Hemodynamic Influences of Major Risk Factors of Cardiovascular Aging

Tutkimustuotos: VäitöskirjaCollection of Articles


Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. Hypertension is a significant predisposing factor for CVD, while cigarette smoking, and dyslipidemias are one of the most important preventable risk factors for CVD. According to the World Health Organization, the prevalence of elevated blood pressure (BP), high plasma cholesterol concentration, and smoking is continuously rising. A large portion of deaths seem to be attributable to the risk factors raised BP, tobacco use and high cholesterol. The existing data about the influence of smoking on BP, wave reflections in the circulation, and arterial stiffness have been contradictory. Low-density lipoprotein cholesterol (LDL-C) has been linked with elevated BP in some studies but the results about the relationship of LDL-C with arterial stiffness have been inconsistent. The atherogenic index of plasma (AIP), defined as the logarithm of triglycerides to high-density lipoprotein cholesterol ratio, is a strong predictor of future CVD. The association of plasma AIP with hemodynamic variables has not been previously investigated. Also, rather limited information has existed about the detailed hemodynamic features of primary aldosteronism (PA) in the present days.

The aim of the present thesis was to study the hemodynamic features associated with smoking, LDL-C, plasma AIP, essential hypertension (EH) and PA. Therefore, hemodynamics influences of these major risk factors of cardiovascular aging were evaluated. In this thesis we assessed differences in hemodynamics between present, previous and never smokers to expand our understanding about the long-term effects of smoking on the cardiovascular system. We investigated the association of LDL-C with hemodynamic variables and examined the association of AIP with hemodynamic variables and more specifically tested the hypothesis whether AIP is related to large arterial stiffness. We then examined the detailed differences in hemodynamics between patients with medicated PA, medicated EH, never- medicated EH, and normotensive controls.

The study populations consisted of subjects without previously diagnosed CVD (other than hypertension), other forms of secondary hypertension but PA (PA was included in study IV), and BP or lipid lowering medications or other medications that have direct influences on cardiovascular function (Study I-III). Hemodynamics were recorded non-invasively using whole body impedance cardiography and continuous radial pulse wave analysis, and the results were adjusted, as appropriate. In Study I, 637 volunteers (19-72 years) without antihypertensive medications were allocated into 3 groups: never smokers (365), present smokers (81) and previous smokers (191). The population of studies II and III consisted of 615 subjects without antihypertensive and lipid-lowering medications. In study IV, 520 subjects were included in the four study groups: medicated PA, medicated EH, never-medicated EH and normotensive controls. The hypertensive groups were matched for age, sex, and body mass index, while the normotensive group was matched to have a similar
sex distribution.

In accordance with previous studies, cigarette smoking (Study I) was not associated with change in BP and arterial stiffness, measured via pulse wave velocity (PWV) recordings between the groups. Importantly, augmentation index (AIx) was increased in present smokers, a finding which had been previously reported in association with acute, chronic, and passive smoking. Additionally, smoking was associated with other changes in hemodynamics: I) present smokers presented with increased stroke index and decreased aortic reflection time during upright position versus previous smokers, II) supine and upright cardiac output was higher in present versus previous smokers, III) in spite of the long abstinence previous smokers had lower cardiac output and higher systemic vascular resistance than never smokers, indicating that the magnitude or risk reduction in previous smokers after quitting smoking appears to be longer than previously anticipated. For the first time our study demonstrated by the use of multivariate regression analyses that higher stroke volume index and shorter aortic reflection time were the putative explanations for the higher AIx in present smokers.

Several hemodynamic changes associated with dyslipidemia were observed in this thesis. LDL-C was an independent explanatory factor for BP, PWV, AIx and systemic vascular resistance (Study II). In contrast, AIP was not related with radial or aortic BP, AIx or systemic vascular resistance, but AIP was directly and independently associated with large arterial stiffness (Study III). However, when the results were adjusted for prevailing central BP, LDL-C was no longer an explanatory factor for arterial stiffness (Studies II and III).

When the hemodynamics were compared between medicated PA patients, medicated and never-medicated EH patients and normotensive controls, PA patients present with higher BP than medicated EH patients and normotensive controls. Extracellular water balance was ~4% higher in PA than in all other groups, while cardiac output was ~8% higher in PA than in medicated EH. PWV was higher in PA than in medicated EH and normotensive controls. Although 82 PA patients were taking concurrent potassium supplements, plasma potassium concentration was lower, while sodium concentration was higher, in the PA patients than in the other groups. In study IV the never-medicated EH patients had the highest PWV when compared with all other groups, indicating long-standing untreated high BP and unawareness of prevailing hypertension.

In conclusion, the examined major risk factors of cardiovascular aging were associated with clear hemodynamic changes and presented with related changes in cardiac function. The present smokers and patients with PA presented with a hyperdynamic circulation. Present smokers also presented with enhanced wave reflection when compared with previous smokers. LDL-C was independently associated with BP via systemic vascular resistance and wave reflection, whereas AIP was directly and independently associated with large arterial stiffness. Altogether, the whole lipid profile is of importance in clinical CVD risk evaluation. The present results also highlighted that in addition to the established methods for the screening and confirmatory testing for PA, the measurement of plasma sodium and potassium concentrations and the evaluation of the detailed hemodynamic features of PA, especially higher extracellular water volume and hyperdynamic circulation in comparison with EH, could be useful in the diagnostics of PA patients in the clinical setting.
KustantajaTampere University
ISBN (elektroninen)978-952-03-1903-8
ISBN (painettu)978-952-03-1902-1
TilaJulkaistu - 2021
OKM-julkaisutyyppiG5 Artikkeliväitöskirja


NimiTampere University Dissertations - Tampereen yliopiston väitöskirjat
ISSN (painettu)2489-9860
ISSN (elektroninen)2490-0028


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