Better cardiovascular health linked to lower ALS risk in large study

People with a history of atherosclerotic cardiovascular disease (ASCVD) may have a higher risk of developing amyotrophic lateral sclerosis (ALS), while those with better cardiovascular health may have a lower risk, a large study suggests.

Among more than 500,000 people from the U.K. who were followed for nearly 14 years, a history of ASCVD was associated with a 43% higher risk of ALS. By contrast, people with the healthiest cardiovascular scores had about half the ALS risk of those with the poorest scores. ASCVD refers to a group of diseases caused by the buildup of fats, cholesterol, and other substances inside arteries. This buildup can restrict blood flow to areas such as the heart or brain.

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Cardiovascular health may be linked to ALS risk

According to the researchers, “these findings support a potential link between [cardiovascular health] and ALS susceptibility, particularly among individuals aged [65 years or younger].”

The study, “Atherosclerotic Cardiovascular Diseases Increase ALS Risk by 82% While Optimal Cardiovascular Health Halves It: A 0.5-Million Prospective Cohort Study,” was published in Annals of Neurology.

ALS is caused by the progressive loss of motor neurons, the nerve cells that control movement. This leads to worsening muscle weakness and can cause problems with swallowing and breathing. Most ALS cases are sporadic, meaning they occur without a family history, and their causes remain unclear. Growing evidence suggests that cardiovascular disease risk factors, including hypertension (high blood pressure) and diabetes, may influence the risk of developing ALS and its progression.

To explore this potential link, researchers used data from the U.K. Biobank to examine whether ASCVD and cardiovascular health were associated with ALS risk.

The analysis included 502,279 participants with an average age of 56.5 years, and 54.4% were women. A history of ASCVD was identified in 57,805 participants (11.5%), including peripheral artery disease (6.3%), coronary artery disease (5.4%), and ischemic stroke (1.5%). Coronary artery disease involves plaque buildup that narrows or blocks blood flow to the heart. Peripheral artery disease involves narrowed blood vessels that restrict blood flow to the limbs. An ischemic stroke occurs when a blockage reduces blood and oxygen flow to part of the brain.

Cardiovascular health was assessed using the Life’s Essential 8 (LE8) score, which combines eight measures: diet, physical activity, tobacco/nicotine exposure, sleep health, body mass index (BMI), blood fats, blood sugar, and blood pressure. Higher scores indicate better cardiovascular health. Among participants with an LE8 category, 62% had moderate cardiovascular health, 14.1% had high cardiovascular health, and 24% had low cardiovascular health.

During a median follow-up of 13.7 years, 675 participants developed ALS. Those with a history of ASCVD had a 43% higher risk of developing ALS than those without ASCVD. Coronary artery disease was associated with a 53% higher risk, while ischemic stroke was associated with an 82% higher risk. No significant association was found between peripheral artery disease and ALS.

ASCVD history over 5 years tied to higher ALS risk

Compared with participants with no history of ASCVD, ALS risk was 61% higher among those whose first ASCVD event occurred more than five years before the study started. The link was stronger among participants 65 or younger: Those with a history of ASCVD had a 65% higher ALS risk than those without one. No significant association was seen in participants older than 65.

Better cardiovascular health showed the opposite pattern. Participants with the healthiest LE8 scores had a 48% lower ALS risk than those with the poorest scores, with the association seen in participants 65 or younger but not in those older than 65.

Among participants 65 or younger, those with both poor cardiovascular health and a history of ASCVD had about 2.4 times the ALS risk of those with good cardiovascular health and no ASCVD.

A genetic analysis also supported a possible link between ASCVD and ALS. A genetic predisposition to coronary artery disease or ischemic stroke was associated with a small but significant increase in ALS risk. No significant association was found for peripheral artery disease.

In conclusion, “prevalent ASCVD was linked to a higher risk of ALS,” whereas those with both “ASCVD and low or moderate [cardiovascular health] exhibited the highest ALS risk.”

The researchers cautioned that although the cardiovascular health scores reflect potentially modifiable health behaviors and health factors, “whether improving [cardiovascular health] can reduce ALS risk remains uncertain and requires further mechanistic and interventional studies,” they wrote.