As the population is aging worldwide, and in spite of all preventive efforts, age-related diseases are increasingly prevalent, such as cardiovascular diseases and cognitive impairment. Different... Show moreAs the population is aging worldwide, and in spite of all preventive efforts, age-related diseases are increasingly prevalent, such as cardiovascular diseases and cognitive impairment. Different vascular risk factors, both the ‘traditional’ modifiable factors, such as hypertension or diabetes, and non-modifiable factors, such as age or gender, can lead to different kind of intertwined micro- and macrovascular diseases in various or multiple simultaneous organs. There is a growing need for knowledge regarding the interplay between different (co)morbidities, the relation of (co)morbidities with the various underlying pathophysiological mechanisms and treatment options of these (co)morbidities. Therefore, the aims of this thesis were to identify patients at high cardiovascular risk and to optimize treatment for these patients. We further unravelled the complexity of various interacting (poly) vascular diseases, ultimately leading to an increased risk of not only cognitive impairment, but also MACE including death. Identification of these patients and better understanding of the interplay and underlying mechanisms of these diseases is the first step towards preventive strategies. Treating these high risk patients can be a therapeutic challenge, but there is growing knowledge regarding both established and evolving therapies to optimize efficacy and efficiency. Show less
Aims Statins reduce cardiovascular risk in patients with acute coronary syndrome (ACS) and normal-to-moderately impaired renal function. It is not known whether proprotein convertase subtilisin... Show moreAims Statins reduce cardiovascular risk in patients with acute coronary syndrome (ACS) and normal-to-moderately impaired renal function. It is not known whether proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide similar benefit across a range of renal function. We determined whether effects of the PCSK9 inhibitor alirocumab to reduce cardiovascular events and death after ACS are influenced by renal function.Methods and results ODYSSEY OUTCOMES compared alirocumab with placebo in patients with recent ACS and dyslipidaemia despite intensive statin treatment. Estimated glomerular filtration rate (eGFR) <30mL/min/1.73 m(2) was exclusionary. In 18 918 patients, baseline eGFR was 82.8 +/- 17.6 mL/min/1.73 m(2), and low-density lipoprotein cholesterol (LDL-C) was 92 +/- 31 mg/dL. At 36 months, alirocumab decreased LDL-C by 48.5% vs. placebo but did not affect eGFR (P = 0.65). Overall, alirocumab reduced risk of the primary outcome (coronary heart disease death, non -fatal myocardial infarction, ischaemic stroke, or unstable angina requiring hospitalization) with fewer deaths. There was no interaction between continuous eGFR and treatment on the primary outcome or death (P = 0.14 and 0.59, respectively). Alirocumab reduced primary outcomes in patients with eGFR >= 90 mUmin/1.73 m(2) (n = 7470; hazard ratio 0.784, 95% confidence interval 0.670-0.919; P= 0.003) and 60 to <90 (n = 9326; 0.833, 0.731-0.949; P=0.006), but not in those with eGFR< 60 (n = 2122; 0.974, 0.805-1.178; P= 0.784). Adverse events other than local injection -site reactions were similar in both groups across all categories of eGFR.Conclusions In patients with recent ACS, alirocumab was associated with fewer cardiovascular events and deaths across the range of renal function studied, with larger relative risk reductions in those with eGFR > 60 mL/min/1.73 m(2). Show less
