Association between high versus low cardiovascular risk in individuals with corresponding unexpected absent versus severe subclinical coronary atherosclerosis, a nationwide, multicenter study

Abstract Background It remains unclear as to why some individuals at low risk of cardiovascular disease (CVD) develop severe coronary atherosclerosis, while those at high CVD risk may remain free from coronary atherosclerosis. Purpose Using Coronary Computed Tomography Angiography (CCTA), we aimed to identify factors associated with absence and severe coronary atherosclerosis in subjects from the general population with very high and low-moderate CVD risk, respectively. Methods We assessed cross-sectionally a nationwide, multicenter population-based cohort, consisting of 30,154 individuals randomly recruited from the general population (age range 50-64 years, 51.4% women). Coronary calcified plaque burden was estimated by coronary artery calcium score (CACS) assessed by CCTA. Absent coronary atherosclerosis was defined as CACS 0 and severe coronary atherosclerosis was defined as CACS ≥301. We investigated only individuals with low-moderate (<5%) and very high CVD risk (≥10%) according to SCORE2 were included. Individuals with CACS 0 and prevalent CVD were excluded, as well as those with moderate CACS (1-300) or SCORE2 risk 5-9%. Out of 26 722 subjects with complete data on CACS and SCORE2, 13 075 were included. Logistic regression was performed adjusted for age and sex. Results The overall distribution of CACS in relation to SCORE2 CVD risk is illustrated in the Figure. Study characteristics are displayed in Table 1. Severe-extensive CACS in combination with low-moderate CVD risk was present in 2.3% (n=296). A further 2.3% (n=311) had very high CVD risk but CACS 0. Factors associated with CACS 0 despite a very-high estimated CVD risk included: lower age, being female, being born in Sweden, not having hypertension or hyperlipidemia, fewer pack-years of smoking, and lower waist circumference in men. On the contrary, severe-extensive CACS despite a low-moderate estimated CVD risk was associated with higher age, being male, being an ex-smoker, reporting more pack-years of smoking, having higher HbA1c, higher BMI, higher waist circumference, and prevalent hyperlipidemia and hypertension (Table 2). Conclusions We identified extreme cardiovascular risk phenotypes (subgroups) in the general population that either lacked coronary calcifications despite being at very high estimated CVD risk or had severe subclinical coronary atherosclerosis despite being at estimated low-moderate CVD risk. Further studies are warranted to elucidate putative enhancing or protective mechanisms explaining this unexpected phenomenon.