Table 2.
A summary of studies that have compared non-HDL-C to either LDL-C or ApoB for prediction of cardiovascular events
| Population | N | End point | Average follow up (years) | Type of analysis and reference (comparator) group for the cohort | HR (95% CI or p value) | Reference | ||
|---|---|---|---|---|---|---|---|---|
| Non-HDL-C | LDL-C | ApoB | ||||||
| Men and women in the Framingham cohort, Framingham Offspring cohort, Lipid Research Clinics Prevalence Study and the Multiple Risk Factor Intervention Trials; 5% diabetics; average BMI 26.0; average TG 157 mg/dl; average VLDL-C 29 mg/dl | 19381; 18363 non-diabetics and 1018 diabetics | CAD death | 13 | Multivariate; Comparator for analyses is non-diabetics with LDL-C <100 mg/dl or non-diabetics with non-HDL-C<130 mg/dl | DIABETICS Non-HDL-C<130 mg/dl; 2.73 (1.27–5.87) Non-HDL-C 130–159 mg/dl; 2.73(1.60–4.66) Non-HDL-C >160 mg/dl; 3.68 (2.51–5.39) NON-DIABETICS Non-HDL-C 130–159 mg/dl; 0.95(0.65–1.39) Non-HDL-C >160 mg/dl; 2.11 (1.52–2.91) | DIABETICS LDL-C <100 mg/dl; 4.63 (2.21–9.70) LDL-C 100–129 mg/dl; 2.93 (1.53–5.61) LDL-C>130 mg/dl; 5.94 (3.64–9.69) NON-DIABETICS LDL-C 100–129 mg/dl; 1.73 (1.07–2.81) LDL-C>130 mg/dl; 3.02(1.94–4.72) | NA | Liu et al 2005 |
| Women free of cardiovascular disease at baseline enrolled in the Women’s Health Study; 3% diabetics; average BMI 26.3 | 15632 | Cardiovascular death or non-fatal myocardial infarction, stroke or coronary revascularization. | 10 | Multivariate; in each analysis, the fifth quintile (Q5) is compared to the reference first quintile (Q1) | Q5:Q1 (>191 mg/dl versus <123 mg/dl); 2.51 (1.69–3.72) | Q5:Q1 (>154 mg/dl versus <98 mg/dl); 1.62 (1.17–2.25) | Q5:Q1 (>126 mg/dl versus <79 mg/dl); 2.50 (1.68–3.72) | Ridker et al 2005 |
| Men and women free of CAD at baseline; Framingham cohort; 6.8% diabetics; average BMI 24; average TG 111mg/dl; average VLDL-C 25 mg/dl | 5794 | Fatal and non-fatal myocardial infarction, acute coronary insufficiency or sudden cardiovascular death | 22 | Multivariate; Comparator for LDL-C analysis is LDL-C <130 mg/dl and for non-HDL-C<160 mg/dl | Non-HDL-C 160–189 mg/dl; 1.64 (1.13–2.40) Non-HDL-C >190 mg/dl; 2.21 (1.57–3.11) 1.008 per mg/dl TG < 200 mg/dl (p < 0.01) 1.006 per mg/dl TG>200 mg/dl (p < 0.01) | LDL-C 130–159 mg/dl; 1.50 (1.05–2.15) LDL-C>160 mg/dl; 2.04 (1.44–2.90) 1.009 per mg/dl TG < 200 mg/dl 1.004 per mg/dl TG>200 mg/dl (p = NS) | NA | Liu et al 2006 |
| Patients enrolled in the SHEP trial; age>60 with mean blood pressure 170/77 mmHg; 10% diabetics; average BMI 27.5; average TG 144 mg/dl; 13% on lipid-lowering therapy | 4736 | Non-fatal myocardial infarction, CAD death | 4.5 | Multivariate; risk is expressed per 40 mg/dl increase in lipid parameters | 1.32 (1.13–1.54) | 1.30 (1.09–1.54) | NA | Frost et al 1996 |
| Men and women free of cardiovascular disease at baseline; individuals enrolled in the Lipid research clinics prevalence program; 4% diabetics; average BMI 26.2; average TG 136 mg/dl; average VLDL-C 27 mg/dl; 2% on lipid-lowering therapy | 4462 | Cardiovascular death | 19 | Corrected for age; comparator for LDL-C analysis is LDL-C <130 mg/dl and for non-HDL-C<160 mg/dl | 30 mg/dl increments correspond to a 19% increase in cardiovascular death in men and 11% in women | 30 mg/dl increments correspond to a 15% increase in cardiovascular death in men and 8% in women | NA | Cui et al 2001 |
| Chinese men and women free of cardiovascular disease at baseline; 13% diabetics; average BMI 23.5; average TG 127 mg/dl. | 3568 | non-fatal myocardial infarction, fatal CAD or coronary revascularization | 13.6 | Multivariate; in each analysis, the fifth quintile (Q5) is compared to the reference first quintile (Q1) | Q5:Q1; 1.98 (1.00–3.92) | Q5:Q1; 1.86 (1.00–3.46) | Q5:Q1; 2.74 (1.45–5.19) | Chien et al 2007 |
| Men and women free of CAD at baseline; Framingham cohort; 4% diabetics. This Framingham cohort is different to that studied by Liu et al (13). | 3322 | myocardial infarction, angina pectoris, coronary insufficiency or cardiovascular death | 15 | Multivariate; Hazard ratios expressed per increase in one standard deviation of the population. Analyses were stratified based on sex. | MALE 1.22 (1.06–1.40) per one standard deviation increase FEMALE 1.28 (1.06–1.56) per one standard deviation increase | MALE 1.11 (0.97–1.27) per one standard deviation increase FEMALE 1.20 (0.99–1.46) per one standard deviation increase | MALE 1.37 (1.20–1.57) per one standard deviation increase FEMALE 1.38 (1.15–1.67) per one standard deviation increase | Ingelsson et al 2007 |
| 1003 men and women with a CAD event and 1885 matched controls enrolled in the EPIC-Norfolk study designed to study determinants of cancer. Participants were apparently healthy and free of cardiovascular disease at baseline. 3% diabetics; average BMI 27; average TG 148 mg/dl; 0% using lipid-lowering therapy | 2888 | Hospital admission for CAD or death secondary to CAD. | 6 years follow up; case control design | Multivariate; in each analysis, the fourth quartile (Q4) is compared to the reference first quartile (Q1). This study reported odds ratio and not hazard ratios (HR) | Q4:Q1; 1.63(1.26–2.11) | Q4:Q1; 1.55 (1.22–1.96) | NA | El Harchaoui et al 2007 |
| Men and women with myocardial infarction or angina pectoris enrolled in the placebo arm of the 4S study; TG <220 mg/dl for enrolment; | 2223 | CAD death or non-fatal myocardial infarction | 5.4 | Multivariate; data reported as relative risk reductions | 16.4% risk reduction (p = 0.002) per 39 mg/dl decrease in non-HDL-C | 12.8% risk reduction (p = 0.024) per 39 mg/dl decrease in LDL-C | 5.3% risk reduction (p = 0.0025) per 10 mg/dl decrease in ApoB | Pedersen et al 1998 |
| Men and women with myocardial infarction or angina pectoris enrolled in the treatment arm (Simvastatin 20 or 40 mg; average 27 mg) of the 4S study; TG <220 mg/dl for enrolment; | 2221 | CAD death or non-fatal myocardial infarction | 5.4 | Multivariate; data reported as relative risk reductions. The absolute reductions in lipid parameters at one year post-randomization were assessed for prognostic significance over the study period | 24.9% risk reduction (p = 0.002) per 39 mg/dl decrease in non-HDL-C 1.7% reduction in events (0.9–2.4) per 1% reduction in non-HDL-C | 27.8% risk reduction (p = 0.024) per 39 mg/dl decrease in LDL-C 1.7% reduction in events (1.0–2.4) per 1% reduction in LDL-C | 8.8% risk reduction (p = 0.0025) per 10 mg/dl decrease in ApoB 1.1% reduction in events (0.3–1.8) per 1% reduction in ApoB | Pedersen et al 1998 |
| Diabetics free of cardiovascular disease at baseline from American Indian Communities (Strong Heart Study); 100% diabetics; average BMI 32; average TG 144 mg/dl; | 2108 | Cardiovascular death or non-fatal CAD, myocardial infarction or stroke. | 9 | Multivariate; values of LDL-C or non-HDL-C were divided into tertiles and in each analysis, the third tertile (T3) is compared to the reference first tertile (T1) | T3:T1 (>161mg/dl versus <127 mg/dl); 2.23 (1.41–3.43) in men; 1.80 (1.32–2.46) in women T3:T1; 1.80 (1.27–2.54) TG<150 mg/dl; 1.52 (1.12–2.07) TG>150 mg/dl | T3:T1 (>115 mg/dl versus <91mg/dl); 1.71 (1.17–2.48) in men; 1.61(1.19–2.17) in women T3:T1; 1.66 (1.17–2.34) TG<150 mg/dl; 1.58 (1.16–2.16) TG>150 mg/dl | NA | Lu et al 2003 |
| Men of Japanese ancestry living in Oahu (The Honolulu Heart Study) free of CAD at baseline | 1751 | Fatal CAD event or non-fatal myocardial infarction | 16 | Multivariate; risk is expressed per 20 mg/dl increase in lipid parameters; stratified as middle aged (50–64 years old) or elderly (65–74 years old) | MIDDLE AGE 1.18 (1.09–1.29) ELDERLY 1.30 (1.11–1.53) | MIDDLE AGE 1.12 (1.02–1.23) ELDERLY 1.24 (1.05–1.48) | NA | Reed and Benfante1992 |
| Mediterranean men and women followed prospectively; 100% diabetics; average BMI 27; average TG 138 mg/dl | 1565 | Cardiovascular mortality | 11 | Multivariate; analyses stratified based on age <70 and >70 years old comparator for LDL-C analysis is LDL-C <111 mg/dl and for non-HDL-C<137 mg/dl and for ApoB <77 mg/dl | AGE <70 Non-HDL-C 137–163 mg/dl; 1.25 (0.54–2.87) Non-HDL-C 164–197 mg/dl; 1.47(0.69–3.12) Non-HDL-C >198 mg/dl; 1.52 (0.72–3.23) AGE >70 Non-HDL-C 137–163 mg/dl; 0.80 (0.53–1.19) Non-HDL-C 164–197 mg/dl; 0.80(0.54–1.19) Non-HDL-C >198 mg/dl; 0.58 (0.36–0.93) | AGE <70 LDL-C 111–136 mg/dl; 0.71 (0.31–1.63) LDL-C 137–165 mg/dl; 1.00(0.49–2.06) LDL-C >166 mg/dl; 1.03 (0.52–2.08) AGE >70 LDL-C 111–136 mg/dl; 0.96 (0.64–1.42) LDL-C 137–165 mg/dl; 0.84 (0.56–1.28) LDL-C >166 mg/dl; 0.59 (0.38–0.95) | AGE <70 ApoB 78–101 mg/dl; 1.33 (0.56–3.15) ApoB 101–126 mg/dl; 1.94(0.84–4.49) ApoB >127 mg/dl; 2.86 (1.22–6.67) AGE >70 ApoB 78–101 mg/dl; 1.18 (0.73–1.91) ApoB 101–126 mg/dl; 1.69(1.08–2.63) ApoB >127 mg/dl; 1.50 (0.93–2.41) | Bruno et al 2006 |
| Patients enrolled in the BARI trial; all had multivessel CAD; 18% diabetics; average TG 184 mg/dl; 13% on lipid-lowering therapy | 1514 | non-fatal myocardial infarction | 5 | Multivariate; risk is expressed per 10 mg/dl increase in lipid parameters | 1.049 (1.006–1.093) | NS 1.033 (0.981–1.088) | NA | Bittner et al 2002 |
| Diabetic cohort 16% with previous myocardial infarction; 100% diabetics; average BMI 29; average TG 230 mg/dl | 1059 | CAD death | 7 | Multivariate; | 1.6 (1.2–2.3); for non-HDL-C >200 mg/dl versus <200 mg/dl; | NS 1.3 (0.9–1.8); for LDL-C >160 mg/dl versus <160 mg/dl | NA | Lehto et al 1997 |
| Diabetic women free of cardiovascular disease at baseline enrolled in the Nurses’ Health study; 100% diabetics; average BMI 30; average TG 200 mg/dl; 4% using lipid-lowering therapy | 921 | Fatal CAD event, non-fatal myocardial infarction or coronary revascularization | 10 | Multivariate; in each analysis, the fourth quartile (Q4) is compared to the reference first quartile (Q1). Non-HDL-C is even more predictive in those with TG>200 mg/dl; discussed in text. | Q4:Q1 (quartile median 224 mg/dl versus 126 mg/dl); 1.97 (1.14–3.43) | Q4:Q1 (quartile median 179 mg/dl versus 98 mg/dl); 1.93 (1.15–3.22) | Q4:Q1 (quartile median 131 mg/dl versus 74 mg/dl); 1.78 (1.02–3.11) | Schulze et al 2004 |
| Diabetic men free of cardiovascular disease at baseline enrolled in the health professionals’ follow up study; 100% diabetics average BMI 27.1; average TG 182 mg/dl; 9% on lipid-lowering therapy | 746 | Fatal CAD, non-fatal myocardial infraction, fatal stroke, non-fatal stroke, coronary revascularization | 6 | Multivariate; in each analysis the fourth quartile (Q4) is compared to the reference first quartile (Q1) | Q4:Q1(>195 mg/dl versus <143 mg/dl); 2.25 (1.24–4.08) | Q4:Q1(>149 mg/dl versus <102 mg/dl); NS 1.63 (0.94–2.81) | Q4:Q1(>119 mg/dl versus <89 mg/dl); 2.31 (1.25–4.27) | Jiang et al 2004 |
| 243 men with a CAD event enrolled in the Health professionals’ follow up study and 496 matched controls; 6% diabetics; average BMI 25.8; average TG 130mg/dl; 0% on lipid-lowering therapy | 739 | Fatal CAD or non-fatal myocardial infarction | 6 years follow up; case control design | Multivariate; in each analysis, the fifth quintile (Q5) is compared to the reference first quintile (Q1) | Q5:Q1; 2.75 (1.62–4.67) | Q5:Q1; 2.07 (1.24–3.45) | Q5:Q1; 2.98 (1.76–5.06) | Pischon et al 2005 |
| 100 patients with non-fatal myocardial infraction before the age of 36 and 100 matched controls (n = 100); 2% diabetics; average BMI 29; average TG 143 mg/dl | 200 | Non-fatal myocardial infraction | Case control | Multivariate; risk is expressed per 1 mg/dl increase in lipid parameters | 1.03 (1.01–1.05) per 1 mg/dl increase | 1.02 (1.01–1.03) per 1 mg/dl increase | 1.02 (1.01–1.04) per 1 mg/dl increase | Rallidis et al 2005 |
Abbreviations: BMI, body mass index; CAD, coronary artery disease; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; NS, not significant; NA, not available; HR, hazard ratio; TG, triglycerides.