Women, polysubstance users at highest risk for early-onset CV events

Alcohol, tobacco, and illicit drug use were associated with a high risk of premature atherosclerotic cardiovascular disease (ASCVD) among younger adults, with women facing the greatest risk, according to results from a retrospective cross-sectional analysis of Veterans Affairs Healthcare data.

Recent epidemiological data demonstrate an increase in all major realms of ASCVD — including ischemic heart disease, ischemic cerebrovascular disease, and peripheral arterial disease — among young and middle-aged adults, Salim S. Virani, MD, PhD, FACC, FAHA, FASCP, of the Section of Cardiovascular Research in the Department of Medicine at Baylor College of Medicine in Houston, and colleagues explained in the journal Heart. And, while this upsurge is primarily blamed on “the global epidemic of metabolic syndrome,” Virani and colleagues noted that “the attributable risk of recreational substances among young adults remains incompletely evaluated.”

Virani and colleagues conducted their analysis in order to evaluate the association of all recreational substances with premature (first ASCVD event at age <55 years for men and <65 years for women) and extremely premature ASCVD (first ASCVD event at age <40 years for men and women).

“We have shown that, compared with patients with non- premature ASCVD, patients with premature and extremely premature ASCVD had a higher prevalence of all recreational substance use,” the study authors reported. “The use of all forms of recreational substances was independently associated with ~1.5–2 times higher likelihood of premature and extremely premature ASCVD. Illicit drug use was associated with ~3 times higher likelihood of both premature and extremely premature ASCVD. Among all illicit drugs, amphetamines and cannabis had the greatest odds of early-onset ASCVD. A graded response relationship exists between increasing number of substances used and higher likelihood of early- onset ASCVD. Finally, we highlight that female users of recreational substances have a greater risk of premature and extremely premature ASCVD compared with their male counterparts.”

In an editorial accompanying the study, Matthew L. Scott, PhD, Kevin S. Murnane, PhD, and Anthony Wayne Orr, PhD, of Louisiana State University Health Shreveport, Louisiana, noted that while the study by Virani et al demonstrates the association between substance use disorder and early-onset ASCVD, “the effect of substance use frequency, dose, and duration cannot be reliably ascertained in this patient sample.” They added that prospective studies should attempt to acquire specific patient reports regarding substance use and current cardiovascular function to “allow for much more detailed risk assessments and disease modelling,” which could eventually be integrated with mechanistic data “to provide a more complete understanding of the risk posed by various non-medical or prescribed substances.”

For their cross-sectional analysis, Virani and colleagues pulled data from the 2014-2015 nationwide Veterans Affairs Healthcare database and the Veterans with premaTure AtheroscLerosis (VITAL) registry. Patients with premature ASCVD (n=135,703; mean [SD] age 49.63 [5.79]; 116,739 [86.1%] male) — including extremely premature ASCVD (n=7,716) — were compared against patients with non-premature ASCVD (first ASCVD event at age ≥55 for men and ≥65 for women; n=1,112,455; mean [SD] age 69.58 [8.92]; 1,104,319 [99.3%] male), with the study authors using multivariable logistic regression models to study the independent association of recreational substances including tobacco, alcohol, and illicit drugs (cocaine, amphetamines, cannabis, and other drugs) with premature and extremely premature ASCVD.

The study authors found that, compared with non-premature ASCVD patients, patients with premature ASCVD had a higher incidence of use of tobacco (62.9% versus 40.6%), alcohol (31.8% versus 14.8%), cocaine (12.9% versus 2.5%), amphetamine (2.9% versus0.5%) and cannabis (12.5% versus 2.7%) (P<0.01 for all comparisons).

“In adjusted models, the use of tobacco ([odds ratio] OR 1.97, 95% CI 1.94 to 2.00), alcohol (OR 1.50, 95% CI 1.47 to 1.52), cocaine (OR 2.44, 95% CI 2.38 to 2.50), amphetamine (OR 2.74, 95% CI 2.62-2.87), cannabis (OR 2.65, 95% CI 2.59-2.71) and other drugs (OR 2.53, 95% CI 2.47-2.59) was independently associated with premature ASCVD,” they wrote.

And, notably, patients with polysubstance use were more likely to have premature ASCVD, they added: “The likelihood of premature ASCVD increased in a graded response manner with increasing number of recreational substances used: use of only 1 substance (OR 2.05, 95% CI 2.02-2.08), only 2 substances (OR 3.45, 95% CI 3.38-3.52), only 3 substances (OR 6.38, 95% CI 6.18-6.58), and ≥4 substances (OR 8.85, 95% CI 8.63-9.08).”

The combined use of cannabis and amphetamine was associated with the highest likelihood of extremely premature ASCVD (OR 7.20, 95% CI 6.15-8.43). And, the authors noted, “Gender interactions with substance use were significant (P-interaction <0.05), with recreational substance use and premature ASCVD showing stronger associations among women than in men with premature ASCVD.”

Virani and colleagues suggested that the increased risk for early-onset ASCVD among women may stem from gender-based disparities in the screening and prevention of substance abuse disorders, which may “hinder appropriate screening and surfacing of the true prevalence of substance use among women.” However, while editorialists Scott, Murnane, and Orr acknowledged this disparity as worrisome, they argued that the differences in age definitions for men and women with premature ASCVD and limitations in the inclusion of women in the VITAL registry make it difficult to discern the true degree of enhanced risk.

“For instance, this study included a total of 1,112,445 patients with non-premature ASCVD, but only 0.7% (n=8137) of those patients were female,” they wrote. “Although the sample size is small, the study demonstrates a clear trend for increased incidence of early-onset ASCVD-related events in women with substance use disorder. However, it should be noted that polysubstance abuse may be more common in men than in women, which may lead to complicated interaction between sex and individual substance use patterns.”

Virani and colleagues acknowledged their predominantly white male cohort as a limitation to their analysis. Other limitations included a lack of patient socioeconomic data, a lack of differentiation between smoking and smokeless tobacco, not accounting for patients taking medically prescribed amphetamines, and not identifying patients with myocardial infarction without obstructive coronary disease.

Despite these limitations, the study authors argued that their findings “support the need for aggressive interventions in implementation and accessibility of drug cessation programs as another key element of the primary prevention of ASCVD.”

Scott, Murnane, and Orr agreed, adding that the results of this and other analyses suggest “the need for a nationwide education campaign on the potential long-term damage being done to the cardiovascular system in patients with substance use disorders. These individuals should be aware of the long- term risk of chronic debilitating ASCVD beyond the acute risk of overdose. In addition, clinicians and primary care providers should begin screening their adult and young adult patients with a history of a substance use disorder for symptoms of premature or extremely premature ASCVDs at earlier stages in their patients’ lives.

“We are only young once, and we should do everything in our power to maintain that state as long as we can,” they added.

  1. Alcohol, tobacco, and illicit drug use were all independently associated with a high risk of premature and extremely premature atherosclerotic cardiovascular disease (ASCVD) among younger adults, according to results from a VA study.

  2. Women and patients who used four or more substances were at the highest risk for early-onset ASCVD, and combined use of cannabis and amphetamine was associated with the greatest risk of extremely premature ASCVD (first ASCVD event before age 40).

John McKenna, Associate Editor, BreakingMED™

This study was supported by a Department of Veterans Affairs Health Services Research & Development Service Investigator Initiated Grant (IIR 16–072), an American Heart Association Beginning Grant- in- Aid (14BGIA20460366), the American Diabetes Association Clinical Science and Epidemiology award (1-14- CE-44), and the Houston VA Health Services Research & Development Center for Innovations grant (CIN13-413).

Coauthor Khurram serves on the advisory board of Medicines company and Regeneron. Coauthor Ballantyne reported grant/research support from Akcea, Amgen, Esperion, Novartis, Regeneron, Sanofi-Synthelabo, NIH, AHA, and AD, and serving as a consultant for Abbott Diagnostics, Akcea, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Denka Seiken, Esperion, Intercept, Matinas BioPharma, Merck, Novartis, Regeneron, and Sanofi-Synthelabo.

Virani reported being the Associate Editor for Innovations for the American College of Cardiology, as well as being on the steering committee for the PALM registry at the Duke Clinical Research Institute.

Scott, Murnane, and Orr had no relationships to disclose.

Cat ID: 138

Topic ID: 85,138,730,102,914,138,139,144,146,925