Elevated Serum Lipid Research Articles

Genetic predictors of common disease: Apolipoprotein E genotype as a paradigm

PURPOSE: Genetic variation of a common genetic polymorphism at the structural locus for apolipoprotein E (apoE) has been associated with risk of elevated serum lipids, coronary artery disease, and Alzheimer disease, all of which are multifactoral disorders and are inherited in a complex fashion. Although the apoE polymorphism is only one risk factor in a complex pattern of inheritance, it gives us a foothold into the understanding of the genetic architecture of these disorders. However, apoE also exemplifies the complications that can arise in the use of genetic markers to predict disease. This paper considers the study of apolipoprotein E genotype effects as an example of the following analytical complications: changes in allele frequencies and allele effects with age, pleiotrophic effects of genetic loci, the existence of more than one alternative allele at a locus, and the expectation of a variety of interactions. METHODS: Publications that exemplify these complications are cited and discussed. No original analyses are presented. RESULTS: There is evidence that the relative frequency of the apoE ϵ4 allele declines with age after the sixth decade of life and that the effects of the APOE allele on lipids also may be age-dependent. Grouping of genotypes may not accurately characterize the effects of individual genotypes. Interactions between APOE genotype and a number of factors, including family history of dementia, are demonstrated for the effects of APOE in Alzheimer disease as well as for the effects of apoE on serum lipids. CONCLUSION: Careful attention must be paid to these and other analytical issues when genotype is a predictor.

Is growth hormone good for the heart?

Growth hormone (GH), probably acting indirectly through locally produced insulin-like growth factor I, stimulates myocardial hypertrophy and increases myocyte contractility. In experimental models insulin-like growth factor I appears to be a key regulator of ventricular hypertrophy. Many adults with growth hormone deficiency (GHD) have reduced left ventricular mass, a lower ejection fraction, and reduced exercise tolerance. Elevated serum lipid levels, increased visceral fat, and early atheroma formation may contribute to an increased mortality rate from cardiovascular disease in these persons, but GH replacement therapy appears to correct many of these abnormalities. GH excess (acromegaly) results in cardiac hypertrophy that can progress to cardiac failure. Treatment with octreotide at least partially reverses cardiac hypertrophy and dysfunction. GH treatment may induce beneficial cardiac hypertrophy in adults without GHD who have dilated cardiomyopathy. Significant cardiac dysfunction has not been reported in children with GHD who are treated with GH, nor have adverse cardiac effects been reported with GH in short children without GHD, including those with Turner syndrome. We now have extensive experience with the therapeutic use of GH in children with cardiac structural abnormalities (e.g., Turner and Noonan syndromes, congenital heart disease), and such use appears to be safe. Furthermore, cardiac complications of GH in children without cardiac disease are rare. Continued observation to ensure that GH therapy has no long-term effects on cardiac anatomy or function in children is necessary. (J Pediatr 1997;131:S70-4)

Diabetic retinopathy and lipid abnormalities.

The relationship of serum lipid levels and diabetic retinopathy has interested clinicians for several decades. Data from both a population-based study of diabetic retinopathy and a controlled, randomized trial of laser photocoagulation and aspirin treatment in diabetic retinopathy have provided further information regarding the importance of the role of serum lipids in patients with elevated serum lipid levels and diabetic retinopathy. Retinal hard exudate, which is accompanied by macular edema, is associated with elevated serum lipid levels. Although the data are observational, visual loss is likely to be associated with retinal hard exudate and serum lipid abnormalities. These relationships are evaluated in the analyses of the data from the Early Treatment Diabetic Retinopathy Study.

Coronary Heart Disease Risk Factors of Eastern Rim and North American Executives

This study investigated the coronary heart disease (CHD) risk factors of 34 East Asian and 60 U.S. Caucasian executives. All subjects were men participating in the Executive Health Enhancement Program, a testing program at The Pennsylvania State University, from 1980 to 1991. The subjects ranged from 30 to 56 years of age. Elevated serum lipids were found in both groups. There were no significant differences in CHD risk factors including % body fat, resting blood pressure, blood glucose, and serum lipids. However, a significantly (p ≤ 0.05) higher percentage of East Asian executives were smokers, although there were no differences in cardiovascular fitness between both groups. The combination of elevated serum lipids and higher percentage of smokers among East Asian executives may partly explain the current increase in CHD in East Asia.

In the absence of the low density lipoprotein receptor, human apolipoprotein C1 overexpression in transgenic mice inhibits the hepatic uptake of very low density lipoproteins via a receptor-associated protein-sensitive pathway.

To study the role of apoC1 in lipoprotein metabolism, we have generated transgenic mice expressing the human APOC1 gene. On a sucrose-rich diet, male transgenic mice with high APOC1 expression in the liver showed elevated levels of serum cholesterol and triglyceride compared with control mice (5.7+/-0.7 and 3.3+/-2.1 vs. 2.7+/-0.1 and 0.4+/-0.1 mmol/liter, respectively). These elevated levels were mainly confined to the VLDL fraction. Female APOC1 transgenic mice showed less pronounced elevated serum lipid levels. In vivo VLDL turnover studies revealed that, in hyperlipidemic APOC1 transgenic mice, VLDL particles are cleared less efficiently from the circulation as compared with control mice. No differences were observed in the hepatic production and extrahepatic lipolysis of VLDL-triglyceride. Also, VLDL isolated from control and APOC1 transgenic mice were found to be equally good substrates for bovine lipoprotein lipase in vitro. These data indicate that the hyperlipidemia in APOC1 transgenic mice results primarily from impaired hepatic VLDL particle clearance, rather than a defect in the hydrolysis of VLDL-triglyceride. To investigate which hepatic receptor is involved in the apoC1-mediated inhibition of VLDL clearance, APOC1 transgenic mice were bred with an LDL receptor-deficient (LDLR(-/-)) background. In addition, control, LDLR(-/-), and LDLR(-/-)/APOC1 mice were transfected with adenovirus carrying the gene for the receptor-associated protein (Ad-RAP). Both serum cholesterol and triglyceride levels were strongly elevated in LDLR(-/-)/APOC1 mice compared with LDLR(-/-) mice (52+/-19 and 36+/-19 vs. 8.4+/-0.9 and 0.5+/-0.2 mmol/liter, respectively), indicating that apoC1 inhibits the alternative VLDL clearance pathway via the remnant receptor. Transfection of LDLR(-/-) mice with Ad-RAP strongly increased serum cholesterol and triglyceride levels, but to a lesser extent than those found in LDLR(-/-)/APOC1 mice (39+/-8 and 17+/-8 vs. 52+/-19 and 36+/-19 mmol/liter, respectively). However, in LDLR(-/-)/APOC1 mice the transfection with Ad-RAP did not further increase serum cholesterol and triglyceride levels (52+/-19 and 36+/-19 vs. 60+/-10 and 38+/-7 mmol/liter, respectively). From these studies we conclude that, in the absence of the LDLR, apoC1 inhibits the hepatic uptake of VLDL via a RAP-sensitive pathway.

Relationship between job stress and plasma fibrinolytic activity in male Japanese workers.

Psychosocial job stress has been shown to be associated with the development of cardiovascular disease. However, the pathophysiological mechanisms underlying this relationship remain unclear. The aim of the present study was to elucidate whether marked job stress affects the parameters of blood coagulation and fibrinolysis, such as plasma fibrinogen concentration, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1) activities, in 213 middleaged male workers in a computer-producing factory. Job stress was measured using a Japanese version of the Job Content Questionnaire (JCQ) developed by Karasek. The mean t-PA activity in workers with lower and higher job demands was 0.23 and 0.18 IU/ml respectively, and this difference was significant (P < 0.05). The mean plasma fibrinogen in workers with lower and higher job decision latitude was 224.8 and 236.3 mg/dl respectively, and the mean PAI-1 activity in workers with lower and higher job strain was 14.9 and 17.7 U/ml respectively, though these differences remained at a borderline level of significance (0.05 < P < 0.10). Multiple regression analyses showed that the parameters of blood coagulation and fibrinolysis were closely associated with the cardiovascular risk factors of age, obesity, blood pressure, elevated serum lipids, and smoking, but that high job demands were significantly related to decreases in t-PA activity, independently of the traditional risk factors. These results suggest that psychosocial job stress may be related, at least partly, to the development of cardiovascular disease via changes in plasma fibrinolytic activity.

APOLIPOPROTEIN E PRODUCED BY AN EPIDERMAL SPECIFIC PROMOTER IN TRANSGENIC MICE: A FEASIBILITY STUDY FOR KERATINOCYTE GENE THERAPY. • 1300

It may be possible to furnish a needed gene product with keratinocytes genetically altered to produce the required protein. However, investigations have been hampered by low initial expression levels from viral promoters. Vectors utilizing mammalian promoters that are normally functional in epidermis, offer potential advantages since the cellular machinery is already set up to express downstream sequences at high levels. We have developed a vector derived from loricrin, the major component of the cornified cell envelope. As an approach to test this promoter in an in vivo protein delivery system we selectively targeted over-expression of Apolipoprotein E(ApoE) in the epidermis of transgenic mice. A functionally impaired form of ApoE is seen in Type III Hyperlipoproteinemia. This is a disorder characterized by elevated serum lipids, accelerated atherosclerosis and cutaneous xanthoma. ApoE is synthesized in most tissues, including the epidermis, however its role in skin remains unknown. Although previous studies have shown that disruption of the cutaneous permeability barrier results in a rapid increase in epidermal ApoE mRNA levels, ApoE-deficient mice do not exhibit abnormalities in permeability barrier function or stratum corneum structure. At birth transgenic mice expressing the ApoE transgene weighed approximately 40% less than normal littermates and exhibited red, tight shiny skin. By 36 hours fissures developed followed by superficial scaling. Severely affected neonates died within 3 days. Histologically, the stratum corneum showed a 3-fold increase in thickness, while the number of nucleated cells revealed no difference from controls. Electron microscopic studies showed apparently normal lipid lamellar granules in the granular layer and lipid multilamellar structures between corneocytes. However, with ruthenium tetroxide staining a large accumulation of lipid was noted both within and between the nucleated cells of the epidermis. Our study suggests that over-accumulation of ApoE in the epidermis may result in abnormal sequestration of lipids that severely retards desquamation and impairs barrier function. In addition, the utility of the loricrin vector for expressing high levels of targeted protein from the epidermis is substantiated.

Serum lipid and glucose concentrations with a propofol infusion for cardiac surgery

To document changes in serum lipids and glucose with a propofol infusion technique for cardiac surgery. Prospective cohort. University teaching hospital. 22 elective cardiac surgical patients. Frequent venous blood sampling. Serum lipids and glucose were measured at 10 time periods perioperatively, from preinduction until 4 hours post-cardiopulmonary bypass. Plasma propofol concentrations were also measured in 10 of these patients. There was a significant increase in glucose (P < 0.0005) and decreases in cholesterol (P < 0.0005), high-density lipoprotein (P = 0.004), and low-density lipoprotein (P < 0.0005); there was no significant change in triglycerides (P = 0.39). The propofol infusion resulted in acceptable plasma levels throughout the procedure and allowed early extubation in the intensive care unit, after a mean (SD) of 7.14 (5.9) hours. There was a strong correlation between triglyceride and propofol levels at most time periods (r = 0.38 to 0.98). This study demonstrates that a propofol infusion technique does not result in elevation of serum lipids and supports its increased popularity in maintenance of anesthesia for cardiac surgery.

Diterpene composition of oils from Arabica and Robusta coffee beans and their effects on serum lipids in man

The cholesterol-raising effect of boiled coffee is caused by diterpenes from coffee oil. In order to identify the diterpene responsible, we analysed the diterpene composition of oils from Arabica (Coffea arabica) and Robusta (Coffea canephora robusta) beans and their effects on serum lipids and thyroid function. During the first 3-week period of a randomized, cross-over trial, 11 healthy, normolipaemic volunteers received per day either 2 g of coffee oil (n = 5) or placebo oil (n = 6). After a 2-week wash-out, the reverse treatments were applied for another 3 weeks. Six subjects received Arabica oil, supplying 72 mg day-1 cafestol and 53 mg day-1 kahweol, and five received Robusta oil, which provided 40 mg of cafestol, 19 mg of 16-O-methyl-cafestol, and 2 mg of kahweol per day. Background diets were constant. The average serum cholesterol levels rose by 0.65 mmol L-1 (13%) on Arabica oil (P < 0.025; 95% CI, 0.21-1.09 mmol L-1) and by 0.53 mmol L-1 (13%) on Robusta oil (NS; 95% CI -0.36-1.42 mmol L-1). The triglycerides levels rose by 0.54 mmol L-1 (71%) on Arabica (P < 0.005; 95% CI, 0.22-0.76 mmol L-1) and 0.49 mmol L-1 (61%) on Robusta oil (P < 0.005; 95% CI, 0.30-0.68 mmol L-1). None of the effects on serum lipids or lipoprotein cholesterol levels was significantly different between Arabica and Robusta oil. Concentrations of serum total and free thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were largely unaffected. Both Arabica and Robusta oil elevated serum lipid levels; therefore, cafestol must be involved and kahweol cannot be the sole cholesterol-raising diterpene. The mode of action of coffee diterpenes does not involve induction of hypothyroidism.

1005-79 Serial 1H NMR Spectroscopic Detection of Myocardial Lipid Accumulation Following Brief Coronary Ischemia and Elevation of Serum Lipids in Dogs

We employed a 1 H NMR surface coil spectroscopic method to continuously monitor myocardial lipid accumulation following 90-min coronary occlusion and 4 hrs reperiusion in 12 dogs. In the 7 saline-treated control dogs, significant myocardial ischemic damage was noted by both triphenyltetrazolium staining and histologic examination. Slight increases (+ 15.5%) in lipid resonances were also observed during 4-hr reperiusion in the reversibly injured subepicardial ischemic/reperfused myocardium, but not the subendo-cardial infarcted region. Transient elevation of serum lipids in 5 dogs from 18 ± 3 mg/dl to 490 ± 182 mg/dl with a 90-min infusion of Intralipid (1 ml/kg bolus followed by 0.025 ml/kg/min) during reperiusion further increased the lipid resonances in the reversibly injured subepicardium (+61.8%). The subendocardial infarcted tissues were only minimally affected. Discontinuation of Intralipid infusion with return of serum lipids (36 ± 14 mg/dl) did not reverse the myocardial lipid accumulation. Ex vivo determinations of tissue triglyceride content and histochemical (Oil-Red-O) staining confirmed the preferential lipid accumulation in the reversibly injured myocytes. Results of the present serial 1 H NMR spectroscopic study confirm our earlier findings and further suggest a preferential and temporal accumulation of lipids in the ischemically jeopardized myocardium. Increases in serum lipid levels could exacerbate their accumulation in the ischemic myocardium.

Age and gender differences in the relationship between heart rate reactivity and elevated serum lipids

Data on serum lipids and heart rate reactivity to a standardized mental arithmetic stressor were collected on 54 healthy men and 73 healthy women. Subjects' ages ranged from 18 to 61 years, allowing analysis of data from both young and older subgroups. MANOVA revealed that age was directly associated with elevated lipids in men and women. There was no significant relationship between reactivity and lipids for either older or younger men. Conversely, young women showed a significant direct relationship between reactivity and Total Cholesterol and LDL, but this was not present for older women. Implications of these data for the previously reported hypothetical relationship between reactivity and lipids are discussed. Limitations of the study are examined, and future directions for research suggested.

Type A behaviour (Jenkins Activity Scale Scores), job satisfaction and risk of coronary heart disease

AbstractAllocated risk of coronary heart disease, from a statistical basis, has traditionally been divided between the effects of a series of well‐recognized biological markers (hypertension, elevated serum lipids and cigarette smoking) and the potential contribution of psychological factors, the most prominent of which, in recent times, has been the Type A behaviour pattern. This article examines the possibility that Type A behaviour, as reflected in Jenkins Activity Survey (JAS) Scale scores, influences coronary risk through an effect on these established biological risk markers, either independently or through the mediating influence of occupational dissatisfaction. The data suggest that some scales of the JAS do relate systematically to a composite biological index of coronary risk, and that this relationship can be better understood in terms of lifestyle than stress factors. The implications for the behavioural prevention of coronary heart disease are discussed.

Effects of dietary therapy on post renal transplant hyperlipidemia. A prospective study

Hyperlipidemia often occurs after renal transplantation and may contribute to increased cardiovascular morbidity. The National cholesterol education program guidelines (NCEP) recommend dietary modification as the initial therapeutic intervention. We evaluated the effects of the AHA Step I and Step II diets on the serum total cholesterol (TC) and the triglyceride (TG) levels in nondiabetic renal transplant patients. Both the AHA Step I (TC 296 +/- 7 vs 294 +/- 9 mg/dL, p = ns) and Step II diets (TC 282 +/- 8 vs 292 +/- 16 mg/dL, p = ns) failed to significantly lower the serum total cholesterol and the triglycerides levels. During this dietary intervention, the patients' body weight and serum creatinine level remained stable. Our data suggest that neither the AHA Step 1 nor the Step II diet are effective in significantly lowering elevated serum lipids in nondiabetic renal transplant recipients.

Hemodynamic stress and experimental aortoiliac atherosclerosis.

Human aortic atherosclerosis is predominantly localized to the infrarenal aorta where flow is bidirectional and wall shear stress oscillates. Similar flow patterns have been related to carotid atherosclerosis. The thoracic aorta is usually spared, where flow and shear stress are unidirectional. We hypothesized that because heart rate and systemic blood pressure modulate flow velocity and shear stress oscillation, both these hemodynamic forces may enhance aortoiliac atherogenesis. Eighteen male cynomolgus monkeys were fed an atherogenic diet for 6 months (mean serum cholesterol = 535 +/- 35 mg/dl). Heart rate was determined with 24-hour electrocardiographic telemetry at monthly intervals and blood pressure was measured by direct arterial cannulation. The product of mean heart rate and mean blood pressure was used to define hemodynamic stress for each animal. Atherosclerotic lesion formation at three standard thoracic aortic sites was quantitatively compared with lesion formation at five standard infrarenal aortoiliac locations with computer-assisted morphometry. There was significantly more plaque in the aortoiliac segment than in the thoracic aorta (12.4% +/- 9.0% vs. 6.4% +/- 4.5% area stenosis, p = 0.02). No correlation was found between the degree of serum lipid elevations and lesion formation in either aortic location. Mean heart rate was 113 +/- 18 beats/min (87 to 163 beats/min) and mean blood pressure was 85 +/- 19 mm/Hg (62 to 130 mm Hg). Heart rate and blood pressure alone were not significantly related to lesion formation. A significant correlation was, however, found between hemodynamic stress and maximum lesion thickness (r = 0.47, p < 0.05) in the aortoiliac region but not in the thoracic aorta (r = 0.19, p > 0.10). This study demonstrates that heart rate and blood pressure exert a mutually potentiating effect on aortoiliac atherosclerosis but not on thoracic aortic atherosclerosis. Regional differences in aortic atherosclerosis may therefore be attributable to the interaction between these hemodynamic forces and the local flow patterns specific to each aortic location. Additional investigation of these hemodynamic factors in relation to human aortic atherosclerosis is warranted.

Etretinate therapy of solar-related kerato acanthoma.

Nineteen patients with a total of 22 keratoacanthomas were treated in this trial with 1 mgm/kg/day of etretinate for six weeks. The patients had predominantly solitary keratoacanthoma, all associated with severe solar damage. There was a provision for reduction of dose and also for extension of length of treatment time for lesions which had responded but had not completely disappeared at the end of six weeks. Sixteen of the nineteen patients cleared without recurrence. Two patients had therapy stopped because of side effects and in these, further treatment was required. These side effects were severe paronychia and elevation of serum lipids. Other side effects were almost exclusively muco-cutaneous. Keratoacanthomas on the head, neck and upper limbs had cleared completely at the end of six weeks therapy, with a variable degree of ridged scarring. Lesions on the lower legs almost invariably required treatment times which were longer than six weeks and could be up to twelve weeks. Etretinate therapy of solar related keratoacanthoma should be considered for large lesions, multiple lesions, lesions in areas which are difficult to treat, and lesions in patients unsuited for destructive therapy or surgery.

Lipopolysaccharide Induced Monocyte Thromboplastin Synthesis and Coagulation Responses in Patients Undergoing Coronary Bypass Surgery after Preoperative Supplementation with n-3 Fatty Acids

Twenty patients with coronary heart disease (CHD) and elevated serum lipids were randomized into 2 groups of 10 to receive encapsulated preparations of either a concentrated ethylester form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or corn oil in doses of 6 g per day, given double blindly for approximately two months prior to coronary bypass surgery. Lipopolysaccharide (LPS) induced monocyte thromboplastin synthesis was studied during the preoperative period and one week following surgery. The ability of n-3 fatty acids to modify tissue factor pathway inhibitor (TFPI) and tissue plasminogen activator inhibitor (PAI-1) was also evaluated along with fibrinogen and thrombin-antithrombin III (TAT) complexes. No significant changes were noted preoperatively. Monocyte reactivity, PAI-1, fibrinogen and TAT increased significantly after surgery. These changes were not modified by preoperative loading with n-3 fatty acids.

P-356 - Preventive effects of magnesium on elevated serum lipid peroxide and aorta cholesterol levels in mice fed an atherogenic diet

P-356 - Preventive effects of magnesium on elevated serum lipid peroxide and aorta cholesterol levels in mice fed an atherogenic diet

Metabolic parameters: how important are pharmacologically-induced changes?

It has been suggested that beta-blockers do not significantly reduce the frequency of coronary disease in hypertensives because they adversely affect the plasma lipoprotein profile. Non-selective beta-blockers cause a significant elevation of triglycerides and a reduction in the level of high-density lipoprotein. Cardioselective beta-blockers have similar, but less marked, effects. The non-selective beta-blockers with intrinsic sympathomimetic activity have little effect on the lipid profile, yet these are the least effective in reducing coronary mortality after myocardial infarction. Elevated blood flow velocity and high catecholamine levels can damage the vascular endothelium. This leads to increased permeability and the deposition of lipids. Beta-blockers reduce peak blood velocity and decrease the activity of catecholamines in plasma, which should reduce endothelial damage and the subsequent formation of plaques. Studies in animals have indeed shown that beta-blockers reduce the level of atherosclerosis, despite an elevation of serum lipids.

Natural history of atherosclerotic renal artery stenosis associated with aortic disease

The natural history of atherosclerotic renal artery stenosis has not been well defined, particularly when discovered in conjunction with aortic disease requiring correction. To better define the natural history of such lesions, 194 sequential aortograms in 48 patients were studied to define predictive criteria for stenoses at risk for progression. Sixty-six unsuspected atherosclerotic renal arterial stenoses were identified on the initial aortograms. Disease progressed in 42 arteries (53%), 14 bilateral and 28 unilateral. Seven arteries developed occlusion. All had stenoses averaging 80% (range 61% to 94%) noted on the most recent aortogram preceding occlusion. Risk factors including smoking, diabetes mellitus, elevated serum lipids, coronary artery disease, peripheral arterial disease, or change in blood pressure or creatinine, did not correlate with degree or rate of progression of the renal artery stenosis. A difference in kidney size, although varying inversely with degree of stenosis, was not a statistically significant marker of disease progression. This analysis suggests that identification of renal arterial stenoses that will progress is best determined by sequential aortography. Highly stenotic vessels are more prone to occlude than those less stenotic. Consequently, individuals with preocclusive lesions should benefit from prophylactic renal revascularization during aortic reconstruction.

The Incidence of Asymptomatic Hypothyroidism in New Referrals to a Hospital Lipid Clinic

As a result of public health and media campaigns there is now considerable public awareness of elevated serum lipids as a risk factor for coronary artery disease. A direct consequence of this has been a great increase in cholesterol screening of asymptomatic individuals; indeed patients detected in this way now constitute a significant proportion of all lipid clinic referrals. Hypercholesterolaemia is a well recognized metabolic consequence of hypothyroidism which will resolve on treatment with L-thyroxine. Before the advent of sensitive biochemical tests of thyroid function, an elevated serum cholesterol concentration was regarded as important supporting evidence in suspected hypothyroidism.’ The development of hypothyroidism is insidious and significant hypercholesterolaemia may develop before the clinical features of hypothyroidism are apparent. In an age of widespread cholesterol screening such patients may present in increasing numbers with hypercholesterolaemia rather than with the more traditional features of hypothyroidism. We assessed the clinical and biochemical thyroid status of new referrals to a hospital lipid clinic. The Lipid Clinic of the Royal Victoria Hospital is a secondary referral centre for the management of dyslipidaemias. Two hundred and twenty new referrals were seen in a one year period. All new referrals undergo a complete physical examination and in particular are assessed with regard to clinical thyroid status by experienced medical staff. A fasting blood specimen is taken for the measurement of total and high density lipoprotein (HDL) cholesterol, triglyceride and for Apoprotein E phenotyping. To exclude a secondary dyslipidaemia, a full biochemistry