Abstract

Background: Patients with apparent treatment-resistant hypertension (aTRH), defined as uncontrolled blood pressure (≥140/90 mmHg) despite use of 3 antihypertensive medications or use of ≥4 medications regardless of blood pressure control, have a higher risk for cardiovascular events compared to hypertensive patients whose blood pressure is controlled with antihypertensive medications. As the incidence of aTRH has been increasing, there is an urgent need toward improving outcomes in this high-risk population. Few data exist regarding whether healthy lifestyle factors, either individually or combined as part of an overall healthy lifestyle, are associated with a better prognosis among individuals with aTRH. The purpose of this study was to assess the association of healthy lifestyle factors with all-cause mortality and secondarily incident cardiovascular events among individuals with aTRH. Methods: We studied participants from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a unique resource with 2,043 participants with aTRH. Six healthy lifestyle factors (normal waist circumference, physical activity ≥4 times/week, non-smoking, moderate alcohol consumption, high Dietary Approaches to Stop Hypertension (DASH) diet score, and low sodium-to-potassium intake ratio) were examined. Results: A higher number of healthy lifestyle factors was associated with a lower risk for all-cause mortality over a mean follow-up of 5.2 years. Multivariable adjusted hazard ratios [HR (95% CI)] for all-cause mortality comparing individuals with 2, 3, 4, and 5-6 versus 0-1 healthy lifestyle factors were 0.78 (0.60-1.00), 0.70 (0.52-0.95), 0.56 (0.38-0.83) and 0.57 (0.32-1.00), respectively (P-trend=0.001). Physical activity (1-3 days/weeks vs. 0 days/week: HR 0.58; 95% CI 0.46-0.73; ≥ 4 days/week: HR 0.58; 95% CI 0.45-0.75) and, separately, non-smoking (HR 0.53; 95% CI 0.40 -0.70) were individual healthy lifestyle factors each significantly associated with a lower risk for all-cause mortality in a fully adjusted model. The HRs (95% CI) of incident cardiovascular events for 2, 3, and 4-6 versus 0-1 healthy lifestyle factors were 1.07 (0.68-1.67), 0.83 (0.48-1.44), and 0.66 (0.34-1.29), respectively (P-trend=0.150), in a fully adjusted model. Conclusions: In conclusion, healthy lifestyle factors, particularly physical activity and non-smoking, were associated with a lower risk for all-cause mortality among individuals with aTRH, a high-risk subgroup of hypertensive individuals who require multiple medications. These data support the concept that the prognosis among individuals with aTRH may be improved by interventions targeting healthy lifestyle factors. Future randomized controlled trials may be warranted to examine whether lifestyle interventions lower mortality risk among adults with aTRH.

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