简介:AbstractThe developmental origins of health and disease theory states that environmental stresses during the early stages of life influence health and risk of developing non-communicable diseases throughout the lifespan of an individual. Developmental plasticity is thought to be a possible underlying mechanism. Here, I discuss a contrasting but complementary genetic hypothesis regarding the developmental origins of health and disease theory: crosstalk between the genomes of the parents and offspring is responsible for shaping and adapting responses to environmental stresses, regulating early growth and predisposition to non-communicable diseases. Genetic variants that are beneficial in terms of responses to early life stresses may have pleiotropic detrimental effects on health later in life, which may change the allele frequencies driven by selection on a population level. Genetic studies on the cohort of children born after assisted reproduction could provide insight regarding the genetic mechanisms of the developmental origins of health and disease theory.
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简介:AbstractDespite overwhelming evidence from large randomized clinical trials supporting a clear benefit of low-density lipoprotein cholesterol (LDL-C) lowering therapy on the primary and secondary prevention of atherosclerotic cardiovascular disease, data from epidemiological and clinical observations demonstrated an increased incidence of hemorrhagic stroke in patients with low LDL-C exposure (<70 mg/dL), especially among East Asians. Meanwhile, emerging studies have reported a paradoxical phenomenon in which hypercholesterolemia is associated with better short-term outcomes in acute coronary syndrome patients, the "lipid paradox." The underlying mechanism for these two closely connected clinical observations is not clear. This review aimed to summarize the evolution and clinical implications of these two low LDL-C related concepts, and proposed a "double-hit" hypothesis that may help explain these phenomena. It is worth noting that in the era of increasing use of high-intensity LDL-C lowering and dual antiplatelet strategies in atherosclerotic cardiovascular disease in patients receiving percutaneous coronary intervention, balancing the risk of thrombosis with bleeding complication should be a priority in clinical practice. Our hypothesis may raise clinicians’ awareness to identify potential high risk patients with low LDL-C (<70 mg/dL), especially among East Asians.