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Manoj Kumar Choudhary: Hemodynamic Influences of Major Risk Factors of Cardiovascular Aging

Manoj Kumar Choudhary
Englanninkielinen väitös. The cardiovascular disease continuum is a chain of events triggered by several cardiovascular risk factors, which if left untreated, inevitably culminates in cardiovascular endpoints like end-stage heart failure, stroke, end-stage renal disease, and death. Existing data about the influences of smoking and plasma lipids on blood pressure and arterial stiffness have been contradictory. Moreover, limited information has existed about the detailed hemodynamic features of primary aldosteronism, the most common form of secondary hypertension, in the present days.

MD Manoj Kumar Choudhary studied in his doctoral dissertation the hemodynamic features associated with smoking, LDL-Cholesterol, plasma AIP, essential hypertension and primary aldosteronism. 

Pathologic aging often starts already in adolescence, though cardiovascular disease events may only appear after reaching the middle age or above. Sydenham, the “English Hippocrates”, provided the theoretical paradigm that “a man is as old as his arteries”. Early detection and treatment of the risk factors that initiate the cardiovascular atherosclerotic continuum could stop or delay its further progression. 

Previously, multiple reports have almost unanimously shown that acute, chronic, or passive smoking are all associated with an increase in wave reflection, however, the underlying mechanisms are not well understood. Similarly, the relationship of LDL cholesterol with arterial stiffness has been inconsistent, while the association of atherogenic index of plasma (Lg10 of triglyceride: high-density lipoprotein cholesterol ratio) with hemodynamic variables has not been previously investigated. On the other hand, previous studies in patients with primary aldosteronism have mainly focused on the features of treatment-resistant hypertension and large arterial stiffness. Only few studies have examined the detailed hemodynamic differences between primary aldosteronism and essential hypertensive patients. 

A comprehensive understanding about the association of smoking and plasma lipids with alterations in cardiovascular function, and hemodynamic characteristics of primary aldosteronism provides a good basis for developing more effective and individualized cardiovascular risk evaluation, and the clinical diagnostic algorithm for primary aldosteronism screening. 

The doctoral study by MD. Manoj Kumar Choudhary is a part of the DYNAMIC study, an ongoing investigation the hemodynamic changes in primary and secondary hypertension versus normotensive controls. 

Our results showed that present smokers and primary aldosteronism patients presented with hyperdynamic circulation; present smokers also presented with enhanced wave reflection when compared with previous smokers. Importantly, for the first time in this thesis we explained the mechanism why wave reflection (measured via augmentation index) is almost always higher in smokers. Our findings indicate that increased augmentation index in present smokers is attributed to an increase in stroke volume and parallel shortening of the aortic reflection time (return time of the reflected pressure wave). 

Additionally, we found evidence that tobacco smoking has long-lasting effects on vascular health and the risk reduction in previous smokers after quitting of smoking appears to take longer than previously anticipated (median abstinence in our study was 10 years). 

LDL cholesterol was independently associated with blood pressure via systemic vascular resistance and wave reflection. Whereas our findings for the first time suggested that atherogenic index of plasma was directly and independently associated with large arterial stiffness. Altogether, the whole lipid profile is of importance in clinical cardiovascular disease risk evaluation as clear associated hemodynamic changes were observed. 

Our study comprises one of the largest groups of primary aldosteronism patients ever studied in one report, originating from a homogenous Finnish population. The results showed that patients with primary aldosteronism are characterized by treatment-resistant hypertension, elevated plasma sodium and reduced potassium concentrations despite potassium supplements, and increased extracellular water volume and cardiac output, when compared with medicated essential hypertensive patients. However, highest large arterial stiffness was detected in never-medicated essential hypertensive patients, which stresses the importance of early diagnosis and treatment of hypertension. 

The diagnosis of primary aldosteronism far from straightforward, under-diagnosis is characteristic of primary care, while high heterogeneity was even revealed in the diagnostic evaluation of primary aldosteronism in specialized care. Reliable, easy-to-perform, and cost-effective diagnostic tests are welcome for the early diagnosis of primary aldosteronism. At present, evaluation of the extracellular water volume status by means of bioimpedance recordings is routine practice in the follow-up of dialysis patients. Our results indicate that the diagnostic screening of primary aldosteronism would benefit from screening of the volume status in these patients e.g. using bioimpedance. 

The author of this thesis, MD. Manoj Kumar Choudhary, comes from Nepal. He earned a Master of Clinical Medicine degree in Internal Medicine (Cardiology) at Sun Yat-Sen University, China, and worked as a specialist in a department of Cardiology in Nepal. Currently he works as a Doctoral candidate at the Faculty of Medicine and Health technology at Tampere University. 

The doctoral dissertation of MD. Manoj Kumar Choudhary in the field of Internal Medicine titled Hemodynamic Influences of Major Risk Factors of Cardiovascular Aging will be publicly examined at the Faculty of Medicine and Health Technology of Tampere University at 12 noon on Friday 9.4.2021 in Arvo building Jarmo Visakorpi Auditorium. The opponent will be Professor Hannu Järveläinen from University of Turku. The custos will be Professor Ilkka Pörsti from the Faculty of Medicine and Health Technology. 

The event can be followed via remote connection 

The dissertation is available online at
http://urn.fi/URN:ISBN:978-952-03-1903-8 

 

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