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. 2013 Sep;33(9):2261-6.
doi: 10.1161/ATVBAHA.112.301120. Epub 2013 Apr 18.

Genetic risk prediction and a 2-stage risk screening strategy for coronary heart disease

Emmi Tikkanen  1 , Aki S Havulinna, Aarno Palotie, Veikko Salomaa, Samuli Ripatti
Affiliations

Genetic risk prediction and a 2-stage risk screening strategy for coronary heart disease

Emmi Tikkanen et al. Arterioscler Thromb Vasc Biol. 2013 Sep.

Abstract

Objective: Genome-wide association studies have identified several genetic variants associated with coronary heart disease (CHD). The aim of this study was to evaluate the genetic risk discrimination and reclassification and apply the results for a 2-stage population risk screening strategy for CHD.

Approach and results: We genotyped 28 genetic variants in 24 124 participants in 4 Finnish population-based, prospective cohorts (recruitment years 1992-2002). We constructed a multilocus genetic risk score and evaluated its association with incident cardiovascular disease events. During the median follow-up time of 12 years (interquartile range 8.75-15.25 years), we observed 1093 CHD, 1552 cardiovascular disease, and 731 acute coronary syndrome events. Adding genetic information to conventional risk factors and family history improved risk discrimination of CHD (C-index 0.856 versus 0.851; P=0.0002) and other end points (cardiovascular disease: C-index 0.840 versus 0.837, P=0.0004; acute coronary syndrome: C-index 0.859 versus 0.855, P=0.001). In a standard population of 100 000 individuals, additional genetic screening of subjects at intermediate risk for CHD would reclassify 2144 subjects (12%) into high-risk category. Statin allocation for these subjects is estimated to prevent 135 CHD cases over 14 years. Similar results were obtained by external validation, where the effects were estimated from a training data set and applied for a test data set.

Conclusions: Genetic risk score improves risk prediction of CHD and helps to identify individuals at high risk for the first CHD event. Genetic screening for individuals at intermediate cardiovascular risk could help to prevent future cases through better targeting of statins.

Keywords: cardiovascular genomics; genetic association; genetic epidemiology; risk factor; risk prediction.

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Figures

Figure 1
Figure 1
Genetic risk score deciles and risk for coronary heart disease. The middle deciles (40%–60%) were used as a reference group.
Figure 2
Figure 2
Changes in C-index in FINRISK cohorts when adding 1) family history of cardiovascular disease and 2) the genetic risk score to the model. The reference model with the traditional risk factors had the C index of 0.849 for CHD, 0.835 for CVD and 0.853 for ACS
Figure 3
Figure 3
Two-stage risk screening of coronary heart disease in a standard population of 100,000 subjects. * Based on guidelines , , the subjects at intermediate risk group (10–20%) are assumed to not receive statin treatment. Statins are currently allocated for the subjects at ≥20% risk group. In addition, subjects with baseline lipid treatment and/or diabetes were assumed treated.
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References

    1. Musunuru K, Kathiresan S. Genetics of coronary artery disease. Annu Rev Genomics Hum Genet. 2011;11:91–108. - PubMed
    1. Schunkert H, Konig IR, Kathiresan S, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011;43:333–338. - PMC - PubMed
    1. Coronary Artery Disease (C4D) Genetics Consortium A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat Genet. 2011;43:339–344. - PubMed
    1. Ripatti S, Tikkanen E, Orho-Melander M, et al. A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses. The Lancet. 2010;376:1393–1400. - PMC - PubMed
    1. Thanassoulis G, Peloso GM, Pencina MJ, Hoffmann U, Fox CS, Cupples LA, Levy D, D’Agostino RB, Hwang SJ, O’Donnell CJ. A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study. Circ Cardiovasc Genet. 2012;5:113–121. - PMC - PubMed

MATERIAL AND METHODS REFERENCES

    1. Vartiainen E, Laatikainen T, Peltonen M, Juolevi A, Mannisto S, Sundvall J, Jousilahti P, Salomaa V, Valsta L, Puska P. Thirty-five-year trends in cardiovascular risk factors in Finland. Int J Epidemiol. 2010;39:504–518. - PubMed
    1. Kattainen A, Salomaa V, Harkanen T, Jula A, Kaaja R, Kesaniemi YA, Kahonen M, Moilanen L, Nieminen MS, Aromaa A, Reunanen A. Coronary heart disease: from a disease of middle-aged men in the late 1970s to a disease of elderly women in the 2000s. Eur Heart J. 2006;27:296–301. - PubMed
    1. National Public Health Institute Methodology report. Health 2000 survey. http://www.terveys2000.fi/doc/methodologyrep.pdf.
    1. Mähönen M, Jula A, Harald K, Antikainen R, Tuomilehto J, Zeller T, Blankenberg S, Salomaa V. The validity of heart failure diagnoses obtained from administrative registers. Eur J Prev Cardiol. 2013;20:254–259. - PubMed
    1. Pajunen P, Koukkunen H, Ketonen M, et al. The validity of the Finnish Hospital Discharge Register and Causes of Death Register data on coronary heart disease. Eur J Cardiovasc Prev Rehabil. 2005;12:132–137. - PubMed

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