Personalized vascular medicine: tailoring cardiovascular disease management to the individual patient

Applying group-level findings to individual patients is an absolute requisite for practicing evidence-based cardiovascular medicine. Yet, because individual patient characteristics may influence the pathophysiology and prognosis of disease and the likelihood of response to therapy, such generalization is often problematic. The difficulties that are related to generalization of group level evidence to individual patients are often not well appreciated and simple pragmatic approaches are usually preferred in clinical practice. As a result, all patients with clinically manifest arterial disease are assumed having equal (>20%) 10-year risk for recurrent vascular events. Moreover, the results of trials are usually implemented in clinical practice by either treating all patients (in the case of a positive trial result) or treating no one (in the case of a negative trial result), expecting the treatment effect for every patient to be similar to that of the average patient in the original trial. In addition, in 95% of patients with hypertension, the underlying cause of hypertension is assumed to be irrelevant, as these patients are diagnosed with so called ‘primary’ or ‘essential’ hypertension. Patients diagnosed with primary hypertension receive the same preferential blood pressure lowering therapy. Finally, the notion that ‘lower is better’ for blood pressure management, although only evidenced in healthy people, is assumed to be also valid in patients with clinically manifest arterial disease. This thesis comprises research articles that investigate whether more differentiation in the above areas is needed. The objectives of this thesis are as follows: Part 1 •To develop and validate a clinical score for prediction of absolute risk for recurrent vascular events in individual patients with various types of arterial disease. •To predict the effect of several types of preventive therapy for individual patients based on randomized trial data. •To evaluate the net benefit of making medical decisions based on predicted risk or predicted treatment effect. Part 2 •To determine the effects of renin-angiotensin-aldosterone system inhibition, sympathoinhibition, and treatment with a thiazide-type diuretic on vascular function, blood pressure and the mechanisms involved in the pathophysiology of obesity-related hypertension. •To quantify the relation between adiposity and hypertension in patients with clinically manifest arterial disease. •To assess the relationship between blood pressure and cardiovascular events and all-cause mortality in patients with clinically manifest arterial disease.