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Epidemiology and Outcomes
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Traditional and Nontraditional Risk Factors Predict Coronary Heart Disease in Chronic Kidney Disease: Results from the Atherosclerosis Risk in Communities Study

Paul Muntner, Jiang He, Brad C. Astor, Aaron R. Folsom and Josef Coresh
JASN February 2005, 16 (2) 529-538; DOI: https://doi.org/10.1681/ASN.2004080656
Paul Muntner
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Jiang He
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Brad C. Astor
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Aaron R. Folsom
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Josef Coresh
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    Figure 1.

    Relative risk of a major coronary heart disease event (myocardial infarction incidence, fatal coronary heart disease, or coronary revascularization) for each quartile increase in systolic blood pressure, body mass index, fibrinogen, total and HDL-cholesterol and triglycerides, waist circumference, leukocyte count, serum albumin, and for current smoking, anemia, and diabetes, by level of kidney function (estimated GFR ≥90, 60 to 89, and 15 to 59 ml/min). Adjusted for age, sex, race and Atherosclerosis Risk in Communities (ARIC) Study field center. Error bars represent 95% confidence intervals.

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    Table 1.

    Characteristicsa of Atherosclerosis Risk in Communities (ARIC) Study participants by level of estimated GFR (≥90, 60 to 89, and 15 to 59 ml/min per 1.73 m2)b

    Risk FactorEstimated GFR (ml/min per 1.73 m2)P Trend
    ≥90 (n = 7213)60–89 (n = 9878)15–59 (n = 807)
    Age (yr)53.454.356.1<0.001
    Men (%)41.944.133.0<0.001
    Black (%)38.617.321.8<0.001
    Traditional risk factors
        current smoking (%)27.821.116.3<0.001
        physically active (%)23.825.825.70.001
        hypertension (%)31.135.257.2<0.001
        systolic BP (mmHg)122.0121.4125.10.217
        BMI (kg/m2)27.427.728.6<0.001
        obesity (BMI ≥30 kg/m2)24.726.733.0<0.001
        glucose (mg/dl)108.9108.8123.0<0.001
        diabetes (%)11.510.219.60.001
        total cholesterol (mg/dl)215.9217.5221.50.002
        HDL cholesterol (mg/dl)55.753.849.9<0.001
        log triglycerides, log (mg/dl)4.714.734.86<0.001
    Nontraditional risk factors
        waist circumference96.496.899.5<0.001
        log Lp(a), log (mg/L)3.984.034.15<0.001
        apolipoprotein-A1 (mg/dl)136.7134.8129.5<0.001
        apolipoprotein-B (mg/dl)92.895.399.6<0.001
        anemia (%)7.96.713.90.023
        leukocyte count (109 cells/L)6.175.986.340.004
        serum albumin (mg/dl)3.853.873.820.358
        fibrinogen (mg/dl)306.4303.3322.20.249
    • ↵a Prevalence and levels for all variables except age, gender, and race are standardized to the ARIC population with CKD (age, 56.1 yr; gender, 33.0% male; and 21.8% black race).

    • ↵b Participants were permitted to be in two groups if they changed level of GFR at visit 2 (e.g., someone with an estimated GFR ≥90 ml/min per 1.73 m2 at baseline and between 60 and 89 at visit 2 is counted in both the ≥90 and 60 to 89 ml/min per 1.73 m2 categories of this table with updated covariates at visit 2). At the ARIC baseline visit, 7213, 7252, and 391 ARIC participants had an estimated GFR ≥90, 60 to 89, and 15 to 59 ml/min per 1.73 m2, respectively. Of those with an estimated GFR ≥90 at visit 1, 2626 participants had an estimated GFR between 60 and 89 at visit 2, and 416 participants with an estimated GFR ≥60 ml/min per 1.73 m2 at visit 1 had an estimated GFR <60 ml/min per 1.73 m2 at visit 2. ARIC, Atherosclerosis Risk in Communities; BMI, body mass index.

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    Table 2.

    Characteristicsa of ARIC Study participants with CKD who did and did not develop a major CHD eventb during 10.5 yr of follow-up

    Risk FactorNo CHD (n = 699)Incident CHD during Follow-upb (n = 108)P Value
    Age (yr)55.858.0<0.001
    Men (%)29.554.7<0.001
    Black (%)9.822.5<0.001
    Traditional risk factors
        current smoking (%)15.124.40.026
        physically active (%)26.421.20.278
        hypertension (%)28.429.80.023
        systolic BP (mmHg)31.841.20.075
        BMI (kg/m2)124.3130.40.007
        obesity (BMI ≥30 kg/m2)55.370.10.013
        glucose (mg/dl)118.9150.0<0.001
        diabetes (%)17.236.3<0.001
        total cholesterol (mg/dl)218.8239.9<0.001
        HDL cholesterol (mg/dl)50.247.70.154
        log triglycerides, log (mg/dl)4.845.05<0.001
    Nontraditional risk factors
        waist circumference99.0102.90.009
        log Lp(a), log (mg/L)4.124.310.125
        apolipoprotein-A1 (mg/dl)129.8127.30.408
        apolipoprotein-B (mg/dl)98.2108.80.003
        anemia (%)13.218.90.124
        leukocyte count (109 cells/L)6.276.84<0.001
        serum albumin (mg/dl)3.843.750.005
        fibrinogen (mg/dl)317.9350.8<0.001
    • ↵a Prevalence and levels reflect the visit at which CKD was first noted (visit 1 for 391 participants and visit 2 for 416 participants) and are standardized for all variables except age, gender, and race to the ARIC population with CKD (age, 56.1; gender, 33.0% male; and 21.8% black race).

    • ↵b CHD events include myocardial infarction incidence, fatal CHD, or coronary revascularization. CKD, chronic kidney disease; CHD, coronary heart disease.

    • View popup
    Table 3.

    Adjusted relative risks of a major CHD event (myocardial infarction incidence, fatal coronary heart disease, or coronary revascularization) associated with selected CHD risk factors among ARIC study participants with CKD

    Risk FactorAdjusted Relative Risk (95% CIa)
    Age, Race, GenderbMultivariate Modelc
    Age, 5 yr1.42 (1.20–1.68)1.33 (1.11–1.60)
    Male gender2.68 (1.81–3.96)3.96 (2.52–6.21)
    Black2.06 (0.67–6.36)1.79 (0.55–5.85)
    Traditional risk factors
        current smoking1.65 (1.01–2.67)1.91 (1.16–3.15)
        physical activity0.79 (0.48–1.28)0.79 (0.48–1.31)
        hypertension2.02 (1.27–3.22)1.79 (1.11–2.89)
        systolic BP, 20 mmHg1.33 (1.13–1.57)1.26 (1.05–1.51)
        BMI, 5 kg/m21.25 (1.05–1.49)1.16 (0.97–1.39)
        obese1.52 (1.02–2.28)1.23 (0.82–1.86)
        glucose, 40 mg/dl1.31 (1.20–1.43)1.26 (1.15–1.39)
        diabetes3.06 (2.01–4.67)2.88 (1.85–4.47)
        total cholesterol, 43 mg/dl1.50 (1.25–1.79)1.46 (1.25–1.70)
        HDL cholesterol, 17 mg/dl0.79 (0.62–1.01)0.93 (0.73–1.19)
        log triglycerides, 0.5 log (mg/dl)1.38 (1.15–1.65)1.12 (0.94–1.33)
    Nontraditional risk factors
        waist circumference, 13 cm1.38 (1.13–1.69)1.24 (1.00–1.55)
        log Lp(a), 1.2 log (mg/L)1.24 (0.98–1.58)1.20 (0.94–1.53)
        apolipoprotein-A1, 31 mg/dl0.88 (0.70–1.12)0.99 (0.78–1.26)
        apolipoprotein-B, 29 mg/dl1.33 (1.13–1.56)1.28 (1.10–1.49)
        anemia1.96 (1.14–3.36)2.01 (1.19–3.42)
        leukocyte count, 1.9 × 109 cells/L1.24 (1.06–1.46)1.10 (0.91–1.34)
        serum albumin, 0.332 mg/dl0.65 (0.54–0.79)0.76 (0.63–0.92)
        fibrinogen, 69 mg/dl1.38 (1.19–1.59)1.23 (1.07–1.41)
    • ↵a CI, confidence interval.

    • ↵b Adjusted for age, race, gender, and field center.

    • ↵c Additionally adjusted for current smoking, diabetes, hypertension, and total cholesterol.

    • View popup
    Table 4.

    Relative riska (95% CI) of a major CHD eventb among ARIC study participants associated with quartile of CHD risk factor by level of kidney function (estimated GFR ≥90, 60 to 89, and 15 to 59 ml/min per 1.73 m2)

    QuartileP Value for Trend
    1234
    Systolic BP (mmHg)<111112–122123–138≥139
        GFR ≥901.001.26 (0.89–1.78)1.93 (1.41–2.63)2.21 (1.56–3.13)<0.001
        60–891.001.07 (0.87–1.32)1.73 (1.44–2.07)2.39 (1.96–2.91)<0.001
        15–591.001.52 (0.82–2.83)1.08 (0.57–2.05)2.37 (1.33–4.21)0.011
    BMI (kg/m2)<24.724.7–27.527.6–31.4≥31.4
        GFR ≥901.001.32 (0.98–1.79)1.67 (1.23–2.26)1.38 (0.99–1.92)0.008
        60–891.001.17 (0.97–1.41)1.36 (1.13–1.65)1.62 (1.32–1.98)<0.001
        15–591.001.14 (0.60–2.17)1.33 (0.72–2.45)1.78 (0.97–3.25)0.052
    Total Cholesterol (mg/dl)<190191–217218–244≥245
        GFR ≥901.001.44 (1.04–1.99)1.73 (1.24–2.42)2.04 (1.50–2.79)<0.001
        60–891.001.19 (0.97–1.45)1.50 (1.22–1.84)2.22 (1.84–2.67)<0.001
        15–591.001.29 (0.68–2.45)1.98 (1.08–3.61)2.25 (1.27–3.99)0.002
    HDL cholesterol (mg/dl)<4040–4950–61≥62
        GFR ≥901.000.77 (0.59–1.00)0.44 (0.32–0.61)0.23 (0.16–0.35)<0.001
        60–891.000.58 (0.50–0.69)0.53 (0.44–0.64)0.27 (0.21–0.35)<0.001
        15–591.000.72 (0.43–1.23)0.73 (0.42–1.30)0.62 (0.34–1.14)0.127
    Triglycerides (mg/dl)<8787–124125–181≥182
        GFR ≥901.001.53 (1.12–2.08)1.77 (1.29–2.44)2.51 (1.85–3.42)<0.001
        60–891.001.47 (1.20–1.80)1.82 (1.49–2.22)2.47 (2.02–3.03)<0.001
        15–591.001.84 (0.92–3.67)1.74 (0.91–3.29)2.73 (1.46–5.10)0.002
    Waist circumference (cm)<9091–99100–108≥109
        GFR ≥901.001.51 (1.09–2.07)1.70 (1.23–2.35)1.81 (1.29–2.54)<0.001
        60–891.001.35 (1.09–1.66)1.45 (1.18–1.79)1.98 (1.59–2.46)<0.001
        15–591.000.82 (0.40–1.65)1.26 (0.67–2.35)1.77 (0.97–3.23)0.013
    Leukocyte count (109 cells/L)<4.95.0–6.06.1–7.2≥7.3
        GFR ≥901.001.55 (1.10–2.19)1.66 (1.15–3.38)2.67 (1.93–3.68)<0.001
        60–891.001.16 (0.95–1.43)1.66 (1.35–2.05)2.42 (1.99–2.95)<0.001
        15–591.001.84 (0.94–3.63)2.09 (1.04–4.21)3.31 (1.74–6.32)<0.001
    Serum albumin (mg/dl)
        GFR ≥901.000.62 (0.45–0.84)0.67 (0.50–0.89)0.46 (0.33–0.65)<0.001
        60–891.000.68 (0.55–0.85)0.81 (0.67–1.00)0.75 (0.61–0.93)0.147
        15–591.000.57 (0.33–0.99)0.52 (0.29–0.92)0.38 (0.20–0.70)0.003
    Fibrinogen (mg/dl)<270271–310311–358≥359
        GFR ≥901.001.32 (0.95–1.83)1.80 (1.31–2.48)2.77 (2.02–3.80)<0.001
        60–891.001.52 (1.27–1.82)2.06 (1.71–2.48)2.54 (2.08–3.09)<0.001
        15–591.001.46 (0.67–3.20)3.68 (1.80–7.52)4.27 (2.09–8.71)<0.001
    • ↵a Adjusted for age, race, gender, and ARIC field center.

    • ↵b Myocardial infarction incidence, fatal coronary heart disease, or coronary revascularization.

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Traditional and Nontraditional Risk Factors Predict Coronary Heart Disease in Chronic Kidney Disease: Results from the Atherosclerosis Risk in Communities Study
Paul Muntner, Jiang He, Brad C. Astor, Aaron R. Folsom, Josef Coresh
JASN Feb 2005, 16 (2) 529-538; DOI: 10.1681/ASN.2004080656

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Traditional and Nontraditional Risk Factors Predict Coronary Heart Disease in Chronic Kidney Disease: Results from the Atherosclerosis Risk in Communities Study
Paul Muntner, Jiang He, Brad C. Astor, Aaron R. Folsom, Josef Coresh
JASN Feb 2005, 16 (2) 529-538; DOI: 10.1681/ASN.2004080656
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