We performed a cross-sectional study in community-dwelling older adults aged 65, and older enrolled in the Health and Retirement Study (HRS). The HRS is a longitudinal study sponsored by the National Institute of Aging and the Social Security Administration, which started in 1992 in the USA. It was established to provide a resource of data on changing health and economic circumstances associated with aging. The study design has been described previously (17). Briefly, participants born between 1931–1941 (age 51–61 at time of study initiation) were recruited and originally consented at the University of Michigan. Additional cohorts have been added since 1992 with a steady state recruitment design. Participants in the HRS complete biennial in home interviews with trained interviewers. The medication use information is available for a subset of participants who completed the 2004 wave and who were part of a Prescription Drug Study (PDS). Additionally, half of the 2004 participants had physical measures performed in 2006 as part of an Enhanced Face-to-Face (EFTF) interview. Participants from the 2004 assessment with both medications use and physical measures data were included in this study (Figure 1).

The HRS contains detailed medication use information through an off-cycle Prescription Drug Study (PDS) drawn from the 2004 wave to examine the impact of Medicare part D implementation. In HRS, 5,654 participants from the 2004 wave were randomly selected for the PDS mail survey (Figure 1). Inclusion criteria were age 65 years or older in 2006 when Medicare part D was implemented and not participating in another mail survey which was occurring at the same time. Three hundred and forty participants died prior to the PDS. Of the remaining 5,314 eligible participants, 4684 returned questionnaires or completed telephone interviews, for a response rate of 88.1%. The medication files contain drug names, dosage, cost, and questions about adherence to medication use.

The overall sample eligible for this study (those who completed the PDS and had 2006 physical measures) includes 1,260 participants, of which 364 were on an ACEi in 2005. ACEi use was categorized as c-ACEi or p-ACEi. c-ACEi include captopril, lisinopril, perindopril, fosinopril, trandolapril, zofenopril, and ramipril, while p-ACEi include enalapril, quinapril, benazepril, and moexipril.

Physical measures were performed in 2006 as part of an Enhanced Face-to-Face (EFTF) interview on a random half sample of the eligible 2004 cohort. These measures were performed in the participants’ homes by trained study personnel. We identified a measure of upper extremity, lower extremity and truncal strength from available measures in HRS. Lung function, a reflection of truncal strength, was determined by peak flow or the peak expiratory flow (PEF) rate, measured 3 times, 30 seconds apart. Handgrip strength was attempted in both hands and measured in only one hand if the participant reported a condition that limited use of one hand such as surgery, swelling, inflammation or severe pain or injury within the last six months. Two measurements were taken and reported in kilograms. To assess lower extremity strength, participants were advised to walk at their normal pace on a 2.5-meter non-carpeted straight path. The time was recorded twice. The walking time was converted to speed and reported as gait speed in meters per second (m/s). Participants were allowed to use a walking aid such as a cane. Physical measures and physical performance measures with more than one recorded measurement were reported as an average of the available values.

Demographic characteristics, medical conditions, the presence of polypharmacy, high-risk medication use and antihypertensive medication use from HRS are included in this study. Information about medication use is obtained from the prescription drug survey as described above. Polypharmacy is defined as the use of 5 or more regularly scheduled medications. High risk medication use includes medications that are associated with falls and/or cognitive impairment and included benzodiazepines, first generation antihistamines, opioid analgesics, alpha-blockers, muscle relaxants, proton pump inhibitors, selective serotonin reuptake inhibitor, nonsteroidal anti-inflammatory drug, urinary antispasmotics and medications used to treat insomnia. Educational level is measured as years of schooling. Medical conditions are reported by the participant who answered ‘yes’ or ‘no’ if their doctor ever told them that they had a stated condition. A modified version of the Mini-Mental Status Exam (MMSE) forms the Total Cognitive Score (18), which measures overall cognitive function, and ranges from 0–35 (higher better). The Total Cognitive Score includes tests of immediate and delayed recall, serial 7s, counting backwards, object naming, recall of both the date and both the president and vice president. Physical measures include blood pressure measured in mmHg, pulse or heart rate in beats per minute (bpm) measured 3 times, 45 seconds apart. Weight and height were recorded and reported as BMI measured in kilogram per meters squared (kg/m2). Waist circumference (centimeter) was measured at the level of the navel.

The objective of the analysis was to examine the differences in physical performance measures in participants on a c-ACEi compared to those on a p-ACEi. Participants’ baseline characteristics were compared using descriptive statistics; two-sample T-test for continuous variables and Chi Square test for categorical variables. Third, we reported the results of linear regression models of the physical performance measures among ACEi subtype users. Adjustments were made for differences noted in Table 1, or based upon biological plausibility. Model assumptions were examined and met. Significance was determined to be a P value of 0.05 or less. All analysis was performed using SPSS version 26, IBM.