OBJECTIVE: The current study was conducted to investigate whether greater arterial stiffening is already present in normolipidemic relatives of patients with familial combined hyperlipidemia (FCHL), as compared with healthy controls, and to establish the factors that are associated with arterial stiffness in comparison with markers of atherosclerosis. METHODS: Seventy-seven FCHL patients, 121 normolipidemic relatives and 72 spouses (controls) underwent ultrasound examination of the common carotid artery to determine the presence of plaques and the degree of arterial stiffness, expressed as stiffness index alpha. RESULTS: Age-adjusted and sex-adjusted analyses revealed that the arterial stiffness index alpha and prevalence of plaques were higher in normolipidemic relatives when compared with spouses, but lower than in FCHL patients (P<0.05). Additional adjustments for visceral obesity, smoking, plasma glucose, insulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, pulse frequency and use of lipid-lowering or antihypertensive medication did not affect the results for arterial stiffness, whereas the adjusted prevalence of atherosclerosis was markedly lowered in FCHL patients. Logistic regression analyses demonstrated that age, male sex, pulse frequency and low-density lipoprotein cholesterol were significant independent determinants of atherosclerotic plaques. In contrast, only age and FCHL family status, that is, belonging to an FCHL family or not, contributed to arterial stiffness. CONCLUSION: Arterial stiffening and atherosclerosis appear to be greater in patients who are prone to develop FCHL, that is, normolipidemic FCHL family members, as compared with controls. These findings may add to our understanding of the increased prevalence of cardiovascular complications in not only FCHL patients, but also their siblings and offspring.