Cardiovascular-kidney-liver-metabolic syndrome in patients with chronic heart failure with mildly reduced ejection fraction and post-infarction cardiosclerosis: prevalence of its components, phenotypic groups and long-term prognosis

Abstract

Background. The relationship between metabolic risk factors, chronic kidney disease (CKD), metabolic-associated fatty liver disease (MAFLD), and cardiovascular diseases (CVD) is highlighted in the concept of сardiovascular-kidney-liver-metabolic syndrome (CKLMS), which is closely associated with competing risks of adverse outcomes. The impact of the burden of CKLMS remains poorly understood in chronic heart failure (HF) in national cohorts. Objective. To evaluate the frequency of CKLMS components, their combinations, and their impact on the long-term prognosis of patients with HF with mildly reduced ejection fraction (LVEF) (HFmrEF) and post-infarction cardiosclerosis. Design and methods. This was a retrospective analysis of data from a prospective, observational, single-center study involving 160 men (median age 62 years) with post-infarction cardiosclerosis and HFmrEF I (15 %) / II (85 %) NYHA functional class, who had been examined in 2018–2020. All patients received optimal medical therapy for HF and concomitant diseases. Follow-up was conducted through telephone contact / clinic visit at intervals of 6-12 months. The average follow-up period was 5 years (62 [49–64] months). Fatal events were assessed (total mortality, death from CVD and non-cardiovascular causes). Depending on the presence of CKLMS diseases (at the start of observational study), namely: obesity, type 2 diabetes mellitus (T2DM) / impaired glucose tolerance (IGT), CKD, MAFLD patients were divided into phenotypic groups. Results. A high frequency of CKLMS diseases was observed. Arterial hypertension (HTN) and dyslipidemia were detected in 92 % and 100 % of patients, respectively. Obesity/overweight and T2DM/IGT were registered in 43 % / 44 % and 32 % / 3 % of patients, respectively. CKD and MAFLD were diagnosed in every fifth patient. The presence of two or more CKLMS diseases was observed in 33 % of the participants. HTN was registered in 91 % of cases in the absence of the analyzed CKLMS diseases; in 96 % of cases in the presence of one, and in 98 % of cases in the presence of two or more CKLMS diseases. The most common phenotypic group of HFmrEF was represented by a combination of CKD + T2DM/IGT + obesity. The five-year survival rate of patients with HFmrEF was 76 %. The leading causes of death were CVD and cancer. The CKD, LVEF, and N-terminal brain natriuretic propeptide (NT-proBNP) were independent predictors of poor prognosis. The presence of CKD in a patient with HFmrEF was associated with a more than 3-fold increased risk of mortality: OR 3,5; 95 % confidence interval (CI) 1,45–8,40; p = 0,005. The highest five-year mortality was observed in individuals with CKD + T2DM/IGT (obesity in 71 % of cases) and CKD + T2DM/IGT + MAFLD (obesity in 69 % of cases). Conclusions. Patients with HFmrEF and post-infarction cardiosclerosis had a higher frequency of metabolic syndrome components: together with a high occurrence of HTN, at least two CKLMS diseases (obesity, T2DM/IGT, CKD, MAFLD) were detected in every third patient. Phenotypic groups of HFmrEF within CKLMS associated with CKD had the most unfavorable prognosis. The presented data confirm the need for an interdisciplinary approach to the management of patients with HF and the use of a personalized strategy based on pathophysiological phenotypes.