Coronary flow reserve in young men with familial combined hyperlipidemia.

BACKGROUND Familial combined hyperlipidemia (FCHL) is a common hereditary disorder of lipoprotein metabolism estimated to cause 10% to 20% of premature coronary heart disease. We investigated whether functional abnormalities exist in coronary reactivity in asymptomatic patients with FCHL. METHODS AND RESULTS We studied 21 male FCHL patients (age, 34.8+/-5.4 years) and a matched group of 21 healthy control subjects. Myocardial blood flow (MBF) was measured at baseline and during dipyridamole-induced hyperemia with PET and 15O-labeled water. The baseline MBF was similar in patients and control subjects (0.79+/-0.19 versus 0.88+/-0.20 mL. g-1. min-1, P=NS). An increase in MBF was seen in both groups after dipyridamole infusion, but MBF at maximal vasodilation was lower in FCHL patients (3.54+/-1.59 versus 4.54+/-1.17 mL. g-1. min-1, P=0.025). The difference in coronary flow reserve (CFR) was not statistically significant (4.7+/-2.2 versus 5.3+/-1.6, P=NS, patients versus control subjects). Considerable variability in CFR values was detected within the FCHL group. Patients with phenotype IIB (n=8) had lower flow during hyperemia (2.5+/-1.2 versus 4.2+/-1.5 mL. g-1. min-1, P<0.05) and lower CFR (3.4+/-2.1 versus 5.4+/-2.0, P<0.05) compared with phenotype IIA (n=13). CONCLUSIONS Abnormalities in coronary flow regulation exist in young asymptomatic FCHL patients expressing phenotype IIB (characterized by abnormalities in both serum cholesterol and triglyceride concentrations). This is in line with previous observations suggesting that the metabolic abnormalities related to the pathophysiology of FCHL are associated with the phenotype IIB.

[1]  T. Lehtimäki,et al.  Linkage of familial combined hyperlipidaemia to chromosome 1q21–q23 , 1998, Nature Genetics.

[2]  H. Hein,et al.  Triglyceride Concentration and Ischemic Heart Disease , 1998 .

[3]  H. Hein,et al.  Triglyceride concentration and ischemic heart disease: an eight-year follow-up in the Copenhagen Male Study. , 1998, Circulation.

[4]  T. Lehtimäki,et al.  Coronary Flow Reserve Is Reduced in Young Men With IDDM , 1998, Diabetes.

[5]  Viikari,et al.  Glucose intolerance in familial combined hyperlipidaemia , 1998 .

[6]  T. Lehtimäki,et al.  Phenotype expression in familial combined hyperlipidemia. , 1997, Atherosclerosis.

[7]  T. Lehtimäki,et al.  In vivo low density lipoprotein oxidation relates to coronary reactivity in young men. , 1997, Journal of the American College of Cardiology.

[8]  J. Viikari,et al.  Influence of cardiovascular risk status on coronary flow reserve in healthy young men. , 1997, The American journal of cardiology.

[9]  L. Peltonen,et al.  No evidence of linkage between familial combined hyperlipidemia and genes encoding lipolytic enzymes in Finnish families. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[10]  F. Crea,et al.  Mechanisms of adenosine-induced epicardial coronary artery dilatation. , 1997, European heart journal.

[11]  M. Omata,et al.  Reduced coronary flow reserve in hypercholesterolemic patients without overt coronary stenosis. , 1996, Circulation.

[12]  J. Viikari,et al.  Coronary flow reserve is impaired in young men with familial hypercholesterolemia. , 1996, Journal of the American College of Cardiology.

[13]  O Muzik,et al.  Early Detection of Abnormal Coronary Flow Reserve in Asymptomatic Men at High Risk for Coronary Artery Disease Using Positron Emission Tomography , 1994, Circulation.

[14]  M. Hayden,et al.  Analysis of DNA changes in the LPL gene in patients with familial combined hyperlipidemia. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[15]  P. Camici,et al.  Relation between myocardial blood flow and the severity of coronary-artery stenosis. , 1994, The New England journal of medicine.

[16]  S. Deeb,et al.  The LPL gene in individuals with familial combined hyperlipidemia and decreased LPL activity. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[17]  P. Marraccini,et al.  Altered coronary vasodilator reserve and metabolism in myocardium subtended by normal arteries in patients with coronary artery disease. , 1993, Journal of the American College of Cardiology.

[18]  A. Takeshita,et al.  Evidence of impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris and normal coronary angiograms. , 1993, The New England journal of medicine.

[19]  M. Taskinen,et al.  Gemfibrozil reduces postprandial lipemia in non-insulin-dependent diabetes mellitus. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[20]  A. Lammertsma,et al.  Use of the left ventricular time-activity curve as a noninvasive input function in dynamic oxygen-15-water positron emission tomography. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[21]  W. Mayhan Endothelium-dependent responses of cerebral arterioles to adenosine 5'-diphosphate. , 1992, Journal of vascular research.

[22]  B. F. Becker,et al.  Different endothelial mechanisms involved in coronary responses to known vasodilators. , 1992, The American journal of physiology.

[23]  S. Antonarakis,et al.  Pedigree and sib-pair linkage analysis suggest the apolipoprotein B gene is not the major gene influencing plasma apolipoprotein B levels. , 1992, American journal of human genetics.

[24]  T. D. de Bruin,et al.  Familial combined hyperlipidaemia: 1973-1991. , 1992, The Netherlands journal of medicine.

[25]  A. L'Abbate,et al.  Coronary vasodilation is impaired in both hypertrophied and nonhypertrophied myocardium of patients with hypertrophic cardiomyopathy: a study with nitrogen-13 ammonia and positron emission tomography. , 1991, Journal of the American College of Cardiology.

[26]  Adriaan A. Lammertsma,et al.  Noninvasive Quantification of Regional Myocardial Blood Flow in Coronary Artery Disease With Oxygen‐15–Labeled Carbon Dioxide Inhalation and Positron Emission Tomography , 1991, Circulation.

[27]  S. Schewe,et al.  Genetic evidence from 7 families that the apolipoprotein B gene is not involved in familial combined hyperlipidemia. , 1990, Atherosclerosis.

[28]  D E Kuhl,et al.  Noninvasive quantification of regional blood flow in the human heart using N-13 ammonia and dynamic positron emission tomographic imaging. , 1990, Journal of the American College of Cardiology.

[29]  M E Phelps,et al.  13N ammonia myocardial imaging at rest and with exercise in normal volunteers. Quantification of absolute myocardial perfusion with dynamic positron emission tomography. , 1989, Circulation.

[30]  F Shishido,et al.  Measurement of absolute myocardial blood flow with H215O and dynamic positron-emission tomography. Strategy for quantification in relation to the partial-volume effect. , 1988, Circulation.

[31]  A. Lusis Genetic factors affecting blood lipoproteins: the candidate gene approach. , 1988, Journal of lipid research.

[32]  M. Taskinen,et al.  Insulin Therapy Induces Antiatherogenic Changes of Serum Lipoproteins in Noninsulin‐Dependent Diabetes , 1988, Arteriosclerosis.

[33]  P. Vanhoutte,et al.  Flow-induced release of endothelium-derived relaxing factor. , 1986, The American journal of physiology.

[34]  P. Lipsky,et al.  Detection of familial hypercholesterolemia by assaying functional low-density-lipoprotein receptors on lymphocytes. , 1986, The New England journal of medicine.

[35]  M J Welch,et al.  Quantification of regional myocardial blood flow in vivo with H2150* , 2005 .

[36]  A. Motulsky,et al.  Hyperlipidemia in coronary heart disease. I. Lipid levels in 500 survivors of myocardial infarction. , 1973, The Journal of clinical investigation.

[37]  A. Motulsky,et al.  Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. , 1973, The Journal of clinical investigation.

[38]  A. Motulsky,et al.  Hyperlipidemia in coronary heart disease. 3. Evaluation of lipoprotein phenotypes of 156 genetically defined survivors of myocardial infarction. , 1973, The Journal of clinical investigation.

[39]  A. Aro,et al.  Family study of serum lipids and lipoproteins in coronary heart-disease. , 1973, Lancet.

[40]  A. Keys CORONARY HEART DISEASE IN SEVEN COUNTRIES , 1971, The Medical journal of Australia.

[41]  A. Lammertsma,et al.  Myocardial blood flow: comparison of oxygen-15-water bolus injection, slow infusion and oxygen-15-carbon dioxide slow inhalation. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[42]  John C. Clark,et al.  Radiochemistry automation for PET , 1993 .

[43]  M. Sugimachi,et al.  Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions. , 1993, The Journal of clinical investigation.

[44]  Victor W. Pike,et al.  Radiopharmaceuticals for Positron Emission Tomography , 1993, Developments in Nuclear Medicine.

[45]  M. Austin Plasma triglyceride and coronary heart disease. , 1991, Arteriosclerosis and thrombosis : a journal of vascular biology.

[46]  S. Grundy,et al.  Familial combined hyperlipidemia workshop , 1989 .

[47]  C. Crouzel,et al.  Current methodology for oxygen-15 production for clinical use. , 1987, International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes.