*2.2.5 High sensitivity C-reactive protein*

Hs-CRP is a marker of inflammation and endothelial dysfunction and subsequent atherosclerosis. It is produced by hepatocytes in response to circulating cytokines, particularly IL-6.18. It is also a robust downstream marker of inflammation, although unlikely to have a causative role in CVD. Consequently, the relationship between elevated hs-CRP and ASCVD risk remains a matter of controversy. The merit of hs-CRP use is because it does require neither sophisticated equipment nor particular operator skills, especially in developing countries. The hs-CRP, which is incorporated in the Reynolds score, may provide supplemental predictive capacity compared with the FRS [38]. Moreover, the 2013 ACC/AHA guidelines on the assessment of CV risk recommend hs-PCR in men (>50 y) and in women (>60 y) at intermediate risk, which are qualified for lipid lowering drugs [39]. In this regard, many studies reported a robust association of hs-CRP with numerous traditional risk factors for CHD such as obesity, diabetes, physical inactivity, smoking, and alcohol use [40–42]. Other studies highlighted the modest relationship between hs-CRP and CVD, because of its variability among age, gender (higher magnitude in men), and ethnicity (higher magnitude in African Americans vs. Caucasians) [43, 44]. A study comprised of aircrew from both African and Caucasian origin reported a net reclassified global ASCVD risk based on 2018 ESC/ESH guidelines chiefly in intermediate risk hypertensive individuals [40].

## *2.2.6 Coronary artery calcium*

Coronary artery calcium (CAC) a powerful novel risk indicator for ASCVD risk. It is linked with an enhanced risk to develop harmful cardiovascular events independently of clinical markers and inflammatory biomarkers [45]. Conversely, a calcium artery score of 0 has a strong negative predictive value for the development of coronary artery diseases (CAD).
