Abstract
Background/Objectives: Cardiovascular disease (CVD) risk may be based on the sequence of hypertension (HTN) and diabetes mellitus (DM) occurrence since the pathophysiological mechanisms might not be the same. The present study examined the risk of CVD according to the precedent relationship between HTN and DM. Methods: Participants with both HTN and DM in a national health screening program in 2015-2016 were divided into two groups based on the order of HTN and DM occurrence: 'HTN → DM' and 'DM → HTN'. The primary outcomes were newly diagnosed myocardial infarction (MI) and ischemic stroke based on the International Classification of Diseases, 10th revision code. Results: Among 914,338 participants, there were 28,368 MI events and 35,632 ischemic stroke events during the follow-up period. The DM → HTN group showed a higher risk of MI (adjusted hazard ratio [aHR]: 1.13 [95% CI: 1.10-1.15]) and ischemic stroke (aHR: 1.06 [95% CI: 1.04-1.09]) than the HTN → DM group. The increased risk of MI in the DM → HTN group was more prominent in females than in males and in those without dyslipidemia than in those with dyslipidemia. A higher risk of MI and ischemic stroke in the DM-HTN group was found in patients with chronic kidney disease (CKD) than in patients without CKD. Conclusions: MI and ischemic stroke were more frequent in patients in the DM → HTN group than in those of the HTN → DM group. When approaching HTN and DM clinically and epidemiologically, two phenotypes based on the order of occurrence should be considered. Given the generalization limitations of Asian patients, who develop DM at an early age compared to other groups, future studies are needed to reveal the underlying mechanism in the precedence relationship between HTN and DM.