Background

Hypertension (HTN) is a common condition in multiple sclerosis (MS), and it is associated with poorer MS outcomes. Recently, a large study showed HTN was 25% more common in MS than non-MS cohorts. It is unknown if the elevated HTN prevalence is because vascular alterations play a primary role in MS pathogenesis or if they are secondary to MS disease processes.

Objectives

To add insight to the MS-HTN relationship, we sought to determine if HTN age at onset (AAO) is earlier in MS patients compared to matched controls.

Methods

Using electronic health records (EHRs) from the Cleveland Clinic Health System (CCF), we identified 141,696 incident HTN diagnoses among Ohio residents between 1/2000-1/2017 who were ≥18 years at 1^st encounter. Incident HTN was defined as the 1^st of ≥2 recorded HTN diagnoses at least 3 months after the 1^st encounter. Similar criteria determined incident MS (N=546). We then matched MS cases to controls on birth year (+/- 3 years), age at 1^st encounter (+/- 3 years), sex, race and ZIP code, allowing for up to 10 matches. By matching in this retrospective cohort, where MS status is the exposure of interest, we remove potential confounding in the observed relationship of interest due to the matched variables. The final data set consisted of 509 MS cases and 4,522 matched controls; 87% MS cases were matched to ≥7 controls. Using HTN AAO as the dependent variable, we conducted Cox Proportional Hazards (CPH) and linear regression (LR) models with standard errors adjusted for intragroup correlations due to matching. Based on quartiles of the distribution of birth year in MS cases (1920-1949, 1950-1957, 1958-1965, 1966-1990), we constructed a categorical variable to be included as a covariate along with age at 1^st encounter, sex, race, and smoking status (ever/never).

Results

Birth year violated the PH assumption, therefore stratified CPH models across birth year categories were conducted. MS and age at 1^st encounter were time-varying, and treated as such. On average MS cases had a 73% increased hazards (HR = 1.73, 95% CI: 1.17, 2.55; p=0.006) for HTN onset, which decreased by 1% per year increase in age. Since the effect of MS was time-varying, we conducted models per birth year category. Interesting, MS was not associated with increased hazards for HTN onset for those born before 1966. In those born after 1965, MS was associated with a 37% increased hazards (HR = 1.37, 95% CI: 1.12, 1.68; p=0.0025), and this effect met the PH assumption.

From the LR model, there was an interaction between MS and birth year, therefore similar stratifed models were conducted. HTN AAO was on average 0.7 years earlier (95% CI: 0.05, 1.4; p=0.04) in MS cases than controls born after 1965. There were no difference for other birth year categories.

Conclusions

In those born after 1965, persons with MS experience an earlier onset of HTN. Future research is needed to characterize these relatioships by sex and race, as well as the timing of HTN onset with respect to MS onset.