Supervised by Professor

Eveliina Upmeier Cholesterol, cardiovascular disease and statin use in older persons. University of Turku, Faculty of Medicine, Department of Geriatrics and Department of Pharmacology, Drug Development and Therapeutics Annales Universitatis Turkuensis, Medica-Odontologica, Turku, Finland, 2016 Older age increases the risk of developing a chronic atherosclerotic cardiovascular disease (CVD), such as coronary heart disease. Complications of CVDs, myocardial infarction or stroke often lead to loss of functional capacity or premature death. Dyslipidemia, high serum levels of total or low-density lipoprotein cholesterol (LDL-c) and low levels of high-density lipoprotein cholesterol (HDL-c), is among the most important modifiable risk factors for CVDs; it can be treated with lifestyle modifications, and with lipidlowering drugs, primarily statins. In older persons, however, the association of cholesterol levels with cardiovascular and all-cause mortality has been inconsistent in previous studies. Furthermore, the beneficial effects of statins in older persons without previous CVD are still somewhat unclear, and older persons are more prone to adverse effects from statins. This thesis presents a prospective cohort study (TUVA), exploring associations of cholesterol levels with mortality and the changes in cholesterol levels of a 70-year-old population in long-term follow-up. Further, prevalence of CVDs, risk factors and preventive medication use in the TUVA cohort is compared with respective prevalences in another age-matched cohort (UTUVA) 20 years later in order to examine the changes in cardiovascular risk over time. Additionally, to evaluate statin use patterns among older persons, an observational register study was conducted covering the total Finnish population aged 70 and older during 2000-2008. Based on individual-level data retrieved from national health registries, the population was classified into low, moderate and high risk groups according to estimated CVD risk. The prevalence, incidence and persistence of statin use among the risk groups was then evaluated based upon yearly statin purchases tracked from the Prescription Register. The prospective cohort study demonstrated that low total cholesterol, LDL-c and HDL-c were associated with higher mortality in a cohort of home-dwelling 70-year-olds. However, after adjusting for traditional cardiovascular risk factors and cancer this association disappeared. Further, low total cholesterol seemed to be protective, whereas low HDL-c strongly predicted increased risk of CVD death. Cholesterol levels of those elderly who remained available for follow-up and were still home-dwelling at the age of 85 seemed to improve with advancing age. Compared to the TUVA cohort, the later born UTUVA cohort had less CVDs and their risk factors were better controlled, which was reflected in the higher use of preventive medications such as statins and antihypertensives. The register studies confirmed that statin use has increased significantly during 2000-2008 among older persons, especially among the oldest (80+) age groups and among those at high risk for cardiovascular events. Two-thirds of new statin users persisted with their use during the four years of follow-up; the most discontinuations were made during the first year of use. In conclusion, statins are commonly used among older age groups in Finland. Most of the older statin users had a high cardiovascular event risk, indicating that the treatment is well directed towards those who are likely to benefit from it the most. No age-limits should be put on the screening and treatment of dyslipidemia in older persons, but the benefits and adverse effects of statin treatment should be carefully weighed based on an individual assessment of the person’s general health status and functional capacity. Physicians should pay more attention to medication adherence, especially when prescribing preventive medications.