Hypertension in the elderly and its relation to cardiovascular outcomes and cost-effectiveness

Abstract

High blood pressure (BP) or hypertension is a major risk factor for adverse cardiovascular and renal outcomes. One of the effective ways to reduce these adverse outcomes is to control elevated BP and achieve target BP. Approximately half of the hypertensive patients receiving anti-hypertensive therapy do not reach their BP targets, especially the elderly who constitute a large proportion of the hypertensive population. Understanding the factors associated with target BP achievement is important in designing interventions to reduce adverse outcomes. Besides achieving the target BP, reducing visit-to-visit systolic BP (SBP) variability is also important, as it is directly associated with cardiovascular events, especially stroke particularly in hypertensive people aged less than 60 years. However, evidence on such relationship in the elderly is limited. There is also limited information on progression and new-onset of comorbid conditions such as diabetes and chronic kidney disease in the elderly who are receiving anti-hypertensive therapy. The objective of this thesis was to identify the barriers in achieving target BP in the elderly and the effect of visit-to-visit SBP variability on cardiovascular adverse outcomes. In addition, the thesis also explores the effect of anti-hypertensive drug treatment specifically angiotensin-converting enzyme inhibitor (ACEI) and thiazide diuretics on: (a) patients with diabetes including the development of new-onset of diabetes; and (b) renal function. The research also aimed to identify – (a) whether the Modification of Diet in Renal Disease (MDRD) equation or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for renal function estimation (i.e. estimated glomerular filtration rate, eGFR) performed better for mortality risk prediction in the elderly; and (b) the cost-effectiveness of ACEI compared to diuretic -based treatment in an elderly hypertensive population. Data from the Second Australian National Blood Pressure study (ANBP2) and its post-trial follow-up were used to address these objectives. In ANBP2 study, 6083 elderly hypertensive patients aged 65-84 years were randomized to receive either ACEI or thiazide-diuretic -based therapy and followed for a median 4.1 years. The post-trial ANBP2 study follow-up was conducted over an additional median of 6.9 years and data were linked with Australian National Death Index data to identify patient survival. The ANBP2 study provided the opportunity to identify factors affecting on-trial target BP achievement and the effect of visit-to-visit SBP variability on cardiovascular outcomes. It also provided information to assess the effects of antihypertensive therapy on diabetes and renal function including the cost-effectiveness of specific antihypertensives. The post-trial data were used to identify long-term effects of antihypertensive drugs on mortality in an elderly hypertensive population, including progression of comorbid conditions. Analysis of data in this group showed that along with clinical factors, demographic factors related to health service delivery such as care-seeking from the same physician were important determinants of attaining good BP control in elderly hypertensive patients. Further analysis demonstrated that higher visit-to-visit SBP variability was directly associated with cardiovascular events, especially stroke (Hazard ratio 2.78; 95% confidence interval 1.28-6.05) irrespective of target BP achievement. Higher SBP variability observed during ANBP2 study also predicted long-term post-trial fatal outcomes. A 44% higher incidence of newly diagnosed diabetes was observed in the elderly patients randomized to thiazide-diuretic based treatment compared to ACEI-based treatment. A rapid decline in renal function (eGFR >3 ml/min/1.73m2 per year) was also observed in those receiving diuretics. In addition, the study showed that compared to the MDRD equation the CKD-EPI equation performs better in the elderly for long-term mortality risk prediction. Finally, the cost-utility analysis suggested that treatment of hypertension with ACEI would be a cost-effective approach compared to diuretic use in this elderly hypertensive population. In summary, findings from the thesis have major implications for future public health interventions and health policy planning for the management of hypertension in the elderly especially considering the increasing burden of cardiovascular diseases. The findings indicate that reducing visit-to-visit SBP variability might be an important objective in treating hypertension in addition to the conventional aim of office BP lowering in elderly hypertensive. The findings also suggest that despite the higher treatment cost of ACEI compared to thiazide diuretic, treatment with ACEI provides greater benefits and is also cost-effective as it reduces the development of comorbidities especially diabetes.