Aging without atherosclerosis: is it possible?

Introduction Atherosclerosis is considered an almost inevitable consequence of aging and the principal substrate of cardiovascular disease. However, a subset of older individuals remains free of clinically detectable atherosclerosis despite exposure to traditional cardiovascular risk factors. Purpose To identify clinical and biochemical factors associated with the absence of atherosclerosis in an elderly population. Methods Cross-sectional study of 1,831 adults aged 65 years and over. Clinical, biochemical and vascular parameters were compared between participants with and without atherosclerosis using χ² and U-Mann–Whitney test. Multivariable logistic regression was applied to identify independent predictors of atherosclerosis absence. Atherosclerosis was defined as the presence of at least one of the following: coronary artery calcium score (CAC) >0, ankle–brachial index (ABI) ≤0.9, or visible any carotid artery stenosis detected by ultrasound examination. Results 1,737 participants (94.9%) had atherosclerosis and 94 (5.1%) had no evidence of atherosclerosis. Individuals without atherosclerosis were more frequently female (77.7% vs. 58.0%; p<0.001) and were younger (median age 70.5 [68.0–73.0] vs. 74.0 [70.0–78.0] years; p<0.001). Hypertension was less prevalent in the group without atherosclerosis (61.7% vs. 73.2%; p=0.02). In terms of laboratory parameters, participants without atherosclerosis had higher HDL cholesterol (58.0 [46.8–71.0] vs. 53.0 [44.5–63.0] mg/dL; p=0.002), lower glucose (101.3 [92.0–112.0] vs. 106.1 [97.0–120.0] mg/dL; p=0.001), lower HbA1c (5.6 [5.4–5.9] vs. 5.7 [5.5–6.1] %; p=0.004), lower homocysteine (12.4 [10.0-15.2]) vs. 13.2 [11.0-16.1] µmol/L; p=0.01), and lower creatinine levels (0.76 [0.69-0.90] vs. 0.83 [0.70-1.00] mg/dl; p=0.001). Iron concentrations were slightly higher in this group (97.5 [84.0-114.9] vs. 92.0 [74.5-112.0] µg/dl, p=0.03). No significant differences were observed for BMI, LDL cholesterol, triglycerides, inflammatory markers, or blood pressure values. In multivariable logistic regression analysis, independent factors associated with the absence of atherosclerosis were female sex (OR 2.283, 95% CI 1.260–4.137), younger age (OR 0.884 per year, 95% CI 0.827–0.923), higher HDL cholesterol (OR 1.018 per mg/dl, 95% CI 1.002–1.034) and higher iron levels (OR 1.009 per µg/dl, 95% CI 1.003–1.016) (Table 1, Figure 1). Conclusions In this elderly cohort, absence of atherosclerosis was independently associated with female sex, younger age within the studied range, higher HDL cholesterol, and higher iron levels. These findings suggest that aging without clinically detectable atherosclerosis is achievable and linked to a favourable lipid profile and selected biological characteristics. The results support the concept of vascular resilience and highlight the importance of lifelong cardiovascular risk factor optimization to promote healthy vascular aging.