction, we expressed effect sizes per 1-SD in urinary collagen I (uCI) or collagen III (uCIII) fragments. In relation to uCI fragments, e’ decreased by 0.183 cm/s (95% confidence interval, 0.017 to 0.350; p = 0.025), whereas E/e’ increased by 0.210 (0.067 to 0.353; p = 0.0012). E/e’ decreased with uCIII by 0.168 (0.021 to 0.316; p = 0.018). Based on age-specific echocardiographic criteria, 182 participants (23.3%) had subclinical diastolic LV dysfunction. Partial least squares discriminant analysis contrasting normal vs. diastolic LV dysfunction confirmed the aforementioned associations with the uCI and uCIII fragments. PICP and TIMP-1 increased in relation to uCI (p<0.0001), whereas these serum markers decreased with uCIII (p≤0.0006). Diastolic LV dysfunction was associated with higher levels of TIMP-1 (653 vs. 696 ng/mL; p = 0.013). In a general population, the non-invasively assessed diastolic LV function correlated inversely with uCI and serum markers of collagen I deposition, but positively with uCIII. These observations generalise previous studies in patients to randomly recruited people, in whom diastolic LV function ranged from normal to subclinical impairment, but did not encompass overt diastolic heart failure.