New strategies for the management of patients with difficult-to-control hypertension

Abstract

Despite the availability of effective pharmacological treatments, at least half of treated hypertensive patients do not achieve blood pressure lowering to <140/90 mmHg and thus remain at increased risk of cardiovascular events, particularly stroke. To reduce the burden of cardiovascular disease, management of hypertension needs to be optimized. This thesis evaluates new strategies for the management of patients with difficult-to-control hypertension. Given that most treatment benefit is to be gained in patients at high risk for cardiovascular events, the first aim of this thesis was to establish risk factors that identify these patients. We studied the association between four electrocardiographic left ventricular hypertrophy criteria (measures of hypertension-mediated organ damage) and recurrent cardiovascular events and concluded that Cornell product and Cornell/strain index are likely to be the most relevant electrocardiographic left ventricular hypertrophy criteria for risk stratification in clinical practice. The second aim of this thesis was to identify reasons for poor blood pressure control. We aimed to improve detection of medication non-adherence by developing a quantitative drug screening method. Prevalence of medication non-adherence as assessed by this quantitative method (taking into account the measured drug concentration in proportion to the population mean) was compared to the prevalence as assessed by conventional, qualitative drug screening (only indicating whether the drug is present or not). The quantitative method showed that 15% of hypertensive patients referred to tertiary care was non-adherent to treatment and was of limited value compared to qualitative drug screening. In addition, a clinical decision tool was developed to guide diagnosis of primary aldosteronism, an important cause of hypertension. This clinical decision tool with seven easy-to-measure clinical variables reduced the number of hypertensive patients to be intensively tested for primary aldosteronism reliably by 8% to 32%. The final aim of this thesis was to evaluate the safety, efficacy and mechanism-of-action of a novel device-based hypertension treatment: endovascular baroreflex amplification (EVBA) by the MobiusHD device. In a non-controlled, observational study, implantation of the MobiusHD device in patients with resistant hypertension substantially lowered blood pressure with sustained effectiveness and an acceptable safety profile during 3-year follow-up. The proof-of-principle study, however, did not show an effect on sympathetic nerve activity. Therefore this study did not prove that the treatment works via the proposed mechanism. Randomized, sham-controlled trials are currently enrolling to study the safety and efficacy of EVBA in the absence of bias that is inherent to non-controlled, observational studies.