Beneficial effects of melatonin on obesity and lipid profile in young Zucker diabetic fatty rats

Abstract: The study objective was to investigate the effects of melatonin on obesity and obesity‐associated systolic hypertension and dyslipidemia in young male Zucker diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome. ZDF rats (n = 30) and lean littermates (ZL) (n = 30) were used. At 6 wk of age, both lean and fatty animals were subdivided into three groups (n = 10): naive (N), vehicle‐treated (V), and melatonin‐treated (M) (10 mg/kg/day) for 6 wk. Vehicle and melatonin were added to the drinking water. Melatonin reduced mean weight gain (51 ± 2/100 g BW) versus N‐ZDF group (58 ± 3, P < 0.05) without food intake differences. M‐ZDF rats showed an apparent reduction in systolic hypertension that proved not to be statistically significant, and a significant improvement in dyslipidemia, with a reduction in hypertriglyceridemia from 580 ± 40 to 420.6 ± 40.9 mg/dL (P < 0.01). Melatonin raised high‐density‐lipoprotein (HDL) cholesterol in ZDF (from 81.6 ± 4.9 to 103.1 ± 4.5 mg/dL, P < 0.01) and ZL rats (from 62.8 ± 4.8 to 73.5 ± 4.8 mg/dL, P < 0.05) and significantly reduced low‐density‐lipoprotein (LDL) cholesterol in ZDF rats from 5.20 ± 0.4 to 4.14 ± 0.3 mg/dL (P < 0.05) but had no effect on total cholesterol levels. To our knowledge, this is the first evidence of a positive effect of melatonin on overweight and lipid pattern of obese Zucker diabetic rats, supporting the proposition that melatonin administration may ameliorate overweight and lipid metabolism in humans. Because these benefits occurred in youth, before advanced metabolic and vascular complications, melatonin might help to prevent cardiovascular disease associated with obesity and dyslipidemia.     

Intima Media Thickness and Endothelial Function in Chronic Hemodialysis Patients

The purpose of our study was to evaluate the intima‐media thickness (IMT) of the carotid and brachial arteries, flow‐mediated dilatation (FMD), and nitroglycerin‐mediated dilatation (NMD) in diabetic and non‐diabetic hemodialysis patients. We also examined the effects of traditional and other risk factors on carotid and brachial IMT, FMD and NMD in all hemodialysis patients. Fifty‐eight adult hemodialysis patients, 14 of whom had diabetes, were studied. They had been on hemodialysis for 1–340 months. Using B‐mode ultrasonography, we measured the carotid and brachial IMT, FMD and NMD, and correlated the values with cardiovascular risk factors. FMD and NMD were significantly lower in diabetic patients (FMD 4.01 ± 0.99 vs. 6.69 ± 2.37 mm; NMD 9.1 ± 1.95 vs. 11.23 ± 2.86 mm), while no such differences were found between the two groups with respect to carotid or brachial IMT. In all patients with respect to age a positive correlation was found with carotid and brachial IMT, and a negative one with FMD and NMD. With respect to hypertension as well as diabetes, a negative correlation was found with FMD and NMD. Age is the most important factor that significantly affected all studied markers of atherosclerosis in hemodialysis patients. The endothelial and smooth vascular functions are significantly impaired in diabetic and hypertensive hemodialysis patients, and hypertension is shown to be an independent risk factor for smooth vascular dysfunction in hemodialysis patients. According to our results, intensive antihypertensive treatment is recommended in hypertensive chronic hemodialysis patients.     

Postheparin plasma triglyceride lipases in chronic hemodialysis: evidence for a role for hepatic lipase in lipoprotein metabolism.

Elevated plasma triglyceride levels frequently occur in patients with chronic renal failure receiving longterm hemodialysis. Postheparin plasma lipolytic activity, an indirect measure of triglyceride removal, is low in hemodialysis patients, but this activity measures both hepatic triglyceride lipase (HTGL) and lipoprotein lipase (LPL). To determine if HTGL and/or LPL are low in hemodialysis patients and related to lipoprotein lipid levels, both activities were measured by a selective antibody-inhibition technique in postheparin plasma from 20 hemodialysis patients with a wide range of plasma triglyceride levels ($\text{104–676}\text{mg}\text{100}\text{ml}$), and the relationships between the enzyme activities and lipoprotein lipid levels were examined. To more accurately compare subjects, the heparin doses were adjusted for the differences in plasma volumes between the hemodialysis patients and the nonuremic control subjects. Hemodialysis patients with elevated plasma triglyceride levels (↑TG) had HTGL levels (148 ± 67 nmole/min/ml, n=10) which were similar to the dialysis patients with normal triglyceride levels (nlTG) (134 ± 64 nmole/min/ml, n=10) and both groups were significantly lower (p<0.05, p<0.02, respectively) than the levels of the control subjects (208 ± 61 nmole/min/ml, n=11). The HTGL levels of the hemodialysis patients with ↑TG correlated inversely with plasma total cholesterol (r_s=−0.833, p<0.01) and the d>1.006 fraction cholesterol (low + high density lipoproteins, r_s=−0.863,p<0.01), but not triglyceride. The activity of HTGL of the entire group of hemodialysis patients correlated with the plasma total cholesterol (r_s=−0.615, p<0.01), d>1.006 fraction cholesterol (r_s=−0.731, p<0.01) and low density lipoprotein cholesterol (r_s=−0.659, p<0.01). The LPL levels of the hemodialysis patients with the ↑TG (52 ± 24 nmole/min/ml) were lower than those with nlTG (70 ± 25 nmole/min/ml) and the levels of both hemodialysis groups were significantly lower (p<0.01, p<0.02, respectively) than the LPL levels in the control subjects (110 ± 43 nmole/min/ml). The ratio of LPL to total postheparin plasma lipolytic activity was lower in the hemodialysis patients with ↑TG (0.32 ± 0.15), than in the hemodialysis patients with nlTG (0.47 ± 0.18, p<0.06) or the control subjects (0.45 ± 0.09, p<0.05). Unlike HTGL, the levels of LPL did not correlate with lipid levels in the hemodialysis patients. Thus, both postheparin plasma HTGL and LPL are low in hemodialysis patients. The relationship between HTGL and low density lipoprotein cholesterol levels suggests a possible role for HTGL in low density lipoprotein catabolism.     

Perilipin‐1 in Hemodialyzed Patients: Association With History of Coronary Heart Disease and Lipid Profile

Perilipin‐1 surrounds lipid droplets in both adipocytes and in atheroma plaque foam cells and controls access of lipases to the lipid core. In hemodialysis (HD) patients, dyslipidemia, malnutrition, inflammation and atherosclerosis are common. Thirty‐six HD patients and 28 healthy volunteers were enrolled into the study. Ten HD patients suffered from coronary heart disease (CHD). Perilipin‐1, triglycerides, total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol (HDL‐C), body mass index, albumin, geriatric nutritional risk index, normalized protein catabolic rate, interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) were measured. Perilipin‐1 did not differ between HD patients and healthy volunteers. IL‐6 and TNF‐α were higher in HD patients. The evaluated nutritional markers and the markers of inflammation did not differ between HD patients with high perilipin‐1 levels and HD patients with low perilipin‐1 levels. Regarding the lipid profile, only HDL‐C differed between HD patients with high perilipin‐1 levels and HD patients with low perilipin‐1 levels, and it was higher in the first subgroup. Perilipin‐1 was significantly higher in HD patients without CHD. Perilipin‐1 is detectable in the serum of HD patients and it is associated with increased HDL‐C and decreased incidence of CHD.     

Hypothyroidism is associated with signs of endothelial dysfunction despite 1-year replacement therapy with levothyroxine

Objective Hypothyroidism is associated with elevated cardiovascular risk, not fully explained by classical risk factors. Instead, endothelial dysfunction may link hypothyroidism to atherosclerosis. The effect of levothyroxine substitution on endothelial function has been sparsely studied and the results are unclear. This study tested endothelial function as estimated by concomitant measurements of endothelial dependent vascular dilatory capacity and plasma concentration of von Willebrand factor antigen in patients with hypothyroidism and further examined the impact of subsequent levothyroxine substitution. Design and patients Sixteen consecutive patients (13 women, 3 men, aged 46 ± 11 years) with hypothyroidism were included and compared to 16 matched healthy controls (13 women, 3 men, aged 49 ± 11 years). Patients with hypothyroidism were reexamined after 3, 6 and 12 months of levothyroxine substitution. Measurements Dilatory responses of the brachial artery to post‐ischaemic increased blood flow (endothelium‐dependent flow‐associated dilatation) and to nitroglycerin (endothelium‐independent nitroglycerin induced dilatation) were measured by ultrasound. Plasma concentrations of von Willebrand factor antigen were measured by ELISA. Results Flow‐associated dilatation was impaired in patients with hypothyroidism as compared to controls (102·7 ± 3·6 vs. 105·6 ± 3·8%, P = 0·04) whereas no differences in plasma concentration of von Willebrand factor antigen were found. One year levothyroxine substitution did not improve flow‐associated dilatation and was associated with an increase of the plasma von Willebrand factor antigen concentration. Conclusions Hypothyroid patients are characterized by endothelial dysfunction sustained despite long‐term levothyroxine substitution and potentially increasing the risk of atherosclerosis. Different estimates of endothelial dysfunction seem unequally influenced by hypothyroidism.     

Minor effects of green tea catechin supplementation on cardiovascular risk markers in active older people: A randomized controlled trial

Aim: Although previous studies have shown that consumption of green tea catechins (GTC) and walking might prevent development of cardiovascular disease (CVD), the effects of GTC supplementation on CVD risk in active older people are unknown. Methods: A total of 52 older adults (male/female 20/32, mean age 69.1 ± 5.9 years) participating in a pedometer‐based walking program were randomly assigned to a GTC group with an intake of 630.9 mg GTC daily (n = 26) or a control group (n = 26) for 14 weeks. Cardiovascular risk markers were measured before and after this trial. Results: In the GTC group, values of the following markers were significantly reduced (P < 0.05) from the beginning to the end of the trial: waist circumference (from 84.2 ± 8.4 to 82.2 ± 8.5 cm), hip circumference (from 95.1 ± 6.9 to 92.2 ± 6.3 cm), total cholesterol (from 233.0 ± 46.3 to 218.8 ± 42.3 mg/dL), low‐density lipoprotein cholesterol (from 130.4 ± 36.2 to 119.1 ± 33.4 mg/dL) and low‐density lipoprotein cholesterol to high‐density lipoprotein cholesterol ratio (from 2.0 ± 1.7 to 1.7 ± 0.5); only hip circumference (from 95.6 ± 8.1 to 94.1 ± 7.6 cm) was significantly reduced (P < 0.05) in the control group. No significant between‐group differences were found for any parameter measured. Conclusions: Although GTC might reduce cholesterol levels, the present randomized control trial suggests that GTC supplementation in active older participants did not significantly affect cardiovascular risk markers. Future studies should identify more effective combinations of GTC supplementation and physical activity. Geriatr Gerontol Int 2013; 13: 622–629.     

Lipid levels in sickle‐cell disease associated with haemolytic severity,vascular dysfunction and pulmonary hypertension

Pulmonary hypertension (PH) in sickle cell disease (SCD) is an emerging and important clinical problem. In a single‐institution adult cohort of 365 patients, we investigated lipid and lipoprotein levels and their relationship to markers of intravascular haemolysis, vascular dysfunction and PH. In agreement with prior studies, we confirm significantly decreased plasma levels of total cholesterol, high‐density lipoprotein‐cholesterol (HDL‐C) and low‐density lipoprotein‐cholesterol (LDL‐C) in SCD versus ethnically‐matched healthy controls. Several cholesterol parameters correlated significantly with markers of anaemia, but not endothelial activation or PH. More importantly, serum triglyceride levels were significantly elevated in SCD compared to controls. Elevated triglyceride levels correlated significantly with markers of haemolysis (lactate dehydrogenase and arginase; both P < 0·0005), endothelial activation (soluble E‐selectin, P < 0·0001; soluble P‐selectin, P = 0·02; soluble vascular cell adhesion molecule‐1, P = 0·01), inflammation (leucocyte count, P = 0·0004; erythrocyte sedimentation rate, P = 0·02) and PH (amino‐terminal brain natriuretic peptide, P = 0·002; prevalence of elevated tricuspid regurgitant velocity (TRV), P < 0·001). In a multivariate analysis, triglyceride levels correlated independently with elevated TRV (P = 0·002). Finally, forearm blood flow studies in adult patients with SCD demonstrated a significant association between increased triglyceride/HDL‐C ratio and endothelial dysfunction (P < 0·05). These results characterize elevated plasma triglyceride levels as a potential risk factor for PH in SCD.     

Effects of prazosin and propranolol on blood pressure and plasma lipids in patients undergoing chronic hemodialysis

Twenty patients receiving hemodialysis who had mild to moderate hypertension were treated with prazosin or propranolol to control predialysis hypertension. Effective blood pressure control was achieved with prazosin (mean dose 8.3 ± 2.2 mg [± standard error of the mean], n = 10) and propranolol (mean dose 123 ± 39 mg, n = 10). Therapy with prazosin did not significantly affect total plasma triglyceride or total cholesterol levels. The level of high-density lipoprotein (HDL) cholesterol tended to increase, but not significantly. However, the HDL₃ subfraction did increase significantly, from 16.3 ± 1.5 to 20.6 ± 1.5 mg/dl (p = 0.05). Propranolol therapy increased plasma triglyceride levels, primarily of the very low density lipoprotein class. HDL cholesterol levels decreased from 44.2 ± 6.7 to 34.7 ± 4.2 mg/dl (p < 0.03). The reduction in the HDL cholesterol levels was attributable to a decrease in HDL₂ cholesterol levels (from 21.3 ± 3.8 to 16.3 ± 3.0 mg/dl, p < 0.04) and HDL₃ cholesterol levels (from 23.0 ± 3.1 to 19.5 ± 2.1 mg/dl, difference not significant). Thus, both prazosin and propranolol are effective in controlling hypertension in patients undergoing hemodialysis. HDL₃ cholesterol levels increased in patients treated with prazosin, but no other significant changes in the plasma lipids occurred. Patients treated with propranolol had a significant decrease in plasma HDL₂ and HDL₃ cholesterol levels.     

Serum Lipoprotein and Apolipoprotein Concentrations in Patients with Hyperthyroidism and the Effect of Treatment with Carbimazole

ABSTRACT Forty patients, 32 women and 8 men, with hyperthyroidism were investigated concerning serum lipoprotein lipid and apolipoprotein concentrations before, during and after treatment with carbimazole to euthyroidism. During the hyperthyroid condition the patients had significantly lower serum concentrations of low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol. The serum lipoprotein triglyceride concentrations were within the normal ranges. During treatment to euthyroidism the low serum concentrations of LDL and HDL cholesterol increased to normal values. LDL and HDL concentrations increased in the female patient group by 46±12 and 25±9% and in the male patient group by 50±12 and 19±11%, respectively. During treatment serum apolipoprotein B and A-I concentrations increased significantly in females by 58±9 and 18±5% and in males by 60±9 and 13±8%, respectively.     

Improvement of Hemorheology by DALI Apheresis: Acute Effects on Plasma Viscosity and Erythrocyte Aggregation in Hypercholesterolemic Patients

Abstract: Plasma viscosity (PV) and erythrocyte aggregation (EA) are determinants of microcirculation, especially under the compromised hemodynamic conditions resulting from atherosclerosis. Direct adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins; it drastically reduces low‐density lipoprotein (LDL)‐cholesterol and lipoprotein (a) (Lp[a]), and may therefore improve PV and EA. The current study was performed to test the effect of DALI on hemorheology. Six hypercholesterolemic patients who had been on regular LDL apheresis for at least several months were treated on a weekly or biweekly basis, on average 5 times each by DALI. Before and after each session, PV was measured by a capillary tube plasma viscosimeter and EA by rotational aggregometry. Single DALI sessions (n = 31) acutely decreased PV from 1.18 ± 0.04 to 1.06 ± 0.3 mPa (?10%) while EA improved from 22.8 ± 4.4 to 13.3 ± 4.5 (arbitrary units) (?42%). LDL‐cholesterol, Lp(a), and very‐low‐density lipoprotein (VLDL)‐cholesterol were effectively reduced while the decrease of triglycerides and fibrinogen was only moderate. DALI apheresis exerted an acute positive effect on blood hemorheology which may have beneficial effects on microcirculation. This hypothesis is in accordance with the clinical observation that in some patients, improvement of angina and/or exercise tolerance can be observed after only a few DALI sessions where changes of coronary stenoses cannot be expected yet.     

Plasma lipoprotein abnormalities in hemodialysis patients--clinical implications and therapeutic guidelines

Patients with advanced stages of chronic kidney disease (CKD) have an increased risk of death from cardiovascular disease (CVD). Dyslipidemias are associated with atherosclerotic vascular changes and the risk of occurrence of acute myocardial infarction in hemodialysis patients. However, management of dyslipidemia in hemodialysis patients does not appear to be actively carried out in routine practice. Presumably, there are three reasons for this reluctance to lipid-lowering in hemodialysis patients. First, there are epidemiological data showing the inverse relationship between cholesterol and mortality rate; a high cholesterol predicts a better survival. Second, lipids are not usually measured using standard fasting serum, but a non-fasting specimen. Third, although hypertriglyceridemia is the most common abnormality, fibrates are contraindicated in patients with renal failure because of a high risk of rhabdomyolysis. These issues are discussed in the current review article. Based on published work, lipid lowering would not increase the death rate if carried out without worsening malnutrition. The National Kidney Foundation K/DOQI Clinical Practice Guidelines recommend a reduction in fasting LDL-C below 100 mg/dL for the prevention of CVD in dialysis patients. Practically, however, the use of non-HDL-C measured by casual blood samples might be sufficient for the risk assessment in many hemodialysis patients. Statins are a good choice for lipid-lowering in dialysis patients. Furthermore, lipoprotein profile might be improved by an inventive use of dialyzer membranes, dialysate solutions, and other dialysis-related medications. For severe hypercholesterolemia, LDL-apheresis is another choice for consideration. Further studies are needed to clearly prove the benefit of lipid reduction in hemodialysis patients and those with CKD at earlier stages.     

柳州市7660例成人血脂状况调查

评价柳州市人群中血脂状况,为人群干预作基线调查。整群抽取柳州市常住居民7660例,男性389b4例,女性3766例,年龄39.5±11.0岁,进行血脂、身高、体重、腰围及臀围等指标检测和统计分析。结果发现,男性和女性总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平均有随年龄增大而增高的趋势。全组高总胆固醇、高甘油三酯、高低密度脂蛋白胆固醇和低高密度脂蛋白胆固醇检出率分别为20.76%、26.37%、17.75%及15.59%。男性高总胆固醇、高甘油三酯及高低密度脂蛋白胆固醇的检出率分别是女性的1.64、2.86及1.52倍。血脂异常率有随年龄增大而增高的趋势。超重和肥胖显著增高血脂异常率。其中以反映腹部脂肪积聚的腰围对血脂的影响更为显著。结果表明,本组人群中血脂异常率较高,高甘油三酯是最常见的血脂异常类型,腰围增大是影响血脂代谢异常的重要因素。     

老年冠心病患者血浆非高密度脂蛋白胆固醇水平的差异

目的探讨在老年冠心病患者的血清非高密度脂蛋白胆固醇的差异。方法选择120例行冠状动脉造影检查的老年患者,冠状动脉造影前空腹采静脉血,分析冠状动脉造影阳性组和对照组之间非高密度脂蛋白胆固醇与其它血脂数据(总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白)差异的显著性及非高密度脂蛋白胆固醇对冠状动脉病变程度的相关性。结果冠状动脉造影阳性组非高密度脂蛋白胆固醇水平显著高于阴性组2.99±1.08mmol/L,一支病变组为3.41±0.59mmol/L,两支病变组为3.70±1.30mmol/L,三支病变组为3.77±1.10mmol/L,(P<0.001)并且非高密度脂蛋白的水平随冠状动脉病变支数逐渐增高,与冠状动脉狭窄分数相关(r=0.36,P<0.001);而两组间甘油三酯,高密度脂蛋白水平无统计学差异(P>0.05)。结论血清非高密度脂蛋白胆固醇对于老年人是一项简便实用的冠心病风险评估指标。     

Effect of cranberry extracts on lipid profiles in subjects with Type 2 diabetes

Aim To examine the effect of cranberry ingestion on lipid profiles in Type 2 diabetic patients taking oral glucose‐lowering drugs. Methods Thirty Type 2 diabetic subjects (16 males and 14 females; mean age 65 ± 1 years) who were taking oral glucose‐lowering medication regularly were enrolled in this randomized, placebo‐controlled, double‐blind study. Changes in lipid profiles, oxidized low‐density lipoprotein (ox‐LDL), glycaemic control, components of the metabolic syndrome, C‐reactive protein (CRP) and urinary albumin excretion (UAE) were assessed after cranberry or placebo treatment for 12 weeks. Results Low‐density lipoprotein (LDL) cholesterol decreased significantly in the cranberry group (from 3.3 ± 0.2 to 2.9 ± 0.2 mmol/l, P = 0.005) and the decrease was significantly greater than that in the placebo group (–0.4 ± 0.1 vs. 0.2 ± 0.1 mmol/l, P < 0.001). Total cholesterol and total : high‐density lipoprotein (HDL) cholesterol ratio also decreased significantly (P = 0.020 and 0.044, respectively) in the cranberry group and the reductions were significantly different from those in the placebo group (P < 0.001 and P = 0.032, respectively). However, ox‐LDL levels did not change significantly in response to cranberry consumption. Neither fasting glucose nor glycated haemoglobin improved in either group. Changes in components of the metabolic syndrome, UAE and CRP were not significantly different between groups. Conclusions Cranberry supplements are effective in reducing atherosclerotic cholesterol profiles, including LDL cholesterol and total cholesterol levels, as well as total : HDL cholesterol ratio, and have a neutral effect on glycaemic control in Type 2 diabetic subjects taking oral glucose‐lowering agents.     

Novel Inflammatory Marker in Dialysis Patients: YKL‐40

YKL‐40 has been introduced as a marker of inflammation in different clinical situations. The association between YKL‐40 and inflammation in chronic renal failure patients has not been researched currently. The objectives of this study were to establish serum YKL‐40 concentrations in dialysis patients with chronic renal failure compared to healthy subjects and to explore its relationships with a proinflammatory cytokine, interleukine‐6 (IL‐6) and an acute phase mediator, high sensitivity C‐reactive protein (hs‐CRP). The study population included hemodialysis patients (N = 43; mean age of 40.9 ± 14.5), peritoneal dialysis patients (N = 38; mean age of 45.8 ± 13.7) and healthy subjects (N = 37; mean age of 45.5 ± 10.6). Serum concentrations of YKL‐40, IL‐6, hs‐CRP and routine laboratory measures were evaluated. Compared to the healthy subjects, hemodialysis and peritoneal dialysis patients had higher concentrations of YKL‐40, IL‐6, hs‐CRP, as well as lower concentrations of hemoglobin, serum albumin and high density lipoprotein‐cholesterol (P < 0.001). YKL‐40 concentrations were positively correlated with serum creatinine (P < 0.001, r = 0.495), IL‐6 (P < 0.001, r = 0.306), hs‐CRP (P = 0.001, r = 0.306) levels and inversely correlated with hemoglobin (P = 0.002, r = ?0.285), serum albumin (P < 0.001, r = ?0.355) and high density lipoprotein‐cholesterol (P = 0.001, r = ?0.306). In multivariate regression analysis YKL‐40 was associated with creatinine, serum albumin and hs‐CRP concentrations after adjustments with covariates. Dialysis patients with chronic renal failure have elevated serum YKL‐40 concentrations. Associations with standard inflammatory parameters suggest that YKL‐40 might be a novel inflammatory marker in this population.     

Small dense low‐density lipoprotein cholesterol is a promising biomarker for secondary prevention in older men with stable coronary artery disease

Aim

The study objective was to investigate whether small dense low‐density lipoprotein cholesterol (sdLDL‐C) is superior to low‐density lipoprotein cholesterol (LDL‐C) and other biomarkers to predict future cardiovascular events (CE) in secondary prevention.

Methods

sdLDL‐C measured by a homogeneous assay, remnant lipoprotein cholesterol, LDL particle diameter and other biomarkers were compared in 345 men aged ≥65 years with stable coronary artery disease. Baseline LDL‐C was 100.5 ± 30.1 mg/dL. CE including cardiovascular death, onset of acute coronary syndrome, need for arterial revascularization, hospitalization for heart failure, surgery procedure for cardiovascular disease and hospitalization for stroke were monitored for 5 years.

Results

CE occurred in 96 patients during the study period. LDL‐C, sdLDL‐C non‐high‐density lipoprotein cholesterol, apolipoprotein B, remnant lipoprotein cholesterol, glucose, glycated hemoglobin and brain natriuretic peptide were significantly higher; LDL particle diameter and apolipoprotein A‐1 were significantly lower in patients with than in those without CE. Age‐adjusted Cox regression analysis showed that sdLDL‐C per 10 mg/dL, but not LDL‐C, was significantly associated with CE (HR 1.206, 95% CI 1.006–1.446). A significant association of sdLDL‐C and incident CE was observed in statin users (HR 1.252, 95% CI 1.017–1.540), diabetes patients (HR 1.219, 95% CI 1.018–1.460), patients without diabetes (HR 1.257, 95% CI 1.019–1.551) and patients with hypertriglyceridemia (HR 1. 376, 95% CI 1.070–1.770).

Conclusions

sdLDL‐C was the most effective predictor of residual risk of future CE in stable coronary artery disease patients using statins and in high‐risk coronary artery disease patients with diabetes or hypertriglyceridemia. Geriatr Gerontol Int 2018; 18: 965–972 .     

Preserved Endothelial Function in Patients With Severe Hypertriglyceridemia and Low Functional Lipoprotein Lipase Activity

Objectives. We sought to determine whether hypertriglyceridemia in patients with lipoprotein lipase (LPL) dysfunction is associated with endothelial dysfunction in resistance vessels of the forearm vasculature.Background. Vasodilator responses to acetylcholine, acting through stimulation of nitric oxide (NO) release from the endothelium, are impaired in hypercholesterolemia and normalized by l-arginine, suggesting dysfunction of the l-arginine/NO pathway. Similar abnormalities have been reported in conditions associated with hypertriglyceridemia, such as non–insulin-dependent diabetes. The relation between endothelial function and plasma triglyceride concentrations has, however, not previously been studied in vivo.Methods. We examined forearm blood flow responses to brachial artery infusions of acetylcholine (alone and with l-arginine) and nitroprusside (an NO donor) in 17 patients with severe hypertriglyceridemia (mean [±SD] plasma triglyceride concentration 1,914 ± 1,288 mg/dl) but normal low density lipoprotein cholesterol (89 ± 31 mg/dl) and in 34 normolipidemic control subjects. Severe LPL dysfunction was demonstrated in 10 of 17 patients.Results. Acetylcholine (7.5 and 15 μg/min) produced similar forearm blood flow responses in hypertriglyceridemic patients (mean [±SEM] 7.7 ± 0.9 and 10.5 ± 1.2 ml/min per 100 ml) and in control subjects (7.5 ± 0.6 and 11.0 ± 0.8 ml/min per 100 ml, p = 0.78 by analysis of variance). Responses to acetylcholine co-infused with l-arginine (10 mg/min) and nitroprusside (3 and 10 μg/min) were also similar in hypertriglyceridemic patients and control subjects (p = 0.93 and p = 0.27 for acetylcholine with l-arginine and nitroprusside, respectively). The ratio response to acetylcholine/response to nitroprusside differed between hypertriglyceridemic patients and control subjects by only 1%. The study had >90% power (alpha = 0.05) to detect a difference >30% in this ratio.Conclusions. Severe hypertriglyceridemia associated with LPL dysfunction is not associated with the degree of endothelial dysfunction seen in moderate hypercholesterolemia when responses to acetylcholine are impaired by >40%.(J Am Coll Cardiol 1997;29:964–8)© 1997 by the American College of Cardiology     

Plasma interleukin-6 and tumor necrosis factor-alpha can predict coronary endothelial dysfunction in hypertensive patients.

Coronary endothelial function is impaired in hypertension; however, the severity of this impairment varies among patients. We aimed to identify the predictors of coronary endothelial dysfunction among clinical variables related to hypertension and atherosclerosis. Twenty-seven untreated, uncomplicated essential hypertensive patients and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using (15)O-water positron emission tomography (PET) at rest and during a cold pressor test (CPT). Coronary vascular resistance (CVR) during CPT was used as a marker of coronary endothelial function. Serum low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, malondialdehyde-LDL, homeostasis model assessment, high-sensitivity C-reactive protein (hs-CRP), and plasma interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were also measured. CVR during CPT was significantly higher in hypertensive patients than in healthy controls (114+/-26 vs. 94+/-12 mmHg/[mL/g/min]; p<0.05). By univariate analysis, CVR during CPT was correlated with LDL cholesterol (r=0.38, p<0.05), IL-6 (r=0.46, p<0.02), and TNF-alpha (r=0.39, p<0.05) in hypertensive patients. By multivariate analysis, IL-6 and TNF-alpha were significant independent predictors of CVR during CPT. Elevated plasma IL-6 and TNF-alpha levels were independent predictors of coronary endothelial dysfunction in hypertensive patients. These results suggest that plasma IL-6 and TNF-alpha might be useful for identifying the high risk subgroup of hypertensive patients with coronary endothelial dysfunction and provide an important clue to link systemic inflammation to the development of coronary atherosclerosis.     

Effects of Direct Adsorption of Lipoproteins Apheresis on Lipoproteins,Low‐Density Lipoprotein Subtypes,and Hemorheology in Hypercholesterolemic Patients with Coronary Artery Disease

Abstract: Direct adsorption of lipoproteins (DALI) apheresis has been shown to reduce effectively low‐density lipoprotein (LDL) cholesterol and lipoprotein (a) concentrations. However, the effects on nontraditional risk indicators such as hemorheology and LDL subtypes have not been investigated so far. Five patients (2 women, 3 men, age 53 ± 8 years) with coronary artery disease and severe LDL hypercholesterolemia regularly treated with other LDL apheresis devices entered the study and were then treated with DALI for the first time. Hemorheological and lipoprotein parameters were measured before and immediately after the initial DALI apheresis as well as before the fourth DALI apheresis. Compared to baseline (before the first DALI apheresis), the following parameters were significantly improved (p < 0.05) after the first DALI apheresis: LDL cholesterol (69 ± 28 versus 208 ± 82 mg/dl) and cholesterol in each LDL subfraction as well as plasma viscosity (1.23 ± 0.04 versus 1.37 ± 0.06 mPa), C‐reactive protein, native blood viscosity, red cell aggregation, and red cell deformability. When parameters before the fourth DALI apheresis were compared to baseline, LDL cholesterol was still lower, and red cell deformability was still improved while cholesterol in each subfraction showed a statistical trend to lower concentrations (0.08 < p < 0.14). In conclusion, DALI apheresis not only reduces LDL cholesterol but also induced a significant reduction of cholesterol in all LDL subfractions and improved various hemorheological parameters.