Exercise testing in asymptomatic patients with heterozygous familial hypercholesterolaemia

Familial hypercholesterolaemia (FH) is a frequent genetic disorder in Europe, affecting one in 500 people in its heterozygous form. Both homozygous and heterozygous forms are correlated with increased incidence of cardiovascular events.

We investigated clinical and biochemical parameters possibly associated with the results of exercise testing (ET) in asymptomatic patients with heterozygous FH. The study population was derived from outpatients of the Lipid Center in our department and consisted of 194 patients with heterozygous FH who had no medical history of coronary artery disease (CAD) or angina-like symptoms and who had agreed to undergo ET.

Sex, body mass index, smoking status, diabetes mellitus, family history of CAD, presence of xanthomas and total cholesterol, triglyceride, low-density and high-density lipoprotein cholesterol, apolipoproteins A and B and lipoprotein (a) levels did not differ significantly between patients with positive and negative ET. Higher fibrinogen levels, arterial hypertension and family history of CAD were more frequent among patients with positive ET. However, in multivariate analysis adjusted for all the aforementioned variables, only high fibrinogen levels were significantly and independently associated with a positive result of ET.

Lipid and coronary risk factor profiles do not seem to predict exercise-induced myocardial ischaemia in asymptomatic patients with heterozygous FH. However, in this high-risk population for cardiovascular events, fibrinogen levels are an independent predictor of positive ET. The adverse effects of FH on the cardiovascular system may be partly mediated by coagulability factors, whose role in the management of FH patients remains to be fully clarified.