BACKGROUND: Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, we assessed whether patients with mutations of low-density lipoprotein (LDL) receptor and apolipoprotein B genes related to familial hypercholesterolaemia (FH) have a different degree of atherosclerosis than those without such mutations. METHOD: In our lipid clinics, 273 patients were selected on the basis of a severe hypercholesterolaemia (cholesterol above 95th percentile) and a family history of early cardiovascular disease. By molecular genetic test, 122 patients were classified as FH. Atherosclerosis was evaluated by the ultrasonographic measurement of intima-media thickness (IMT) in the carotid and femoral arteries. RESULT: Despite the fact that non-FH individuals had a higher prevalence of obesity, hypertension, diabetes and hypertriglyceridaemia, FH individuals had significantly greater carotid and femoral IMT than non-FH patients: difference between carotid and femoral IMT, respectively, 0.19 mm (95% CI, 0.08-0.29; P < 0.001) and 0.20 mm (95% CI, 0.09-0.35; P = 0.001), respectively. These differences remained statistically significant after adjustment for the various risk factors as well as in sub-analysis restricted to the patients with LDL-cholesterol between 240 and 300 mg dL-1 (range with similar distribution in the two groups). When classified according to the severity of their mutations, FH individuals with null LDL receptor allele tended to have thicker carotid IMT than FH individuals carrying the LDL receptor-defective allele. CONCLUSION: Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher degree of atherosclerosis. This suggests that molecular genetic identification of FH may be helpful to evaluate better the coronary heart disease risk in these patients.
BACKGROUND: Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, we assessed whether patients with mutations of low-density lipoprotein (LDL) receptor and apolipoprotein B genes related to familial hypercholesterolaemia (FH) have a different degree of atherosclerosis than those without such mutations. METHOD: In our lipid clinics, 273 patients were selected on the basis of a severe hypercholesterolaemia (cholesterol above 95th percentile) and a family history of early cardiovascular disease. By molecular genetic test, 122 patients were classified as FH. Atherosclerosis was evaluated by the ultrasonographic measurement of intima-media thickness (IMT) in the carotid and femoral arteries. RESULT: Despite the fact that non-FH individuals had a higher prevalence of obesity, hypertension, diabetes and hypertriglyceridaemia, FH individuals had significantly greater carotid and femoral IMT than non-FH patients: difference between carotid and femoral IMT, respectively, 0.19 mm (95% CI, 0.08-0.29; P < 0.001) and 0.20 mm (95% CI, 0.09-0.35; P = 0.001), respectively. These differences remained statistically significant after adjustment for the various risk factors as well as in sub-analysis restricted to the patients with LDL-cholesterol between 240 and 300 mg dL-1 (range with similar distribution in the two groups). When classified according to the severity of their mutations, FH individuals with null LDL receptor allele tended to have thicker carotid IMT than FH individuals carrying the LDL receptor-defective allele. CONCLUSION: Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher degree of atherosclerosis. This suggests that molecular genetic identification of FH may be helpful to evaluate better the coronary heart disease risk in these patients.
Authors: Albert Wiegman; Samuel S Gidding; Gerald F Watts; M John Chapman; Henry N Ginsberg; Marina Cuchel; Leiv Ose; Maurizio Averna; Catherine Boileau; Jan Borén; Eric Bruckert; Alberico L Catapano; Joep C Defesche; Olivier S Descamps; Robert A Hegele; G Kees Hovingh; Steve E Humphries; Petri T Kovanen; Jan Albert Kuivenhoven; Luis Masana; Børge G Nordestgaard; Päivi Pajukanta; Klaus G Parhofer; Frederick J Raal; Kausik K Ray; Raul D Santos; Anton F H Stalenhoef; Elisabeth Steinhagen-Thiessen; Erik S Stroes; Marja-Riitta Taskinen; Anne Tybjærg-Hansen; Olov Wiklund Journal: Eur Heart J Date: 2015-05-25 Impact factor: 29.983
Authors: Mahtab Sharifi; Elizabeth Higginson; Sven Bos; Angela Gallivan; Darren Harvey; Ka Wah Li; Amali Abeysekera; Angela Haddon; Helen Ashby; Kate E Shipman; Jackie A Cooper; Marta Futema; Jeanine E Roeters van Lennep; Eric J G Sijbrands; Mourad Labib; Devaki Nair; Steve E Humphries Journal: Atherosclerosis Date: 2017-05-13 Impact factor: 5.162
Authors: Richard Ceska; Gustavs Latkovskis; Marat V Ezhov; Tomas Freiberger; Katarina Lalic; Olena Mitchenko; Gyorgy Paragh; Zaneta Petrulioniene; Belma Pojskic; Katarina Raslova; Aleksandr B Shek; Branislav Vohnout; Tereza Altschmiedova; Veronika Todorovova Journal: Curr Atheroscler Rep Date: 2019-06-22 Impact factor: 5.113