Influence of diastolic dysfunction on cognitive impairment and prognosis in patients with coronary artery disease
Keywords:diastolic dysfunction, cognitive impairment, left ventricular filling pressure, ischemic heart disease, endpoint determination
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.
Fischer, M., Baessler, A., Hense, H. W., Hengstenberg, C., Muscholl, M., Holmer, S., Döring, A., Broeckel, U., Riegger, G., & Schunkert, H. (2003). Prevalence of left ventricular diastolic dysfunction in the community. Results from a Doppler echocardiographic-based survey of a population sample. European Heart Journal, 24(4), 320-328. https://doi.org/10.1016/s0195-668x(02)00428-1
van Riet, E. E., Hoes, A. W., Wagenaar, K. P., Limburg, A., Landman, M. A., & Rutten, F. H. (2016). Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. European Journal of Heart Failure, 18(3), 242-252. https://doi.org/10.1002/ejhf.483
de Bruijn, R. F., Portegies, M. L., Leening, M. J., Bos, M. J., Hofman, A., van der Lugt, A., Niessen, W. J., Vernooij, M. W., Franco, O. H., Koudstaal, P. J., & Ikram, M. A. (2015). Subclinical cardiac dysfunction increases the risk of stroke and dementia: the Rotterdam Study. Neurology, 84(8), 833-840. https://doi.org/10.1212/WNL.0000000000001289
Alosco, M. L., Gunstad, J., Jerskey, B. A., Clark, U. S., Hassenstab, J. J., Xu, X., Poppas, A., Cohen, R. A., & Sweet, L. H. (2013). Left atrial size is independently associated with cognitive function. International Journal of Neuroscience, 123(8), 544-552. https://doi.org/10.3109/00207454.2013.774396
Schneider, P., Buerger, K., Teipel, S., Uspenskaya, O., Hartmann, O., Hansson, O., Minthon, L., Rujescu, D., Moeller, H. J., Zetterberg, H., Blennow, K., Ernst, A., Bergmann, A., & Hampel, H. (2011). Antihypertensive therapy is associated with reduced rate of conversion to Alzheimer's disease in midregional proatrial natriuretic peptide stratified subjects with mild cognitive impairment. Biological Psychiatry, 70(2), 145-151. https://doi.org/10.1016/j.biopsych.2011.01.036
Moser, D. J., Hoth, K. F., Robinson, R. G., Paulsen, J. S., Sinkey, C. A., Benjamin, M. L., Schultz, S. K., & Haynes, W. G. (2004). Blood Vessel Function and Cognition in Elderly Patients With Atherosclerosis. Stroke, 35(11), e369-e372. https://doi.org/10.1161/01.STR.0000145050.35039.51
Kerola, T., Nieminen, T., Hartikainen, S., Sulkava, R., Vuolteenaho, O., & Kettunen, R. (2010). B-type natriuretic peptide as a predictor of declining cognitive function and dementia - a cohort study of an elderly general population with a 5-year follow-up. Annals of Medicine, 42(3), 207-215. https://doi.org/10.3109/07853891003652542
Yasar, S., Lin, F. M., Fried, L. P., Kawas, C. H., Sink, K. M., DeKosky, S. T., Carlson, M. C., & Ginkgo Evaluation of Memory (GEM) Study Investigators. (2012). Diuretic use is associated with better learning and memory in older adults in the Ginkgo Evaluation of Memory study. Alzheimer's & Dementia, 8(3), 188-195. https://doi.org/10.1016/j.jalz.2011.03.010
Sacre, J. W., Ball, J., Wong, C., Chan, Y. K., Stewart, S., Kingwell, B. A., & Carrington, M. J. (2018). Mild cognitive impairment is associated with subclinical diastolic dysfunction in patients with chronic heart disease. European Heart Journal - Cardiovascular Imaging, 19(3), 285-292. https://doi.org/10.1093/ehjci/jex169
Nagueh, S. F., Smiseth, O. A., Appleton, C. P., Byrd, B. F., 3rd, Dokainish, H., Edvardsen, T., Flachskampf, F. A., Gillebert, T. C., Klein, A. L., Lancellotti, P., Marino, P., Oh, J. K., Popescu, B. A., & Waggoner, A. D. (2016). Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography, 29(4), 277-314. https://doi.org/10.1016/j.echo.2016.01.011
Parker, A. S., Himali, J. J., Beiser, A. S., Short, M. I., Kautz, T., Vasan, R. S., & Seshadri, S. (2020). Diastolic dysfunction and cognitive impairment. Alzheimer’s & Dementia, 16(S6), Article e038487. https://doi.org/10.1002/alz.038487
Echouffo-Tcheugui, J. B., Erqou, S., Butler, J., Yancy, C. W., & Fonarow, G. C. (2016). Assessing the Risk of Progression From Asymptomatic Left Ventricular Dysfunction to Overt Heart Failure: A Systematic Overview and Meta-Analysis. JACC: Heart Failure, 4(4), 237-248. https://doi.org/10.1016/j.jchf.2015.09.015
Shah, A. M., Claggett, B., Kitzman, D., Biering-Sørensen, T., Jensen, J. S., Cheng, S., Matsushita, K., Konety, S., Folsom, A. R., Mosley, T. H., Wright, J. D., Heiss, G., & Solomon, S. D. (2017). Contemporary Assessment of Left Ventricular Diastolic Function in Older Adults: The Atherosclerosis Risk in Communities Study. Circulation, 135(5), 426-439. https://doi.org/10.1161/CIRCULATIONAHA.116.024825
Vogel, M. W., Slusser, J. P., Hodge, D. O., & Chen, H. H. (2012). The Natural History of Preclinical Diastolic Dysfunction: A Population-Based Study. Circulation: Heart Failure, 5(2), 144-151. https://doi.org/10.1161/CIRCHEARTFAILURE.110.959668
Ladeiras-Lopes, R., Araújo, M., Sampaio, F., Leite-Moreira, A., & Fontes-Carvalho, R. (2019). The impact of diastolic dysfunction as a predictor of cardiovascular events: A systematic review and meta-analysis. Revista Portuguesa de Cardiologia, 38(11), 789-804. https://doi.org/10.1016/j.repc.2019.03.007
How to Cite
LicenseAuthors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)