Multiple Sclerosis-associated Cardiovascular Disease–Related Mortality: A Retrospective Cohort Study Using Real-world Data from the USA, 1999–2023
Mohamed Hemida Saleh1, Alyaa Ahmed Ibrahim1, Mirna Hussein1, Mahmoud Tablawy2, Maryam Saghir3, Nafila Zeeshan4, Ahmed Hamza5, Maliha Khalid6, Eshal Saghir7, Omar Rabie8, Waheed Qaisi9, Mostafa Alagamy10, Muhammad Raza Sarfraz11, Amro Ali12
1Alexandria Faculty of Medicine, Alexandria, Egypt, 2Faculty of Medicine, Al-azhar University, Cairo, Egypt, 3Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan, 4Dow Medical College, Karachi, Pakistan, 5Department of Neuroscience, University of Pittsburgh, Pennsylvania, USA, 6Jinnah Sindh Medical University, Karachi, Pakistan, 7Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan, 8Faculty of Medicine, Helwan University, Cairo, Egypt, 9An-Najah National University, Department of Medicine, 10Kasr Alainy Faculty of Medicine - Cairo University,Cairo, Egypt, 11Allied Hospital, Faisalabad Medical University, Faisalabad, Pakistan, 12Department of Medicine, Community Regional Medical Center, Fresno, California, USA
Objective:
To investigate the mortality trends in adults in the United States specifically attributed to Multiple Sclerosis-associated Cardiovascular Disease (MS-CVD).
Background:
Cardiovascular disease represents a significant comorbidity and cause of mortality in individuals with MS. Despite known overlapping risk factors, comprehensive national mortality trends focusing on this specific association have not been extensively characterized.
Design/Methods:
We analyzed U.S. mortality data from CDC WONDER (1999–2023) for adults aged 25 and older. Deaths were identified where MS (ICD-10: G35) and cardiovascular disease (ICD-10: I00–I99) were listed as contributing or underlying causes. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated. Joinpoint regression was employed to determine annual percent change (APC) and average annual percent change (AAPC).
Results:
A total of 53,903 deaths from MS-CVD were recorded between 1999 and 2023 among adults aged 25 and older. The overall AAMR significantly increased from 0.78 in 1999 to 1.21 in 2023 (AAPC: 1.50, 95% CI: 1.13 to 1.86; p< 0.001), with an acceleration from 0.87 in 2018 to 1.24 in 2021 (APC: 12.83; p= 0.02). Sex-stratified analysis revealed higher mortality in women (35,157 deaths) compared to men (18,746 deaths), with women exhibiting higher AAMRs throughout the period (e.g., 1.45 in 2023 vs. 0.92 in men). Non-metropolitan regions had a higher overall AAMR (0.92) than metropolitan areas (0.88). While non-Hispanic White individuals accounted for the largest number of deaths (45,242), the non-Hispanic Black population showed the highest AAMR (1.59 in 2020). The +65 age group had the highest number of deaths (30,974) and a significant AAMR increase from 2.19 in 1999 to 4.17 in 2023.
Conclusions:
Mortality from MS-associated Cardiovascular Disease has significantly increased in the United States over the past 25 years. This upward trend is particularly pronounced in women, residents of non-metropolitan areas, and the non-Hispanic Black population, highlighting critical disparities in MS-CVD outcomes.
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