Protective Effect of Calcium Channel Blockers Against Frailty in Older Adults with Hypertension

Hypertension and sarcopenia, significant features of frailty, share an association with high risk of atherosclerosis.1 If atherosclerosis were their common pathway, treatment of hypertension could have a risk-reducing effect on frailty prevalence similar to its role in cardiovascular disorders.1 Few studies have investigated the association between antihypertensive drugs and frailty syndrome. A cross-sectional study revealed that angiotensin receptor blockers were negatively associated with frailty syndrome in women, but the association was positive in men.2 Hence, the relationship between antihypertensive drugs and frailty syndrome is ill defined. The purpose of this cross-sectional study was to establish the relationship between blood pressure and frailty and to assess the effect of antihypertensive agents on frailty prevalence. Older adults aged 65 to 90 with hypertension (≥160/90 mmHg) (N = 138) were recruited from the outpatient clinics of a medical center and received a comprehensive geriatric assessment by a geriatric physician. The definition of frailty proposed by Fried was used;3 the five components of frailty are weight loss, exhaustion, low physical activity, slow walking speed, and weakness. Participants were classified as frail if they had three or more of the five frailty components, as prefrail if they had one or two, and nonfrail if they had none. The prevalence of prefrailty was 66% (n = 91) and of frailty was 14% (n = 20). Prefrail and frail participants had higher systolic blood pressure (139.0 and 137.9 vs 128.9 mmHg) and pulse pressure (60.1 and 61.8 vs 52.2 mmHg) than nonfrail participants, and participants with well-controlled blood pressure were less likely to be prefrail (78.7%) or frail (86.67%) (P = 0.44) than those with poor blood pressure control. Calcium channel blocker (CCB) use was significantly negatively associated with frailty. Nonfrail participants were more likely to use CCBs (74.1%) than prefrail (54.9%) and frail (50.0%) participants. Participants using CCBs had a lower than 70% risk of prefrailty or frailty (odds ratio (OR) = 0.30, 95% confidence interval (CI) = 0.10–0.83). Additional multivariate models showed a persistently lower risk for prefrailty and frailty associated with CCB use (OR = 0.26, 95% CI = 0.09–0.77) (Table 1). Participants using CCBs were significantly less likely to have weak handgrip strength (71.3% vs 88.4%, P = .05; mean difference 3.26 kg, P = .03) than those not using CCBs. The further multivariate model did not change the association. Systolic blood pressure and pulse pressure were positively associated with frailty status, and hypertensive treatment, especially with CCBs, was associated with less risk of frailty syndrome. Blood pressure control may be associated with control of frailty. Some studies have revealed that antihypertensive medicines are associated with components of frailty.4-6 The Health, Aging and Body Composition Study,4 the Women's Health and Aging Study,5 and a randomized controlled trial study6 showed that angiotensin-converting enzyme inhibitors may have benefits for components of frailty. The current study further found that CCBs might have a protective effect against frailty. Two possible mechanisms may link high blood pressure; antihypertensive medicine, especially CCBs; and frailty. First, atherosclerosis links high blood pressure and sarcopenia, one of the components of frailty. Atherosclerosis was associated with greater risk of frailty.7 Second, impaired cognitive function may link high blood pressure and frailty. Participants with hypertension had poorer cognitive function,8 and cognitive function was worse in prefrail and frail individuals than in those who were robust.9 Furthermore, weakness and walking speed were most consistently linked to poor cognition in all domains.9 A meta-analysis concluded that CCBs and renin-angiotensin system blockers may help prevent cognitive decline and dementia.10 Together, antihypertensive treatment, especially CCBs, was negatively associated with frailty, and this mechanism may help prevent cognitive function decline. The current study also found that older adults taking CCBs were significantly less likely to have weak handgrip strength than those not taking CCBs. Therefore, atherosclerosis and cognitive impairment may be part of the mechanism involved in the association between CCBs and frailty. High blood pressure was positively associated with frailty, and antihypertensive medication, especially CCBs, had a protective effect against frailty, suggesting that blood pressure control may be beneficial for frailty prevention. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Chuang: study concept and design, analysis and interpretation of data, preparation of manuscript. Pan: study concept and design, interpretation of data. Chang: analysis and interpretation of data, preparation of manuscript. Wu: interpretation of data. Chen, Hsu: acquisition of subjects and data, critical manuscript revision, interpretation of data. Sponsor's Role: None.