Non-conventional risk and prognostic factors in coronary heart disease : studies on heart rate variability, alcohol consumption, inflammation and depression

Background and aims: Although, there has been a drop in age-specific coronary heart disease (CHD) incidence, and its prognosis has improved considerably in most parts of the industrialized world, CHD is still by far the leading cause of death in industrialized countries. The established, conventional risk factors, i.e. hypertension, hypercholesterolemia, smoking, diabetes mellitus, obesity, and physical inactivity, are only partly responsible for the development of CHD. Recently, many relatively novel risk and prognostic factors had been proposed. Heart rate variability (HRV), alcohol consumption, inflammation and depression are among the most important novel factors. In this thesis we investigated their interrelations and their relation to CHD. Methods: We used the corresponding data of three large population based studies, that of the Healthier Female Heart (HFH) Study, the Stockholm Female Coronary Risk (FemCorRisk) Study, and the Stockholm Heart Epidemiology Program (SHEEP). Cross-sectional relationships between the non-conventional risk factors were investigated in the HFH study (paper I-III). The HFH study included consecutive women patients who were hospitalized for acute myocardial infarction, and/or underwent percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. We examined these patients in a stable phase, one year and five months after their index event. Ambulatory 24-hour ECG recordings were analyzed, and HRV was calculated. Self-reported consumption of individual alcoholic beverage types was assessed using a standardized questionnaire. Circulating levels of inflammatory markers were determined. Depression, vital exhaustion, and self-rated health were assessed by questionnaires. We examined the association between alcohol consumption and progression of coronary artery atherosclerosis (paper IV) using serial quantitative coronary angiography (QCA) in the FemCorRisk Study, which included middle-aged women patients who were hospitalized with acute myocardial infarction or unstable angina pectoris. We also assessed the long-term prognostic importance of HRV on mortality in these women (paper V), i.e. in a patient population, which was largely neglected in previous research. We examined if depression increases the risk for first myocardial infarction in the case-control SHEEP study. Depression was defined as history of hospitalization for the clinical diagnosis based on the data of the computerized Swedish hospital discharge registry (paper VI). Results and Conclusions: HRV. We found that wine intake was associated with increased HRV independently of potential confounding factors and intake of other beverages in women with CHD. In contrast, consumption of beer, spirits or the total amount of alcohol did not relate to any of the HRV parameters (paper I). Concentration of IL-6 showed an inverse relation to HRV even after adjustment for potential confounding factors (paper II). HRV parameters predicted all-cause and cardiovascular mortality in a 9-year follow-up even after controlling for established prognostic factors (paper V). Alcohol consumption. Our finding that wine intake is associated with HRV suggests that HRV may be an important linking factor between CHD and wine drinking (paper I). We also demonstrated that moderate alcohol consumption is inversely associated with progression of coronary atherosclerosis regardless of the beverage type (paper IV). Inflammation. The inverse association between HRV and IL-6 suggests that increased inflammatory activity might represent a new auxiliary mechanism linking autonomic dysfunction, as reflected by decreased HRV, to poor prognosis in CHD (paper II). Our results do not suggest that inflammation is a major mediator between depression and CHD (paper III, VI). However, self rated health and vital exhaustion, constructs also referring to one s subjective well-being, showed an inverse relation to circulating levels of inflammatory markers (paper III). Depression. In the SHEEP study we found that hospitalization for depression, especially if repeated, was a considerable risk factor for AMI, and was also associated with poor short-term prognosis after the coronary event. Socio-economic position, lifestyle factors, lipid profile, coagulation, inflammatory and other factors could only partly explain our findings (paper VI)