Importance of LDL/HDL cholesterol ratio as a predictor for coronary heart disease events in patients with heterozygous familial hypercholesterolaemia: a 15-year follow-up (1987-2002)

SUMMARY This study evaluated the prognostic significance of several risk factors on the outcome of coronary heart disease (CHD) in 639 cardiovascular disease-free subjects with heterozygous familial hypercholesterolaemia (FH). During the 15-year follow-up, 53 (18%) men and 34 (9.8%) women had a CHD event (men vs women, p < 0.001). The age-adjusted 15-year event rate was 3% (87 events/2915 person-years). Smoking increased the CHD risk (hazard ratio = 2.45, p < 0.001), women had a 74% lower risk of a vascular event, compared to men, after controlling for the post-menopausal status (hazard ratio = 0.26, p < 0.001). A one-unit difference in low density lipoprotein (LDL)/high density lipoprotein cholesterol (HDL) cholesterol ratio was associated with a 17% higher risk (hazard ratio = 1.17, p < 0.05); hypertension increased the risk for an adverse event (hazard ratio = 3.02, p < 0.05) and a 1 mg/dl increase in plasma fibrinogen level was associated with a 4% higher CHD risk (hazard ratio = 1.04, p < 0.05). With the power of the 15 years of prospective evaluation, the study shows that increased smoking, hypertension and LDL cholesterol levels eight times more than HDL cholesterol predicts an adverse CHD event, in patients with FH.

[1]  W. Kannel,et al.  Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. , 2020, Annals of internal medicine.

[2]  M C Hjortland,et al.  High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. , 1977, The American journal of medicine.

[3]  L. Wilhelmsen,et al.  Fibrinogen as a risk factor for stroke and myocardial infarction. , 1984, The New England journal of medicine.

[4]  S. Thompson,et al.  HAEMOSTATIC FUNCTION AND ISCHAEMIC HEART DISEASE: PRINCIPAL RESULTS OF THE NORTHWICK PARK HEART STUDY , 1986, The Lancet.

[5]  Vesa Manninen,et al.  Joint Effects of Serum Triglyceride and LDL Cholesterol and HDL Cholesterol Concentrations on Coronary Heart Disease Risk in the Helsinki Heart Study: Implications for Treatment , 1992, Circulation.

[6]  H. Hobbs,et al.  Molecular genetics of the LDL receptor gene in familial hypercholesterolemia , 1992, Human mutation.

[7]  D. Reed,et al.  Low serum cholesterol and mortality. Which is the cause and which is the effect? , 1995, Circulation.

[8]  B. Wilcken Reviews and Notes: Genetics: The Metabolic and Molecular Bases of Inherited Disease , 1995, Annals of Internal Medicine.

[9]  J P Kane,et al.  Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: correlation with high density lipoproteins. , 1996, Journal of the American College of Cardiology.

[10]  M. Elisaf,et al.  Lp(a) levels in Greek patients with heterozygous familial hypercholesterolemia. , 1996, International journal of cardiology.

[11]  L. Chambless,et al.  Gender differences in ischaemic heart disease mortality and risk factors in 46 communities: an ecologic analysis , 1997 .

[12]  F. Kronenberg,et al.  Concentrations of the atherogenic Lp(a) are elevated in FH. , 1998, European journal of human genetics : EJHG.

[13]  M. Kashyap Mechanistic studies of high-density lipoproteins. , 1998, The American journal of cardiology.

[14]  R. Westendorp,et al.  Additional risk factors influence excess mortality in heterozygous familial hypercholesterolaemia. , 2000, Atherosclerosis.

[15]  L. Iacoviello,et al.  Familial hypercholesterolaemia. , 2001, Lancet.

[16]  J J Kastelein,et al.  Mortality over two centuries in large pedigree with familial hypercholesterolaemia: family tree mortality study. , 2001, BMJ : British Medical Journal.

[17]  F. Chaves,et al.  Importance of HDL cholesterol levels and the total/ HDL cholesterol ratio as a risk factor for coronary heart disease in molecularly defined heterozygous familial hypercholesterolaemia. , 2001, European heart journal.

[18]  D. Mikhailidis,et al.  Beyond LDL-C – The Importance of Raising HDL-C , 2002, Current medical research and opinion.

[19]  Christodoulos Stefanadis,et al.  Risk stratification of coronary heart disease in Greece: final results from the CARDIO2000 Epidemiological Study. , 2002, Preventive medicine.

[20]  D. Panagiotakos,et al.  Association of leisure-time physical activity on inflammation markers (C-reactive protein, white cell blood count, serum amyloid A, and fibrinogen) in healthy subjects (from the ATTICA study). , 2003, The American journal of cardiology.