Useful research would be to create EXACT protocols that lower LDL-C and thus prevent strokes. If competent mentors and senior researchers existed, then we would have useful research! But alas, they don't exist! Everything in stroke is a shitshow! Your best bet is to not have a stroke!
Systematic analysis of the burden of ischemic stroke attributable to high LDL-C from 1990 to 2021
Jiahao Tang1,2,3†
Guoyang Zhou2,3†
Shunan Shi1,2,3
Yuexin Lu1,2,3
Lin Cheng2,3
Jianping Xiang4
Shu Wan2,3*
Ming Wang2,3*- 1The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- 2Brain Center, Zhejiang Hospital, Hangzhou, Hangzhou, China
- 3Zhejiang Province Engineering Research Center for Precision Medicine in Cerebrovascular Diseases, Zhejiang Hospital, Hangzhou, China
- 4ArteryFlow Technology Co., Ltd., Hangzhou, China
Background: Low-density lipoprotein cholesterol (LDL-C) is a public health concern linked to ischemic stroke. The study aimed to describe the epidemiological characteristics of ischemic stroke attributable to high LDL-C from 1990 to 2021.
Methods: In this study, we analyzed data from the Global Burden of Disease 2021 to present trends in ischemic stroke related to high LDL-C over the past 30 years. The relationship between disease burden and the Socio-Demographic Index (SDI) was examined. To assess international health disparities, we applied the Slope Index of Inequality (SII) and the Concentration Index (CI). Furthermore, we conducted a frontier analysis to identify areas for improvement and developmental gaps among nations, and employed the Bayesian Age-Period-Cohort (BAPC) model to forecast the disease burden for the next 15 years.
Results: In 2021, the incidence of ischemic stroke attributed to high LDL-C significantly increased compared to 1990, with a more pronounced growth rate in males. The burden mainly affects individuals aged 70 to 84. Analysis using the age-period-cohort model indicates that mortality rates and DALYs rise with age, while period and cohort effects exhibit a gradual decline. Across different SDI regions, trends generally follow a similar downward path, with a narrowing gap in disease burden among regions with varying SDI levels. However, the disease burden in high SDI countries remains significant, indicating potential for reduction. Predictions for the next 15 years suggest that while the global disease burden will decrease, there may be an increase among individuals under 55.
Conclusion: Compared to 1990, the overall age-standardized burden of ischemic stroke related to high LDL-C has been controlled. However, disparities persist across different SDI regions. We have observed an increasing burden among younger populations. Consequently, countries and regions must adopt new measures tailored to their SDI levels, with a specific emphasis on younger individuals. It is essential to develop prevention and treatment strategies aimed at high-risk groups.
1 Introduction
Ischemic stroke represents a serious global health challenge, ranking among the top causes of long-term disability and mortality worldwide (1). Historically, ischemic stroke has been a significant contributor to overall disease burden, with notable shifts in its epidemiology over the past three decades. From 1990 to 2021, the disease burden showed a declining trend, with the average annual percent change (AAPC) in the age-standardized incidence rate (ASIR), mortality rate (ASMR), and disability-adjusted life years (ASDR) for ischemic stroke being −0.57 (95% CI: −0.66 to −0.48), −1.60 (95% CI: −1.81 to −1.39), and −1.37 (95% CI: −1.53 to −1.20), respectively (2). Over these 30 years, the burden of ischemic stroke attributable to metabolic risks, environmental and occupational risks, and behavioral risks all showed a declining trend. Among these, metabolic-related factors remained the primary risk factors for ischemic stroke, with a population attributable fraction (PAF) of 76.88% (2). Among these, high low-density lipoprotein (LDL) cholesterol had a PAF of 25.78%, making it a significant cause of ischemic stroke among metabolic factors, second only to high systolic blood pressure (2).
Although the age-standardized disease burden of ischemic stroke has decreased, there were still 7,804,449 cases of ischemic stroke globally in 2021 (95% UI, 6,719,760–8,943,692), imposing a significant economic burden on public health systems (2). Additionally, due to more advanced medical facilities in developed countries and regions compared to the poorer infrastructure and medical conditions in developing and underdeveloped areas, there are significant disparities in disease burden across different regions. Furthermore, there are differences in disease burden across different age groups and genders. Therefore, a more detailed analysis of the disease burden related to ischemic stroke risk factors is still necessary, which may provide new insights for reducing this burden.
Hyperlipidemia, particularly low-density lipoprotein cholesterol (LDL-C), is a well-established risk factor for cardiovascular disease and a key driver of ischemic stroke (3–6). Among ischemic stroke cases, high LDL cholesterol (LDL-C) has a population attributable fraction (PAF) of 25.78%, making it a significant cause of ischemic stroke among metabolic factors, second only to high systolic blood pressure (2). Through lipid-lowering drug interventions, dyslipidemia is a modifiable risk factor for ischemic stroke, and its control can prevent the occurrence and recurrence of stroke. Studies have shown that actively lowering cholesterol levels with high doses of atorvastatin can reduce the incidence of stroke by 33% and recurrent stroke by 16% in patients with carotid artery stenosis (7).
Despite ongoing interventions to manage cholesterol levels, the efficacy of these efforts in reducing ischemic stroke burden due to high LDL-C remains uncertain (8). In a study involving 213,380 individuals, only 51.8% of very high-risk (VHR) patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (DM2) achieved the lipid-lowering target (LDL-C < 70 mg/dl) (9). As economic development progresses, high-energy, high-cholesterol, and high-fat diets are becoming more common among people, coupled with a lack of exercise and increased life stress, which may further increase the burden of ischemic stroke due to dyslipidemia.
To further assess the disease burden of ischemic stroke caused by dyslipidemia, this study utilizes GBD 2021 data to explore the long-term trends, regional disparities, and future projections of ischemic stroke burden related to high LDL-C from 1990 to 2021. By providing these insights, we aim to assist healthcare professionals and policymakers in developing effective strategies to mitigate the health risks and burden associated with ischemic stroke.
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