Accelerated cardiovascular risk in patients with FH phenotype
medwireNews: Patients with levels of low-density lipoprotein (LDL) cholesterol normally seen in familial hypercholesterolaemia (FH) have the cardiovascular risk of someone decades older than they are, shows a population-based study.
The analysis of 68,565 people from six US cohorts found that men with LDL cholesterol levels of 190 mg/dL or higher had the coronary heart disease (CHD) risk of a person 10 to 20 years older. And the effect was even more pronounced for women, whose CHD risk was accelerated by 20 to 30 years.
Researcher Donald Lloyd-Jones (Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA) and colleagues say that these may be particularly helpful comparisons to make during treatment discussions with patients. For example, a 25-year-old woman with FH could be told that, if she remained untreated, her cardiovascular risk would be equivalent to that of a 55-year-old.
“Such an analogy, paired with counseling about how to improve risk, may motivate behavioral changes and the adoption of and adherence to evidence-based medications”, the team writes in Circulation.
In total, 5.6% of the study participants had LDL cholesterol levels of 190 mg/dL or above, and these people had a significantly increased risk of nonfatal myocardial infarction or CHD death, relative to people with lower cholesterol levels.
The risk increase varied with age, being highest, at 5.0-fold, among people aged 20–29 years, and reducing with older age, an effect that editorialists Fatima Rodriguez and Joshua Knowles, from Stanford University in California, USA, attribute to survival bias, caused by FH patients dying at younger ages.
Female gender had a marked effect. Among people aged 20–29 years, for example, the risk increase associated with high LDL cholesterol was a nonsignificant 2.7-fold in men but a significant 7.8-fold in women, and the corresponding risk increases were 3.6-fold versus 6.8-fold among 30–39-year-olds and 2.8-fold versus 3.5-fold among 40–49-year-olds. The gender disparity disappeared in older age groups.
When the researchers used stricter clinical definitions of FH, the prevalence fell to between 0.5% and 3.3% – more in line with the reported prevalence of FH – but the associated CHD risk estimates were little changed. They say that this, in combination with the reported “vast underdiagnosis of FH”, supports simplified, less strict diagnostic criteria for FH.
In their editorial, Rodriguez and Knowles stress that the reported risk of CHD among patients with genetically confirmed FH is even higher than that found in the current study. However, they say that the findings do have important implications for “the broader population”.
Based on event rates in the USA, “[e]arly-onset CHD death associated with the FH phenotype would cause more deaths in adults <60 years of age than homicide and would be comparable to road accidents”, they say.
The editorialists conclude: “The evidence is now overwhelming that FH and the FH phenotype are important, underrecognized, and undertreated conditions resulting in premature cardiovascular deaths.”
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