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Triglyceride as a risk factor for ischaemic heart disease in British men: effect of adjusting for measurement error
M Egger1, G D Smith, D Pfluger
1Department of Social Medicine, University of Bristol, UK. m.egger@bristol.ac.uk
Insights
Measurement imprecision impacts ischaemic heart disease risk estimates. Adjusting for this imprecision strengthens the association between triglycerides and IHD risk, suggesting hypertriglyceridaemia may be an independent risk factor.
Area of Science:
- Cardiovascular Epidemiology
- Biomarker Measurement Error
- Lipid Metabolism
Background:
- Accurate assessment of lipid profiles is crucial for estimating cardiovascular disease risk.
- Measurement imprecision in lipid assays can potentially bias risk estimates.
- Understanding the impact of measurement error on risk prediction is vital for public health.
Purpose of the Study:
- To evaluate how imprecision in measuring total cholesterol and high-density lipoprotein (HDL) cholesterol affects the estimated risk of ischaemic heart disease (IHD) associated with plasma triglyceride levels.
- To quantify the influence of laboratory error and within-person variation on IHD risk prediction.
Main Methods:
- Utilized data from the Caerphilly Heart Disease Study (CHDS), a prospective cohort of 2512 middle-aged men.
- Estimated measurement imprecision for triglycerides, total cholesterol, and HDL cholesterol through sub-studies.
- Calculated multivariable logistic regression models for major IHD events, both adjusted and unadjusted for measurement imprecision.
Main Results:
- Adjusting for measurement imprecision strengthened the association between all lipid factors and IHD.
- The odds ratio for a one standard deviation increase in triglycerides rose from 1.36 to 1.57 after accounting for imprecision.
- Triglycerides showed a stronger association with IHD than total or HDL cholesterol when adjusted for measurement imprecision and other lipids, but this effect diminished with additional covariate adjustments.
Conclusions:
- Triglyceride levels in the CHDS demonstrated an association with IHD risk independent of total and HDL cholesterol, particularly after adjusting for measurement imprecision.
- The independent effect of triglycerides was attenuated when adjusted for other cardiovascular risk factors, suggesting underlying metabolic disturbances like insulin resistance.
- Total cholesterol remained a significant risk factor across all models, highlighting its consistent role in IHD prediction.
Objective:
To assess the influence of differential precision in the measurement of the correlated variables total cholesterol and high density lipoprotein (HDL) cholesterol on the estimates of the risk of ischaemic heart disease (IHD) associated with plasma triglyceride levels.
Design, Setting And Participants:
The Caerphilly Heart Disease Study (CHDS), a prospective cohort study of 2512 middle-aged men living in the town of Caerphilly, south Wales, UK. The results from two sub-studies were used to estimate the degree of measurement imprecision (laboratory error and within-person variation) in triglycerides, total cholesterol and HDL cholesterol.
Main Outcome Measures:
Multivariable risk estimates for major IHD calculated from logistic regression analysis, adjusted and not adjusted for measurement imprecision. Major IHD events were defined as death from IHD, clinical non-fatal myocardial infarction or electrocardiographic myocardial infarction.
Results:
There were 261 men with major IHD events during follow-up. In age-adjusted analyses, taking measurement imprecision into account strengthened associations with IHD for all lipid factors. The odds ratio (OR) for one S.D. increase in triglycerides, ignoring measurement imprecision, was 1.36 (95% confidence interval [95% CI] 1.20-1.55) but 1.57 (95% CI 1.30-1.89) when taking imprecision into account. The standardised odds ratio for triglycerides adjusted for measurement imprecision and the two other lipid factors was 1.35 (95% CI 1.09-1.69). In this model, the triglyceride level showed a stronger association than total cholesterol (OR 1.28; 95% CI 1.05-1.56) and HDL cholesterol (OR for one S.D. decrease 1.20; 95% CI 0.97-1.49). When adding fasting blood glucose and diastolic blood pressure, however, the effect of triglycerides was reduced and ceased to be statistically significant (OR 1.19; 95% CI 0.95-1.49). This was further attenuated upon inclusion of body mass index, smoking status and history of pre-existing IHD. Total cholesterol remained a statistically significant (P < 0.05) risk factor in all models.
Conclusions:
In contrast to other cohort studies, triglyceride concentration in the CHDS shows an association with the risk of IHD which is independent of total and HDL cholesterol. This effect was pronounced after adjustment for measurement imprecision. It was reduced, however, when adjusted for other factors. While hypertriglyceridaemia may exert an influence independent of other lipid factors, insulin resistance is probably the underlying metabolic disturbance.