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Is the use of cholesterol in mortality risk algorithms in
clinical guidelines valid? Ten years prospective data from
the Norwegian HUNT 2 study
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A b s t r a c t

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.

Methods
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).
Results 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
-1 increase] 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.

Conclusion
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.