Search

The goal of this study is to quantify the assumptions associated with the Wasserman-Hansen (WH) and Fitness Registry and the Importance of Exercise: A National Database (FRIEND) predictive peak oxygen consumption (pVO 2 ) equations across body mass index (BMI). Assumptions in pVO 2 for both equations were first determined using a simulation and then evaluated using exercise data from the Stanford Exercise Testing registry. We calculated percent-predicted VO 2 (ppVO 2 ) values for both equations and compared them using the Bland-Altman method. Assumptions associated with pVO 2 across BMI categories were quantified by comparing the slopes of age-adjusted VO 2 ratios (pVO 2 /pre-exercise VO 2 ) and ppVO 2 values for different BMI categories. The simulation revealed lower predicted fitness among adults with obesity using the FRIEND equation compared to the WH equations. In the clinical cohort, we evaluated 2471 patients (56.9% male, 22% with BMI >30 kg/m 2 , pVO 2 26.8 mlO 2 /kg/min). The Bland-Altman plot revealed an average relative difference of -1.7% (95% CI: -2.1 to -1.2%) between WH and FRIEND ppVO 2 values with greater differences among those with obesity. Analysis of the VO 2 ratio to ppVO 2 slopes across the BMI spectrum confirmed the assumption of lower fitness in those with obesity, and this trend was more pronounced using the FRIEND equation. Peak VO 2 estimations between the WH and FRIEND equations differed significantly among individuals with obesity. The FRIEND equation resulted in a greater attributable reduction in pVO 2 associated with obesity relative to the WH equations. The outlined relationships between BMI and predicted VO 2 may better inform the clinical interpretation of ppVO 2 values during cardiopulmonary exercise test evaluations., (© 2024 World Obesity Federation.)

Purpose: There is a need for better understanding the factors that modulate left atrial (LA) dysfunction. Therefore, we determined associations of clinical and biochemical biomarkers with serial changes in echocardiographic indexes of LA function in the general population., Methods: We measured LA maximal and minimal volume indexes (LAVImax and LAVImin) by echocardiography and LA reservoir strain (LARS) by two-dimensional speckle-tracking in 627 participants (mean age 50.8 years, 51.2% women) at baseline and after 4.8 years., Results: During follow-up, LARS decreased significantly in men (-.90%, P = .033) but not in women (-.23%, P = .60). In stepwise regression analysis, stronger decrease in LARS over time was associated with male sex, a higher age, body mass index (BMI), mean arterial pressure (MAP) and serum insulin at baseline and with a greater increase in BMI and MAP over time (P ≤ .018). Similarly, an increased risk of developing or retaining abnormal LARS was observed in older participants, in subjects with a higher baseline BMI, MAP, heart rate (HR), troponin T and ΔMAP, and in those who used β-blockers at baseline. Both LAVImax and LAVImin increased significantly over time (P ≤ .0007). This increase was associated with a higher baseline age, pulse pressure and a lower HR at baseline and a greater increase in pulse pressure over time (P ≤ .029). Higher serum insulin and D-dimer were independently associated with a stronger increase in LAVImin (P ≤ .0034)., Conclusion: Subclinical worsening in LA dysfunction was associated with older age, hypertension, obesity, insulin resistance and troponin T levels. Cardiovascular risk management strategies may delay LA deterioration., (© 2024 Wiley Periodicals LLC.)

Aims: Epidemiological studies should substantiate the paradigm that endothelial dysfunction contributes to the development of heart failure with preserved ejection fraction (HFpEF). We investigated the association of cardiac remodeling and dysfunction with peripheral vasoreactivity in the general population., Methods: In 424 individuals, we echocardiographically assessed cardiac structure and function and determined digital vasomotor function by photoplethysmography (PPG) during reactive hyperemia (RH). We regressed echocardiographic indexes and abnormalities on RH ratios averaged for 30 s time intervals. We derived sex-specific peripheral vasoreactivity profiles from PPG time-series and compared their echocardiographic phenotypes., Results: Higher left ventricular (LV) mass index and lower E/A ratio and e' peak and left atrial reservoir strain were independently related to lower RH ratios. Participants with LV hypertrophy or diastolic dysfunction presented significantly lower RH ratios during the 30 to 240s intervals than normal counterparts. Low RH responders (n = 250) presented higher odds for LV hypertrophy (adjusted OR: 2.60; p = .0040) and LV diastolic dysfunction (adjusted OR: 2.66; p = .0037) than moderate-to-high responders (n = 174)., Conclusion: The association between subclinical heart maladaptation and decreased microvascular reactivity supports the involvement of endothelial dysfunction in HFpEF pathogenesis. Time-integrated profiling of microvascular vasoreactivity may enable early detection of HFpEF in the community., (© 2021 John Wiley & Sons Ltd.)

Background Prematurity disrupts the perinatal maturation of the microvasculature and macrovasculature and confers high risk of vascular dysfunction later in life. No previous studies have investigated the crosstalk between the microvasculature and macrovasculature in childhood. Methods and Results In a case-control study, we enrolled 55 children aged 11 years weighing <1000 g at birth and 71 matched controls (October 2014-November 2015). We derived central blood pressure (BP) wave by applanation tonometry and calculated the forward/backward pulse waves by an automated pressure-based wave separation algorithm. We measured the renal resistive index by pulsed wave Doppler and the central retinal arteriolar equivalent by computer-assisted program software. Compared with controls, patients had higher central systolic BP (101.5 versus 95.2 mm Hg, P <0.001) and backward wave amplitude (15.5 versus 14.2 mm Hg, P =0.029), and smaller central retinal arteriolar equivalent (163.2 versus 175.4 µm, P <0.001). In multivariable analyses, central retinal arteriolar equivalent was smaller with higher values (+1 SD) of central systolic BP (-2.94 µm; 95% CI, -5.18 to -0.70 µm [ P =0.011]) and forward (-2.57 µm; CI, -4.81 to -0.32 µm [ P =0.026]) and backward (-3.20 µm; CI, -5.47 to -0.94 µm [ P =0.006]) wave amplitudes. Greater renal resistive index was associated with higher backward wave amplitude (0.92 mm Hg, P =0.036). Conclusions In childhood, prematurity compared with term birth is associated with higher central systolic BP and forward/backward wave amplitudes. Higher renal resistive index likely moves reflection points closer to the heart, thereby explaining the inverse association of central retinal arteriolar equivalent with central systolic BP and backward wave amplitude. These observations highlight the crosstalk between the microcirculation and macrocirculation in children. Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT02147457.

Background Stiffening and calcification of the large arteries are forerunners of cardiovascular complications. MGP (Matrix Gla protein), which requires vitamin K-dependent activation, is a potent locally acting inhibitor of arterial calcification. We hypothesized that the central hemodynamic properties might be associated with inactive desphospho-uncarboxylated MGP (dp-uc MGP ). Methods and Results In 835 randomly recruited Flemish individuals (mean age, 49.7 years; 45.6% women), we measured plasma dp-uc MGP , using an ELISA -based assay. We derived central pulse pressure and carotid-femoral pulse wave velocity (PWV) from applanation tonometry and calculated forward and backward pulse waves using an automated, pressure-based wave separation analysis algorithm. Aortic PWV (n=657), central pulse pressure, forward pulse wave, and backward pulse wave mean± SD values were 7.34±1.64 m/s, 45.2±15.3 mm Hg, 33.2±10.2 mm Hg, and 21.8±8.6 mm Hg, respectively. The geometric mean plasma concentration of dp-uc MGP was 4.09 μg/L. All hemodynamic indexes increased across tertiles of dp-uc MGP distribution. In multivariable-adjusted analyses, a doubling of dp-uc MGP was associated with higher PWV (0.15 m/s; 95% CI, 0.01-0.28 m/s), central pulse pressure (1.70 mm Hg; 95% CI, 0.49-2.91 mm Hg), forward pulse wave (0.93 mm Hg; 95% CI, 0.01-1.84 mm Hg), and backward pulse wave (0.71 mm Hg; 95% CI, 0.11-1.30 mm Hg). Categorization of aortic PWV by tertiles of its distribution highlighted a decreasing trend of PWV at low dp-uc MGP (<3.35 μg/L) and an increasing trend at high dp-uc MGP (≥5.31 μg/L). Conclusions In people representative for the general population, higher inactive dp-uc MGP was associated with greater PWV , central pulse pressure, forward pulse wave, and backward pulse wave. These observations highlight new avenues for preserving vascular integrity and preventing cardiovascular complications (eg, by improving a person's vitamin K status).

Background: Recent studies in patients and general population have reported the role of left ventricular (LV) longitudinal strain (LS) as an independent predictor of outcome. However, there are few data on changes in LS over time. We therefore investigated in a general population clinical correlates of temporal changes in LS. We also explored the potential correlation between temporal changes in LV volumes and LS., Methods and Results: We measured LV end-systolic (ESV) and end-diastolic (EDV) volumes by conventional echocardiography and LS by 2D speckle tracking in 627 participants (mean age 50.6 years, 51.4% women; 41.3% hypertensives) at baseline and after 4.7 years. For statistical analysis, we used the absolute values of LS. In stepwise regression, the magnitude of the decrease in all LV LS indexes over time was greater in men than in women (P < 0.0001). Higher baseline mean arterial pressure (MAP), a larger longitudinal increase in MAP, and stopping diuretic treatment during follow-up were related to larger decreases in LS indexes. In multivariable-adjusted analysis, we observed an inverse correlation between baseline ESV and LV LS (P ≤ 0.0017). Similarly, lower baseline LS and a larger decrease in LS over time were correlated with a lesser longitudinal decrease in ESV (P ≤ 0.0004)., Conclusions: A significant decrease in LS over time was associated with male sex, higher baseline MAP, ∆MAP, and alteration in antihypertensive treatment. We suggested an interaction between a longitudinal decrease in LV deformation and adverse cardiac remodeling, while underscoring the importance of deformation analysis based on LS assessment in patients at risk., (© 2018 Wiley Periodicals, Inc.)

Background Serial imaging studies in the general population remain important to evaluate the usefulness of pathophysiologically relevant biomarkers in predicting progression of left ventricular (LV) remodeling and dysfunction. Here, we assessed in a general population whether these circulating biomarkers at baseline predict longitudinal changes in LV structure and function. Methods and Results In 592 participants (mean age, 50.8 years; 51.4% women; 40.5% hypertensive), we derived echocardiographic indexes reflecting LV structure and function at baseline and after 4.7 years. At baseline, we measured alkaline phosphatase, markers of collagen turnover (procollagen type I, C-terminal telopeptide, matrix metalloproteinase-1) and high-sensitivity cardiac troponin T. We regressed longitudinal changes in LV indexes on baseline biomarker levels and reported standardized effect sizes as a fraction of the standard deviation of LV change. After full adjustment, a decline in LV longitudinal strain (-14.2%) and increase in E/e' ratio over time (+18.9%; P≤0.019) was associated with higher alkaline phosphatase activity at baseline. Furthermore, longitudinal strain decreased with higher levels of collagen I production and degradation at baseline (procollagen type I, -14.2%; C-terminal telopeptide, -16.4%; P≤0.029). An increase in E/e' ratio over time was borderline associated with lower matrix metalloproteinase-1 (+9.8%) and lower matrix metalloproteinase-1/tissue inhibitor of metalloproteinase-1 ratio (+11.9%; P≤0.041). Higher high-sensitivity cardiac troponin T levels at baseline correlated significantly with an increase in relative wall thickness (+23.1%) and LV mass index (+18.3%) during follow-up ( P≤0.035). Conclusions We identified a set of biomarkers predicting adverse changes in LV structure and function over time. Circulating biomarkers reflecting LV stiffness, injury, and collagen composition might improve the identification of subjects at risk for subclinical cardiac maladaptation.

Background: Population 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 Results: In 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)., Conclusions: Hyperinsulinemia 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., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: No longitudinal study compared associations of echocardiographic indexes of diastolic left ventricular function studies with conventional (CBP) and daytime ambulatory (ABP) blood pressure in the general population., Methods and Results: In 780 Flemish (mean age, 50.2 years; 51.7% women), we measured left atrial volume index (LAVI), peak velocities of the transmitral blood flow (E) and mitral annular movement (e') in early diastole and E/e' 9.6 years (median) after CBP and ABP. In adjusted models including CBP and ABP, we expressed associations per 10/5-mm Hg systolic/diastolic blood pressure increments. LAVI and E/e' were 0.65/0.40 mL/m 2 and 0.17/0.09 greater with higher systolic/diastolic ABP ( P ≤0.028), but not with higher baseline CBP ( P ≥0.086). e' was lower ( P ≤0.032) with higher diastolic CBP (-0.09 cm/s) and ABP (-0.19 cm/s). When we substituted baseline CBP by CBP recorded concurrently with echocardiography, LAVI and E/e' remained 0.45/0.38 mL/m 2 and 0.15/0.08 greater with baseline ABP ( P ≤0.036), while LAVI (+0.53 mL/m 2 ) and E/e' (+0.19) were also greater ( P <0.001) in relation to concurrent systolic CBP. In categorized analyses of baseline data, sustained hypertension or masked hypertension compared with normotension or white-coat hypertension was associated with greater LAVI (24.0 versus 22.6 mL/m 2 ) and E/e' (7.35 versus 6.91) and lower e' (10.7 versus 11.6 cm/s; P ≤0.006 for all) with no differences ( P ≥0.092) between normotension and white-coat hypertension or between masked hypertension and sustained hypertension., Conclusions: ABP is a long-term predictor of diastolic left ventricular function, statistically outperforming distant but not concurrent CBP. Masked hypertension and sustained hypertension carry equal risk for deterioration of diastolic left ventricular function., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

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 BPb and UCd 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 BPb. 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 UCd. Models including both exposure indexes did not allow differentiating whether LV dysfunction was predominately related to BPb or UCd. Diastolic LV function was not associated with BPb or UCd (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., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)