Biomarkers of atrial fibrillation-related pathways and left atrial structure and function in an overweight and obese population.

Background: Exploring longitudinal associations of blood biomarkers with left atrial (LA) structure and function can enhance our understanding of atrial fibrillation (AF) etiopathogenesis. Methods: We studied 532 participants of the PREDIMED-Plus trial, a multicenter randomized trial in overweight and obese adults with metabolic syndrome. At baseline, 3 and 5 years after randomization, participants underwent transthoracic echocardiography and provided blood for serum biomarker measurements [propeptide of procollagen type I (PICP), high-sensitivity (hs) troponin T (hsTnT), hs C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)]. Outcomes of interest included LA peak systolic longitudinal strain (LA PSLS), LA volume index (LAVi), LA function index (LAFi), and LA stiffness index (LASi). We performed cross-sectional and longitudinal analyses to evaluate relationships between log-transformed biomarkers and echocardiographic measurements using multiple linear regression and mixed models. Results: The participants in this analysis had a mean age of 65.0 (SD 4.8) years, and 40% were females. At baseline, increased NT-proBNP and hsTnT were associated with larger LAVi and worse LA function as measured by the LAFi, LASi, and LA PSLS. Longitudinally, higher NT-proBNP, but not higher hsTnT, was associated with increased LAVi and worsening LA function. Over 5 years, 1 unit increase in log(NT-proBNP) was associated with steeper decline in LA PSLS (-0.19%, 95% CI -0.35%, -0.02%) and greater increase in LAVi (0.28 mL/m2, 95% CI 0.10, 0.45) each year. PICP, hsCRP, and 3-NT did not show consistently significant associations with LA outcomes at baseline and through 5 years. Conclusion: In an overweight and obese population, higher NT-proBNP was associated with LA volume enlargement and worsening LA function over 5 years. The implications of these findings for the prevention and prediction of AF warrant further investigation.

Associations of Alcohol Consumption With Left Atrial Morphology and Function in a Population at High Cardiovascular Risk.

BACKGROUND: Excessive alcohol consumption has been associated with increased risk of atrial fibrillation, although the underlying mechanisms remain unclear. An enlarged left atrium and impaired left atrial function may lead to atrial fibrillation. The association of alcohol consumption with structural and functional left atrial measures, however, has received limited attention. METHODS AND RESULTS: We studied 503 participants from the PREDIMED-Plus (Prevención con Dieta Mediterránea) trial, a randomized trial testing intensive weight loss intervention with an energy-reduced Mediterranean diet and physical activity promotion in preventing cardiovascular disease in adults with metabolic syndrome. Participants underwent transthoracic echocardiography at baseline, year 3, and year 5 of the study. Outcomes of interest included volume index and reservoir, conduit, and contractile strains of the left atrium. Alcohol consumption was calculated through food frequency questionnaires and presented as drinks consumed per day. Multiple linear regression and mixed models estimated the association of alcohol consumption with left atrial measurements at baseline and through follow-up. Cross-sectionally, higher alcohol consumption (per 1 drink/day increases) was associated with larger left atrial volume (0.65 mL/m2 [95% CI, 0.18-1.11]) and lower left atrial reservoir and contractile strain (-0.44% [95% CI, -0.87 to -0.01]; and -0.44% [95% CI, -0.75 to -0.14]). Baseline alcohol consumption was not associated with changes in left atrial measurements, but increases in alcohol consumption (per 1 drink/day increase) during follow-up were associated with left atrial enlargement (0.71 mL/m2 [95% CI, 0.17-1.26]). CONCLUSIONS: In a population at high cardiovascular risk, increased alcohol consumption was associated with left atrial enlargement and worsening atrial function. REGISTRATION: URL: http://www.controlled-trials.com; Unique identifier: ISRCTN89898870.

Association of alcohol consumption with circulating biomarkers of atrial fibrillation-related pathways in a population at high cardiometabolic risk.

Background: The effect of alcohol consumption on cardiovascular health, including atrial fibrillation risk, remains controversial. Evaluating the association of alcohol consumption with circulating atrial fibrillation-related biomarkers may help better understand the relevant mechanistic underpinnings. Methods: We studied 523 participants from 3 sites for the PREDIMED-Plus study, a weight-loss randomized intervention trial in metabolically unhealthy adults. N-terminal pro-B-type natriuretic protein (NTproBNP), high sensitivity troponin-T (hsTnT), high-sensitivity C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and procollagen type 1 carboxy-terminal propeptide (PICP) were measured in fasting serum samples at baseline and years 3 and 5 of follow-up. We calculated alcohol consumption in drinks/day (1 drink = 14 grams alcohol) with validated food frequency questionnaires at each visit. Using multiple linear regression and mixed models we estimated the association of alcohol consumption with log-transformed biomarkers at baseline and longitudinally adjusting for potential confounders. Results: Among 523 participants (mean age: 65 years, 40% female), mean alcohol consumption was 1 drink/day. Cross-sectionally, alcohol consumption was not associated with cardiac biomarker concentrations. Longitudinally, compared to non-consumers, heavy drinkers (≥4 drinks/day) had smaller increases in hsTnT (ß: -0.11, 95%CI: -0.20, -0.01)and PICP (ß: -0.15, 95%CI: -0.30, 0.01) over the 5-year follow-up. In contrast, those who increased alcohol consumption over the 5-year period experienced greater increases in hsCRP (ß: 0.42, 95%CI: 0.11, 0.73) compared to those whose drinking behavior stayed the same. Conclusion: Alcohol consumption was associated with complex changes in circulating biomarkers, including comparatively lower fibrotic and myocardial damage, but higher levels of overall inflammation over time. These results underscore the need for further research to better understand the effects of alcohol on cardiovascular health.

Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits.

Objectives: To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS). Methods: A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] < 1.0 cm2) and normal left ventricular ejection fraction (LVEF). Patients were classified as: high-gradient (HG, mean gradient ≥ 40 mmHg), normal-flow low-gradient (NFLG, mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2). Results: Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3-30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12-0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13-0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20-0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively. Conclusions: Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.