Controlling Cholesterol: Stroke Prevention and Updated ASA Guidelines

The American Stroke Association (ASA) released updated guidelines for stroke prevention, focusing on effective management of cardiovascular (CV) health through lifestyle modifications, increased physical activity, and medical interventions. The “2024 Guideline for the Primary Prevention of Stroke” replaces the 2014 guidelines to include changes to identifying and managing risk factors, healthy lifestyle suggestions, health equity, as well sex- and gender-specific recommendations for women.

For patients with high levels of LDL-C, proper management of cholesterol through diet and medical interventions can help reduce risk of heart disease and stroke. Image Credit: © freshidea - stock.adobe.com

According to the American Heart Association, 80% of strokes are preventable and are the fifth leading cause of death and disability in the United States. Each year, 600,000 people in the US have their first stroke despite opportunities for prevention. Strokes occur when blood flow to the brain is interrupted, resulting in a lack of oxygen that leads to permanent damage and cognitive impairments. There are various factors associated with an increased risk of stroke such as genetics and social determinants of health (SDOH), which are unavoidable factors. However, high blood pressure (BP), obesity, elevated blood sugar, and elevated cholesterol, are modifiable and treatable.^1-3

“The most effective way to reduce the occurrence of a stroke and stroke-related death is to prevent the first stroke—referred to as primary prevention,” Cheryl D Bushnell, MD, MHS, FAHA, chair of the guideline writing group, professor and vice chair of research in the department of neurology at Wake Forest University School of Medicine in Winston-Salem, North Carolina, said in a news release. “Some populations have an elevated risk of stroke, whether it be due to genetics, lifestyle, biological factors and/or SDOH, and in some cases, people do not receive appropriate screening to identify their risk.”²

Low-density lipoprotein cholesterol (LDL-C) is a known contributor to the development of cardiovascular diseases (CVDs) that increase risk of heart attack and stroke. High cholesterol levels play a significant role in the potential for stroke due to the build-up of fatty deposits in the arteries leading to atherosclerosis, resulting in blood clots and impaired blood flow.^4,5

“There's a reason why low-density lipoprotein, or LDL, has been deemed bad cholesterol,” said Erin McConnell, PharmD, program manager of pharmacy quality at the University of Pittsburgh Medical Center. “It promotes arterial plaque formation, which can lead to heart attacks and strokes.”⁶

For patients with high levels of LDL-C, proper management of cholesterol through diet and medical interventions can help reduce risk of heart disease and stroke. Results from a post-hoc subgroup analysis in the SPARCL trial (NCT00147602) in 2006 demonstrated that 80 mg of atorvastatin daily reduced the overall incidence of strokes in 4731 patients with elevated LDL-C levels. During a median follow-up of 5 years, 265 patients receiving atorvastatin compared with 311 patients receiving placebo had a fatal or nonfatal stroke (5-year absolute reduction in risk, 2.2 percent; adjusted hazard ratio, 0.84; 95 percent confidence interval, 0.71 to 0.99; P=0.03; unadjusted P=0.05).^7,8

There are various available methods of managing cholesterol, which can reduce the risk of stroke by over 10%. Lifestyle modifications are a crucial method of reducing cholesterol, and thereby risk of stroke. Diet plays a significant role in cholesterol levels and foods high in saturated fats, processed meats, and fried foods increase LDL-C. A diet composed of lean meats and produce encourage healthy cholesterol levels to decrease risk of complications. The updated guidelines recommend utilizing Life’s Essential 8, which contains a plethora of suggestions for healthy nutrition, regular physical activity, healthy sleep, weight management, managing BP and blood sugar, and controlling cholesterol. A Mediterranean diet is highly recommended for healthy and high-risk populations.²

Additionally, LDL-C lowering drugs such as statins, selective cholesterol absorption inhibitors, or PSCK9 inhibitors have shown success for patients who require medical interventions alongside implementation of lifestyle modifications.

“It's really important that we have lipid lowering therapies on board. They can play a role in both secondary and primary prevention. As I've mentioned, a lot of the drugs like statins, the PCSK9s, and ACLI inhibitors definitely have data to show that they play a role other than lipid lowering themselves. So generally, we do want total cholesterol to be less than 150 milligrams per deciliter and LDL cholesterol to be less than 100,” said McConnell.⁶

Beyond LDL-C lowering drugs, the updated stroke prevention guidelines highlight the potential use of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), which received a class 1a recommendation for stroke risk reduction. In the SUSTAIN 6 trial (NCT01720446) evaluating use of semaglutide in 2735 patients type 2 diabetes, occurrence of nonfatal stroke occurred in 1.6% of patients compared with 2.7% of those receiving placebo (hazard ratio, 0.61; 95% CI, 0.38 to 0.99; P=0.04).^9,10

However, access to GLP-1 RAs can prove to be challenging due to drug availability and well as SDOH. GLP-1 RAs have shown to be efficacious treatments for a variety of conditions, such as weight loss and diabetes, leading to concerns that widespread use for multiple indications may strain health care resources and limit access for patients in need. Additionally, GLP-1 RAs for weight loss have gained significant media attention and popularity amongst celebrities, as well as individuals who may not need medical interventions for effective weight loss.¹¹

“They're not really being kind of presented to people as therapies for a disease. It's more kind of cosmetically related weight loss,” said W. Timothy Garvey, MD, associate director of the department of nutrition sciences at the School of Health Professions at the University of Alabama Birmingham. “This leads to people kind of availing themselves of the medications that really don't need them, and we have shortages of these medications, so it just means there's less medicine to go around for patients that really do need them.”¹¹

SDOH are significant barriers to care for patients across disease states. Economic status, education, race or ethnic background, cultural beliefs, availability to healthy food, among others, can all interfere with individuals’ ability to identify and mitigate risk factors or afford the therapies that enable them to do so. The guideline suggests screening for SDOH to ensure early identification of potential barriers using evolving evidence-based interventions.^2,3

The updates also offer sex- and gender-specific recommendations for women, as well as transgender and gender-diverse patients. Women should be screened for stroke risk in the presence of use of oral contraceptives, high BP during pregnancy, other pregnancy complications such as premature birth, endometriosis, premature ovarian failure and early onset menopause, according to the guidelines. Transgender women and gender fluid patients taking estrogen also have an increased risk and should be evaluated to identify and intervene prior to the event of a stroke.^2,3

“This guideline is important because new discoveries have been made since the last update 10 years ago,” said Bushnell. “Understanding which people are at increased risk of a first stroke and providing support to preserve heart and brain health can help prevent a first stroke.”²

The “2024 Guideline for the Primary Prevention of Stroke” is a resource for clinicians to use as a guide to various prevention strategies to reduce stroke risk and improve CV health for individuals with no history of stroke. According to the ASA, learning the warning signs of stroke—using the abbreviation FAST, which stands for face drooping, arm weakness, speech difficulty, time to call 911—and preventative measures are the best way to avoid strokes.² By focusing on both modifiable risk factors and the impact of SDOH, the new guidelines offer a comprehensive approach to stroke prevention. As advancements continue in CV care, these updates will serve as a valuable tool for clinicians in reducing the burden of stroke and improving patient outcomes.

REFERENCES

1. About stroke. American Heart Association. Accessed October 21, 2024. https://www.stroke.org/en/about-stroke

2. New guideline: Preventing a first stroke may be possible with screening, lifestyle changes. News Release. October 21, 2024. Accessed October 21, 2024. https://www.eurekalert.org/news-releases/1061735

3. Bushnell C, Kernan W, Sharrief A, et al. 2024 guideline for the primary prevention of stroke: a guideline from the american heart association/american stroke association. Stroke. October 21, 2024. doi:10.1161/STR.0000000000000475

4. High cholesterol. Stroke Association. Accessed October 21, 2024. https://www.stroke.org.uk/stroke/managing-risk/high-cholesterol#:~:text=Excess%20cholesterol%20enters%20your%20bloodstream,brain%20and%20cause%20a%20stroke.

5. Heart attack and stroke survivors neglect LDL cholesterol despite increased risk. American Heart Association. August 23, 2023. Accessed October 21, 2024. https://newsroom.heart.org/news/heart-attack-and-stroke-survivors-neglect-ldl-cholesterol-despite-increased-risk

6. The role of cholesterol management in cardiovascular risk reduction. Pharmacy Times. September 23, 2024. Accessed October 22, 2024. https://www.pharmacytimes.com/view/the-role-of-cholesterol-management-in-cardiovascular-risk-reduction

7. Lipitor in the prevention of stroke, for patients who have had a previous stroke (sparcl). ClinicalTrials.gov Identifier: NCT00147602. Updated April 22, 2015. Accessed October 21, 2024. https://clinicaltrials.gov/study/NCT00147602

8. Amarenco P, Bogousslavsky J, Goldstein L, et al. high-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. August 10, 2006. doi: 10.1056/NEJMoa061894

9. Trial to evaluate cardiovascular and other long-term outcomes with semaglutide in subjects with type 2 diabetes (sustain™ 6). ClinicalTrials.gov Identifier: NCT01720446. Updated June 27, 2019. Accessed October 22, 2024. https://clinicaltrials.gov/study/NCT01720446

10. Marso S, Bain S, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. November 10, 2016. doi:10.1056/NEJMoa1607141

11. Physician calls for national dialogue on inequitable access to lifesaving glp-1 medications. Pharmacy Times. June 23, 2024. Accessed October 22, 2024. https://www.pharmacytimes.com/view/physician-calls-for-national-dialogue-on-inequitable-access-to-lifesaving-glp-1-medications