In 2019, cardiovascular disease accounted for 1/3  (17.9 million) deaths in the world, with the majority of them (85%) resulting from ischemic heart disease and stroke (Figure 1). These two acute types of cardiovascular disease are caused by occlusion of blood vessels in the heart/brain, which cuts off blood supply to these regions. The most common underlying reason of this blood flow restriction is atherosclerosis.

Atherosclerosis is a chronic inflammatory process that involves the accumulation of lipid particles within the vessel walls across the vascular tree (primarily heart, brain, lower limb), which results in acute atherosclerotic cardiovascular disease (ASCVD) events, such as heart attack and stroke.

Certain risk factors have been identified as associated with increased susceptibility to the development of atherosclerosis (Figure 2).

Non-modifiable factors include:

• age – the risk of atherosclerosis naturally increases with age as the vascular tree is exposed to risk factors for a longer time;
• sex– men and women experience ASCVD differently (before the age of 80, men are more likely to have a heart attack compared to women, but the trend reverses after 80 y.o.; at the same time, women are more likely to experience a stroke compared to men, even in younger age groups). This observation can be partially explained by different exposure of men vs women to some of the modifiable atherosclerosis risk factors (e.g. in some populations men are more likely to smoke, develop type 2 diabetes, and hypertension compared to women) or inherent differences between the sexes (hormones). However, a lot of cardiovascular events in younger women (15-20%) occur in the absence of known risk factors, which warrants future research.
• ethnicity – some ethnicities experience a higher burden of type 2 diabetes and hypertension, which might affect increase their risk of ASCVD compared to the general population;
• genetic factors – history of a cardiovascular event (heart attack/stroke in parents or siblings) increases individual risk of atherosclerosis and should be accounted for by healthcare providers

Modifiable risk factors can be further divided into 3 groups:

1. Metabolic 

• high blood pressure
• high body-mass index
• diabetes
• kidney dysfunction
• high LDL cholesterol

2. Behavioral

• Diet
• Smoking
• Alcohol consumption
• Low physical activity

3. Environmental

• Air pollution
• Stress

All these factors can be addressed/changed by targeted health behavior interventions, which will be discussed further in the “Prevention, diagnosis, and treatment of atherosclerosis” section of this chapter. 

Section summary

Atherosclerosis, a leading cause of mortality globally, remains a concern despite advancements in research and treatment approaches. Currently, the majority of cardiovascular deaths occur in low/middle-income countries, which highlights the importance of effective primary and secondary prevention strategies, access to healthcare, education, and other social determinants of health. Multiple risk factors have been identified as associated with atherosclerosis, While modifiable factors (diet, smoking, physical activity, etc)  can be changed by behavioral interventions, non-modifiable factors (sex, genetics, ethnicity) should be considered in research and treatment strategies.

References

• https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
• https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(20)30117-0/fulltext#section-3d6acba1-acea-4be2-8dc9-b7e14e5b6583
• https://www.sciencedirect.com/science/article/pii/S0735109720377755?via%3Dihub
• https://www.mdpi.com/1422-0067/23/6/3346
• https://www.nature.com/articles/s41574-022-00746-8

Review questions