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Genetica, stile di vita e malattia coronarica

 

E' ormai assodato che fattori genetici contribuiscano al rischio cardiovascolare ed è altrettanto assodato che uno stile di vita non corretto rappresenti un'importante fattore di rischio. È stato dimostrato più volte che la modifica dello stile di vita e cioè astensione dal fumo, controllo dell'obesità, attività fisica regolare e correzione della dieta sia in grado di ridurre il rischio cardiovascolare. Quello che non è ancora chiaro è se gli effetti benefici dello stile di vita corretto siano estrapolabili anche a chi ha una predisposizione genetica alle malattie cardiovascolari. Khera e Coll. si sono accinti all'impresa studiando oltre 55.000 pazienti di quattro studi, di cui tre prospettici e dei quali erano disponibili i genotipi. Dallo studio è emersa la conferma del ruolo predittivo indipendente dei fattori genetici e di quelli comportamentali e, dato di grande interesse pratico, che anche nei portatori di anomalie genetiche che predispongono alla malattia coronarica, uno stile di vita corretto riduce del 50% il rischio.

 


Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease

Khera AV, Emdin CA, Drake I, Natarajan P, Bick AG, Cook NR, Chasman DI, Baber U, Mehran R, Rader DJ, Fuster V, Boerwinkle E, Melander O, Orho-Melander M, Ridker PM, Kathiresan S

New Engl J Med 2016 [Epub ahead of print]

 

BACKGROUND: Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease. The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown.
METHODS: Using a polygenic score of DNA sequence polymorphisms, we quantified genetic risk for coronary artery disease in three prospective cohorts — 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women’s Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) — and in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors: no current smoking, no obesity, regular physical activity, and a healthy diet.
RESULTS: The relative risk of incident coronary events was 91% higher among participants at high genetic risk (top quintile of polygenic scores) than among those at low genetic risk (bottom quintile of polygenic scores) (hazard ratio, 1.91; 95% confidence interval [CI], 1.75 to 2.09). A favorable lifestyle (defined as at least three of the four healthy lifestyle factors) was associated with a substantially lower risk of coronary events than an unfavorable lifestyle (defined as no or only one healthy lifestyle factor), regardless of the genetic risk category. Among participants at high genetic risk, a favorable lifestyle was associated with a 46% lower relative risk of coronary events than an unfavorable lifestyle (hazard ratio, 0.54; 95% CI, 0.47 to 0.63). This finding corresponded to a reduction in the standardized 10-year incidence of coronary events from 10.7% for an unfavorable lifestyle to 5.1% for a favorable lifestyle in ARIC, from 4.6% to 2.0% in WGHS, and from 8.2% to 5.3% in MDCS. In the BioImage Study, a favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category.
CONCLUSIONS: Across four studies involving 55,685 participants, genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. Among participants at high genetic risk, a favorable lifestyle was associated with a nearly 50% lower relative risk of coronary artery disease than was an unfavorable lifestyle.

 

New Engl J Med 2016 [Epub ahead of print]