Background The use of statins for primary prevention of cardiovascular diseases is associated with different benefit and harm outcomes. The aime of this study is how important these outcomes are... Show moreBackground The use of statins for primary prevention of cardiovascular diseases is associated with different benefit and harm outcomes. The aime of this study is how important these outcomes are for people and what people's preferences are. Methods We conducted a preference-eliciting survey incorporating a best-worst scaling (BWS) instrument in Iran from June to November 2019. The relative importance of 13 statins-related outcomes was assessed on a sample of 1085 participants, including 913 general population (486 women) and 172 healthcare providers from the population covered by urban and rural primary health care centers. The participants made trade-off decisions and selected the most and least worrisome outcomes concurrently from 13 choice sets; each contains four outcomes generated using the balanced incomplete block design. Results According to the mean (SD) BWS scores, which can be (+ 4) in maximum and (- 4) in minimum, in the general population, the most worrisome outcomes were severe stroke (3.37 (0.8)), severe myocardial infarction (2.71(0.7)), and cancer (2.69 (1.33)). While myopathy (- 3. 03 (1.03)), nausea/headache (- 2.69 (0.94)), and treatment discontinuation due to side effects (- 2.24 (1.14)) were the least worrisome outcomes. Preferences were similar between rural and urban areas and among health care providers and the general population with overlapping uncertainty intervals. Conclusion The rank of health outcomes may be similar in various socio-cultural contexts. The preferences for benefits and harms of statin therapy are essential to assess benefit-harm balance when recommending statins for primary prevention of cardiovascular diseases. Show less
This thesis examines how both genetic and more conventional epidemiological endeavors may complement research into effects of statin therapy. These include a pharmacogenetic GWAS meta-analysis... Show moreThis thesis examines how both genetic and more conventional epidemiological endeavors may complement research into effects of statin therapy. These include a pharmacogenetic GWAS meta-analysis on statin-induced HDL-C response by the Genomic Investigation of consortium, which identified CETP as a loci of interest, and two-sample Mendelian randomization studies utilizing summary level data from the GIST and other GWAS consortia on fasted blood lipids and type 2 diabetes. We additionally examine the issue of survival bias in Mendelian randomization studies. Finally, we show that intra-individual lipid variability associates with worse neurocognitive outcomes in older individuals at high risk for vascular disease, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest. Show less
Aim of this thesis was to investigate pharmacogenetic effects on response to statin treatment and the genetics of lipid metabolism and cardiovascular disease. In chapter 4 the first results of the... Show moreAim of this thesis was to investigate pharmacogenetic effects on response to statin treatment and the genetics of lipid metabolism and cardiovascular disease. In chapter 4 the first results of the Genomic investigation of Statin Therapy (GIST) consortium are presented. We identified and validated two new GWAS loci to be associated with LDL-cholesterol response after statin treatment. In addition, we confirmed two previous identified loci. In chapter 5 we showed that we were not able to identify any loci associated with differential event reduction after statin therapy within the PROSPER study. The results presented in chapter 8 show that even at old age a genetic predisposition to high LDL-cholesterol is a risk factor for mortality. The results of this thesis show that currently the possibilities to personalize statin treatment based on genetic variants is limited. New research methods will hopefully give new opportunities to improve cardiovascular disease treatment and give more insight into the biological mechanisms of statin treatment. Show less
Cardiovascular disease is the principal cause of mortality in patients with type 2 diabetes mellitus. The present thesis describes a study, designed at a time-point when no primary prevention trial... Show moreCardiovascular disease is the principal cause of mortality in patients with type 2 diabetes mellitus. The present thesis describes a study, designed at a time-point when no primary prevention trial had yet been performed to investigate the effects of statin therapy on patients with type 2 diabetes without cardiovascular disease. We have performed a randomized, double-blind placebo-controlled trial in 250 type 2 diabetic patients without manifest cardiovascular disease. The aim of the study was to study non-invasively the effect of two year statin therapy on the vessel wall. We found no effect of two year statin therapy on carotid IMT as a reflection of the progress of atherosclerosis. We found no effect on endothelial function as assessed by FMD. The effect of statin therapy on CRP, as a marker for low grade inflammation, was only significant in a high- risk subgroup with the metabolic syndrome and a high LDL-cholesterol. There was no effect of two-year statin therapy on the prevalence of silent myocardial ischemia. In spite of these findings, we observed a lower cardiovascular event rate in patients on statin therapy, which is in line with other clinical trials. Show less
