Antihypertensive Medications and Risk of Heat‐Related Illness During Heatwaves: Self‐Controlled Case Series

PURPOSE: To investigate whether antihypertensive medications modify the risk of heat-related illness during heatwaves among adults with hypertension in Japan. METHODS: We identified adults with hypertension in Tsukuba City administrative claims data between April 2014 and March 2019. Average daily temperature was derived from Japan Meteorological Agency data. We used a self-controlled case series (SCCS) design to estimate incidence rate ratios (IRRs) for heat-related illness during 5-day pre-heatwave, heatwave and 5-day post-heatwave periods compared to baseline within individuals. The main analysis was stratified by person-time prescribed antihypertensives (angiotensin-converting enzyme [ACE] inhibitors/angiotensin II receptor blockers [ARBs], calcium channel blockers [CCBs] or non-loop diuretics) and person-time not prescribed antihypertensives, with drug-temperature interaction assessed. Subgroup analyses were conducted for each antihypertensive class. All models were adjusted for age and season. RESULTS: We observed a greater increase in the rate of heat-related illness during heatwaves versus baseline among person-time prescribed antihypertensives (IRR: 1.64, 95% CI: 1.53-1.75) than among person-time not prescribed antihypertensives (IRR: 1.42, 95% CI: 1.27-1.58), with evidence of drug-temperature interaction (p < 0.01). When examining individual drug classes, ACE inhibitors/ARBs and CCBs were associated with an increased risk of heat-related illness during heatwaves, whereas there was no evidence of an effect with diuretics. CONCLUSIONS: Our findings indicate that people taking antihypertensives are more vulnerable to heat-related illnesses during heatwaves. More research is required to explore whether this is a causal effect of the medication or due to differences between those who are treated and untreated with antihypertensives that are related to the outcome. Climate change is increasing the frequency and intensity of heatwaves worldwide. Older adults with morbidities, such as hypertension, are particularly at risk of heat‐related illness. Antihypertensive medications, used to treat hypertension, can affect how the body regulates temperature and fluid balance, which may increase heat‐related illness risk. In this study we compared the rate of heat‐related illness events during heatwave periods to normal temperature periods within an individual. We then compared the increase in heat‐related illness during heatwaves during time using antihypertensives and time not using antihypertensives. We found that there was a greater increase in heat‐related illness rates during heatwaves when taking antihypertensives than when not taking antihypertensives. When we looked at individual antihypertensive medication classes, we found that this pattern was consistent for angiotensin‐converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) and calcium channel blockers but not for non‐loop diuretics. This finding suggests that people who are taking antihypertensives are particularly vulnerable to heat‐related illness during heatwaves. However, more research is required to assess whether the increased risk is caused by the medication.