Airborne particles and cardiovascular morbidity in severe inherited hypercholesterolemia: Vulnerable endothelium under multiple attacks

Abstract

Despite recent advances in the research related to air pollution and associated adverse cardiovascular events, the combined effects of air pollution, climate change, and SARS‐CoV‐2 infection on cardiovascular health need to be researched further. This Commentary addresses their impacts on cardiovascular health in the approximately 25 million people with a severe form of inherited hypercholesterolemia, called familial hypercholesterolemia (FH). The arterial endothelium in these individuals is potentially under multiple attacks caused by particles of both endogenous and exogenous origin. Thus, they have a lifelong highly elevated level of circulating low density lipoprotein (LDL) cholesterol which drives premature atherosclerosis. The high levels of LDL particles, often associated with an elevated level of circulating lipoprotein(a) particles, are both capable of inducing and maintaining endothelial dysfunction. Such pre‐existing endothelial dysfunction can be exacerbated by exposure to SARS‐CoV‐2 viral particles, by exposure to fine particulate matter generated by climate change‐associated wildfires, and by dehydration during deadly heatwaves linked to the globally rising temperatures. The external factors can severely worsen the pre‐existing endothelial dysfunction, and thereby significantly increase the risk of a cardiovascular event in the exposed FH patients.

Wildfire smoke exposure and cardiovascular disease—should statins be recommended to prevent cardiovascular events?

“…In general, exposure to wildfire smoke has been shown to increase cardiovascular-related health issues such as acute myocardial infarction, cardiovascular mortality, cardiovascular emergency department visits and hospitalization, cardiac arrest, as well as heart failure (16)(17)(18)(19). Especially vulnerable are those individuals who have pre-existing cardiovascular disease who, when exposed to external factors such as wildfire smoke-generated PM 2.5 particles, can severely worsen their pre-existing endothelial dysfunction (20)(21)(22). Even acute exposure to PM 2.5 particle pollution is associated with increased cardiovascular morbidity and mortality (18).…”

“…Additionally, diabetics are at increased risk from PM 2.5 particle exposure because of pre-existing endothelial dysfunction as well as autonomic dysfunction due to diabetic neuropathy ( 20 ). Similarly, we proposed that patients with familial hypercholesterolemia, who have pre-existing endothelial dysfunction from lifelong exposure to elevated LDL-cholesterol levels, are likely to be at increased risk if exposed to PM 2.5 particles ( 22 ). Lastly, the majority of patients presenting with an acute coronary syndrome have endothelial dysfunction, and in a 6-year follow-up study, endothelial dysfunction was an independent significant positive predictive value for major adverse cardiovascular events (hazard ratio 2.04, 95% confidence interval 1.43–2.89, P < 0.001) ( 25 ).…”