Obesity and cardiovascular risk factors in type 2 diabetes: results from the Swedish National Diabetes Register

OBJECTIVES: To compare obese with normal and overweight type 2 diabetic patients regarding body mass index (BMI) and cardiovascular risk factors, and to analyse changes in weight versus risk factors. DESIGN AND SETTING: A cross-sectional study of 44 042 type 2 patients, and a 6-year prospective study of 4468 type 2 patients. RESULTS: Obese patients (BMI > or = 30 kg m(-2)), 37% of all patients, had high frequencies of hypertension (88%), hyperlipidaemia (81%) and microalbuminuria (29%). Only 11% had blood pressure <130/80 mmHg. Their ratio of triglycerides to HDL cholesterol was considerably elevated, whilst the mean total and LDL cholesterol were similar as in normal weight subjects. Obese patients had elevated odds ratios for hypertension, hyperlipidaemia and microalbuminuria: 2.1, 1.8 and 1.4 in the cross-sectional study, similarly confirmed in the prospective 6-year study. BMI was an independent predictor of these risk factors (P < 0.001), although only slightly associated with HbA1c and not with total or LDL cholesterol. A change in BMI during the prospective study was related to a change in HbA1c in patients treated with diet and oral hypoglycaemic agents (OHAs) but not with insulin. In all patients, an increase in BMI was related to the development of hypertension, and a change in BMI to change in blood pressure, also mostly confirmed when treated with diet, OHAs or insulin. CONCLUSIONS: The high frequencies of risk factors in obese type 2 patients implies an increased risk of cardiovascular disease and the need for therapeutic measures. The paradox that hypoglycaemic treatment accompanied by weight gain may increase cardiovascular risk factors seems to be verified here concerning hypertension but not concerning microalbuminuria.     

Efficacy of cholesterol levels and ratios in predicting future coronary heart disease in a Chinese population

In this study, we assessed the efficacy of various lipid and lipoprotein measurements at baseline for predicting the risk for coronary heart disease (CHD) and determined the associated risk of CHD in subgroups stratified by different lipid and lipoprotein screening strategies to evaluate the adequacy of current total and low-density lipoprotein (LDL) cholesterol-based approaches in lipid management. We analyzed data from the Chin-Shan Community Cardiovascular Cohort study, a Chinese population-based prospective cohort study that began in 1990. During an 8-year follow-up period, 213 of 3,159 participants (6.7%) without CHD (aged > or =35 years) developed CHD. The total cholesterol/high-density lipoprotein (HDL) cholesterol ratio was the most powerful lipoprotein predictor of future CHD (hazard ratio 1.21 for a 1.0 increment in ratio; p <0.001). Subjects with "high-risk" LDL cholesterol levels (>160 mg/dl) and low total cholesterol/HDL cholesterol ratios (< or =5) had an incidence of CHD similar to those with low levels of both LDL cholesterol (< or =130 mg/dl) and total cholesterol/HDL cholesterol ratios (4.9% vs 4.6%). In contrast, subjects with "low-risk" LDL cholesterol levels (< or =130 mg/dl) and high total cholesterol/HDL cholesterol ratios (>5) had a 2.5-fold higher incidence of CHD than those with similar LDL cholesterol levels but low total cholesterol/HDL cholesterol ratios (p <0.001). Compared with using an LDL cholesterol level of 130 mg/dl as the cut-off point, using a total cholesterol/HDL cholesterol ratio of 5 was associated with superior specificity (73% vs 59%, p <0.001) and accuracy (72% vs 58%, p <0.001), and similar sensitivity (50% vs 53%). Our data indicate that current guidelines for lipid management may misclassify subjects with high levels of HDL and LDL cholesterol as well as those with low levels of HDL and LDL cholesterol. Using the ratio of total to HDL cholesterol as the initial screening tool can obviate this discrepancy.     

A population-based, cross-sectional comparison of lipid-related indexes for symptoms of atherosclerotic disease

Current lipid guidelines recommend that therapy be targeted primarily at low-density lipoprotein (LDL) cholesterol, and that other lipid indexes may be used as secondary or supplementary targets. Emerging data have suggested that measures such as non-high-density lipoprotein (HDL) cholesterol, apolipoprotein-B, or the total/HDL cholesterol ratio may be more predictive of cardiovascular risk than LDL cholesterol. We conducted a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey to directly compare the strengths of the associations among various lipid-related indexes and clinical features consistent with atherosclerotic disease. From approximately 9,500 data sets in the overall analysis, the apolipoprotein-B/HDL cholesterol ratio emerged as the strongest correlate (odds ratio 1.177 per 1 mg/dl increment, 95% confidence interval 1.063 to 1.302, p <0.01), followed by the total or non-HDL cholesterol/HDL cholesterol ratio (odds ratio for each 1.070 per 1 mg/dl increment, 95% confidence interval 1.024 to 1.118, p <0.01), followed by the triglyceride/HDL cholesterol ratio (odds ratio 1.033 per 1 mg/dl increment, 95% confidence interval 1.011 to 1.056, p <0.01). Neither LDL cholesterol nor the LDL/HDL cholesterol ratio correlated significantly. Parallel analyses comparing tertile extremes and analyses in subgroups determined by gender, age, and body mass index revealed similar findings. The LDL/HDL cholesterol ratio was only significant for lean patients. In conclusion, these observations add to the published data suggesting that LDL cholesterol may not be the best target of lipid-lowering treatment strategies.     

Prevalence of low high-density lipoprotein cholesterol in patients with documented coronary heart disease or risk equivalent and controlled low-density lipoprotein cholesterol

Current guidelines identify low-density lipoprotein (LDL) cholesterol as the primary target for cardiovascular prevention but also recognize low high-density lipoprotein (HDL) cholesterol as an important secondary target. This study was conducted to determine the prevalence of low HDL cholesterol in a contemporary ambulatory high-risk population across various LDL cholesterol levels, including patients taking statins. Screening of 44,052 electronic medical records from a primary care practice identified 1,512 high-risk patients with documented coronary heart disease (CHD) or CHD risk equivalents. Low HDL cholesterol (< or =40 mg/dl in men, < or =50 mg/dl in women) was present in 66% of the 1,512 patients. Low HDL cholesterol was prevalent across all LDL cholesterol levels but most prevalent in patients with LDL cholesterol < or =70 mg/dl (79% vs 66% in those with LDL cholesterol 71 to 100 mg/dl and 64% in patients with LDL cholesterol >100 mg/dl, p <0.01). Low HDL cholesterol was equally and highly prevalent in patients taking statins (67%) and those not taking statins (64%) (p = NS). HDL cholesterol and LDL cholesterol levels correlated poorly (R(2) = 0.01), and this was unaffected by gender or statin treatment. In conclusion, in high-risk patients with CHD or CHD risk equivalents, low HDL cholesterol levels remain prevalent despite statin treatment and the achievement of aggressive LDL cholesterol goals.     

Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia

Ezetimibe is a lipid-lowering drug that inhibits the intestinal absorption of dietary and biliary cholesterol by blocking passage across the intestinal wall. The efficacy and safety of adding ezetimibe to ongoing statin therapy in patients with primary hypercholesterolemia was evaluated in a randomized, double-blind, placebo-controlled study. The study group included 769 adults (aged > or =18 years) with primary hypercholesterolemia who had not achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel II goals with dietary alteration and statin monotherapy. Patients receiving a stable dose of a statin for > or =6 weeks were randomized to receive concurrent treatment with placebo (n = 390) or ezetimibe (n = 379), 10 mg/day, in addition to continuing their open-label statin for 8 weeks. The primary efficacy variable was the percent change in low-density lipoprotein (LDL) cholesterol from baseline with statin monotherapy to end point after intervention (secondary variables: high-density lipoprotein [HDL] cholesterol and triglycerides). Ongoing statin therapy plus ezetimibe led to changes of -25.1% for LDL cholesterol (HDL cholesterol +2.7%; triglycerides -14.0%) compared with LDL cholesterol -3.7% (p <0.001), HDL cholesterol +1.0% (p <0.05), and triglycerides -2.9% (p <0.001) for placebo added to ongoing statin therapy. Among patients not at LDL cholesterol goal at on-statin baseline, 71.5% receiving statin plus ezetimibe versus 18.9% receiving statin plus placebo reached goal at end point (odds ratio 23.7; p <0.001). The co-administration of statin and ezetimibe was generally well tolerated. Adding ezetimibe to ongoing statin therapy led to substantial additional reduction in LDL cholesterol levels, facilitating attainment of NCEP goals. Ezetimibe offers a new therapeutic option for patients receiving statins who require further reduction in LDL cholesterol.     

Plasma oxysterols and vitamin E concentrations and lipid profile in morbidly obese women

Morbid obesity (BMI > or = 40 kg/m2) is accompanied by lipid disturbances which may be involved in the increased incidence of atherosclerosis, arterial hypertension and non-insulin-dependent diabetes mellitus. The aim of the study was to assess concentrations of total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides (TG), products of cholesterol peroxidation--oxysterols, and the major lipophilic antioxidant--vitamin E, in morbidly obese women without coexisting diseases. The study was performed in 11 morbidly obese women (BMI 42.21 +/- 2.21 kg/m2) and 11 healthy volunteers (BMI 23.0 +/- 2.31 kg/m2). Obese women demonstrated higher concentrations of TG (2.03 +/- 0.78 vs. 0.99 +/- 0.37 mmol/l; p < 0.05), 7-ketocholesterol (7-K) (89.85 +/- 63.03 vs. 41.90 +/- 17.33 ng/ml; p < 0.05) and 7-hydroxycholesterol (7-OH) (456.04 +/- 199.22 vs. 132.37 +/- 53.96 ng/ml; p < 0.05), and lower HDL-cholesterol level (0.74 +/- 0.10 vs. 1.30 +/- +/- 0.17 mmol/l; p < 0.05) compared to the control group, while there were no significant differences between the two groups in concentrations of TC, LDL-cholesterol and vitamin E. Plasma vitamin E/(TC + TG) ratio was lower in obese women (6.42 +/- 2.61 vs. 10.76 +/- 4.57 mumol/mmol; p < 0.05). Tocoferols concentration correlated positively with TG (r = 0.45; p < 0.05) and negatively with 7-OH (r = -0.44; p < 0.05) levels. Moreover, concentration of 7-K correlated positively with the level of HDL (r = 0.54; p < 0.05). In conclusion, despite normal TC and LDL-cholesterol concentrations, there are disturbances in cholesterol peroxidation processes, with the rise in oxysterol levels and the decrease in vitamin E concentration in lipoproteins, which may be involved in the increased incidence of cardiovascular diseases in morbidly obese women.     

Competing impact of excess weight versus cardiorespiratory fitness on cardiovascular risk

Obesity is a risk factor for cardiovascular disease, whereas high cardiorespiratory fitness (CRF) is cardioprotective. This study evaluated the competing effect of weight and fitness on biomarkers of cardiovascular risk in a nationally representative sample of 2,112 adults (20 to 49 years of age; body mass index [BMI] > or =18.5 kg/m(2)) without previously diagnosed cardiovascular disease from the National Health and Nutrition Examination Survey 1999 to 2002. CRF levels were assigned using age- and gender-specific reference points of estimated maximal oxygen consumption calculated from submaximal graded exercise treadmill testing. CRF was also categorized by sample-specific tertiles of maximal oxygen consumption. Weight was categorized using BMI. Fasting insulin level >12.2 mU/L, C-reactive protein level > or =3.0 mg/L, and total cholesterol/high-density lipoprotein ratio (TC/HDL) >5 characterized increased cardiovascular risk. CRF and BMI were independently associated with increased fasting insulin and C-reactive protein (p <0.05). When patients with low, moderate, and high CRF were further stratified as normal, overweight, or obese, weight remained significantly associated with increased fasting insulin, C-reactive protein, and TC/HDL (p <0.001), but CRF did not. Logistic regressions evaluating increased fasting insulin, C-reactive protein, and TC/HDL demonstrated no significant differences in overweight/obese patients by CRF level after adjustment for other factors. Significant differences were present between normal-weight and overweight or obese patients regardless of fitness level. Analyses using tertiles of CRF yielded similar results. In conclusion, patients who are "fat but fit" require weight-loss interventions to improve their cardiovascular risk profiles. Future interventions should emphasize weight control, even for those with high CRF.     

Cardiology management improves secondary prevention measures among patients with coronary artery disease

OBJECTIVES: The goal of this study was to determine if cardiology subspecialty involvement improves the attainment of recommended low-density lipoprotein (LDL) cholesterol and blood pressure (BP) targets in coronary artery disease (CAD) patients. BACKGROUND: The impact of physician specialty on secondary prevention measures for CAD in ambulatory care is unknown. METHODS: This was a retrospective cohort study of 13,995 patients with CAD seen at eight ambulatory care Veteran Affairs facilities from 1998 to 2000. Patients with cardiology involvement were defined as those seen in cardiology clinic in addition to primary care. The main outcomes of interest were LDL cholesterol < or =100 mg/dl and BP < or =130/85 mm Hg. Multivariable hierarchical regression analyses were used to determine the independent association of cardiology involvement with improved LDL cholesterol and BP control. RESULTS: Overall, 3,771 (27.0%) patients had cardiology involvement. A higher proportion of patients with cardiology involvement achieved LDL cholesterol (55.6% vs. 45.6%; p < 0.01) and BP (45.3% vs. 35.9%; p < 0.01) goals. In multivariable hierarchical regression analysis, cardiology involvement was independently associated with better LDL cholesterol (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.40 to 1.82) and BP (OR, 1.52; 95% CI, 1.32 to 1.77) control. The benefit of cardiology involvement was consistent across a range of LDL and BP targets, in analysis of LDL and BP as continuous outcomes, and among subgroups of high-risk patients, including diabetic patients, the elderly, and those with prior revascularization. CONCLUSIONS: Cardiology involvement is associated with better LDL cholesterol and BP control among CAD patients. However, significant room for improvement in secondary prevention measures remains, irrespective of physician specialty.     

Usefulness of total cholesterol/HDL-cholesterol ratio in the management of diabetic dyslipidaemia.

AIMS: Our aim was to evaluate the usefulness of the total cholesterol/HDL-cholesterol ratio (TC/HDL) in predicting the cardiovascular risk of Type 2 diabetic patients. METHODS: Prospective cohort study with inclusion of 418 Type 2 diabetic individuals with follow-up until the appearance of a cardiovascular event. The predictive power of updated mean lipid values during follow-up was analysed by means of Cox proportional hazard models. An estimate was made of the relative risk (RR) conferred by high levels of TC/HDL stratified by LDL-cholesterol levels. RESULTS: Sixty-six cardiovascular events occurred during an average follow-up of 4.7 years (sd 1.5). The main lipid predictor of vascular events was mean TC/HDL ratio [hazard ratio (HR) = 1.46; 95% confidence interval (CI) 1.25, 1.7; P < 0.0001]. In the multivariate model with simultaneous inclusion of mean TC/HDL and mean LDL-cholesterol, both were significant predictors of cardiovascular disease [HR (1 unit) = 1.37; 95% CI 1.16, 1.62; P = 0.0003 and HR (1 mmol/l) = 1.5; 95% CI 1.04, 2.18; P = 0.03, respectively]. The LDL adjusted RR for cardiovascular events due to high TC/HDL ratio, with 4.5 cut-off point, was 2.5 (95% CI 1.4, 4.3; P = 0.0007). For the stratum of subjects with average LDL cholesterol < 3.5 mmol/l, RR was 1.2 (95% CI 0.5, 2.8; P = NS) and for the stratum of average LDL cholesterol > 3.5 mmol/l, RR was 4 (95% CI 1.8, 9; P = 0.00013), with heterogeneity among strata (P = 0.044). CONCLUSIONS: It could be useful to include the TC/HDL ratio in treatment guides for diabetic dyslipidaemia, given their high predictive value and strong interaction with LDL cholesterol.     

Serum Ferritin level,microalbuminuria and non-alcoholic fatty liver disease in type 2 diabetic patients

BackgroundNon-alcoholic fatty liver disease (NAFLD) was considered one of the most common causes of chronic liver disease and is considered the hepatic manifestation of type 2 diabetes mellitus (T2DM). The factors that lead to marked fibrosis and liver cell injury in NAFLD are still remaining undiscovered.Patients and methodsThis study included (40) type 2 diabetic patients with NAFLD and (40) diabetic patients without NAFLD beside 15 healthy persons as a control group. All of them were subjected to full history taking, thorough clinical examination with especial stress on body weight (BW), height, body mass index (BMI), waist-hip ratio, blood pressure. Laboratory tests included serum total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL), fasting blood glucose (FBG) and 2-h postprandial blood glucose (PBG), serum Ferritin and urine microalbuminuria (MAU).ResultsDuration of diabetes, BW, BMI and blood pressure were significantly higher in NAFLD group (P = 0.001). FBG, PBG, TC, TG, LDL, serum Ferritin and MAU were significantly increased in NAFLD group with significant difference between two studied groups as regard HDL. There was a highly significant correlation between serum Ferritin with BW, BMI, duration of diabetes, TC, TG, LDL and MAU. There was a significant correlation between serum Ferritin with age, waist hip ratio, duration of diabetes, SBP, FBG, PBG and HDL. There was a significant correlation between MAU and age, weight, BMI, waist hip ratio, duration of diabetes, DBP, FBG TC, TG, LDL and HDL.ConclusionNAFLD is a common liver disorder in diabetic patients. NAFLD is significantly associated with microalbuminuria and elevated serum Ferritin.     

Reciprocal association between visceral obesity and adiponectin: in healthy premenopausal women

BACKGROUND: Obesity is one of the well-known risk factors of vascular disorders; however, the molecular mechanisms underlying the association between the two remain undetermined. Previous studies have demonstrated that the plasma levels of adiponectin, an adipose-derived hormone, are reduced in obese subjects, and that this hypoadiponectinemia is associated with ischemic heart disease. In this study, we sought to identify the primary determinants of plasma adiponectin levels in healthy premenopausal women. METHODS AND RESULTS: We analyzed the plasma adiponectin concentrations in age-matched healthy obese premenopausal women [n=37, body mass index (BMI)> or= 25 kg/m(2)] and in healthy nonobese premenopausal women (n = 23, BMI < 25 kg/m(2)). Visceral and subcutaneous fat (VCF and SCF) areas were determined by abdominal computed tomography (CT) scan. Plasma levels of adiponectin in obese subjects were lower than in nonobese subjects (3.24 +/- 1.08 vs. 4.90 +/- 2.06 ug/ml, P < 0.01). Significant, univariate inverse correlations were observed between adiponectin levels and visceral fat areas (r = -0.643, p < 0.001), subcutaneous fat areas (r = -0.407, p < 0.01), and hsCRP (r = -0.36, p = 0.007). Plasma levels of adiponectin correlated positively with insulin sensitivity [quantitative insulin sensitivity check index (QUICKI): r = 0.38, p = 0.005] and high-density lipoprotein (HDL) cholesterol (r = 0.44, p = 0.001), and negatively with low-density lipoprotein (LDL) cholesterol (r = -0.29, p = 0.028), triglyceride (r = -0.33, p = 0.013), and BMI (r = -0.48, p < 0.001). By multivariate analysis, only visceral fat areas affected adiponectin plasma levels (beta = -0.016, p < 0.05, R(2) = 0.504). Plasma levels of HDL cholesterol remained significantly correlated to plasma adiponectin concentrations in multivariate analysis (beta = 0.067, p < 0.05). CONCLUSIONS: These results collectively indicate that plasma HDL cholesterol levels and visceral fat masses are independently associated with plasma adiponectin concentrations.     

Which features of the metabolic syndrome predict the prevalence and clinical outcomes of angiographic coronary artery disease?

BACKGROUND: The prevalence of the metabolic syndrome (MS) is growing. The Adult Treatment Panel (ATP) III provided a uniform definition of MS but no information on its predictive ability. METHODS: We tested the ability of MS and its components to predict angiographic coronary artery disease (CAD) and incident death/myocardial infarction (D/MI) over 2.8 +/- 2.3 years in a large cohort of patients undergoing angiography. ATP-III criteria were used for fasting glucose (FG), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and blood pressure (BP); body mass index (BMI) >27 kg/m(2) was used as a surrogate for waist circumference. RESULTS: 3,128 subjects were studied; 65% had advanced CAD (>/=70% stenosis), and 35%, no CAD. MS was present in 64% (high FG 40%; high TG 52%; low HDL 71%; high BP 76%; high BMI 58%). Presence of CAD was predicted by MS [adjusted odds ratio (OR) = 1.30, 95% CI 1.10-1.55, p = 0.003] and, individually, by high FG (OR = 1.90, CI 1.63-2.23) and low HDL (OR = 1.38, CI 1.18-1.62). In multivariable modeling, CAD was predicted by high FG (OR = 1.80, CI 1.51-2.16) and low HDL (OR = 1.57, CI 1.31-1.89) as well as by age, gender, family history, smoking, and LDL cholesterol (all p < 0.001). For secondary risk of incident D/MI, only high FG of MS features was predictive (adjusted hazard ratio 1.46, CI 1.17-1.82, p = 0.001), and this risk was carried by diabetes (adjusted hazard ratio 1.71, p < 0.001); other predictors were age, heart failure, revascularization strategy, renal insufficiency, prior MI, and number of diseased vessels. CONCLUSION: MS has primary predictive ability for CAD, carried primarily by high FG and low HDL. Secondary predictive ability of MS features for clinical outcomes, in the setting of established CAD, is carried by diabetes alone. Dysglycemia deserves specific attention as a target for prevention and treatment.     

The effect of L-thyroxine replacement therapy on lipid based cardiovascular risk in subclinical hypothyroidism

The aim of our study was to assess the changes in serum lipid profiles after replacement therapy with L-T4 in patients with subclinical hypothyroidism (SCH), and to see whether there is an improvement in dyslipidemia based cardiovascular risk. Thirty non-smoker pre-menopausal women with newly diagnosed SCH (TSH between 4 and 10 microIU/ml) were involved in our study; twenty-six euthyroid healthy subjects were used as control group. TSH, free T3 (FT3), free T4 (FT4), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were measured before and after 6 months of L-T4 (50-100 microg/ day) therapy. TSH levels were targeted as < 2.0 microIU/ml. LDL-C was calculated using the Friedewald formula, while the cardiovascular risk was assessed with the TC/HDL-C ratio. Pre-treatment serum TC and LDL-C concentrations in SCH patients were significantly higher than those of euthyroid subjects (199.8 +/- 22.2 vs 181.5 +/- 24.6 mg/dl, p < 0.01; 146.3 +/- 26.1 vs 124.8 +/- 12 mg/dl, p < 0.001, respectively). TC, LDL-C levels and the TC/HDL-C ratio were reduced significantly after 6-month replacement therapy (-21.1 +/- 34.4 mg/dl or -10.5%, p < 0.01; -21.5 +/- 30.3 mg/dl or -14.7%, p < 0.001, respectively; and TC/HDL-C from 4.8 +/- 0.6 to 4.1 +/- 0.5 mg/dl, p < 0.01), while body mass index (BMI) values did not change. In conclusion, even mild elevations of TSH are associated with changes in lipid profile significant enough to raise the cardiovascular risk ratio, and these changes are corrected once the patients have been rendered euthyroid.     

The effects of uncoupling protein-1 genotype on lipoprotein cholesterol level in Korean obese subjects

Uncoupling protein-1 (UCP-1) plays a major role in thermogenesis, and has been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of A-3826G polymorphism of the UCP-1 gene on the plasma lipid profiles in 190 Korean obese subjects with a body mass index (BMI) more than 30 kg/m2. Height, weight, BMI, wait-to-hip ratio (WHR), obesity index, and body composition were measured and genotype of UCP-1 was analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. Serum concentrations of fasting glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride were measured. The frequencies of UCP-1 genotypes were AA type, 22.1%; AG type, 53.7%; and GG type, 24.2%; and the frequency of G allele was 0.51. Among many parameters, diastolic blood pressure (DBP) (P = .023) and low-density lipoprotein (LDL) cholesterol (P = .011) were significantly higher in AG and GG types compared with AA type, whereas HDL cholesterol was significantly lower in GG type compared with other types (P < .05). Atherogenic index was significantly higher in GG type compared with AA type (P = 0.027). LDL-to-HDL cholesterol ratio was significantly increased in the order of AA < AG < GG types (P = .001). When the subjects were divided into a normal group and a hyper-LDL cholesterolemia group by LDL cholesterol level of 3.626 mmol/L (140 mg/dL), the frequency of hyper-LDL cholesterolemia was significantly higher in GG type compared with other types by Fisher's exact (chi-square) test (P = .05). When logistic regression analysis was conducted to find the risk factors of hyper-LDL cholesterolemia, the odds ratio was 4.115 (P = .03) for GG type of UCP-1 gene. These results suggest that the GG type of the UCP-1 gene has a strong association with increased LDL cholesterol level and might be a significant risk factor for hyper-LDL cholesterolemia among Korean obese subjects.     

Relation between obesity and severity of coronary artery disease in patients undergoing coronary angiography

We examined the relations among body mass index (BMI), extent of coronary artery disease, and frequency of high-risk coronary anatomy (HRCA) in 928 consecutive patients who underwent coronary angiography during a 6-month period. HRCA was defined as >or=50% stenosis of the left main coronary artery and/or significant 3-vessel coronary artery disease (>or=70% narrowing). BMI was classified into 5 subgroups: low (<21 kg/m(2)), normal (21 to 24 kg/m(2)), overweight (25 to 29 kg/m(2)), obese (30 to 34 kg/m(2)), and severely obese (>or=35 kg/m(2)). Obese patients (BMI >or=30 kg/m(2)) were younger (61.4 +/- 10.7 vs 65.3 +/- 11.4 years, p <0.0001) and had higher prevalences of hyperlipidemia, systemic hypertension, and diabetes mellitus. HRCA was present less often in obese patients (56 of 245, 23%, vs 250 of 683, 37%, p = 0.0002). Multivariate regression analysis showed that advancing age (p <0.0001), male gender (p = 0.007), diabetes mellitus (p = 0.0004), and hyperlipidemia (p = 0.0008) were independent predictors of high-risk anatomy, whereas obesity remained a significant negative independent predictor (p = 0.02). Late (30 to 36 months) mortality was not different between obese (6.9%) and nonobese (8.2%) patients but was significantly higher in patients with HRCA (12.4%) than in those without HRCA (5.6%, p = 0.0003). In conclusion, obese patients who were referred for coronary angiography were younger and had a lower prevalence of HRCA. Obese patients were probably referred for angiography at an earlier stage of their disease, thus explaining the "obesity paradox" in several reports of better short-term outcome in obese patients who undergo cardiac procedures.     

Clinical, anthropometric, metabolic and insulin profile of men with fast annual growth rates of benign prostatic hyperplasia.

The purpose of this study was to test the hypothesis of a causal relationship between high insulin levels and the development of benign prostatic hyperplasia (BPH) and to determine the clinical, anthropometric, metabolic and insulin profile in men with fast-growing BPH compared with men with slow-growing BPH. The present study was designed as a risk factor analysis of BPH in which the estimated annual BPH growth rate was related to components of the metabolic syndrome. Two hundred and fifty patients referred to the Urological Section, Department of Surgery, Central Hospital, Varberg, Sweden, with lower urinary tract symptoms with or without manifestations of the metabolic syndrome were consecutively included. The prevalences of atherosclerotic disease manifestations, non-insulin-dependent diabetes mellitus (NIDDM) and treated hypertension were obtained. Data on blood pressure, waist and hip measurement, body height and weight were collected and body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples were drawn from fasting patients to determine insulin, total cholesterol, triglycerides, HDL and LDL cholesterol, uric acid, alanine aminotransferase (ALAT) and prostate-specific antigen (PSA). The prostate gland volume was determined using ultrasound. The median annual BPH growth rate was 1.04 ml/year. Men with fast-growing BPH had a higher prevalence of NIDDM (p = 0.023) and treated hypertension (p = 0.049). These patients were also taller (p=0.004) and more obese as measured by body weight (p<0.001), BMI (p=0.026), waist measurement (p <0.001), hip measurement (p = 0.006) and WHR (p=0.029). Moreover, they had elevated fasting plasma insulin levels (p = 0.018) and lower HDL cholesterol levels (p = 0.021) than men with slow-growing BPH. The annual BPH growth rate correlated positively with diastolic blood pressure (rs = 0.14; p = 0.009), BMI (rs = 0.24; p < 0.001) and four other expressions of obesity and fasting plasma insulin level (rs = 0.18; p = 0.008), and negatively with the HDL cholesterol level (rs = -0.22; p = 0.001). In conclusion, the data suggest that NIDDM, hypertension, tallness, obesity, high insulin and low HDL cholesterol levels constitute risk factors for the development of BPH. The results also suggest that BPH is a component of the metabolic syndrome and that BPH patients may share the same metabolic abnormality of a defective insulin-mediated glucose uptake and secondary hyperinsulinaemia, as patients with the metabolic syndrome. The findings support the hypothesis of a causal relationship between high insulin levels and the development of BPH, and give rise to a hypothesis of increased sympathetic nerve activity in men with BPH.     

Association between paraoxonase-1 activity and lipid peroxidation indicator levels in people living in the Antalya region with angiographically documented coronary artery disease

Background: Paraoxonase‐1 (PON1) is a high‐density lipoprotein (HDL)‐associated enzyme capable of hydrolyzing lipid peroxides. Thus, PON1 plays a preventing role in atherosclerosis by protecting against lipid peroxidation. Hypothesis: The incidence of coronary artery disease (CAD) is high in the Turkish population, and many risk factors have been studied as determinants of CAD. In Turkish people living in the Antalya region, we aimed to determine serum PON1 activity and its relation to lipoproteins and lipid peroxidation markers. Methods: We measured the activity of serum PON1 together with concentrations of a variety of lipid constituents—total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), very low‐density lipoprotein cholesterol (VLDL‐C), HDL cholesterol (HDL‐C), triglycerides (TG), apolipoprotein (apo) A‐I, apoB, and lipid peroxidation indicators (conjugated diene [CD] and thiobarbituric acid‐reactive substances [TBARS])—in 108 patients with CAD and 64 healthy subjects (controls). Results: We found that the PON1 activity was significantly reduced in patients with CAD (222.37 ± 11.31 IU/l)compared with controls (331.75 ± 20.98 IU/l). These patients had significantly lower HDL‐C, PON1/HDL‐C, apoA‐I, PON1/ApoA‐I, and ApoA‐I/ApoB, and higher LDL‐C, TC/HDL‐C, LDL‐C/HDL‐C, apoB, CD and TBARS than did controls. Total cholesterol and apoA‐I concentrations were significantly higher in women than in men in both groups. After multiple logistic regression analysis, TBARS (odds ratio [OR] 568.87; p = 0.000), age (OR 1.10; p = 0.000), gender (OR 4.58; p = 0.008), apoA‐I/apoB (OR 0.046; p = 0.003), and PON1/apoA‐I (OR 0.58; p = 0.007) were independently indicative of the presence of CAD. Conclusions: This is the first report of decreased serum PON1 activity and increased lipid peroxidation indicators (CD and TBARS) of patients with CAD living in Antalya, Turkey. Our results indicate that TBARS levels, age, gender, apoA‐1/ApoB, and PON1/apoA‐I ratios are important markers of CAD.     

Effect of orlistat-assisted weight loss in decreasing coronary heart disease risk in patients with syndrome X

This study describes the changes in risk factors for coronary heart disease in obese persons with syndrome X after orlistat-assisted weight loss. Data were available for 1,700 patients who completed 52 weeks of weight loss; 128 were defined as having syndrome X by being in the quintile with the highest plasma triglyceride levels (>2.2 mM/L) and the lowest high-density lipoprotein cholesterol (HDL, <1.0 mM/L) concentrations. Initial characteristics of those with syndrome X were similar to the 119 subjects (non-syndrome X) in the lowest quintile of plasma triglyceride (<0.975 mM/L) and highest quintile of HDL cholesterol (>1.5 mM/L). Subjects were placed on a calorie-restricted diet, and randomized to receive orlistat or placebo. Initial values were higher in those with syndrome X for diastolic blood pressure (p = 0.03), plasma insulin (p = 0.0001), triglyceride (p = 0.0001) concentrations, and ratio of low-density lipoprotein cholesterol to HDL cholesterol (p = 0.0001), and were lower for HDL cholesterol (p = 0.001) concentrations. Weight loss was greater in both groups of orlistat-treated patients (p = 0.026); in those with syndrome X, it was associated with a significant reduction in plasma insulin (p = 0.019) and triglyceride (p = 0.0001) concentrations, an increase in HDL cholesterol concentration, and a decrease in low-density lipoprotein/HDL cholesterol ratio (p = 0.0001). There were no significant changes in plasma insulin, triglycerides, or HDL cholesterol concentration in the non-syndrome X group. In conclusion, weight loss attenuates coronary heart disease risk factors in obese persons with syndrome X, and the risk factor reduction is enhanced with administration of orlistat.     

Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events

Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio <2.5 had no increase in risk of coronary heart disease when using CEE with or without MPA (odds ratio 0.60, 95% confidence interval 0.34 to 1.06), whereas women with an LDL/HDL cholesterol ratio > or =2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL ratio <2.5 when predicting coronary heart disease benefit on hormone therapy. In conclusion, postmenopausal women with undesirable lipid levels had excess coronary heart disease risk when using CEE with or without MPA. However, women with favorable lipid levels, especially LDL/HDL cholesterol ratio <2.5, did not have increased risk of coronary heart disease with CEE with or without MPA irrespective of hs-CRP.     

Effect of acute myocardial infarction on cholesterol ratios

OBJECTIVE: In patients with acute myocardial infarctions (MIs), cholesterol levels are no longer valid after 24 h from presentation because acute MI causes a rapid decline in serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. The objective of this study was to evaluate the effect of acute MI on the total cholesterol/HDL cholesterol ratio and the LDL cholesterol/HDL cholesterol ratio. METHODS: The study consisted of 45 patients who were admitted to the hospital with acute MIs. Serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were determined on day 1 post-MI and day 4 post-MI. The total cholesterol/HDL cholesterol ratio and the LDL cholesterol/HDL cholesterol ratio were calculated. Serum lipid levels and cholesterol ratios were compared between day 1 post-MI and day 4 post-MI. RESULTS: From day 1 post-MI to day 4 post-MI, the mean (+/- SD) serum levels of total cholesterol (188.4 +/- 52.5 vs. 170.5 +/- 57.2 mg/dL, respectively; p = 0.01), LDL cholesterol (120.3 +/- 48.9 vs. 105.9 +/- 43.0 mg/dL, respectively; p = 0.009), and HDL cholesterol (45.0 +/- 18.5 vs 39.3 +/- 16.1 mg/dL, respectively; p < 0.001) decreased, but the mean serum level of triglycerides (119.2 +/- 81.2 vs 149.3 +/- 68.3 mg/dL, respectively; p = 0.006) increased. The cholesterol ratios, however, remained unchanged between day 1 post-MI and day 4 post-MI. The total cholesterol/HDL cholesterol ratio was 4.59 +/- 1.84 on day 1 post-MI and 4.67 +/- 1.77 on day 4 post-MI (change not significant). The LDL cholesterol/HDL cholesterol ratio was 2.96 +/- 1.58 on day 1 post-MI and 2.99 +/- 1.44 on day 4 post-MI (change not significant). CONCLUSION: Acute MI does not affect the cholesterol ratios. Therefore, when the absolute levels of serum cholesterol are no longer valid (beyond 24 h after an MI), the cholesterol ratios still could be useful for cholesterol risk assessment in patients with acute MIs.