Abstract

Abstract Background and Aims Impaired kidney function increase the risk of cardiovascular disease. However, it remains unclear whether this crosstalk between organs already exists at early stages in the disease trajectory and whether this risk varies with age and other factors. We aim to investigate the association between renal dysfunction and early structural and functional cardiac abnormalities in a cohort of participants referred to a cardiology outpatient department. Method We included participants from HELPFul (i.e. HEart failure with Preserved ejection Fraction in patients at risk for cardiovascular disease), a case-cohort study at Dutch cardiology outpatient clinics, who were aged 45 years and older without history of cardiovascular disease. A random sample of participants enriched with cases (defined as an early filling (E) to early diastolic mitral annular velocity (e’) (E/e’) ratio of ≥8 measured with echocardiography) was included in our study. Routine care measurements, including echocardiography and laboratory testing at the outpatient clinic were collected for all participants. An expert panel decided on presence or absence of heart failure with preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD), guided by available international guidelines. The association between renal function, in terms of estimated glomerular filtration rate (eGFR) categories, and diagnosis of HFpEF and LVDD was assessed with multivariable logistic regression analyses, adjusted for cardiovascular and lifestyle risk factors. The association between renal function, in terms of creatinine and cystatin C levels, and echocardiographic parameters, including E/e’ ratio, LAVI (Left atrial volume index), LVMI (left ventricular mass index), and E/A (early (E) to late (A) ventricular filling ratio, was assessed with multivariable linear regression analyses, adjusted for age, sex, cardiovascular and lifestyle risk factors. Adjusted odds ratios (OR) were reported and the corresponding 95% confidence interval (95%CI). Results 777 participants were included, mean age 62.9 (SD: 9.3) years, 67.3% were female. Hundred and fifty-six (20.1%) participants had mild renal dysfunction (eGFR: 60-89 ml/min/1.73 m2), and 24 (3.1%) moderate renal dysfunction (eGFR: 30-59 ml/min/1.73 m2). HFpEF and LVDD was more common in participants with moderate renal dysfunction (13% and 33%, respectively) than in those with normal renal function (6% and 16%, respectively). In the multivariable regression model. participants with both mild and moderate renal dysfunction had a higher likelihood of being diagnosed with HFpEF (OR: 2.82, 95%CI: 1.32 to 5.91; and OR: 5.37, 95%CI: 1.11 to 19.88, respectively), LVDD (OR: 2.08, 95%CI: 1.28 to 3.36; and OR: 2.92, 95%CI: 1.04 to 7.55, respectively), compared with participants with a normal renal function. However, no significant association between creatinine or cystatin C with E/e’, LAVI, LVMI, and E/A ratio was found after adjustment for age, sex, and cardiovascular risk and lifestyle factors. Conclusion Mild renal dysfunction is related to both LVDD and HFpEF, however, this might be partly explained by a higher age in patients with renal dysfunction. Further studies are warranted to determine if preventive cardiac treatment in patients with early renal dysfunction will benefit clinical outcomes.

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