The complex interplay between fitness, genetics, lifestyle, and inflammation in the pathogenesis of coronary atherosclerosis: lessons from the Amazon rainforest

Far from only being a modern disease, atherosclerosis has also been reported also in ancient civilizations, as shown in some studies conducted on Mummies from different latitudes. Conventional cardiovascular (CV) risk factors can explain more than 90% of the attributable risk of coronary artery disease (CAD). In this regard, Tsimane Aborigenous of Amazon rainforest, conducting a subsistence lifestyle with low prevalence of CV risk factors, present the lowest reported prevalence of CAD in the world, despite an elevated inflammatory burden. Experimental and clinical studies have supported the theory that other factors, like genetics and inflammation, are involved in atherosclerosis. Indeed, a large clinical randomized study (CANTOS trial) tested the anti-inflammatory properties of canakinumab, and provided the first evidence to support the ‘inflammation hypothesis’. Another field of research, based on Mendelian randomization studies, supports the appealing hypothesis that correcting CV risk factors earlier in life, may prevent or delay the progression of CAD. All these data prove that atherosclerosis is the expression of a complex, dynamic, and continuous interaction between environment and genetics that begins at conception and continues through adulthood.