ABC | Volume 111, Nº1, July 2018

Original Article Pereira et al. Genes and coronary artery disease risk Arq Bras Cardiol. 2018; 111(1):50-61 as shown by inter-deciles p values (1st decile: OR = 0.612 (0.439 – 0.853), p = 0.004; 9th decile: OR =0.957 (01.400 – 2.734), p < 0.0001 and last decile: OR = 2.472 (1.755 – 3.482), p < 0.0001) (Figure 2). A logistic regression analysis was performed with GRS quartiles, using the first as the reference category. Results showed an increase in CAD risk with statistical significance across the 2 nd , 3 rd and 4 th quartiles with respective ORs and CIs of 1.372 (1.114 – 1.689), 1.878 (1.522 – 2.317) and 2.588 (2.090 – 3.204), respectively (data not shown). A multivariable predictive model for CAD incorporating GRS quartiles and TRFs is presented in Table 3. The 4 th GRS quartile has intermediate contribution to CAD phenotype – OR = 2.727 (2.162 – 3.439), greater than dyslipidemia – OR = 1.298 (1.023 – 1.646) and hypertension – OR = 2.067 (1.744 – 2.450). The reduced contribution of dyslipidemia on CAD risk may be due to standard use of statins in CAD patients. Extended adjustment for cofounding variables (gender, age, heart rate, PWV, low exercise level, BMI and family history of CAD) revealed modest increases in the OR for TRFs and the 2 nd and 3 rd quartiles of GRS. We used VIF to test for multi-collinearity among the variables included in our GRS adjusted logistic regression model. Tolerance and VIF were respectively > 0.1 and < 10 attesting for no significant collinearity between variables included in the adjustment model. Table 1 – Baseline characteristics of our study population Variables Cases (n = 1566) Controls (n = 1322) p value Age, years 53.3 ± 8.0 52.7 ± 7.8 0.053 Male Gender, n (%) 1238 (79.1%) 1010 (76.4%) 0.087 Dyslipidemia † , n (%) 1398 (89.3) 1103 (83.4) 0.0001 Total Cholesterol, mg/dl 180.0 (154.0 – 213.0) 205.0 (181.0 – 234.0) < 0.0001 LDL, mg/dl 104.6 (82.8 – 128.7) 127.2 (104.7 – 152.3) < 0.0001 HDL, mg/dl 41.0 (35.0 – 49.0) 48.0 (41.0 – 57.0) < 0.0001 Triglycerides, mg/dl 141.0 (102.0 – 210.0) 121.0 (89.0 – 174.0) < 0.0001 Apolipoprotein B, mg/dl 93.9 (75.5 – 113.3) 92.5 (43.0 – 115.8) < 0.0001 Lipoprotein (a), mg/dl 20.4 (9.2 – 62.0) 12.8 (8.8 – 29.3) < 0.0001 Diabetes, n (%) 533 (34.0) 175 (13.2) < 0.0001 Fasting glucose, mg/dl 106.0 (96.0 – 129.0) 99.0 (91.0 – 109.0) < 0.0001 Hypertension, n (%) 1114 (71.1) 700 (53.0) < 0.0001 SBP, mmHg 137.9 ± 20.8 136.2 ± 18.1 0.024 DBP, mmHg 82.6 ± 11.8 83.9 ± 11.1 0.002 Heart rate, bpm 68.8 ± 12.5 72.3 ± 11.5 < 0.0001 PWV, m/s 8.6 ± 1.9 8.3 ± 1.7 < 0.0001 Smoking status • , n (%) 730 (46.6) 309 (23.4) < 0.0001 Level of exercise * , n (%) 573 (36.6) 761 (57.6) < 0.0001 Alcohol, g/day 24.7 ± 49.7 18.2 ± 28.2 < 0.0001 BMI, kg/m 2 28.6 ± 4.2 28.1 ± 4.5 0.007 Waist/Height 0.61 ± 0.06 0.59 ± 0.07 < 0.0001 Family history, n (%) 373 (23.8) 167 (12.6) < 0.0001 Hemoglobin, g/dl 14.6 (13.8 – 15.4) 14.7 (14 – 15.4) 0.001 Leucocytes, 103/µl 7.1 (6 – 8.3) 6.6 (5.6 – 7.8) < 0.0001 Fibrinogen, mg/dl 387 (337 – 444) 361 (315 – 409) < 0.0001 Homocysteine, µmol/L 12.2 (10 – 14.9) 11.4 (9.7 – 13.6) < 0.0001 Hs-CRP, mg/L > 3, n (%) 648 (41.4) 496 (37.5) 0.035 † Controls: LDL > 140 mg/dL, HDL < 40 mg/dL for men and < 45 mg/dLfor women; triglycerides > 150mg/dL, APO B > 100 mg/dL. Cases: LDL > 100 mg/dL; triglycerides > 150 mg/dL, HDL < 40 mg/dL for men and < 45 mg/dL for women;APO B > 100 mg/dL, non HDL > 130 mg/dL; * More than 40 min/week; • Current smokers or < 5 years of cessation; HDL: high density lipoprotein; LDL: low density lipoprotein; SBP: systolic blood pressure; DBP: diastolic blood pressure; PWV: pulse wave velocity; BMI: body mass index; Hs-CRP: high sensitivity C-reactive protein. Categorical variables compared by the Chi-square test. Continuous variables expressed as mean ± standard deviation (using Student’s t-test) and biochemical variables as median (1st quartile – 3rd quartile) (using Mann-Whitney’s test). Statistical significance: p < 0.05. 53

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