Table 3.
Epidemiologic Studies of TGs and CVD
| Study | Study Population | Findings |
|---|---|---|
| Reykjavik and the EPIC-Norfolk studies and 27 prospective studies (68) | Nested case-control comparisons of two different prospective, population-based cohorts (n = 44 and n = 237) | In the Reykjavik study, TG concentrations in the highest tertile were associated with increased odds of CHD (OR, 2.04; 95% CI, 1.78 to 2.32) after adjustment for age and sex compared with the lowest tertile. Further adjustment for risk factors and other lipid measures attenuated the risk (OR, 1.43; 95% CI, 1.23 to 1.65). Similar findings were seen in the EPIC-Norfolk cohort. |
| Meta-analysis of 29 studies (n = 262,525 participants) | In the meta-analysis of 29 studies, TG concentrations in the highest tertile were associated with increased risk of adverse CV outcomes (OR, 1.72; 95% CI, 1.56 to 1.90) compared with the lowest tertile after multivariable adjustment for age, sex, smoking, lipid concentrations. and blood pressure | |
| Mean follow-up, 12.1 y | ||
| CCHS (74) | Cross-sectional prospective cohort study of 13,981 participants | Elevated nonfasting TG levels ≥442.5 mg/dL were associated with increased risk of MI (HR, 2.4 for men, 5.4 for women), IHD (HR, 1.5 for men and 2.6 for women) and death (HR, 1.8 for men and 3.3 for women) compared with TG levels <88.5 mg/dL after multivariable adjustment. |
| Mean follow-up, 26 y | ||
| CCHS (78) | Cross-sectional prospective cohort study of 13,956 participants | Elevated nonfasting TG levels ≥443 mg/dL were associated with increased risk of ischemic stroke (HR, 2.5 for men and 3.8 for women) compared with TG levels <89 mg/dL after multivariable adjustment. |
| Mean follow-up, 26 y | ||
| CGPS and CCHS (106) | Cross-sectional prospective cohort study of 113,554 participants | Elevated nonfasting TG levels ≥440 mg/dL associated with increased risk of heart failure (HR, 2.6 in CGPS and HR 2.3 in CCHS) compared with TG levels <88 mg/dL) after multivariable adjustment |
| Mean follow-up, ≤23 y | LDL-C concentrations were not associated with risk of heart failure. | |
| Women’s Health Study (73) | Cross-sectional prospective study of 26,509 healthy US women | Elevated nonfasting TG levels (highest tertile) were associated with increased risk of CV events (HR, 1.98) compared with those in the lowest tertile after full adjustment for risk factors, including HDL-C and measures of insulin resistance. |
| Median follow-up, 11.4 y | Elevated fasting TG levels were not independently associated with adverse CV events (P for trend = 0.90) because the relationship was nonsignificant after adjustment for HDL-C and measures of insulin resistance. | |
| In secondary analysis stratified by time since last meal, TG levels measured 2–4 hours postprandially had the strongest association with CV events (HR, 4.48) for the highest vs lowest tertiles after full multivariable adjustment | ||
| Emerging Risk Factors Collaboration (72) | Meta-analysis of 302,430 individuals without vascular disease from 68 long-term prospective studies | After adjustment for nonlipid factors, TG levels were associated with risk of CHD (HR, 1.37; 95% CI, 1.31 to 1.42). |
| Follow-up, 2.79 million person-y | After further adjustment for HDL-C and non-HDL-C, TG levels were not significantly associated with risk of CHD (HR, 0.99; 95% CI, 0.94 to 1.05). | |
| Copenhagen Ischemic Heart Disease Study (60) | 5414 patients with IHD | Calculated remnant cholesterol levels in the highest tertile were associated with an increased risk of all-cause mortality (HR, 1.3; 95% CI 1.2 to 1.5) compared with the lowest tertile. |
| 35,836 person-y of follow-up | Directly measured RC levels in the highest tertile were associated with an increased risk of all-cause mortality (HR, 1.1; 95% CI 1.0 to 1.3) compared with the lowest tertile. | |
| JHS and FOCS (64) | Observational primary prevention cohorts | In a combined patient-level analysis, measured RLP-C and IDL-C were associated with an increased risk of CHD (HR, 1.23, 95% CI, 1.06 to 1.42; and HR, 1.26, 95% CI, 1.08 to 1.47, respectively) |
| 4114 US black participants from the JHS with a mean follow-up of 5.6 y | After adjustment for HDL-C and LDL-C, all associations were attenuated. | |
| 818 predominantly white participants from FOCS with a mean follow-up of 7.5 y | ||
| China Kadoorie Biobank (107) | Prospective cohort study of 4662 individuals | NMR spectroscopy–measured RC concentrations were associated with increased risk of MI (OR, 1.27; 95% CI, 1.15 to 1.39 per SD increase) and ischemic stroke (OR, 1.20; 95% CI, 1.09 to 1.32 per SD increase) but not intracerebral hemorrhage (OR, 1.04; 95% CI 0.95 to 1.13 per SD). |
| PROVE IT-TIMI 22 study (108) | 4162 patients hospitalized for ACS and were randomized to atorvastatin 80 mg or pravastatin 40 mg daily. | On-treatment TG levels <150 mg/dL were associated with lower CHD risk compared with higher TG levels (HR, 0.80; 95% CI, 0.66 to 0.97; P = 0.025) after multivariable adjustment. |
| For each 10-mg/dL lowering in on-treatment TG level, the incidence of death, MI, and recurrent ACS was lower by 1.6% (P < 0.001) or 1.4% (P = 0.01) after adjustment for LDL-C or non–HDL-C respectively. | ||
| IDEAL and TNT trials (109) | Post hoc analysis of two prospective, randomized, multicenter studies comparing the efficacy of moderate and high-intensity statin therapy for prevention of recurrent cardiovascular events in patients with established CHD | Patients in the highest quintile of TG concentration had a higher risk of CV events compared with the lowest quintile (HR, 1.63; 95% CI, 1.46 to 1.81). |
| IDEAL: compared efficacy of atorvastatin 80 mg vs simvastatin 20–40 mg; Median follow-up, 4.8 y; n = 7232 | After adjustment for HDL-C and apoB/ApoA-1, the relationship between TG levels and CV events was attenuated (HR, 1.19; 95% CI, 1.06 to 1.35, for fifth vs first quintile). | |
| TNT: atorvastatin 80 mg vs atorvastatin 10 mg; median follow-up, 4.9 y; n = 8547 | After further adjustment for other risk factors (diabetes, body mass index, glucose, hypertension, and smoking) the relationship between TG levels and CV events was nonsignificant (HR, 1.10; 95% CI, 0.97 to 1.24, for fifth vs first quintile). |
Abbreviations: ACS, acute coronary syndrome; CCHS, Copenhagen City Heart Study; CGPS, Copenhagen City General Population; EPIC, European Prospective Investigation of Cancer; FOCS, Framingham Offspring Cohort Study; IDEAL, Incremental Decrease in End Points Through Aggressive Lipid Lowering; JHS, Jackson Heart Study; NMR, nuclear magnetic resonance; PROVE IT-TIMI 22, Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction; RLP-C, remnant lipoprotein cholesterol; TNT, Treating to New Targets.