Influence of diastolic dysfunction on cognitive impairment and prognosis in patients with coronary artery disease

Abstract

The aim of the study is to evaluate the influence of left ventricular diastolic dysfunction on cognitive impairment and prognosis in patients with coronary artery disease.

Materials and methods. A total of 110 patients, treated for coronary artery disease (CAD) between 2014–2016, underwent a general clinical examination and dynamic follow-up at the Cardiology Department of P. L. Shupyk NMAPE. All the patients had hospitalizations for percutaneous coronary intervention, acute myocardial infarction with or without ST-segment elevation, or unstable angina within 6 months to 24 months before the examination. Exclusion criteria were acute infectious diseases, alcohol dependence, drug addiction, mental disorders; prosthetic heart valves, severe rheumatic or degenerative changes of the mitral valve; a history (or ECG recording) of atrial fibrillation / flutter or stroke. The patients were divided into three groups depending on the stage of diastolic dysfunction: the first group consisted of 39 patients with CAD and normal diastolic function; the second – 43 patients with CAD and diastolic dysfunction (DD) of the impaired relaxation type; the third – 28 patients with CAD and DD of pseudonormalization or restriction types. In addition to clinical examination and medical history taking, all the patients underwent echocardiographic examination, ultrasound examination of the brachiocephalic arteries at the extracranial level, biochemical blood analysis, as well as a testing based on cognitive function scales.

Statistical analysis of the data obtained was carried out using Microsoft Excel, IBM SPSS Statistics v.23. The data were presented as arithmetic mean ± standard deviation (M ± SD) or as a percentage for categorical values with Pearson’s Chi-square (χ²) calculation. Differences in mean values were considered statistically significant at P < 0.05. The normality of the data distribution was checked using the Shapiro-Wilk test (a hypothesis of the normal distribution was rejected at values of P < 0.05). Endpoint analysis was performed by constructing Kaplan–Meier curves. Statistically significant differences in the survival curves were assessed using the Gehan’s–Wilkokson test (P < 0.05).

Results. According to the results of the Kruskal–Wallis one-way analysis of variance, the state of diastolic function appeared to have a significant effect on the total score on the MMSE scale (P = 0.0002). Analysis of the risk factors for the onset of cognitive dysfunction, according to the MMSE scale indicators, showed that the probability of developing cognitive dysfunction greatly increased with an increase in the E/e' value (OR 6.03, 95 % CI 2.32–15.69, P = 0.0002), worsening of the diastolic function state (OR 3.18, 95 % CI 1.18–8.59, P = 0.023), as well as with an increase in the Hb1AC level (OR 2.65, 95 % CI 1.08–6, 48, P = 0.033). The probability of developing cognitive dysfunction on the MoCA scale increased only with worsening of diastolic function (OR 2.86, 95 % CI 1.18–6.94, P = 0.020 pectoris functional class, age of cardiovascular disease (CVD) diagnosis, CVD duration, a number of years of education, smoking status, statin intake, systolic blood pressure, diastolic blood pressure, total cholesterol level, HbA1c level, left ventricular mass index (LVMI) and left atrial (LA) volume index after excluding statistically insignificant and uninformative ones, only the LVFP indicator significantly influenced the total score on the MMSE scale (OR 1.28, 95 % CI 1.11–1.47; P = 0.0007). The area under the AUC curve was 0.76, the standard error was 0.05, and 95 % CI was 0.667––0.838. At the same time, the sensitivity and specificity of the E/e' value above 10.5, in relation to cognitive impairments on the MMSE scale were 56.2 % and 87.2 %, respectively. When analyzing all endpoints depending on the DD group, a statistically significant difference in the Kaplan-Meier curves with respect to atrial fibrillation was revealed (P1,2 = 0.55, P1,3 = 0.016, P2,3 = 0.002, respectively). There was also a statistically significant difference in the Kaplan-Meier curves relative to hospitalizations for heart failure (P1,2 = 0.55, P1,3 = 0.07, P2,3 = 0.006, respectively).

Conclusions. A statistically significant effect of DD on the development of cognitive impairment in patients with coronary artery disease was revealed. The risk of developing cognitive impairment according to the MMSE scale increased mostly with the LVFP value increase (OR 6.03, 95 % CI 2.32–15.69, P = 0.0002), and according to the MoCA scale – with the stage of diastolic function worsening (OR 2.86, 95 % CI 1.18–6.94, P = 0.02). The results of direct multiple logistic regression found that among the numerous risk factors, only the LVFP indicator significantly influenced the MMSE total score (OR 1.28, 95 % CI 1.11–1.47; P = 0.0007). The analysis of all endpoints between the diastolic dysfunction groups showed that the Kaplan–Meier curves separated to become statistically significantly different in the development of atrial fibrillation (P1,2 = 0.55, P1,3 = 0.016, P2,3 = 0.002, respectively) and hospitalization for cardiac failure (P1,2 = 0.55, P1,3 = 0.07, P2,3 = 0.006, respectively), but not in all-cause-deaths, stroke, acute myocardial infarction, unstable angina or coronary revascularization.