- May 25, 2009
Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid?
Rationale, aims and objectives Many clinical guidelines for cardiovascular disease (CVD) prevention contain risk estimation charts/calculators.
These have shown a tendency to overestimate risk, which indicates that there might be theoretical ﬂaws in the algorithms.
Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate that the predictive properties of cholesterol might not be as straightforward as widely assumed.
Our aim was to document the strength and validity of total cholesterol as a risk factor for mortality in a well-deﬁned, general Norwegian population without known CVD at baseline.
We assessed the association of total serum cholesterol with total mortality, as well as mortality from CVD and ischaemic heart disease (IHD), using Cox proportional hazard models.
The study population comprises 52 087 Norwegians, aged 20–74, who
participated in the Nord-Trøndelag Health Study (HUNT 2, 1995–1997) and were followed-up on cause-speciﬁc mortality for 10 years (510 297 person-years in total).
Among women, cholesterol had an inverse association with all-cause Mortality [hazard ratio (HR): 0.94; 95% conﬁdence interval (CI): 0.89–0.99 per 1.0 mmol L -1increase] as well as CVD mortality (HR: 0.97; 95% CI: 0.88–1.07).
The association with IHD mortality (HR: 1.07; 95% CI: 0.92–1.24) was not linear but seemed to follow a ‘U-shaped’ curve, with the highest mortality <5.0 and 7.0 mmol L-1
. Among men, the association of cholesterol with mortality from CVD (HR: 1.06; 95% CI: 0.98–1.15) and in total (HR: 0.98; 95% CI: 0.93–1.03) followed a ‘U-shaped’ pattern.
Our study provides an updated epidemiological indication of possible errors
in the CVD risk algorithms of many clinical guidelines. If our ﬁndings are generalizable,
clinical and public health recommendations regarding the ‘dangers’ of cholesterol should be revised.
This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneﬁcial.