Elevated serum lipids in hypogonadal men with and without hyperprolactinemia

STUDY OBJECTIVE: To determine whether men with hypogonadism are at risk for hyperlipidemia. DESIGN: Case-control study. SETTING: Neuroendocrine clinical center of a referral-based university medical center. PATIENTS: Consecutive sample of 18 men with testosterone deficiency who had prolactin-secreting pituitary adenomas, 15 men with acquired secondary hypogonadism and normal prolactin levels, and 33 normal male controls. MEASUREMENTS AND MAIN RESULTS: We found a significant elevation in fasting cholesterol (6.23 +/- 0.28 mmol/L [mean +/- SE] compared with 5.17 +/- 0.13 mmol/L [241 +/- 11 mg/dL compared with 200 +/- 5 mg/dL], P less than 0.01), low density lipoprotein (LDL) cholesterol (4.11 +/- 0.23 mmol/L compared with 3.34 +/- 0.13 mmol/L [159 +/- 9 mg/dL compared with 129 +/- 5 mg/dL], P less than 0.05), and triglycerides (1.85 +/- 0.26 mmol/L compared with 1.11 +/- 0.07 mmol/L [164 +/- 23 mg/dL compared with 98 +/- 6 mg/dL], P less than 0.001) in men with hyperprolactinemia compared with controls. In the normoprolactinemic hypogonadal men, cholesterol (6.28 +/- 0.34 mmol/L [243 +/- 13 mg/dL], P less than 0.01), LDL cholesterol (4.34 +/- 0.34 mmol/L [168 +/- 13 mg/dL], P less than 0.01), and triglycerides (1.61 +/- 0.18 mmol/L [143 +/- 16 mg/dL], P less than 0.05) were also significantly higher than in the controls, and were the same as in the hyperprolactinemic men. High density lipoprotein (HDL) cholesterol did not differ among the three groups. CONCLUSIONS: Hypogonadism in men, with or without hyperprolactinemia, may be associated with elevation of fasting serum cholesterol, LDL cholesterol, and triglycerides compared with normal men. These data suggest that serum lipid levels should be evaluated in hypogonadal men. The presence of lipid abnormalities may affect the decision to treat testosterone deficiency in these patients.     

Relation of serum total sialic acid concentrations with diabetic complications and cardiovascular risk factors in Kuwaiti Type 2 diabetic patients

Serum total sialic acid is a marker of the acute phase response. Elevated levels have also been associated with cardiovascular disease in the general Caucasian population and especially in Type 2 diabetic subjects. The purpose of this study was to estimate serum total sialic acid concentrations among Kuwaiti Type 2 diabetic subjects and to investigate its association with macro and microvascular diabetes-related complications in that population. Serum total sialic acid levels were estimated by an enzymatic spectro-photometric assay in two groups of subjects: (i) 358 Kuwaiti Type 2 diabetics (156 men and 202 women) referred for their annual evaluation to the specialised diabetic clinic at the main university teaching hospital in Kuwait, and (ii) 47 healthy age and sex matched non-diabetic Kuwaiti control population (13 men and 34 women). Serum sialic acid levels were significantly higher (P<0.001) among the diabetic patients (mean+/-S.D.) (81.2+/-13.2 mg/dl) compared to the non-diabetic controls (66.9+/-11.0 mg/dl). Kuwaiti diabetic women had significantly higher concentrations compared to diabetic men (85.2+/-12.1 vs. 75.9+/-13.0 mg/dl, P<0.001). Among the controls there was no significant gender difference in sialic acid levels of women, (68.3+/-11.6 mg/dl) versus men (63.2+/-8.2 mg/dl). The gender difference in the diabetic patients was unrelated to the degree of obesity. Significant correlations were found between serum total sialic acid concentrations and such cardiovascular risk factors as plasma levels of apolipoprotein B, low density lipoprotein cholesterol, triglycerides and uric acid in the diabetic subjects. Furthermore, there was a significant elevation in serum total sialic acid concentrations with increasing urinary albumin excretion, P<0.001, but not with retinopathy or neuropathy.     

Serum lipids in north Indian children treated for kawasaki disease

A prospective cross sectional analysis of serum lipids was carried out in 20 children aged between 1.3 and 16 years with Kawasaki disease (KD). The controls were siblings of other patients. The mean interval between diagnosis of the disease and time of assay was 2.6 years (range 0.41 to 6 years). Standard biochemical methods were employed for determination of various components of the lipid profiles. There were significant differences in high-density lipoprotein cholesterol (HDL-C) (40.37 +/- 12.0 mg/dL versus 53.49 +/- 4.31 mg/dL, P < 0.001) and low-density lipoprotein cholesterol (LDL-C) concentrations (77.76 +/- 26.25 mg/dL versus 57.7 +/- 23.2 mg/dL, P < 0.05) between the cases and controls. Lower HDL-C levels persisted at 1-3 and more than 3 years of disease duration. No significant differences were seen in the values of other parameters in the lipidogram, such as total cholesterol (TC), triglycerides (TG), and very low-density lipoprotein cholesterol (VLDL-C). Premature atherosclerosis that occurs in KD may be secondary to these lipid metabolism abnormalities.     

Lipoprotein profile in men with peripheral vascular disease. Role of intermediate density lipoproteins and apoprotein E phenotypes.

BACKGROUND. The role of lipoprotein disturbances in the development of peripheral vascular disease (PVD) has not been sufficiently clarified. METHODS AND RESULTS. The relations among concentrations of intermediate density lipoproteins (IDL), apoprotein (apo) B, apo E, and other lipoproteins were studied in 102 men with PVD and 100 healthy men who formed the control group. Patients with PVD had significantly higher levels of serum triglycerides, very low density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL proteins, IDL cholesterol, and IDL triglycerides and lower levels of high density lipoproteins (HDL) than controls. Serum cholesterol and triglycerides were normal in 30 patients (cholesterol, less than 5.2 mmol/l; triglycerides, less than 2.3 mmol/l), who had significant increases in IDL triglycerides and significant decreases in HDL cholesterol compared with the 47 controls, who had normal cholesterol and triglyceride levels. Patients with more severe distal involvement showed higher cholesterol and triglycerides carried by IDL and a greater reduction in HDL cholesterol. Smoking patients with PVD showed increased VLDL cholesterol and VLDL triglycerides and lower HDL concentrations. Apo E polymorphism in our study population does not differ from that reported for other European populations. Alleles epsilon 2 and epsilon 4 had a major impact on serum triglycerides and VLDL lipids in our patients with PVD. CONCLUSIONS. Lipoprotein disturbances are a major risk factor for PVD. IDL abnormalities play an important role in the development and severity of PVD and should also be considered a vascular risk factor in normocholesterolemic and normotriglyceridemic patients.     

Lipoprotein (a) in a population-based study: more significant in Turkish women than men?]

OBJECTIVE: Serum lipoprotein(a) [Lp(a)] concentrations, determined in 665 persons in the 2003/04 survey of the Turkish Adult Risk Factor Study, were investigated in regard to distribution, determinants and relationship to cardiovascular risk factors, metabolic syndrome (MS) and coronary heart disease (CHD). METHODS: Diagnosis of MS was based on Adult Treatment Panel III criteria, that of CHD on the presence of clinical findings and Minnesota coding of resting electrocardiograms. Metabolic syndrome was observed in 44%, CHD in 14% of the study sample. Behring nephelometry was used for Lp(a) values measurements which were log-transformed for analyses because of skewing. RESULTS: Geometric mean values of Lp(a) in 286 men and 379 women, aged 55.5 +/-12.0 years, were 9.46+/-2.90 mg/dL and 10.46+/-3.00 mg/dL (p>0.2), respectively. Apart from a slight correlation with age, Lp(a) exhibited significant positive correlations with apolipoproteins A-I and B, low density lipoprotein-cholesterol (LDL-C) (r =0.15), total cholesterol, high density lipoprotein-cholesterol (HDL-C), systolic blood pressure and log C-reactive protein, and inverse ones with thyroid stimulating hormone (r =-0.25) in men, and log gamma glutamyltransferase in women. Further 10 variables were not significantly correlated in either gender. In linear regression analyses for independent covariates of Lp(a), positive associations were noted with serum total cholesterol and systolic blood pressure, and inverse ones with waist circumference, triglycerides and (only in women) with gamma glutamyltransferase. Logistic regression analyses revealed in men no association with either MS or CHD likelihood. Among women, age-adjusted Lp(a) was associated inversely at a borderline significance with MS, as did levels of Lp(a) >30 mg/dl vs. the remaining sample, controlled for age and MS, display an odds ratio (OR) of 1.62 for prevalent CHD (p=0.20). An OR of 1.92 (p<0.19) was noted in all adults for the coexistence of Lp(a) >30 mg/dl and LDL-C >150 mg/dl, after controlling for age, MS, smoking status and LDL-C categories. CONCLUSION: Lipoprotein(a), the variance of which is known to be overwhelmingly due to the apo(a) isoforms, proved to have a significant inverse independent association with a measure of abdominal obesity. Lipoprotein(a) levels appeared not to be associated with risk for MS or CHD among men. In women, however, high Lp(a) levels were accompanied with an environment less prone to MS, and - without attaining significance -- tended to be associated with CHD likelihood, independent of age and MS. Further studies are warranted in this area.     

Antiproteinuric effect of niceritrol,a nicotinic acid derivative,in chronic renal disease with hyperlipidemia: a randomized trial

PURPOSE: Lipoprotein (a) [Lp(a)] levels increase in patients with renal disease. We administered niceritrol, a nicotinic acid derivative, to patients with chronic renal disease and a high serum Lp(a) level, and studied its effects on lipid metabolism, proteinuria, and renal function. METHODS: Thirty-three patients with chronic renal disease whose serum Lp(a) levels were > or = 15 mg/dL were randomly (but not blindly) assigned to treatment with niceritrol (n = 16) or to an untreated control group (n = 17). Parameters of lipid metabolism, excretion of urinary protein, and renal function were examined for 12 months. RESULTS: Changes in urinary protein excretion, as well as Lp(a) levels, differed significantly between the two groups. The mean (+/- SD) change from baseline in excretion of urinary protein was 0.77 +/- 1.23 g/d in the control group compared with -1.41 +/- 2.26 g/d in the niceritrol group at 12 months (P =0.003). Mean Lp(a) levels increased by 3 +/- 10 mg/dL in the control group compared with a decrease of 10 +/- 13 mg/dL in the niceritrol group at 12 months (P =0.004). The mean creatinine clearance declined by 10 +/- 12 mL/min in the control group, compared with 1 +/- 13 mL/min in the niceritrol group at 12 months (P =0.06). CONCLUSION: Lipid levels improved with niceritrol treatment, whereas the excretion of urinary protein decreased, perhaps slowing the rate of loss of renal function in chronic renal disease.     

Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age

PURPOSE: Because the effects of androgen replacement on lipoprotein levels are uncertain, we sought to determine the effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in elderly men. SUBJECTS AND METHODS: One hundred and eight healthy men more than 65 years of age who had serum testosterone concentrations >1 SD below the mean for young men were randomly assigned to receive either testosterone (54 men; 6 mg/day) or placebo (54 men) transdermally in a double-blind fashion for 36 months. Serum concentrations of lipids and apolipoproteins were measured, and cardiovascular events recorded. RESULTS: Serum total cholesterol concentrations decreased in both the testosterone-treated men and placebo-treated men, but the 3-year mean (+/- SD) decreases in the two groups (testosterone treated, -17 +/- 29 mg/dL; placebo treated, -12 +/- 38 mg/dL) were not significantly different from each other (P = 0.4). Similarly, serum low-density lipoprotein (LDL) cholesterol levels decreased in both treatment groups, but the decreases in the two groups (testosterone treated, -16 +/- 24 mg/dL; placebo treated, -16 +/- 33 mg/dL) were similar (P = 1.0). Levels of high-density lipoprotein (HDL) cholesterol, triglycerides, and apolipoproteins A-I and B did not change. Lipoprotein(a) levels increased in both groups by similar amounts (testosterone treated, 3 +/- 9 mg/dL; placebo treated, 4 +/- 6 mg/dL; P = 1.0). The number of cardiovascular events was small and did not differ significantly between the testosterone-treated men (9 events) and the placebo-treated men (5 events) during the 3-year study (relative risk = 1.8; 95% confidence interval: 0.7 to 5.0). CONCLUSIONS: As compared with placebo, transdermal testosterone treatment of healthy elderly men for 3 years did not affect any of the lipid or apolipoprotein parameters that we measured. The effect of testosterone treatment on cardiovascular events was unclear, because the number of events was small.     

Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease.

The prevalence of abnormalities of lipoprotein cholesterol and apolipoproteins A-I and B and lipoprotein (a) [Lp(a)] was determined in 321 men (mean age 50 +/- 7 years) with angiographically documented coronary artery disease and compared with that in 901 control subjects from the Framingham Offspring Study (mean age 49 +/- 6 years) who were clinically free of coronary artery disease. After correction for sampling in hospital, beta-adrenergic medication use and effects of diet, patients had significantly higher cholesterol levels (224 +/- 53 vs. 214 +/- 36 mg/dl), triglycerides (189 +/- 95 vs. 141 +/- 104 mg/dl), low density lipoprotein (LDL) cholesterol (156 +/- 51 vs. 138 +/- 33 mg/dl), apolipoprotein B (131 +/- 37 vs. 108 +/- 33 mg/dl) and Lp(a) levels (19.9 +/- 19 vs. 14.9 +/- 17.5 mg/dl). They also had significantly lower high density lipoprotein (HDL) cholesterol (36 +/- 11 vs. 45 +/- 12 mg/dl) and apolipoprotein A-I levels (114 +/- 26 vs. 136 +/- 32 mg/dl) (all p less than 0.005). On the basis of Lipid Research Clinic 90th percentile values for triglycerides and LDL cholesterol and 10th percentile values for HDL cholesterol, the most frequent dyslipidemias were low HDL cholesterol alone (19.3% vs. 4.4%), elevated LDL cholesterol (12.1% vs. 9%), hypertriglyceridemia with low HDL cholesterol (9.7% vs. 4.2%), hypertriglyceridemia and elevated LDL cholesterol with low HDL cholesterol (3.4% vs. 0.2%) and Lp(a) excess (15.8% vs. 10%) in patients versus control subjects, respectively (p less than 0.05). Stepwise discriminant analysis indicates that smoking, hypertension, decreased apolipoprotein A-I, increased apolipoprotein B, increased Lp(a) and diabetes are all significant (p less than 0.05) factors in descending order of importance in distinguishing patients with coronary artery disease from normal control subjects. Not applying a correction for beta-adrenergic blocking agents, sampling bias and diet effects leads to a serious underestimation of the prevalence of LDL abnormalities and an overestimation of HDL abnormalities in patients with coronary artery disease. However, 35% of patients had a total cholesterol level less than 200 mg/dl after correction; of those patients, 73% had an HDL cholesterol level less than 35 mg/dl.     

Lipoprotein(a) in coronary heart disease: a case-control study

To determine the significance of lipoprotein(a) levels in coronary heart disease patients, a case-control study was performed with 48 newly diagnosed coronary heart disease patients and 23 controls who were evaluated using clinical history and biochemical examination. Lipoprotein(a) was measured by quantitative latex-enhanced immunoturbidimetric method. Geometric means of biochemical parameters were obtained. Comprehensive lipid tetrad index was calculated using a previously validated formula. There was no significant difference in prevalence of diabetes, hypertension and smoking in cases and controls. Dietary intake of calories, fats, fatty acids and antioxidant vitamins was also similar. The levels of fasting glucose, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides were not significantly different in cases and controls (p > 0.05). Low-density lipoprotein/high-density lipoprotein ratio (4.33 +/- 1.5 vs 4.29 +/- 1.8) and total cholesterol/high-density lipoprotein ratio (6.59 + 1.7 vs 6.69 +/- 2.2) were similar. The mean lipoprotein(a) levels were significantly greater in cases (11.95 +/- 2.8 mg/dL, range 1-102 mg/dL) as compared to controls (6.68 +/- 3.4 mg/dL, range 1-73 mg/dL) (t = 2.08, p = 0.041). As compared to controls, in coronary heart disease cases, mean lipoprotein(a) levels in patients upto 50 years (10.27 +/- 2.8 vs 7.27 +/- 3.4 mg/dL) as well as those over 50 years (12.99 +/- 2.9 vs 4.91 +/- 3.5 mg/dL) were significantly more (p < 0.05). Coronary heart disease patients had a slightly greater prevalence of high lipoprotein(a) levels, 20 mg/dL or more (31.3 vs 13.0%; chi 2 = 2.83, l-tailed p < 0.05). Comprehensive lipid tetrad index (total cholesterol x triglycerides x lipoprotein(a) divided by high-density lipoprotein cholesterol) was also slightly higher in cases (14688.2 +/- 3.6) than in controls (8358.2 +/- 4.3) (t = 1.68, 1-tailed p < 0.05). This study shows that lipoprotein(a) levels are significantly more in both younger and older coronary heart disease patients as compared to controls.     

Oxidized low density lipoprotein is a prognostic marker of transplant-associated coronary artery disease

Retrospective studies identified oxidized low density lipoprotein (LDL) in the blood as a diagnostic marker of coronary artery disease (CAD). This prospective study sought to determine the prognostic value of oxidized LDL for CAD in cardiac transplant patients. Oxidized LDL was measured in 99 cardiac transplant patients with normal coronary angiograms at baseline and was measured again after a median follow-up of 2 years at the time of a second angiogram. Twenty-one patients developed angiographically detectable cardiac transplant vasculopathy (cases), and 78 individuals did not (controls). Cases had significantly higher baseline plasma levels of oxidized LDL than did controls: 1.18+/-0.70 versus 0.57+/-0.20 mg/dL (mean+/-SD, P<0.0001). The increase of oxidized LDL at the end of the follow-up was significantly higher in cases than in controls: 0. 75+/-0.73 mg/dL versus 0.14+/-0.27 mg/dL (P<0.0001). Baseline levels of oxidized LDL predicted cardiac transplant vasculopathy (chi(2)=16, P<0.0001) independent of pretransplant ischemic cardiomyopathy, time after transplantation, age, and serum levels of LDL and high density lipoprotein cholesterol. The development of transplant CAD was associated with a further increase of plasma levels of oxidized LDL (chi(2)=14, P=0.0002). Oxidized LDL is a prognostic marker of transplant CAD.     

Determinants of serum HDL-C level in a Tehran urban population: the Tehran Lipid and Glucose Study

BACKGROUND AND AIM: Decreased serum high-density lipoprotein cholesterol (HDL-C) is one of the most common lipid disorders in patients with coronary artery disease (CAD). Existing evidence suggests that every 1 mg/dL decrease in serum HDL-C increases the risk of CAD by 2-3%. This study was performed in the year 2000 to study HDL-C determinants in a Tehran population. METHODS AND RESULTS: We studied 9514 subjects (3942 men and 5572 women) aged 20-69 years, who participated in the Tehran Lipid and Glucose Study (TLGS), completed a personal history questionnaire (especially concerning physical activity and cigarette smoking), and underwent a clinical examination including anthropometric and blood pressure measurements. Serum total cholesterol, triglyceride and HDL-C levels were measured, and OGTT was used to define diabetic patients according to WHO criteria. The women had a significantly higher mean HDL-C level than the mean (45 +/- 11 vs 38 +/- 9 mg/dL; p < 0.001); low HDL-C levels (< 35 mg/dL) were observed in 31% of the men and 13% of the women (p < 0.001). Obese subjects (BMI > or = 30 kg/m2) had a significantly lower HDL-C level than the normal subjects (42 +/- 11 vs 44 +/- 11 mg/dL: p < 0.001), and those with truncal obesity (WHR > or = 0.95 in men and > or = 0.8 in women) lower HDL-C levels than the normal subjects (37 +/- 9 vs 39 +/- 10 mg/dL in men and 44 +/- 11 vs 42 +/- 11 mg/dL in women; p < 0.001 for both). Smokers had a significantly lower HDL-C level than non-smokers (38 +/- 10 vs 43 +/- 11 mg/dL; p < 0.001) and a low HDL-C level was twice as common (36.4 vs 18.2%). Passive smokers also had lower HDL-C levels (42 +/- 11 vs 43 +/- 11 mg/dL; p < 0.001). Mean serum HDL-C was significantly lower in hypertriglyceridemic than those with normal triglycerides levels (men: 4 +/- 8 vs 40 +/- 9 mg/dL, p < 0.001; women: 40 +/- 10 vs 47 +/- 11 mg/dL, p < 0.01). Mean HDL-C levels were similar in subjects with different degrees of physical activity, as well as between diabetics and non-diabetics and hypertensive and normotensive subjects. Multiple stepwise regression analysis showed that the determinants of serum HDL-C levels were, in order of entering the model: hypertriglyceridemia (OR 3.4, p < 0.001), male sex (OR 3.1, p < 0.001), cigarette smoking (OR 1.7, p < 0.001), obesity (OR 1.4, p < 0.01), age (OR 0.9, p < 0.05), high WHR (OR 1.2, p < 0.05), and passive smoking (OR 1.1, p < 0.05). Physical activity, hypertension, and diabetes mellitus did not enter the predictive model. CONCLUSION: Apart from age and sex which are constitutional, and unmodifiable variables, the determinants of HDL-C level (hypertriglyceridemia, obesity, truncal obesity, cigarette smoking, and passive smoking) can be used in community CAD prevention programmes.     

Serum lipids,lipoproteins and apolipoproteins levels in patients with nonalcoholic steatohepatitis

GOALS/BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a form of liver disease that is histologically indistinguishable from alcoholic hepatitis but occurs in persons who do not consume alcohol in excess. The objectives of this study are to measure serum levels of lipids, lipoproteins and apolipoproteins (apo AI, apo B), lipoprotein (a) [Lp (a)] in patients with nonalcoholic steatohepatitis (NASH), and to investigate the relationship with liver histology. STUDY: The scope of this study is composed of 36 patients (27 males, 9 females) with NASH, diagnosed by biochemical liver function tests, sonographic examination of liver and liver biopsy and 32 healthy adults as a control group (22 males, 10 females). Serum lipids, lipoproteins and apo AI, apo B, and Lp (a) measurements were taken in the study group and controls, and a correlation with histopathologic findings was searched for. RESULTS: Serum mean levels (+/- SD as mg/dl) of total cholesterol (201.05 +/- 34.48), triglyceride (225.94 +/- 156.50), and LDL-cholesterol (111.77 +/- 19.85) in patients with NASH were significantly higher than those of the control group (170.68 +/- 31.06; 138.81 +/- 49.96; 100.68 +/- 17.98; respectively) and serum HDL-cholesterol level (41.22 +/- 2.47) was less than that of the control group (45.06 +/- 8.32) (P = 0.017). The serum mean level of apo AI (151.54 +/- 30.90) in the study group was lower than that of the controls (160.62 +/- 22.11), but the difference was not significant (P = 0.17). However, the serum apo AI level in patients with liver fibrosis (140.62 +/- 35.62) was significantly lower than that of patients without liver fibrosis (164.57 +/- 25.47) (P = 0.01). The serum mean level of apo B (89.80 +/- 20.62) in the patients was significantly higher than the control group (73.25 +/- 25.39) (P = 0.004), but not correlate with liver histopathology. The serum Lp (a) levels in both the patients (13.09 +/- 9.61) and the controls (12.01 +/- 7.50) were not different (P = 0.61). Hypertriglyceridemia (above 220 mg/dL) had a positive correlation with steatosis of the liver (r = 0.333, P = 0.04) and a negative correlation with liver fibrosis (r = -0.438, P = 0.008). There was a significant negative correlation between apo AI and steatosis (r = -0.360, P = 0.03), inflammation (r = -0.364, P = 0.03) and fibrosis of liver (r = -0.418, P = 0.01). A positive correlation of serum LDL-cholesterol (r = 0.507, P = 0.002) and Lp(a) (r = 0.394, P = 0.01) concentrations with liver fibrosis was also noted. CONCLUSIONS: Abnormalities of lipid metabolism such as the increase of serum triglyceride, cholesterol and LDL-cholesterol level and decrease of HDL-cholesterol may be the contributing factors in the development of NASH. The decrease in apo AI and the increase in LDL and Lp (a) in patients were correlated with liver fibrosis. Apo AI may be a serum marker for liver fibrosis in patients with NASH.     

Lipoprotein (a) levels and apolipoprotein (a) isoform size in patients with subclinical hypothyroidism: effect of treatment with levothyroxine.

The increased risk for ischemic heart disease (IHD) associated with subclinical hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited information on the effect of SH on lipoprotein (a) [Lp(a)], which is considered a significant predictor of IHD. Serum Lp(a) levels are predominantly regulated by apolipoprotein [apo(a)] gene polymorphisms. The aim of our study was to evaluate the Lp(a) levels and apo(a) phenotypes in patients with SH compared to healthy controls as well as the influence of levothyroxine substitution therapy on Lp(a) values in relation to the apo(a) isoform size. Lp(a) levels were measured in 69 patients with SH before and after restoration of a euthyroid state and in 83 age- and gender-matched healthy controls. Apo(a) isoform size was determined by sodium dodecyl sulfate (SDS) agarose gel electrophoresis followed by immunoblotting and development via chemiluminescence. Patients with SH exhibited increased Lp(a) levels compared to controls (median value 10.6 mg/dL vs. 6.0 mg/dL, p = 0.003]), but this was not because of differences in the frequencies of apo(a) phenotypes. There was no association between thyrotropin (TSH) and Lp(a) levels in patients with SH. In subjects with either low (LMW; 25 patients and 28 controls) or high (HMW; 44 patients and 55 controls) molecular weight apo(a) isoforms, Lp(a) concentrations were higher in patients than in the control group (median values 26.9 mg/dL vs. 21.8 mg/dL, p = 0.02 for LMW, and 6.0 mg/dL versus 3.3 mg/dL, p < 0.001 for HMW). Levothyroxine treatment resulted in an overall reduction of Lp(a) levels (10.6 mg/dL baseline vs. 8.9 mg/dL posttreatment, p = 0.008]). This effect was mainly evident in patients with LMW apo(a) isoforms associated with high baseline Lp(a) concentrations (median values 26.9 mg/dL vs. 23.2 mg/dL pretreatment and posttreatment, respectively; p = 0.03). In conclusion, even though a causal effect of thyroid dysfunction on Lp(a) was not clearly demonstrated in patients with SH, levothyroxine treatment is beneficial, especially in patients with increased baseline Lp(a) levels and LMW apo(a) isoforms.     

Lipoprotein(a) level and lipids in type 2 diabetic patients and their normoglycemic first-degree relatives in type 2 diabetic pedigrees

We investigated alterations of serum levels of Lp(a) and lipid profiles in type 2 diabetic patients and their normoglycemic first-degree relatives to evaluate the potential genetic association among these subjects. Serum Lp(a), triglycerride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein (LDL-C) levels were analyzed in 62 type 2 diabetic patients and 67 normoglycemic first-degree relatives from 29 type 2 diabetic pedigrees, and 45 healthy controls without family histories of diabetes. Dyslipidemia was observed in diabetics and their normoglycemic first-degree relatives. While higher serum TG levels were observed in both type 2 diabetics and their first-degree relatives than those in controls, higher TG levels in diabetics were found when compared with those in first-degree relatives. Meanwhile, lower serum HDL-C levels were observed in both type 2 diabetic patients and their first-degree relatives than those in controls. No significant difference of serum TC and LDL-C levels was found among the three groups. On the other hand, we did not observe significant differences of serum Lp(a) levels between type 2 diabetic patients and normoglycemic first-degree relatives, nor were any significant differences observed between diabetic patients and healthy controls (24.6+/-19.9 vs. 25.8+/-21.2, and 21.3+/-20.5 mg/dl). Although the average serum Lp(a) levels were similar in all subgroups, we did observe a positive correlation of Lp(a) between type 2 diabetic patients and their offspring (r=0.448, P<0.01), suggesting a potential genetic control for Lp(a) levels in type 2 diabetics families.     

Do Turkish adults really have lower serum levels of high-density lipoprotein cholesterol?

BACKGROUND: Coronary heart disease is the leading cause of death in Turkey. The Turkish Heart Study and TEKHARF study have been carried out at various times and in different parts of Turkey and have suggested that the Turkish population has a low high-density lipoprotein-cholesterol (HDL-C) level. However, in our daily practice, mean HDL-C levels were not as low as previously reported. Here, we investigated the lipid profile, especially the HDL-C level, in the population of the Duzce region of northwest Turkey. METHODS: Serum triglyceride, total cholesterol, and HDL-C levels were measured in 674 healthy volunteers (398 women and 276 men); low-density lipoprotein cholesterol (LDL-C) levels were calculated using the Friedewald equation. RESULTS: The mean serum HDL-C level was 46.1 +/- 9.8 mg/dl in men and 53.2 +/- 10.7 mg/dl in women; these values are higher than expected based on the Turkish Heart Study. The mean serum total cholesterol level was 196.7 +/- 43.2 mg/dL in men and 198.4 +/- 43.9 mg/dL in women; the mean LDL-C level was 119.6 +/- 34.9 mg/dL in men and 118.7 +/- 34.1 mg/dL in women; and the mean serum triglyceride level was 151.4 +/- 80.9 mg/dL in men and 132.1 +/- 68.9 mg/dL in women. CONCLUSIONS: Our finding that the HDL-C level in this population was higher than the previously reported levels in Turkey indicates that HDL-C levels may not be as low as previously thought. We believe that lower HDL-C levels that were previously reported might be due to the difference between techniques of analysis, nutritional status, and percent of subjects who were fasting in the day of analysis or improper subject inclusion which did not reflect the Turkish population causing selection bias.     

Serum Lp(a) level as a predictor of vein graft stenosis after coronary artery bypass surgery in patients

Although the serum lipoprotein fraction Lp(a) has been associated with coronary artery atherosclerosis, its relationship to narrowing of saphenous vein grafts has not previously been elucidated. We therefore measured serum Lp(a) levels in 167 symptomatic patients undergoing cardiac catheterization who had had coronary artery bypass surgery 0.7 to 14.3 years earlier. Lp(a), total cholesterol, and total triglyceride levels were compared with the degree of saphenous vein graft stenosis to test for any association. Serum Lp(a) levels were significantly associated with the degree of stenosis of saphenous vein grafts (r = .24, p = .002). Mean Lp(a) levels (mg/dl) in the 135 patients with stenosis were almost double (32.0 +/- 32.7, mean +/- SD) those in the 32 patients with no graft stenosis (16.7 +/- 22.6; p = .002). Graft stenosis was not associated with previous myocardial infarction, hypertension, obesity, diabetes, or smoking. Serum cholesterol levels (mg/dl) were slightly higher in the stenosis group (251.3 +/- 69) than in the no-stenosis group (231.8 +/- 48.8), but the difference was of borderline significance (p = .06). A stepwise increase in mean Lp(a) was found in groups of patients with increasing vein graft stenosis. At a serum Lp(a) level of 31.6 mg/dl or above, 92% of the patients demonstrated vein graft stenosis. Thus, patients with elevated Lp(a) levels have an increased risk of developing saphenous vein graft stenosis after coronary bypass surgery.     

Low-density lipoprotein particle size, triglyceride-rich lipoproteins, and glucose tolerance in non-diabetic men with essential hypertension

The aim of the study is to investigate serum lipoproteins abnormalities including low-density lipoprotein (LDL) particle size, and their relationship with other cardiovascular risk factors in men with essential hypertension. Plasma glucose and serum insulin levels during oral glucose tolerance test (OGTT), serum lipoprotein(a), apolipoprotein (apo) A-I. apo B. cholesterol and triglycerides in serum and in lipoproteins, and LDL particle diameter were measured in thirty-eight consecutive newly-diagnosed non-diabetic untreated hypertensive men and 38 healthy male controls. Plasma glucose at baseline, 60 and 120 min during OGTT was significantly higher in patients than controls whereas serum insulin levels did not differ between patients and controls. Serum apo B and triglycerides were significantly raised in patients compared with controls (1.08 +/- 0.17 g/L [mean +/- SD] vs 0.97 +/- 0.22 g/L. p < 0.05, and 1.56 +/- 0.90 mmol/L vs 1.15 +/- 0.57 mmol/L, p < 0.05, respectively). Very-low-density lipoprotein (VLDL) triglycerides and LDL-cholesterol were increased in patients compared with controls (0.89 +/- 0.79 mmol/L and 0.54 +/- 0.35 mmol/L, p < 0.05, and 4.08 +/- 0.85 mmol/L and 3.60 +/- 0.92 mmol/L, p < 0.05, respectively) whereas high-density lipoprotein (HDL) cholesterol was lower in patients compared with controls 0.95 +/- 0.22 mmol/L and 1.07 +/- 0.20 mmol/L, p < 0.05). Adjustment for body mass index, abdominal/hip perimeter ratio and area under the glucose curve did not attenuate the relationship between hypertension and VLDL-triglycerides. Six patients and two controls had a mean LDL diameter < or = 25.5 nm and in the former serum triglycerides ranged from 1.86 mmol/L to 2.37 mmol/L. Mean LDL particle diameter in both patients and controls showed an inverse relationship with log-transformed serum triglycerides (r = - 0.51, p < 0.001 and r = - 0.47, p < 0.005, respectively). Among patients, those with serum triglycerides > or = [corrected] 1.58 mmol/L had a lesser mean LDL diameter than those with triglycerides above this threshold (25.78 +/- 0.47 nm vs 26.30 +/- 0.35 nm, p < 0.001). Higher plasma glucose, serum apo B and LDL-cholesterol as well as the decrease in serum HDL-cholesterol in patients with hypertension are consistent with high coronary heart disease risk. Not only mild hypertriglyceridemia but also high-normal serum triglycerides in themselves or as a surrogate of a predominance of small dense LDL particles in plasma convey an additional risk for cardiovascular disease in hypertensive patients even though routine plasma lipids are within or near normal range.     

Efficacy and tolerability of combined treatment with L-carnitine and simvastatin in lowering lipoprotein(a) serum levels in patients with type 2 diabetes mellitus

Lipoprotein(a) [Lp(a)] concentration is generally related to coronary artery disease (CAD) and cerebrovascular disease. However, at present, few interventions are available to lower Lp(a) concentrations. We investigated the effects of l-carnitine, co-administered with simvastatin, on hyper-Lp(a) in patients with type 2 diabetes mellitus. We conducted an open, randomised, parallel-group study, in one investigational center (University hospital). Fifty-two patients with type 2 diabetes mellitus, a triglyceride serum levels <400mg/dL (<4.5 mmol/L), and Lp(a) serum levels >20mg/dL (0.71 mmol/L) were randomised to receive simvastatin alone (n=26) or simvastatin plus l-carnitine (n=26) for 60 days. Simvastatin was administered, in both groups, at a dosage of 20 mg/day, while l-carnitine was administered at a dosage of 2g/day once daily. Both treatments were given orally. Serum levels of triglycerides, total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol (total cholesterol minus HDL cholesterol), apolipoprotein B, and Lp(a) were measured at baseline and 60 days after starting treatment. No difference in time by groups (simvastatin and simvastatin plus l-carnitine) were observed in the reduction of LDL cholesterol, non-HDL cholesterol, and apoB serum levels. On the other hand, Lp(a) serum levels increase from baseline to 60 days in the simvastatin group alone versus a significant decrease in the combination group. Our findings provide support for a possible role of combined treatment with l-carnitine and simvastatin in lowering Lp(a) serum levels in patients with type 2 diabetes mellitus than with simvastatin alone. Our results strongly suggest that l-carnitine may have a role among lipid-lowering strategies.     

Quantification of lipoprotein(a) and apolipoprotein(a) in plasma and lipoprotein fractions in the hypertriglyceridemic state.

Lipoprotein(a) [Lp(a)] is a risk factor for coronary heart disease (CHD) in particular in association with high low density lipoprotein (LDL) cholesterol concentrations. Hypertriglyceridemia on the other hand has been found to be associated with low Lp(a) values. This observation could be confirmed in 851 patients of the outpatient lipid clinic. Lp(a) median levels were 2.7-fold higher in patients with triglycerides below 200 mg/dl as compared with patients expressing triglyceride levels above 200 mg/dl (19 vs 7 mg/dl, P < 0.0001). In contrast to these data apolipoprotein(a) [apo(a)] has been detected in triglyceride-rich lipoproteins (TRL). To find out whether the presence of apo(a) in TRL is determined by the concentration of these particles, apo(a) concentrations were measured in TRL in fasting plasma of ten hypertriglyceridemic patients and ten normal controls with Lp(a) serum levels above 25 mg/dl. The apo(a) concentration in TRL did not show statistically significant differences between controls and patients (2.0+/-0.9 vs 1.8+/-1.6 mg/dl). In the second part of the study apo(a) levels in TRL were measured before and after fat feeding in eight healthy volunteers. Again no significant differences were observed in the apo(a) concentrations of the d < 1.006 a ml fraction before and after fat feeding (1.03+/-1.06 vs 0.81+/-0.63 mg/dl). In summary, this study fails to show an association of apo(a) with TRL for different states of hypertriglyceridemia. This negative finding is shown for constant particle numbers but might not be true if the particle number in TRL increases.