Table 2. Associations of Risk Factors and Biomarkers With Incident CHD by Age at Onset.
| Clinical risk factorsa | Incident CHD, adjusted HR (95% CI) | P value for interactionb | |||
|---|---|---|---|---|---|
| At age <55 y | At 55 to <65 y | At 65 to <75 y | At age ≥75 y | ||
| BMI, per SD increment | 1.47 (1.24-1.74) | 1.40 (1.29-1.51) | 1.33 (1.24-1.42) | 1.12 (1.01-1.24) | .002 |
| BMI categories | |||||
| Overweight (25.0 to <30.0) | 2.13 (1.10-4.14) | 1.78 (1.39-2.28) | 1.78 (1.48-2.14) | 1.12 (0.91-1.39) | .004 |
| Obese (≥30.0) | 4.33 (2.31-8.11) | 2.76 (2.15-3.55) | 2.14 (1.74-2.62) | 1.32 (1.02-1.71) | <.001 |
| Current smoker | 3.92 (2.32-6.63) | 2.97 (2.37-3.71) | 1.89 (1.54-2.32) | 1.89 (1.42 - 2.52) | .003 |
| Diabetes | 10.71 (5.57-20.60) | 10.92 (8.44-14.13) | 4.49 (3.46-5.83) | 3.47 (2.47-4.87) | <.001 |
| Metabolic syndrome | 6.09 (3.60-10.29) | 4.45 (3.62-5.47) | 2.82 (2.40-3.30) | 1.79 (1.48-2.17) | <.001 |
| Hypertension | 4.58 (2.76-7.60) | 2.38 (1.93-2.94) | 2.06 (1.76-2.43) | 1.64 (1.36-1.98) | <.001 |
| Systolic BP, per SD increment, mm Hg | 2.24 (1.84-2.74) | 1.61 (1.48-1.76) | 1.48 (1.38-1.59) | 1.26 (1.15-1.37) | <.001 |
| Physical inactivityc | 1.53 (0.92-2.55) | 1.59 (1.30-1.96) | 1.43 (1.22-1.67) | 1.21 (1.00-1.46) | .25 |
| Parental MI at age <60 y | 2.19 (1.26-3.81) | 2.07 (1.64-2.61) | 1.60 (1.31-1.96) | 1.18 (0.88-1.57) | .02 |
| Lipids and lipoproteins, per SD increment | |||||
| Cholesterol | |||||
| Total | 1.39 (1.12-1.73) | 1.43 (1.32-1.56) | 1.24 (1.16-1.34) | 1.12 (1.02-1.22) | <.001 |
| LDL | 1.38 (1.10-1.74) | 1.44 (1.31-1.57) | 1.24 (1.16-1.34) | 1.12 (1.02-1.22) | .001 |
| HDL | 0.39 (0.27-0.55) | 0.50 (0.44-0.56) | 0.61 (0.56-0.67) | 0.77 (0.70-0.86) | <.001 |
| Total/HDL cholesterol ratio | 2.40 (1.90-3.05) | 2.21 (2.01-2.43) | 1.76 (1.63-1.91) | 1.40 (1.27-1.55) | <.001 |
| Triglycerides | 2.14 (1.72-2.67) | 1.80 (1.64-1.97) | 1.61 (1.49-1.74) | 1.30 (1.18-1.43) | <.001 |
| Triglyceride/HDL cholesterol ratio | 2.27 (1.83-2.81) | 1.92 (1.75-2.10) | 1.69 (1.57-1.82) | 1.34 (1.22-1.48) | <.001 |
| Non-HDL cholesterol | 1.67 (1.36-2.04) | 1.67 (1.54-1.81) | 1.41 (1.32-1.51) | 1.21 (1.11-1.32) | <.001 |
| Apolipoprotein B | 1.89 (1.52-2.35) | 1.78 (1.65-1.93) | 1.52 (1.42-1.62) | 1.26 (1.15-1.38) | <.001 |
| Apolipoprotein A-I | 0.69 (0.51-0.94) | 0.61 (0.55-0.68) | 0.76 (0.70-0.82) | 0.88 (0.80-0.97) | <.001 |
| Lipoprotein(a) | 1.22 (0.92-1.62) | 1.27 (1.15-1.42) | 1.11 (1.03-1.21) | 1.10 (1.00-1.21) | .15 |
| LDL particles | |||||
| Totald | 1.75 (1.42-2.15) | 1.59 (1.45-1.74) | 1.36 (1.27-1.47) | 1.24 (1.13-1.36) | <.001 |
| Largee | 1.02 (0.74-1.42) | 1.04 (0.92-1.17) | 1.01 (0.92-1.11) | 1.10 (0.99-1.23) | .67 |
| Mediume | 1.13 (0.80-1.60) | 1.16 (1.02-1.32) | 1.08 (0.98-1.19) | 0.99 (0.88-1.10) | .32 |
| Smalle | 2.25 (1.76-2.89) | 1.93 (1.73-2.15) | 1.57 (1.43-1.72) | 1.37 (1.22-1.53) | <.001 |
| LDL particle average sized | 0.64 (0.50-0.80) | 0.74 (0.67-0.82) | 0.80 (0.74-0.86) | 0.89 (0.81-0.97) | .01 |
| TRL particles | |||||
| Total | 1.74 (1.44-2.10) | 1.55 (1.42-1.70) | 1.38 (1.28-1.48) | 1.24 (1.13-1.35) | <.001 |
| Very large | 1.27 (1.16-1.40) | 1.16 (1.10-1.23) | 1.18 (1.13-1.23) | 1.11 (1.03-1.19) | .20 |
| Large | 1.66 (1.43-1.93) | 1.39 (1.29-1.51) | 1.34 (1.26-1.43) | 1.20 (1.10-1.31) | .002 |
| Medium | 1.80 (1.14-2.84) | 1.64 (1.37-1.96) | 1.52 (1.32-1.75) | 1.23 (1.06-1.43) | .05 |
| Small | 0.84 (0.73-0.96) | 0.99 (0.89-1.09) | 1.01 (0.93-1.10) | 1.15 (0.99-1.33) | .04 |
| Very small | 1.77 (1.43-2.18) | 1.53 (1.40-1.67) | 1.34 (1.24-1.44) | 1.19 (1.09-1.31) | <.001 |
| TRL cholesterol | 1.66 (1.35-2.02) | 1.32 (1.21-1.44) | 1.31 (1.22-1.41) | 1.14 (1.04-1.26) | .006 |
| TRL triglycerides | 1.77 (1.47-2.12) | 1.55 (1.41-1.69) | 1.39 (1.30-1.49) | 1.24 (1.14-1.36) | <.001 |
| TRL particle average size | 2.21 (1.68-2.90) | 1.64 (1.47-1.83) | 1.53 (1.41-1.67) | 1.27 (1.14-1.41) | <.001 |
| HDL particles | |||||
| Total | 0.96 (0.73-1.27) | 0.81 (0.72-0.90) | 0.90 (0.83-0.98) | 0.93 (0.85-1.03) | .21 |
| Large | 0.74 (0.65-0.85) | 0.76 (0.72-0.80) | 0.80 (0.76-0.84) | 0.91 (0.83-0.99) | .001 |
| Medium | 0.65 (0.47-0.90) | 0.54 (0.48-0.62) | 0.72 (0.66-0.79) | 0.85 (0.76-0.94) | <.001 |
| Small | 1.60 (1.24-2.08) | 1.42 (1.28-1.57) | 1.29 (1.20-1.40) | 1.09 (0.99-1.19) | <.001 |
| HDL particle average size | 0.50 (0.36-0.69) | 0.54 (0.48-0.61) | 0.66 (0.60-0.72) | 0.89 (0.80-0.98) | <.001 |
| Inflammatory, per SD increment | |||||
| CRP | 1.76 (1.37-2.27) | 1.67 (1.50-1.86) | 1.62 (1.49-1.77) | 1.25 (1.12-1.39) | <.001 |
| Fibrinogen | 1.49 (1.22-1.81) | 1.50 (1.40-1.61) | 1.29 (1.20-1.37) | 1.18 (1.09-1.28) | <.001 |
| ICAM-1 | 1.52 (1.26-1.82) | 1.49 (1.39-1.59) | 1.33 (1.25-1.42) | 1.20 (1.09-1.32) | .002 |
| GlycA | 1.84 (1.49-2.27) | 1.61 (1.47-1.77) | 1.47 (1.36-1.58) | 1.18 (1.07-1.31) | <.001 |
| Metabolic, per SD increment | |||||
| Hemoglobin A1c | 1.38 (1.26-1.50) | 1.32 (1.28-1.37) | 1.24 (1.20-1.28) | 1.14 (1.07-1.22) | <.001 |
| LPIR score | 6.40 (3.14-13.06) | 2.61 (2.08-3.28) | 2.09 (1.77-2.48) | 1.15 (1.00-1.33) | <.001 |
| Homocysteine | 1.03 (0.79-1.35) | 1.21 (1.10-1.33) | 1.12 (1.04-1.22) | 1.05 (0.95-1.16) | .18 |
| Citrate | 0.97 (0.73-1.29) | 1.05 (0.95-1.16) | 1.01 (0.93-1.09) | 0.98 (0.89-1.08) | .80 |
| Branched-chain amino acids | 1.47 (1.20-1.80) | 1.41 (1.29-1.53) | 1.31 (1.22-1.40) | 1.12 (1.02-1.23) | .002 |
| Valine | 1.51 (1.22-1.87) | 1.41 (1.29-1.54) | 1.30 (1.21-1.40) | 1.11 (1.01-1.22) | .001 |
| Leucine | 1.30 (1.03-1.64) | 1.34 (1.22-1.47) | 1.22 (1.13-1.32) | 1.05 (0.96-1.16) | .005 |
| Isoleucine | 1.50 (1.23-1.83) | 1.37 (1.26-1.49) | 1.32 (1.24-1.42) | 1.18 (1.08-1.29) | .04 |
| Alanine | 1.10 (0.85-1.41) | 1.18 (1.07-1.30) | 1.17 (1.09-1.27) | 0.99 (0.90-1.09) | .03 |
| eGFR | 1.27 (1.12-1.43) | 0.99 (0.89-1.09) | 0.96 (0.88-1.04) | 1.06 (0.97-1.15) | .01 |
| Creatinine | 0.55 (0.41-0.74) | 0.99 (0.89-1.09) | 1.07 (0.99-1.15) | 0.95 (0.87-1.04) | <.001 |
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); CHD, coronary heart disease; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate; GlycA, glycan biomarker of N-acetyl side chains of several acute-phase proteins; HDL, high-density lipoprotein; HR, hazard ratio; ICAM-1, Intercellular adhesion molecule 1; LDL, low-density lipoprotein; LPIR, lipoprotein insulin resistance; MI, myocardial infarction; TRL, triglyceride-rich lipoprotein.
Hazard ratios (95% CI) were obtained from stratified Cox proportional hazards regression models (stratified on age groups and blood draw time categories) adjusted for model 1 covariates (baseline race/ethnicity, educational level, menopause, postmenopausal hormone use, randomized treatment assignment, and interactions between the risk factor of interest and age groups). The following were log transformed: CRP, homocysteine, large HDL particles, lipoprotein(a), LPIR score, medium TRL particles, small TRL particles, total/HDL cholesterol ratio, triglycerides, triglyceride/HDL cholesterol ratio, and TRL triglycerides. eTable 1 in the Supplement provides the SDs.
Likelihood ratio test (3 df) of the null hypothesis that the risk factor or biomarker has the same effect across age groups. P value for interaction determined as risk factor × age group.
Physical inactivity: less than 7.5 metabolic equivalent task hours per week.
Included model 1 covariates plus LDL particle concentration and LDL particle average size.
Included model 1 covariates plus other LDL subclasses (large, medium, or small LDL particles).