Evaluating the Risk of Macrovascular Events and Mortality Among People With Multiple Sclerosis in England

Abstract

IMPORTANCE People with multiple sclerosis (MS) are associated with an increased risk of cardiovascular disease and mortality; however, evidence from population-based studies is sparse.OBJECTIVE To assess whether the risk of macrovascular events and mortality differs among people with MS compared with a matched population without MS in England. DESIGN, SETTING, AND PARTICIPANTSA population-based retrospective matched cohort study was conducted in general practices registered with the Clinical Practice Research Datalink in England between January 1, 1987, and September 30, 2018, with a mean (SD) follow-up of 11.3 (6.5) years. A total of 12 251 patients with MS were matched with up to 6 people without MS (n = 72 572) by age, sex, and general practice. People with 3 or more diagnoses of MS recorded during the study period were included. The first MS diagnosis was considered as index date.EXPOSURES Multiple sclerosis status. Analyses were also stratified by sex.MAIN OUTCOMES AND MEASURES Main outcomes were acute coronary syndrome, cerebrovascular disease, any macrovascular disease (including peripheral arterial disease), and mortality (all-cause mortality and cardiovascular disease-specific mortality). Cox proportional hazards regression and Fine and Gray proportional subhazard regression models were used to assess differences in rates.RESULTS A total of 12 251 people with MS (66.9% women; mean [SD] age, 44.9 [13.3] years) were matched with 72 572 people without MS (69.8% women; mean [SD] age, 44.9 [13.3] years). As compared with people without MS, people with MS were associated with a 28% increased hazard of acute coronary syndrome (hazard ratio [HR], 1.28; 95% CI, 1.09-1.51), 59% increased hazard of cerebrovascular disease (HR, 1.59; 95% CI, 1.32-1.92), 32% increased hazard of any macrovascular disease (HR, 1.32; 95% CI, 1.15-1.52), 3.5-fold increased hazard of all-cause mortality (HR, 3.46; 95% CI, 3.28-3.65), and 1.5-fold increased hazard in cardiovascular disease mortality (HR, 1.47; 95% CI,. Differences in macrovascular events were more pronounced among women than men. Mortality risk was also higher for women than men. Treatment with lipid-lowering medications (mainly statins) was associated with lower mortality rates among people with MS.CONCLUSIONS AND RELEVANCE This study suggests that MS is associated with an increased risk of cardiovascular and cerebrovascular disease that is not completely accounted for by traditional vascular risk factors. Given the adverse effects of these comorbidities on outcomes in patients with MS, further investigation is needed.

Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis

“…Evidence of an increased effect of thrombin in vivo has been found in individuals at high risk of developing clinically significant thromboembolism in both the veins and arteries [ 42 ]. The reports related to vascular disease in MS, confirm an increased risk of ischemic events associated with abnormal coagulation cascade and an over-activity of platelets, especially ischemic stroke, myocardial infarction and venous thromboembolism [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 43 ]. A large Danish population-based cohort study revealed that death caused by vascular or cardiac diseases (mainly stroke and deep vein thrombosis) was the most frequently listed reason for death in MS.…”

Multiple Sclerosis in the Campania Region (South Italy): Algorithm Validation and 2015–2017 Prevalence

“…Considering that previously published MS case-finding algorithms to identify people with MS using administrative healthcare databases varied in relation to the number of MS records considered for each patient for case identification [26][27][28][29], we aimed to validate two versions of the algorithm (aim 1), which considered the presence of: 1) at least one MS record during the study period; and 2) at least two MS records during the study period. To validate the algorithm, we merged our dataset with a clinical registry and identified individuals who accessed the MS Clinical Care and Research Centre at the "Federico II" University of Naples using the information provided by the algorithm.…”

“…Previously published MS case-finding algorithms to identify people with MS from administrative healthcare databases used one to three MS records for case identification [26][27][28][29]. Our algorithm used one MS record for case identification and had high sensitivity (99.0%) at detecting MS cases from a clinical registry.…”

“…Not least, we excluded MS patients who were receiving care in the Campania Region but were actually living elsewhere, which could have overinflated MS prevalence in other Italian studies [14,27]. Other international cohorts included a nationwide cohort in France (>100,000 individuals with MS) [16], and a cohort representative of the UK population (>10,000 individuals with MS) [26], which, however, lack linkage to clinical datasets for validation of case-finding algorithms and clinical outcomes. In Germany, a cohort of >30,000 individuals has been described, though limited by the lack of linkage to clinical datasets and by the risk of multiple counting of patients who changed of insurance number during the study period [45].…”

Association between pre-diabetes and microvascular and macrovascular disease in newly diagnosed type 2 diabetes

“…To reduce missing data for study covariates in the year following the diagnosis of type 2 diabetes, we used the latest clinical recording for individuals with missing values within 5 years before the start of the study period. [35][36][37] Individuals with missing data on smoking were classified as non-smokers if there was no indication in the past of the individual being a smoker. 35 36 secondary analyses We undertook two secondary analyses.…”