Comparison of lovastatin and probucol in treatment of familial and non-familial hypercholesterolemia: different effects on lipoprotein profiles

In order to compare the effects of lovastatin and probucol on lipoprotein profiles, we treated 32 familial hypercholesterolemia (FH) heterozygotes and 26 patients with non-familial hypercholesterolemia for 14 weeks with either probucol (1 g/d) or lovastatin (40-80 mg/d) in a randomized double-blind study. Lovastatin at 80 mg/d reduced low density lipoprotein (LDL)-cholesterol and apo B by more than 40% in both familial and non-familial hypercholesterolemia (non-FH). Probucol reduced LDL-cholesterol by 10-17% while LDL-apo B levels were not influenced at all (FH) or fell by 13% (non-FH). Analysis of LDL composition demonstrated that the LDL-cholesterol lowering effect of probucol in FH was entirely due to reduction in the proportion of cholesterol in LDL with no reduction in LDL mass. Serum high density lipoprotein2 (HDL2)-cholesterol levels fell by 27-33% during probucol, whereas HDL2-cholesterol increased by 10-18% with lovastatin 80 mg/d. These changes in HDL2 were not mediated by lipoprotein lipase or hepatic lipase, both of which are known to participate in regulation of this lipoprotein.     

Lipoproteins and apolipoproteins in young male survivors of myocardial infarction

Plasma and lipoprotein cholesterol, triglycerides, apolipoproteins (apo) A-I, A-II, B and phospholipid concentrations were measured at 10 days and 4 months after myocardial infarction (MI) in 60 young Kuwaiti male MI survivors below the age of 40 years. Controls were matched for age, relative weights, smoking, dietary habits and physical activities. The young MI survivors had significantly higher levels of total and LDL-cholesterol, and ratios of LDL/HDL- and LDL/HDL2-cholesterol. Total VLDL and LDL triglycerides, and phospholipids were also elevated in MI survivors compared to controls. Similarly, plasma and LDL-apo B as well as the ratios of apo B/apo A-I were higher in the MI group. There was no significant change in the levels of VLDL and HDL3-cholesterol and of apo A-II in these patients compared to their controls. Concentrations of HDL- and HDL2-cholesterol and of plasma and HDL apo A-I were significantly lower in the young MI survivors compared to the control subjects. The better discriminating lipoproteins and apolipoproteins in MI patients in descending order were HDL2-cholesterol greater than apo B greater than apo A-I greater than VLDL-triglyceride greater than HDL-cholesterol greater than LDL/HDL2-cholesterol greater than triglycerides. The data indicate that measurement of HDL2-cholesterol, apo B and apo A-I may be useful indicators in assessing coronary artery disease risk than triglycerides (TG), total cholesterol (TC), LDL-cholesterol and HDL-cholesterol.     

Effect of intensive lipid-lowering strategy on low-density lipoprotein particle size in patients with type 2 diabetes mellitus

A preponderance of small dense LDL particles is strongly associated with the occurrence of atherosclerotic disease. Although several studies have documented an increased prevalence of small dense LDL particles in diabetes mellitus no data are available to show the effect of lipid-lowering treatment upon the improvement of LDL particle size. In the present study we examined the effect of lipid-lowering treatment, following an intensive lipid-lowering strategy for 30 weeks pursuing ADA recommended target lipid levels, on LDL particle size in 50 type 2 diabetic patients with moderate hyperlipidemia. At week 0, 24 patients (48%) were characterized by small dense LDL phenotype pattern B. After the treatment period a shift towards normal LDL particle size was observed in 17 patients but seven patients (29%) showed the more atherogenic LDL subclass pattern B. After treatment, plasma HDL-cholesterol was significantly lower (P<0.05) in these patients compared to those who had LDL subclass pattern A. Multivariate regression analysis revealed VLDL-cholesterol or triglycerides and HDL(3)-cholesterol as independent determinants for LDL particle size. Change in HDL(2)-cholesterol was an independent determinant for change in LDL particle size. In conclusion, a strategy of intensive lipid-lowering, with the intention to reduce triglyceride levels below 1.7 mmol/l, may be insufficient to ensure improvement in LDL size in all patients.     

Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials

Aims

This analysis assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in patients with or without metabolic syndrome (MetS) using pooled data from 10 phase 3 ODYSSEY trials.

Materials and Methods

Data from 4983 randomized patients (1940 with MetS; 1642 with diabetes excluded) were assessed in subgroups by MetS status. Efficacy data were analysed in 4 pools per study design: 2 placebo‐controlled pools (1 using alirocumab 150 mg every 2 weeks [Q2W], 1 using 75/150 mg Q2W) with background statin, and 2 ezetimibe‐controlled pools (both alirocumab 75/150 mg Q2W), 1 with and 1 without background statin. Alirocumab 75/150 mg indicates possible dose increase from 75 to 150 mg at Week 12 based on Week 8 LDL‐C.

Results

LDL‐C percentage reduction from baseline at Week 24 with alirocumab was 63.9% (MetS) and 56.8% (non‐MetS) in the pool of alirocumab 150 mg Q2W, and 42.2% to 52.2% (MetS) and 45.0% to 52.6% (non‐MetS) in 3 pools using 75/150 mg Q2W. Levels of other lipid and lipoprotein parameters were also improved with alirocumab treatment, including apolipoprotein B, non‐high‐density lipoprotein cholesterol (non‐HDL‐C), lipoprotein(a) and HDL‐C. Overall, the percentage change at Week 24 in LDL‐C and other lipids and lipoproteins did not vary by MetS status. Adverse event rates were generally similar between treatment groups, regardless of MetS status; injection‐site reactions occurred more frequently in alirocumab vs control groups.

Conclusions

Across study pools, alirocumab‐associated reductions in LDL‐C, apolipoprotein B, and non‐HDL‐C were significant vs control, and did not vary by MetS status.     

Mildly elevated homocysteine concentrations impair endothelium dependent vasodilation in hypercholesterolemic patients

BACKGROUND: Elevated low density lipoproteins (LDL)-cholesterol and homocysteine levels have both been found to be associated with an increased risk for atherosclerotic vascular disease. To assess the effects of elevated homocysteine levels in hypercholesterolemic subjects on endothelial function, we examined basal and stimulated nitric oxide (NO) mediated vasodilation in the forearm vascular bed in hypercholesterolemic subjects with normal or elevated homocysteine levels. METHODS: Twenty-seven white subjects (age: 48 +/- 12 years) with elevated LDL-cholesterol (> or = 160 mg/dl) were divided into two groups with normal (n = 11) or mildly elevated (n = 16) homocysteine plasma concentration. We used strain gauge plethysmography to measure changes in forearm blood flow in response to intraarterial administration of increasing doses of acetylcholine (3, 12, 24, 48 microg/min), sodium nitroprusside (200, 800, 3200 ng/min), and N-monomethyl L-arginine (L-NMMA) (1, 2, 4 micromol/min). Total homocysteine plasma concentrations were determined by high performance liquid chromatography fluorimetry. RESULTS: Endothelium independent vascular relaxation tested by i.a. sodium nitroprusside and changes in forearm blood flow after i.a. L-NMMA indicating basal production and release of nitric oxide were similar between the two groups with normal or elevated homocysteine levels. In contrast, endothelium dependent vasodilation as assessed by the administration of i.a. acetylcholine differed between the groups with normal or elevated homocysteine levels for all doses tested (MANOVA P < 0.01: ACH 48 microg/min: 480 +/- 237% with normal vs 234 +/- 130% with elevated homocysteine; P < 0.002). This was significant even after taking possible covariates such as age, blood pressure, body mass index, LDL-, high density lipoproteins (HDL)-cholesterol, and trigylcerides into account (MANOVA P < 0.02). CONCLUSIONS: From our study we conclude that homocysteine impairs endothelium dependent vasodilation in subjects with elevated LDL-cholesterol levels. The most intriguing finding is that even mildly elevated homocysteine levels seem to be of crucial importance for deterioration of endothelial function, especially if other cardiovascular risk factors such as hypercholesterolemia preexist.     

Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores

There were 21 patients with rapidly progressive multiple sclerosis (MS) treated on a phase 1/2 study of intense immune suppressive therapy and autologous hematopoietic stem cell (HSC) support with no 1-year mortality. Following transplantation, one patient had a confirmed acute attack of MS. Neurologic progression defined by the expanded disability status scale (EDSS) did not increase in disability by 1.0 or more steps in any of 9 patients with a pretransplantation EDSS of 6.0 or less. In 8 of 12 patients with high pretransplantation disability scores (EDSS > 6.0), progressive neurologic disability as defined by at least a 1-point increase in the EDSS has occurred and was manifested as gradual neurologic deterioration. There were 2 patients with a pretransplantation EDSS of 7.0 and 8.0 who died from complications of progressive disease at 13 and 18 months following treatment. Our experience suggests that intense immune suppression using a total body irradiation (TBI)-based regimen and hematopoietic stem cell transplantation (HSCT) are not effective for patients with progressive disease and high pretransplantation disability scores. Further studies are necessary to determine the role of intense immune suppressive therapy and HSC support in ambulatory patients with less accumulated disability and more inflammatory disease activity. Specifically, more patients and longer follow-up would be required in patients with an EDSS of 6.0 or less before drawing conclusions on this subgroup.     

LDL-cholesterol,HDL-cholesterol or triglycerides--which is the culprit?

Dyslipidaemia in patients with type 2 diabetes commonly consists of elevated triglyceride levels; normal or slightly elevated low-density lipoprotein (LDL)-cholesterol levels with a preponderance of small, dense LDL particles; and low high-density lipoprotein (HDL)-cholesterol levels with a preponderance of small, dense HDL. These abnormalities are closely connected, with prolonged residence of high levels of triglyceride-rich particles in the circulation favoring abnormalities in LDL and HDL. Each of these factors has been associated with endothelial dysfunction; each contributes directly or indirectly to atheroma formation, with small, dense LDL and triglyceride-rich remnants increasing deposition of cholesteryl ester in vessel walls. This process is facilitated by reduced reverse cholesterol transport in association with low levels of HDL-cholesterol and abnormal HDL. Lipid-lowering therapy focused on LDL-cholesterol reduction is highly successful in preventing coronary disease in diabetic patients. Additional strategies for treating the cluster of risk factors in dyslipidaemia are necessary to further reduce atherosclerotic disease in this population.     

辛伐他汀并非诺贝特治疗急性冠脉综合征的疗效

目的：探讨联合应用辛伐他汀和非诺贝特对急性冠脉综合征（ACS）患者血脂参数及炎症因子的影响。方法：共人选58例ACS患者．随机分为：辛伐他汀组（20mg／d，18例）；非诺贝特组（200mg／d，18例）；联合治疗组（辛伐他汀20rag／d＋非诺贝特200mg／d，22例），疗程均为6个月。观察治疗前、后血清总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL—C）、一氧化氮（NO）、内皮素（ET）和C反应蛋白（CRP）含量的变化，以及药物不良反应。结果：各组治疗后血清TC、LDL-C、TG水平显著降低（P均〈0.05），血清HDL—C水平有不同程度增高。其中以联合治疗组最为明显（P均〈0．05）。和辛伐他汀组相比，非诺贝特组TC和LDL-C水平无明显差异（P〉0．05），而TG水平显著降低，HDL—C水平明显增高（P〈0．05），与治疗前相比，各组治疗后血清NO水平增高，CRP和ET水平降低（P〈0．05），联合治疗组较辛伐他汀组、非诺贝特组更显著（P均〈0.05），三组均无不良反应。结论：联合辛伐他汀和非诺贝特治疗可以更全面地改善ACS患者的血脂异常，其改善内皮功能和降低炎症因子的作用较单药治疗更有效。     

Effect of metabolic control on plasma lipids and lipoproteins in insulin-dependent diabetes in children and adolescents

Plasma triglycerides, total cholesterol, phospholipids, HDL-cholesterol, HDL-phospholipids, apolipoproteins A-I and B, haemoglobin AIc and C-peptide were measured in 113 children and adolescents (49 males and 64 females) with insulin-dependent diabetes. These patients were divided into four groups according to sex and age (more or less than 12 years old) and into three subgroups according to metabolic control. In female adolescents with poor control, triglycerides and apolipoprotein B were increased whereas HDL-cholesterol, HDL-phospholipids and (HDL/LDL + VLDL)-cholesterol were significantly decreased. In poorly-controlled male adolescents, similar changes were observed except for HDL-cholesterol and HDL-phospholipids which were not significantly decreased. In adolescents, haemoglobin AIc correlated directly with triglycerides, total cholesterol, phospholipids, apolipoprotein B and inversely with HDL-cholesterol, HDL-phospholipids and (HDL/LDL + VLDL)-cholesterol. In children aged less than 12 years, no significant change of HDL-cholesterol or apolipoprotein B was observed even in the poorly-controlled group.     

Homocysteine, lipid profile, nitric oxide, vitamin B12, and folate values in patients with premature coronary artery disease and their children

The plasma concentrations of homocysteine and lipoprotein A are independent risk factors for atherosclerotic vascular disease. Nitric oxide (NO) and folate values are also important in atherogenesis. The authors aimed to evaluate these parameters in patients having coronary artery bypass surgery (CABS) before 50 years of age and in their children. In 31 patients having CABS, 47 children of these patients, and 28 normal control subjects, homocysteine, NO, vitamin B12, folate, lipoprotein A, triglyceride, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, apolipoprotein A1, and apolipoprotein B values were determined. Homocysteine values of the patients with premature coronary heart diseases and their children were significantly higher than those of controls (p < 0.031 and p < 0.006, respectively). Also, NO levels were significantly higher in both groups than in controls (p < 0.001 and p < 0.031, respectively). B12 values were significantly higher in both groups (p < 0.05 and p < 0.033, respectively). Lipoprotein A levels were higher in both groups but not significantly so.     

Cardiovascular profile improvement during Natalizumab treatment

Cardiovascular comorbidities are associated with the risk of MS progression. Thus, we aim to measure variations of cardiovascular risk factors during Natalizumab treatment and their possible clinical associations. Seventy-one relapsing-remitting MS patients treated with Natalizumab were followed-up during a 12.9?±?6.2 months. Cardiovascular risk factors were recorded on first and last study visits: systolic blood pressure, uric acid, total cholesterol, LDL, HDL, and triglycerides. EDSS progression and relapse occurrence were recorded. At multilevel mixed-effects linear regression models, the population presented with a significant reduction of total cholesterol (Coeff?=??7.340; 95%CI?=??13.152--1.527; p?=?0.013), and of HDL cholesterol (Coeff?=??3.473; 95%CI?=??6.333--0.613; p?=?0.017), and a non-significant reduction of LDL cholesterol (Coeff?=??1.872; 95%CI?=??8.481–0.736; p?=?0.053), and of triglycerides (Coeff?=??8.815; 95%CI?=??34.011–5.380; p?=?0.094). Uric acid levels increased during the study period (Coeff?=?0.159; 95%CI?=?0.212–0.340; p?=?0.038). No significant associations were found with clinical outcomes. Serum lipids decreased and anti-oxidant uric acid increased during Natalizumab treatment. These biomarkers need to be further explored in relation to clinical outcomes on larger cohorts with longer follow-ups.

     

The fat mass and obesity-associated FTO rs9939609 polymorphism is associated with elevated homocysteine levels in patients with multiple sclerosis screened for vascular risk factors

The previously reported link between homocysteine and obesity, both identified as established risk factors for multiple sclerosis (MS), has not previously been studied in relation to the fat mass and obesity-associated (FTO) gene. Aim: To investigate the mechanism underlying homocysteine accumulation in MS patients. A total of 114 patients and 195 population-matched controls were analysed for the FTO rs9939609 polymorphism. Homocysteine levels were measured in a subgroup of 60 patients and 87 controls screened for multiple vascular risk factors. After adjustment for potential confounders, the risk-associated FTO rs9939609 A-allele was associated with raised homocysteine levels (p?=?0.003) in patients diagnosed with MS, but not in controls. Homocysteine levels correlated positively with body mass index (BMI) (p?=?0.045) and total cholesterol levels (p?=?0.048). Both homocysteine (p?=?0.011) and BMI (p?=?0.017) were significantly reduced with higher intake of folate in the diet. Higher BMI also correlated with increased intake of saturated/trans fat (p?<?0.01) and low physical activity (p?<?0.006). Daily intake of at least five fruits and vegetables had a favourable lowering effect on the Expanded Disability Status Scale (EDSS) (p?=?0.035), while smoking increased MS disability (p?<?0.001). This study has shown for the first time that having a diagnosis of MS moderates the effect of the FTO rs9939609 polymorphism on homocysteine levels. This is consistent with the role of FTO in demethylation and epigenetic changes. Identification of FTO rs9939609 reinforces the importance of adequate fruit, vegetable and folate and restriction of saturated/trans fat intake in the diet.     

Hyperapobetalipoproteinemia: the major dyslipoproteinemia in patients with chronic renal failure treated with chronic ambulatory peritoneal dialysis

In the present study, plasma cholesterol, triglyceride, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, and the major protein in LDL, apoB, were measured in 28 patients with chronic renal failure treated with hemodialysis and in 28 patients with chronic renal failure treated with chronic ambulatory peritoneal dialysis (CAPD). Elevated plasma triglycerides and reduced HDL cholesterol were frequent in both the hemodialysis and CAPD patients. However LDL levels were significantly higher in the CAPD patients as evident both by LDL cholesterol and LDL apoB. Even so, only one of the CAPD patients was hypercholesterolemic whereas 14 (or 50%) had hyperapobetalipoproteinemia (HyperapoB). Insulin-dependent diabetes was more frequent in the CAPD group but only 2 of the 9 insulin-dependent diabetics in this group had HyperapoB, and therefore, diabetes mellitus cannot account for the difference between the 2 groups. Thus HyperapoB appears to be a prevalent dyslipoproteinemia in CAPD patients and as such might be another factor which places CAPD patients at particularly increased risk of atherosclerosis.     

Serum homocysteine levels and cardiovascular morbidity in obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular morbidity and mortality. Elevated levels of serum homocysteine are also associated with cardiovascular morbidity and mortality. We aimed to investigate serum homocysteine levels and conventional cardiovascular risk factors (cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides) in OSAS patients with and without cardiovascular diseases (CVD). METHODS AND RESULTS: Levels of homocysteine, cholesterol, LDL, HDL and triglycerides were measured in 114 obese, male participants after overnight fasting. The presence of OSAS was determined by standard overnight polysomnography. The cases included OSAS patients (apnea-hypopnea index: AHI5) with CVD (OSAS+CVD group) (n:25) and without CVD (OSAS-CVD group) (n:47). Control group was patients without OSAS (AHI<5) with CVD (CVD group) (n:42). The serum homocysteine levels were significant.     

Follow-Ups of Metabolic,Inflammatory and Oxidative Stress Markers,and Brachial–Ankle Pulse Wave Velocity in Middle-Aged Subjects without Metabolic Syndrome

This study investigates the association among metabolic risk factors, inflammatory and oxidative stress markers, and brachial–ankle pulse wave velocity (ba-PWV). We conducted a 3-year longitudinal, observational study of 288 middle-aged adults not meeting the criteria for metabolic syndrome (MetS) at the initial screening. We measured metabolic risk factors, inflammatory and oxidative stress markers, and ba-PWV. Within the 3-year study period, 15.6% (45 out of 288) of participants developed MetS. At the 3-year follow-up, patients were categorized as those with MetS (n = 45) and those without MetS (n = 243). Patients with MetS had significantly unfavorable initial measurements of baseline body mass index (BMI), waist circumference (WC), blood pressure (BP), triglyceride (TG), high-density lipoprotein (HDL)-cholesterol, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index, and ba-PWV. After 3 years, participants without MetS showed significant increases in WC, diastolic BP (DBP), total- and low-density lipoprotein (LDL)-cholesterol, malondialdehyde (MDA), oxidized-LDL (ox-LDL), and ba-PWV and a significant decrease in HDL-cholesterol and free fatty acids (FFA). Subjects who developed MetS showed significant increases in BMI, WC, BP, TG, glucose, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), MDA, ox-LDL, and ba-PWV and a significant decrease in HDL-cholesterol. Changes in BMI, WC, BP, TG, HDL-cholesterol, glucose, HOMA-IR index, FFA, C-reactive protein (P = .022), IL-6 (P = .004), leukocyte count (P < .001), MDA (P = .002), ox-LDL (P = .015), and ba-PWV (P = .001) differed significantly between the two groups after adjustment for baseline values. Changes in ba-PWV were positively correlated with the changes in systolic and DBP, total-cholesterol, glucose, leukocyte count, and MDA. The age-related increase in arterial stiffness is greater in the presence of MetS with higher levels of inflammatory and oxidative stress markers.     

Elevated plasma homocysteine levels are associated with disability progression in patients with multiple sclerosis

The aims of this study were to verify whether hyperhomocysteinemia is associated with disability progression in Multiple Sclerosis (MS) patients and whether TNF pathways and cellular adhesion molecules (CAM) are involved in this process. This study included 180 MS patients, who were divided according to their levels of homocysteine (Hyperhomocysteinemia ≥11.35 μmol/L) and 204 healthy individuals (control group). MS patients showed higher levels of homocysteine (p?<?0.001), tumor necrosis factor alpha (TNF-α, p?<?0.001), TNF receptor 1 (TNFR1, p?=?0.038), TNF receptor 2 (TNFR2, p?<?0.001), and lower levels of PECAM (p?=?0.001), ICAM (p?<?0.001) and VCAM (p?=?0.005) than controls. The multivariate binary logistic regression analysis showed that plasma levels of homocysteine, TNFR1, TNFR2 and PECAM were associated with the presence of disease. MS patients with hyperhomocysteinemia showed higher disease progression evaluated by the Multiple Sclerosis Severity Score (MSSS, p?<?0.001), disability evaluated by Expanded Disability Status Score EDSS (p?<?0.001), TNFR1 (p?=?0.039) and ICAM (p?=?0.034) than MS patients with lower levels of homocysteine. Hyperhomocysteinemia was independently associated with MSSS in MS patients, but were not associated with TNF-α, TNFR, and CAM. Homocysteine levels was higher in progressive forms than relapsing-remitting MS (p?<?0.001), independently of sex and age. In conclusion, this is the first study in which homocysteinemia was associated with progression of the disease (MSSS), although this finding was not directly related to TNF-α and TNFR pathways or to CAM.     

Metabolic disorders contribute to subclinical coronary atherosclerosis in patients with coronary calcification

This investigation determined the prevalence of low-density lipoprotein (LDL) subclass distribution abnormalities, elevated lipoprotein(a) (Lp(a)), and elevated total plasma homocysteine in asymptomatic subjects with subclinical coronary artery disease determined by electron beam tomography (EBT). Fifty-five percent of subjects were classified as higher risk patients and 45% as lower risk patients, employing the National Cholesterol Education Program (NCEP) lipid criteria. EBT was performed in 296 consecutive asymptomatic subjects, and blood was analyzed for total, LDL, and high-density lipoprotein (HDL) cholesterol, triglycerides, LDL subclass distribution by S(3) gradient gel electrophoresis, Lp(a), and total homocysteine. Disorders of LDL subclass distribution were the most common disorder with 60.6% of the population expressing a distribution in the small regions IIIa + IIIb of >20%; and this was more common in the NCEP higher risk group (LDL cholesterol > or =130 and/or HDL cholesterol <35 mg/dl) (p <0.0004). A Lp(a) value >25 mg/dl was found significantly more often in the NCEP higher (36.9%) compared with lower (14.3%) risk group (p <0.001). None of the laboratory measurements correlated with the calcium score or calcium score percentile rank, with the exception of a weak correlation of mean LDL peak particle diameter and calcium percentile (r = 0.14, p = 0.02). Determination of metabolic disorders in addition to LDL cholesterol and HDL cholesterol increased the diagnostic yield from 55.1%, based on NCEP lipid criteria, to 84.1% with the addition of LDL subclass distribution, Lp(a), and total homocysteine. We conclude that: (1) disorders of LDL subclass distribution and elevated Lp(a) occur frequently in NCEP higher risk patients with subclinical coronary artery disease and are the only identifiable disorders in lower NCEP risk patients; and (2) electron beam tomographic evaluation and determination of LDL subclass distribution and Lp(a) should be considered for incorporation into primary prevention guidelines.     

Lipid and lipoprotein abnormalities in diabetic patients with peripheral vascular disease

Coronary heart disease in insulin-dependent (IDDM) and in non-insulin-dependent diabetes (NIDDM) is associated with lipid and lipoprotein changes favouring atherosclerosis. Whether lipid and lipoprotein abnormalities are associated also with peripheral vascular disease in both types of diabetes is largely unknown. Therefore, we studied lipid and lipoprotein levels and their association with claudication in a representative sample of diabetic and non-diabetic subjects in East Finland. Altogether 87 subjects had IDDM (43 men, 44 women), 264 subjects NIDDM (126 men, 138 women) and 120 subjects were non-diabetic controls (63 men, 57 women). Patients with IDDM had an increased level of HDL and HDL2-cholesterol and patients with NIDDM a decreased level of HDL and HDL2-cholesterol and an increased level of total, LDL and VLDL triglycerides than did non-diabetic subjects. Analyses in both types of diabetes by claudication status revealed that total and LDL-cholesterol and total and VLDL triglycerides tended to be higher and HDL and HDL2-cholesterol lower in those having claudication as compared to those without a claudication symptom. Similarly, total cholesterol/HDL-cholesterol ratio and LDL-cholesterol/HDL-cholesterol ratio were also more atherogenic in patients with claudication than in those without claudication. In conclusion, our results indicate that in both types of diabetes peripheral vascular disease is associated with lipid and lipoprotein abnormalities favouring atherosclerosis.     

Nuclear magnetic resonance-determined lipoprotein abnormalities in nonhuman primates with the metabolic syndrome and type 2 diabetes mellitus

The lipid profile in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) is commonly characterized by increased levels of triglycerides and decreased levels of high-density lipoprotein (HDL) cholesterol. However, within each lipoprotein class, the changes are more complex. The present study defined the characteristics of dyslipidemia among nonhuman primates, using nuclear magnetic resonance (NMR) spectroscopy as well as the classic beta-quantification method, and examined the pattern of multiple lipoprotein fractions in relation to the main factors identified with the MetS. Seventy-three rhesus monkeys were classified into 3 groups: healthy monkeys, monkeys with MetS, and monkeys with T2DM. Characteristics of dyslipidemia in the MetS and T2DM groups included increased levels of triglyceride-rich very low-density lipoprotein, intermediate-density lipoprotein, and small, dense, low-density lipoprotein (LDL) particles. Reduced concentrations of large LDL and large HDL particles together with reduction of LDL and HDL particle sizes were also observed. Correlation analysis revealed that poor glycemic and lipid profiles, glucose intolerance, and insulin resistance were associated with an atherogenic NMR profile. Compared with the conventional lipid panel, the NMR lipoprotein profile presented in greater detail distinctive differences between the dyslipidemia of the MetS and that of diabetes and demonstrated significant and divergent shifts in both particle size and number within lipoprotein classes between those 2 groups. Detailed lipoprotein profiling may provide additional indicators for more timely intervention. Rhesus monkeys are likely to provide an excellent model for novel drug testing designed to address the specific differences in lipoprotein fraction profile across these 3 groups that reflect the progression of pathophysiology from normal to overt diabetes.     

Coronary disease risk prediction algorithm warranting incorporation of C-reactive protein in Turkish adults, manifesting sex difference

Background and aimAn algorithm is needed for predicting coronary heart disease (CHD) risk in Turkish adults who have a high prevalence of metabolic syndrome (MetS).Methods and resultsTen-year risk of CHD was estimated in 2232 middle-aged adults free of CHD at baseline, followed over 7.6-years. Cox proportional hazard regression was used to predict CHD. Discrimination was assessed with area under receiver operating characteristics curve (AROC). CHD developed in 302 subjects. In multivariable analysis, high-density lipoprotein (HDL)-cholesterol levels were borderline predictive in men; smoking status and HDL-and low-density lipoprotein (LDL)-cholesterol levels were not predictive in women. Age, presence of diabetes, systolic blood pressure and C-reactive protein (CRP) were predictors in both sexes, while smoking status and LDL-cholesterol were so in men only. AROC of the model was 0.789 in men, and 0.806 in women (p < 0.001 each). An algorithm using the stated seven variables was derived separately for each sex. After age adjustment, men and women in the highest quintile of risk score were significantly and 20–27-fold more likely to develop CHD than those in the lowest quintile.ConclusionsIn a population with prevalent MetS, low-grade inflammation is independently relevant for CHD, as are serum lipoproteins and smoking status. The derived algorithm is effective in estimating CHD risk among Turkish adults.