Key result
Premature ASCVD affects ~48% of patients and is linked to smoking, dyslipidemia, and family history.
Why the study?
Premature ASCVD is a growing concern with unclear distinctions between it as a unique entity or an earlier manifestation of shared risk exposures in high-risk regions.
What is the clinical and risk-factor profile of premature ASCVD compared to later-onset ASCVD in a Middle Eastern cohort?
Cross-Sectional (n=2,763)
Yes
What is the clinical and risk-factor profile of premature ASCVD compared to later-onset ASCVD in a Middle Eastern cohort?
In a Middle Eastern cohort, premature ASCVD is disproportionately driven by smoking, family history, and atherogenic dyslipidemia, whereas later-onset ASCVD is more strongly associated with the accumulation of comorbidities like hypertension and diabetes.
Background: Premature atherosclerotic cardiovascular disease (ASCVD) represents a growing clinical and public health concern, particularly in regions with a high burden of modifiable risk factors. Whether premature ASCVD reflects a distinct pathophysiological entity or an earlier manifestation of shared risk exposures remains incompletely understood. This study aimed to characterize the clinical profile of premature ASCVD and to examine its relationship with conventional cardiovascular risk factors within a Middle Eastern cohort. Methods: This pooled observational analysis included 2763 adults with established ASCVD derived from multiple cardiovascular registries and a prospective cohort. Premature ASCVD was defined using sex-specific age thresholds (<55 years in men and <65 years in women). Multivariable logistic regression analyses, including sex-stratified models, were performed to evaluate associations between premature presentation and cardiovascular risk factors, including smoking, family history, lipid parameters, and cardiometabolic comorbidities. Results: Among 2763 participants in the pooled clinical cohort, 1335 (48.3%) met the study definition of premature ASCVD. Compared with later-onset disease, premature ASCVD was strongly associated with current smoking, family history of premature cardiovascular disease, and a more atherogenic lipid profile, including higher levels of low-density lipoprotein cholesterol, triglycerides, and non-high-density lipoprotein cholesterol. In contrast, later-onset ASCVD was characterized by a higher prevalence of hypertension and diabetes mellitus. These patterns were consistent across sex-stratified analyses. Despite high rates of secondary prevention therapy use, a substantial residual atherogenic burden was observed among patients with premature ASCVD. Conclusions: In this predominantly coronary cohort, the findings suggest that premature and later-onset ASCVD occur within a broadly overlapping risk-factor landscape, but that the relative distribution of these factors differs according to age at first clinical presentation. The greater prevalence of smoking, family history, and atherogenic lipid abnormalities among younger patients may reflect earlier or greater exposure to these factors, whereas the greater burden of hypertension, diabetes mellitus, and other chronic comorbidities among older patients is consistent with their progressive accumulation with age. These cross-sectional associations should not be interpreted as demonstrating distinct causal mechanisms or age-independent risk profiles.
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Alkouri et al. (2026) conducted a cross-sectional in Atherosclerotic cardiovascular disease (ASCVD) (n=2,763). Premature ASCVD (<55 years in men, <65 years in women) vs. Later-onset ASCVD was evaluated on Cardiovascular risk factor profiles. Premature ASCVD (present in 48.3% of patients) was strongly associated with current smoking, family history, and an atherogenic lipid profile compared to later-onset disease.
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