Table 5.
Main characteristics and results of studies assessing improvement of predictive capacity of classical cardiovascular risk functions after inclusion of genetic information
| Author | Population | Clinical outcome | Genetic variants | Other covariates
|
Results
|
||||
|---|---|---|---|---|---|---|---|---|---|
| Risk factors | Family history | Association | Discrimination | NRI | Clinical NRI | ||||
| Case-control | |||||||||
| Davies et al105 | OHGS3,323Ca/2,319 Co WTCC: 1,926 Ca/2,938 Co |
CAD | One SNP(9p21) 12 SNPs (related and unrelated CVRF) |
Yes | No | NR | ΔAUC 0.003 ΔAUC 0.008‡ |
– | – |
| Anderson et al106 | Patients undergoing coronary angiography: 1,086 Ca/482 Co | CAD | 5 SNPs (related and unrelated CVRF) | Yes | Yes | OR 1.24‡ | ΔAUC 0.008 | 16.0%‡ | 28.3%‡ |
| Qi et al107 | Hispanic: 1,989 Ca/2,096 Co | Ml | 3 SNPs (related and unrelated CVFR) | Yes | No | OR 1.18‡ | ΔAUC 0.010‡ | – | – |
| Qi et al108 | Type II DM patients: 1,076 Ca/1,430 Co |
CAD | 5 SNPs (related and unrelated CVRF) | Yes | No | OR 1.19‡ | – | – | |
| Lv et al105 | Chinese Han population: 1,007 Ca/889 Co | CAD | 8 SNPs (related and unrelated CVRF) | Yes | No | OR 1.28‡ | ΔAUC 0.022‡ | – | – |
| Patel et al110 | US population: 1,338 Ca/1,649 Co (>70 years) | Ml <70 years | 11 SNPs | Yes | Yes | OR 1.12‡ | ΔAUC 0.012‡ | – | – |
| Case-cohort | |||||||||
| Hughes et al111 | Middle-aged men, European general population 632 Ca/1,361 subcohort |
CAD | 11 SNPs + two haplotypes 11 SNPs + 4 SNPs (unrelated CVRF) |
Yes Yes |
No No |
NR NR |
ΔAUC 0.009 ΔAUC 0.011‡ |
7.5%‡ 6.5%‡ |
6.3% 5.1% |
| Vaarhorst et al112 | European general population 742 Ca/2,22l subcohort | 12.1 years follow-up, CAD | 29 SNPs (unrelated CVRF) | Yes | No | HR 1.12‡ | 2.8%‡ | NR | |
| Cohort | |||||||||
| Morrison et al113 | ARIC, US general population 13,907 | 13 years follow-up, 1,452 CAD | 10 SNPs – White population 11 SNPs – Black population |
Yes | No | HR 1.10‡ HR 1.20‡ |
ΔAUC 0.002 ΔAUC 0.011‡ |
NR | NR |
| Kathiresan et al114 | Malmö, European general population, 4,232 | 10.6 years follow-up, 238 CVD | 9 SNPs, lipid-related | Yes | No | HR 1.15‡ | ΔAUC 0.003 | – | – |
| Talmud et al115 | NPHS-II, UK middle-aged men, 2,742 | 15 years follow-up, 270 CAD | 1 SNP(9p21) | Yes | Yes | AA versus AG 1.38‡ AA versus GG 1.57‡ |
ΔAUC 0.02 | 13.8%‡ | NR |
| Brautbar et al116 | ARIC, US general population (Whites), 9,998 | 14.6 years follow-up, 1,349 CAD | 1 SNP(9p21) | Yes | No | HR 1.20‡ | ΔAUC 0.004‡ | 0.8% | 6.2‡ |
| Paynter et al117 | WGHS, US middle-aged White women, 22,192 |
10.2 years follow-up, 1,349 CVD | 1 SNP(9p21) | Yes | Yes | AA versus AG 1.25‡ AA versus GG 1.32‡ |
ΔAUC 0.002 | Framingham, 2.7% Reynolds, 0.2% |
NR |
| Paynter et al118 | WGHS, US White women, 19,313 | 12.3 years follow-up, 777 CVD | 101 SNPs 12 SNPs (related and unrelated CVRF) |
Yes | Yes | HR 1.00 HR 1.04 |
ΔAUC 0.000 ΔAUC 0.001 |
0.5% 0.5% |
NR |
| Ripatti et al119 | General European population, 30,725 | 10.7 years follow-up, 1,264 CHD | 13 SNPs (related and unrelated CVRF) | Yes | Yes | HR 1.66(Q5 versus Q1)‡ | ΔAUC 0.001 | 2.2% | 9.7%‡ |
| Shiffman et al120 | CHS, US old population (>65 years), 4,284 | 12.6 years follow-up, Ml | 1 SNP(9p2l) 1 SNP(KIF6719 Arg) carriers |
Yes | No | HR 1.22 (White men)‡ HR 1.16 (White women)‡ HR NR (Black men)HR 1.42 (White men)‡ HR 1.05 (White women) |
ΔAUC 0.005 ΔAUC 0.002 ΔAUC 0.034 ΔAUC 0.015‡ ΔAUC −0.001 |
2.1% −1.8% 18.2%‡ 2.7% 0.7% |
|
| Thanassoulis et al121 | Framingham, US general population, 3,014 | 11 years follow-up, 182 hard CHD | 13 SNPs (related and unrelated CVRF) | Yes | Yes | HR 1.07‡ | ΔAUC 0.002 | 19.0%‡ | NR |
| Lluis-Ganella et al122 | General population, Framingham 3,537 + REGICOR 2,351 |
11.9 years follow-up, 536 CHD | 8 SNPs (unrelated CVRF) | Yes | Yes | HR 1.13‡ | ΔAUC No | 6.4% | 17.4%‡ |
| Gransbo et al123 | Malmö, 24,777 | 11.7 years follow-up, 2,668 CVD | 9p21 variant | Yes | No | HR 1.17‡ | ΔAUC 0.001 | 1.2%‡ | – |
| Isaacs et al124 | Erasmus Family study 2,269 + Rotterdam Study 8,130 | 9.5 years follow-up, 924 CHD | Lipid-related GRS | Yes | No | GRSTC HR 1.09‡ GRSLDL HR 1.08‡ GRSHDL HR 0.99 GRSTG HR 1.04 |
ΔAUC 0.000 | – | – |
| Ganna et al125 | 6 Swedish cohorts, 10,612 | 781 CHD | GRSglobal, 395 GRSCHD, 46 |
Yes | No | HR 1.54‡ HR 1.52‡ |
ΔAUC 0.002 ΔAUC 0.004‡ |
4.2%‡ 4.9%‡ |
– |
| Tikkanen et al126 | 4 Finnish cohorts, 24,124 | 12 years follow-up, 1,093 CHD | 28 SNPs (related and unrelated CVRF) | Yes | Yes | HR 1.27‡ | ΔAUC 0.003‡ | 5.0%‡ | 27.0%‡ |
Notes:
‡
P-value<0.05.
Abbreviations: ARIC, Atherosclerosis Risk in Communities study; CAD, coronary artery disease; Ml, myocardial infarction; CVD, cardiovascular disease; OHGS, Ottawa Heart Genomics Study; WTCCC, Wellcome Trust Case Control Consortium; Ca, Cases; Co, Controls; DM, diabetes mellitus; NPHS-11: Northwick Park Heart Study 11; WGHS, Women Genome Health Study; CHS, Cardiac Health Study; REGICOR, Registre Gironi del Cor (Girona Heart Registry); OR, odds ratio; HR, hazard ratio; NR, not reported; AUC, area under the receiver operating curve; NRI, Net Reclassification Index; CVRF, cardiovascular risk factors; GRS, genetic risk score; SNP, single nucleotide polymorphism.