Relationships between lipoprotein components and risk of ischaemic and haemorrhagic stroke in the Apolipoprotein MOrtality RISk study (AMORIS)

Objectives. To compare lipoprotein components associated with ischaemic and haemorrhagic stroke by age and gender in the Apolipoprotein MOrtality RISk (AMORIS) Study (n = 148 600). Design. Prospective follow‐up study (11.8, range 7–17 years) of fatal and nonfatal ischaemic and haemorrhagic stroke through linkage with Swedish hospital discharge and mortality registers. Setting. Measurements of lipoprotein components from health check‐ups in the larger Stockholm area. Results. Ischaemic stroke was more common than haemorrhagic stroke (5 :1), but case fatality was higher in haemorrhagic stroke. An elevated apoB/apoA‐1 ratio and triglycerides, non‐HDL cholesterol, low HDL cholesterol, and the total cholesterol to high‐density cholesterol (TC/HDL‐C) ratio were associated with increased incidence of nonfatal and fatal ischaemic stroke as well as all cerebrovascular events (n = 7480) in both genders. The associations were somewhat stronger for nonfatal than fatal events. In ischaemic stroke the apoB/apoA‐1 ratio was a stronger predictor than the TC/HDL‐C ratio in all subjects, in those below 65 years of age and in those with LDL‐C below 3 mmol L^?1. Haemorrhagic stroke was not associated with elevated atherogenic lipoproteins except for increased risk of fatal haemorrhagic stroke in women with a high apoB/apoA‐I ratio. Conclusions. Dyslipidaemia is associated with an increased risk of ischaemic stroke but few relations were seen in haemorrhagic stroke. Use of the apoB/apoA‐I ratio as a marker of dyslipidaemia is at least as efficient as conventional lipids, for the identification of subjects at increased risk of stroke, especially ischaemic stroke. Practical advantages, fasting is not needed, speak in favour of using apoB and apoA‐1 in stroke risk prediction.     

Stroke mortality and the apoB/apoA-I ratio: results of the AMORIS prospective study

Objectives. LDL cholesterol is a well‐established risk factor for myocardial infarction, but not for stroke. The main objective of the present study was to determine if the risk of stroke is related to the balance between the proatherogenic apoB lipoprotein particles and the antiatherogenic apoA‐I particles as is the case for myocardial infarction. Subjects and design. A total of 98 722 men and 76 831 women were recruited from screening programmes. The prospective risk and the relationships between five different types of fatal strokes and the lipid fractions, apoB, apoA‐I and the apoB/apoA‐I ratio (automated immunoturbidimetry) were examined. The results were compared with the risks of other ischaemic and non‐ischaemic fatalities. Results. Mean follow‐up was 10.3 years. High apoB and low apoA‐I values were significantly related to risk of stroke. The odds ratio comparing the upper 10th versus the 1st decile of the apoB/apoA‐I ratio for all strokes adjusted for age, gender, total cholesterol (TC) and triglycerides (TG) was 2.07 (95% CI: 1.49–2.88), P < 0.0001. The strongest association was for ischaemic stroke. Low apoA‐I was a common abnormality in all stroke subtypes including subarachnoidal and haemorrhagic strokes. In multivariate analyses the apoB/apoA‐I ratio was a stronger risk predictor than total/HDL and LDL/HDL cholesterol ratios. The apoB/apoA‐I ratio was linearly related to the risk of stroke although the slope was less than observed for the risk of fatal myocardial infarction. For all ischaemic events pooled together the age‐, gender‐, TC‐ and TG‐adjusted odds ratio, 10th vs. 1st decile, was 3.13 (95% CI: 2.66–3.69), P < 0.0001. By contrast, there was no relationship between the apoB/apoA‐I ratio and risk of cancer or any other non‐ischaemic causes of death. Conclusions. These observations link the apoB/apoA‐I ratio to the risk of fatal stroke in a similar fashion as for myocardial infarction and other ischaemic events. Our findings indicate that the apoB/apoA‐I ratio, which indicates the ‘cholesterol balance’, is a robust and specific maker of virtually all ischaemic events.     

Relationships between lipoprotein components and risk of myocardial infarction: age, gender and short versus longer follow-up periods in the Apolipoprotein MOrtality RISk study (AMORIS)

Objectives. Examine and compare lipoprotein components associated with fatal and nonfatal acute myocardial infarction (AMI) by time period in the Apolipoprotein MOrtality RISk (AMORIS) Study. Design. Prospective follow‐up study of nonfatal and fatal myocardial infarction through linkage with Swedish hospital discharge and Swedish mortality registers. Setting. Measurements of lipoprotein components from health check‐ups in the larger Stockholm area. Subjects. The AMORIS subjects (n = 149 121) free of AMI at blood sampling were followed from 1985 to 2002 with respect to n = 6794 first cases of AMI. Results. Hazard ratios of nonfatal and fatal AMI by lipoprotein parameters were highly significant and about equally strong in both genders. Apolipoprotein B (apoB), nonhigh density cholesterol and low density cholesterol predicted nonfatal AMI (NFAMI) better than fatal AMI, but high density cholesterol or apolipoprotein A‐1 did not. Atherogenic components were weaker predictors after 1997 than before. In multivariate analyses apoB/apoA‐1 was a better predictor than TC/HDL‐C. ApoB/apoA‐1 added clinically significant information to TC/HDL‐C in men as reflected by a net reclassification improvement (NRI) of 9.4% (P < 0.0001). Conclusion. ApoB, apoB/apoA‐1 and non‐HDL‐C were found about equally predictive with LDL‐C being slightly less, but multivariate analyses showed apoB/apoA‐1 to be the strongest predictor. Attenuation of prediction ability between nonfatal and fatal AMI may be due to modern treatment of CHD after a NFAMI and attenuation of hazard ratios after 1997 may be due to selection of lower risk subjects surviving to 1997.     

[HDL‐C/apoA‐I]: A multivessel cardiometabolic risk marker in women with T2DM

Aims

Although women have higher high‐density lipoprotein cholesterol (HDL‐C) than have men, their HDL particles are also prone to become small, dense, and dysfunctional in case of type 2 diabetes mellitus (T2DM). To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL‐C to its main apolipoprotein (apoA‐I) as [HDL‐C/apoA‐I]. This ratio estimates HDL sizes and provides indices as to their number, cholesterol load, and density.

Methods

We stratified 280 Caucasian T2DM women according to [HDL‐C/apoA‐I] quartiles (Q) to determine how they are segregated according to cardiometabolic risk, β‐cell function, glycaemic control, and vascular complications. Five parameters were derived from combined determination of HDL‐C and apoA‐I: HDL size, HDL number, cholesterol load per particle (pP), apoA‐I pP, and HDL density.

Results

An adverse cardiometabolic profile characterized QI and QII patients whose HDLs were denser and depleted in apoA‐I, whereas QIII patients had HDLs with characteristics closer to those of controls. QIV patients had HDLs of supernormal size/composition and a more favourable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, and β‐cell function (32% vs 23%); exogenous insulin (44 vs 89 U·d^?1); and glycaemic control (glycated haemoglobin, 56 vs 61 mmol·mol^?1), associated with lower prevalence of microvascular/macrovascular complications: all‐cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all‐cause macroangiopathy 19% vs 31%; and coronary artery disease 6% vs 24% (P < .05).

Conclusion

[HDL‐C/apoA‐I] can stratify T2DM women according to metabolic phenotype, macrovascular and coronary damage, β‐cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women.     

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.     

Apolipoprotein A‐I deficiency does not affect biliary lipid secretion and gallstone formation in mice

Background/Aims: Apolipoprotein A‐I (apo A‐I) is the main protein component of plasma high‐density lipoproteins (HDL) and a key determinant of HDL cholesterol levels and metabolism. The relevance of HDL in controlling the traffic of cholesterol from plasma into bile has been partially addressed. The aim of this study was to evaluate the role of apo A‐I expression in controlling the secretion of biliary lipids as well as the risk of gallstone disease in vivo. Methods: We evaluated biliary lipid secretion and bile acid homeostasis in mice deficient for apo A‐I compared with wild‐type animals when fed with low‐ or high‐cholesterol diets. In addition, we assessed the importance of murine apoA‐I expression for gallstone formation after feeding a lithogenic diet. Results: Bile acid pool size and faecal excretion were within the normal range in chow‐ and cholesterol‐fed apo A‐I knockout (KO) mice. Basal biliary cholesterol secretion was comparable and increased similarly in both murine strains after cholesterol feeding. Lithogenic diet‐fed apo A‐I KO mice exhibited an impaired hypercholesterolaemic response owing to a lower increase in cholesterol levels transported in large lipoproteins. However, the lack of apo A‐I expression did not affect biliary cholesterol precipitation or gallstone formation in lithogenic diet‐fed mice. Conclusions: These findings indicate that biliary lipid secretion, bile acid metabolism and gallstone formation are independent of apo A‐I expression and plasma HDL cholesterol levels in mice.     

The effect of fenofibrate on HDL cholesterol and HDL particle concentration in postmenopausal women on tibolone therapy

Background Low high‐density lipoprotein (HDL) cholesterol and particle concentration are risk factors for coronary heart disease in women. Tibolone lowers HDL cholesterol and HDL particle concentration, an effect that could be reversed by the peroxisome proliferator‐activator receptor‐α agonist fenofibrate. Objective To assess the effects of fenofibrate on plasma HDL particles in postmenopausal women taking tibolone therapy. Design and participants Randomized crossover study conducted in a women’s health clinic. Fourteen postmenopausal women taking tibolone 2·5 mg daily for menopausal symptoms were randomized to either fenofibrate 160 mg daily or no treatment for 8 weeks, followed by a 3‐ week wash‐out for fenofibrate and then crossed over to alternate therapy for another 8 weeks. The main outcome measure was changes in plasma HDL cholesterol concentration, apoA‐I and apoA‐II, LpA‐I and LpA‐I‐A‐II. Results After 8 weeks of fenofibrate therapy, there was no change in HDL cholesterol, 1·13 ± 0·06 v 1·16 ± 0·06 mmol/l (P = 0·47) or apoA‐I, 1·19 ± 0·05 v 1·20 ± 0·05 g/l (P = 0·23). LpA‐I fell significantly 0·35 ± 0·03 v 0·29 ± 0·02 (P = 0·02) but there was a rise in apoA‐II, 0·35 ± 0·01 v 0·39 ± 0·01 g/l (P = 0·01). There was a significant fall in total cholesterol, triglycerides, low‐density lipoprotein cholesterol and apoB. Conclusion In women taking tibolone, fenofibrate increases plasma apoA‐II concentration and effects a redistribution of HDL subfractions but does not correct tibolone‐induced changes in HDL cholesterol or HDL particle concentration. The mechanism and significance of this require further investigation.     

Apolipoprotein B, non-HDL cholesterol and LDL cholesterol for identifying individuals at increased cardiovascular risk

Abstract. Holewijn S, den Heijer M, Swinkels DW, Stalenhoef AFH, de Graaf J. (Address: Division of Vascular Medicine, Department of General Internal Medicine; Department of Epidemiology and Biostatistics; Department of Endocrinology; and Department of Laboratory Medicine; Laboratory of Clinical Chemistry, all at the Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands) Apolipoprotein B, non‐HDL cholesterol and LDL cholesterol for identifying individuals at increased cardiovascular risk. J Intern Med 2010; 268 : 567–577. Background. To compare apolipoprotein B (apoB), nonhigh‐density lipoprotein‐cholesterol (non‐HDL‐c) and low‐density lipoprotein‐cholesterol (LDL‐c) for identifying individuals with a deteriorated cardiovascular (CV) risk profile, including a panel of subclinical atherosclerosis measurements and prevalent cardiovascular disease (CVD) in a Dutch population‐based cohort. Methods. Clinical and biochemical measurements and a panel of noninvasive parameters of subclinical atherosclerosis were determined in 1517 individuals, aged 50–70 years. Results. Both men and women with increasing levels of apoB and non‐HDL‐c were more obese, had higher blood pressure and fasting glucose levels, and a more atherogenic lipid profile. Furthermore, compared to the reference group (composed of those with apoB, non‐HDL‐c and LDL‐c levels in the bottom quartiles), participants with high apoB and high non‐HDL‐c levels had a lower ankle–brachial index at rest (?3.5% and ?3.1%, respectively) and after exercise (?6.3% and ?4.7%, respectively), a thicker near wall (+4.8% and +4.2%, respectively), far wall (both +6.2%), and mean intima–media thickness (+5.7% and +5.3%, respectively) and more plaques (+54.2% and +54.3%, respectively). In addition, they also showed increased stiffness parameters (e.g. pulse wave velocity both +3.6%). Less clear differences in CV risk profile and subclinical atherosclerosis parameters were observed when participants were stratified by LDL‐c level. Furthermore, apoB but not LDL‐c detected prevalent CVD, and non‐HDL‐c only detected prevalent CVD in men. The discriminatory power for prevalent CVD expressed as area under the receiver operating characteristic curve was 0.60 (P < 0.001) for apoB, 0.57 (P = 0.001) for non‐HDL‐c and 0.54 (P = 0.108) for LDL‐c. Conclusion. Our data support the use of first apoB and secondly non‐HDL‐c above LDL‐c for identifying individuals from the general population with a compromised CV phenotype.     

Lipid-altering efficacy and safety profile of combination therapy with ezetimibe/statin vs. statin monotherapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials

Aim: This post hoc analysis compared the lipid‐altering efficacy and safety of ezetimibe 10 mg plus statin (EZE/statin) vs. statin monotherapy in hypercholesterolaemic patients with and without diabetes. Methods: A pooled analysis of 27 previously published, randomized, double‐blind, active‐ or placebo‐controlled clinical trials comprising 21 794 adult patients with (n = 6541) and without (n = 15253) diabetes receiving EZE/statin or statin alone for 4–24 weeks evaluated percentage change from baseline in lipids and other parameters. Consistency of the treatment effect across the subgroups was tested using treatment × subgroup interaction. No multiplicity adjustments were made. Results: Treatment effects within both subgroups were generally consistent with the overall population. EZE/statin was more effective than statin alone in improving low‐density lipoprotein cholesterol (LDL‐C), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), triglycerides (TGs), non‐HDL‐C, apolipoprotein (apo) B and high‐sensitivity C‐reactive protein (hs‐CRP) in the overall population and both subgroups. Patients with diabetes achieved significantly larger reductions in LDL‐C, TC and non‐HDL‐C compared with non‐diabetic patients. Incidences of adverse events or creatine kinase elevations were similar between groups. A small but significantly higher incidence of alanine aminotransferase or aspartate aminotransferase elevations was seen in patients receiving EZE/statin (0.6%) vs. statin monotherapy (0.3%) in the overall population. Conclusions: Treatment with EZE/statin vs. statin monotherapy provided significantly larger reductions in LDL‐C, TC, TG, non‐HDL‐C, apo B and hs‐CRP and significantly greater increases in HDL‐C, with a similar safety profile in patients with and without diabetes. Reductions in LDL‐C, TC and non‐HDL‐C were larger in patients with diabetes than in patients without diabetes.     

Carotid intima‐media thickness and apolipoprotein B/apolipoprotein A‐I ratio in middle‐aged patients with Type 2 diabetes

Aims To explore the association between carotid intima‐media thickness (IMT) and the apolipoprotein B (apoB)/apolipoprotein A‐I (apoA‐I) ratio compared with conventional lipids in middle‐aged patients with Type 2 diabetes. Methods We analysed data from 247 patients with Type 2 diabetes, aged 55–66 years, in the Cardiovascular Risk factors in Patients with Diabetes—a Prospective study in Primary care (CARDIPP‐1) study. Primary care nurses measured blood pressure and anthropometric characteristics. Blood samples were taken for laboratory analyses. The carotid IMT was determined by ultrasonography at the University Hospital in Linköping and at the County Hospital Ryhov, Jönköping, Sweden. Results The ApoB/apoA‐I ratio (r = 0.207, P = 0.001), apoB (r = 0.166, P = 0.009) and non‐high‐density lipoprotein cholesterol (non‐HDL‐c) (r = 0.129, P = 0.046) correlated with IMT. Conventional lipids, high‐sensitivity C‐reactive protein (hsCRP), glycated haemoglobin (HbA_1c) and systolic blood pressure were not significantly correlated to IMT. A stepwise logistic regression analysis was conducted with IMT as the dependent variable and the apoB/apoA‐I ratio, HbA_1c, hsCRP, low‐density lipoprotein cholesterol (LDL‐c), total cholesterol, non‐HDL‐c and treatment with statins as independent variables. Following adjustment for age and gender, only the apoB/apoA‐I ratio remained significantly associated with IMT (odds ratio 4.3, 95% confidence intervals 1.7–10.8, P = 0.002). Conclusions We conclude that there was a significant association between the apoB/apoA‐I ratio and IMT in middle‐aged patients with Type 2 diabetes. The association was independent of conventional lipids, hsCRP, glycaemic control and use of statins.     

Sex differences in lipid profiles in relation to the progression of glucose abnormalities

Background: In the present study, we investigated the role of changes in blood lipids in the abolition of the lower cardiovascular risk associated with the female gender in individuals with type 2 diabetes mellitus (T2DM). Methods: An oral glucose tolerance test (OGTT) was performed in 1091 consecutive patients (478 men and 613 women) and patients were divided into groups as follows: (i) those with normal glucose tolerance (NGT; n = 589); (ii) those with pre‐diabetes (pre‐T2DM), who were further divided into those with impaired fasting glucose (IFG; n = 212), impaired glucose tolerance (IGT; n = 84), and both IFG and IGT (IFG/IGT; n = 102); and (iii) those with T2DM (n = 104). Total cholesterol, triglycerides, high‐density lipoprotein–cholesterol (HDL‐C), low‐density lipoprotein–cholesterol (LDL‐C), apolipoprotein (apo) A‐I, apoB, and the apoB:apoA‐I ratio were determined in each patient. Differences in lipids between the different groups were assessed using Student’s t‐test. Results: Significantly higher triglyceride levels and an apoB:apoA‐I ratio were found in NGT men (P < 0.0001), along with lower HDL‐C and apoA‐I (P < 0.0001). Men in the pre‐T2DM group maintained a higher apoB:apoA‐I ratio (P < 0.05) and lower HDL‐C (P < 0.0001) compared with women. In the T2DM group, only HDL‐C was lower in men compared with women (P < 0.05). Conclusions: The progression of glucose intolerance from NGT to pre‐T2DM and T2DM exhibits striking sex differences regarding the lipid profile. The data demonstrate a worsening of plasma lipid composition in women who become diabetic. This could explain, at least in part, the loss of the more favorable cardiovascular risk normally associated with NGT women.     

Low HDL‐cholesterol is common in European Type 2 diabetic patients receiving treatment for dyslipidaemia: data from a pan‐European survey

Aims To measure the prevalence of low high‐density lipoprotein (HDL)‐cholesterol (men < 1.03 mmol/l; women < 1.29 mmol/l) in European Type 2 diabetic patients receiving treatment for dyslipidaemia. Methods The pan‐European Survey of HDL‐cholesterol measured lipids and other cardiovascular risk factors in 3866 patients with Type 2 diabetes and 4436 non‐diabetic patients undergoing treatment for dyslipidaemia in 11 European countries. Results Diabetic patients were more likely to be obese or hypertensive than non‐diabetic patients. Most patients received lifestyle interventions (87%) and/or a statin (89%); treatment patterns were similar between groups. Diabetic patients had [means (SD)] lower HDL‐cholesterol [1.22 (0.37) vs. 1.35 mmol/l (0.44) vs. non‐diabetic patients, P < 0.001] and higher triglycerides [2.32 (2.10) vs. 1.85 mmol/l (1.60), P < 0.001]. More diabetic vs. non‐diabetic patients had low HDL‐cholesterol (45% vs. 30%), high triglycerides (≥ 1.7 mmol/l; 57% vs. 42%) or both (32% vs. 19%). HDL‐cholesterol < 0.9 mmol/l was observed in 18% of diabetic and 12% of non‐diabetic subjects. Differences between diabetic and non‐diabetic groups were slightly greater for women. LDL‐ and total cholesterol were lower in the diabetic group [3.02 (1.05) vs. 3.30 mmol/l (1.14) and 5.12 (1.32) vs. 5.38 mmol/l (1.34), respectively, P < 0.001 for each]. Conclusions Low HDL‐cholesterol is common in diabetes: one in two diabetic women has low HDL‐cholesterol and one diabetic man in four has very low HDL‐cholesterol. Management strategies should include correction of low HDL‐cholesterol to optimize cardiovascular risk in diabetes.     

Amelioration of cardiovascular risk factors with partial biochemical control of acromegaly

Objective Complete remission of acromegaly is associated with favourable changes in cardiovascular risk parameters. We evaluated the effects of suboptimal therapy on haemodynamic, metabolic, inflammatory and coagulation cardiovascular risk indices. Design and methods Eighteen acromegalic patients on somatostatin analogues, with incomplete biochemical control, were evaluated at diagnosis and 6 months after treatment and compared to 15 healthy age‐ and body mass index (BMI)‐matched controls. Measurements of blood pressure, GH, IGF‐I, glucose, insulin, glycated haemoglobin (HbA1c), lipids, apolipoprotein A1 (apoA1), apoB, high‐sensitivity C‐reactive protein (hs‐CRP), fibrinogen, plasminogen activator inhibitor 1 (PAI‐1), tissue plasminogen activator (tPA) and circulating thrombomodulin were performed in all study participants, followed by an oral glucose tolerance test (OGTT). Insulin sensitivity (IS) was expressed by the Matsuda index (OGTT_ISI). Results Partial control of acromegaly resulted in a significant reduction in systolic and diastolic blood pressure, glucose, insulin, HbA1c, total (T‐C) and low density lipoprotein cholesterol (LDL‐C) and triglyceride levels, and a significant increase in apoA1, high density lipoprotein cholesterol (HDL‐C) and OGTT_ISI compared to pretreatment levels. Plasma fibrinogen and PAI‐1 levels fell significantly [respectively (mean ± SEM), 11·04 ± 0·41 vs. 10·12 ± 0·34 µmol/l, P = 0·003 and 9·6 ± 1·97 vs. 6·55 ± 1·89 µg/l, P < 0·001]. However, a marked reduction in tPA [median (IQR) 5·1 (2·5–15) vs. 3·4 (2·4–8·6) µg/l, P = 0·031] and an increase in hs‐CRP [median (IQR) 0·05 (0·03–0·11) vs. 0·1 (0·06–0·23) mg/l, P < 0·001] were also noted. On treatment, acromegalic patients were comparable to controls, except for OGTT_ISI, lipoprotein(a) [Lp(a)], fibrinogen and tPA and HDL‐C levels. Thrombomodulin and apoB levels were not affected by treatment. Conclusions Partial control in disease activity following somatostatin analogues results in significant improvement in a considerable number of cardiovascular risk markers in acromegaly.     

Individuals with high total cholesterol/hdl cholesterol ratios are insulin resistant

Jeppesen J, Facchini FS, Reaven GM. (The Department of Medicine, Stanford University School of Medicine, Stanford, and Shaman Pharmaceuticals Inc., South San Francisco, CA, USA). Individuals with high total cholesterol/hdl cholesterol ratios are insulin resistant. Journal of Internal Medicine 1998; 243 : 293–98.

Objectives

To define the pathophysiologic characteristics of patients at high risk for coronary heart disease due to an increased ratio of total cholesterol (TC) to high density lipoprotein-cholesterol (HDL-C).

Design

Cross-sectional.

Setting

Clinical Research Center.

Subjects

One hundred-20 healthy, non-diabetic, normotensive, volunteers were screened for this study. From this pool, 40 individuals (20 females and 20 males) with the highest and the lowest TC/HDL-C ratios were selected for comparison.

Main Outcome Measures

Values for body mass index (BMI), ratio of waist to hip girth (WHR), and blood pressure were obtained on all patients. In addition, measurements were made of fasting lipid and lipoprotein concentrations, plasma glucose and insulin responses to an oral glucose challenge, and insulin resistance as assessed by the insulin suppression test.

Results

Age, BMI, and WHR were the same in the two groups. However, the group with a high TC/HDL-C ratio had higher (P < 0.05) systolic and diastolic blood pressures. In addition, patients with a high TC/HDL-C ratio had significantly higher (P < 0.001) very low density (VLDL) and low density lipoprotein (LDL)-cholesterol concentrations and lower HDL-cholesterol concentrations, with significant (P < 0.001) correlations between the TC/HDL-C ratio and VLDL (r= 0.60), LDL (r= 0.54), and HDL (r=? 0.73) cholesterol concentrations. Patients with a high TC/HDL-C ratio were also significantly (P < 0.05–0.001) more insulin resistant, glucose intolerant with a greater plasma insulin response to oral glucose, and hypertriglyceridemic.

Conclusions

The results indicate that an increase in LDL-cholesterol concentration is not necessarily the major contributor to a high ratio of TC/HDL-C. Furthermore, individuals with this epidemiologic designation are insulin resistant, and liable to all the other abnormalities associated with this metaboic defect.

     

Acute hepatitis C infection lowers serum lipid levels

Summary. Chronic hepatitis C infection is associated with hypolipidaemia that resolves with viral clearance. Lipid levels in a subgroup of patients rebound to levels that may increase the risk of coronary heart disease. The impact of acute hepatitis C infection and its clearance on lipid levels is unknown. We undertook a retrospective evaluation of subjects with acute hepatitis C infection evaluating lipid levels before, during and following acute infection. Thirty‐eight subjects with acute hepatitis C infection had lipid levels available. Twelve patients had pre‐infection and intra‐infection lipid levels available. Cholesterol (197.8–152.4 mg/dL, P = 0.025), low‐density lipoprotein (LDL) (116.1–76.3 mg/dL, P = 0.001) and non‐high‐density lipoprotein (non‐HDL) cholesterol (164.0–122.7 mg/dL, P = 0.007) decreased dramatically during acute hepatitis C virus infection. Nineteen patients who achieved viral clearance had lipid levels available during infection and following resolution of infection. In these patients, cholesterol (145.0–176.0 mg/dL, P = 0.01), LDL (87.0–110.1 P = 0.0046) and non‐HDL cholesterol (108.6–133.6 mg/dL, P = 0.008) increased significantly. No change was seen in patients who developed chronic infection. Four patients had lipid levels before, during and following resolution of infections and had increased postinfection LDL, cholesterol and non‐HDL cholesterol from pre‐infection levels, indicating acute infection may be associated with an increase in postinfection lipid levels and may confer an increased risk of coronary heart disease. Acute hepatitis C infection results in hypolipidaemia with decreased LDL, cholesterol and non‐HDL cholesterol levels that increase following infection resolution. Levels may increase above pre‐infection baseline lipid levels and should be monitored.     

Errors that result from using the TC/HDL C ratio rather than the apoB/apoA-I ratio to identify the lipoprotein-related risk of vascular disease

The objective of this analysis was to demonstrate the frequency and extent of error that results from using the TC/HDL C ratio rather than the apoB/apoA-I ratio to estimate the lipoprotein-related risk of vascular disease within 94,667 men and 75,675 women in the Apoprotein-related Mortality Risk (AMORIS) cohort. The odds ratio (OR) for the risk of fatal myocardial infarction was determined for 1 SD change in the apoB/apoA-I ratio and all the conventional cholesterol ratios--TC/HDL C ratio, LDL C/HDL C ratio, non-HDL C/HDL C ratio. In both men and women, the apoB/apoA-I ratio was significantly greater than any of the cholesterol ratios, which, in fact, differed little. Therefore, the apoB/apoA-I ratio was taken as the most accurate index of the lipoprotein-related risk of vascular disease. Using Receiver Operating Characteristic analysis, it was demonstrated that the diagnostic accuracy of the apoB/apoA-I ratio was significantly greater than any cholesterol ratio in those with an LDL cholesterol <3.6 mmol L(-1) compared to those with an LDL cholesterol >3.6 mmol L(-1). Indeed, the difference between the apoB/apoA-I OR compared with the TC/HDL C OR progressively widened as risk increased. This suggests that the advantage of the apoB/apoA-I ratio is greatest in the population at highest risk. The distribution of subjects by quintiles showed in both genders that whilst agreement was greatest at the extremes, even at these points there was substantial discordance between the TC/HDL C and the apoB/apoA-I ratios. Within the middle of the distribution, less than 50% of the values were concordant. Finally, when comparing the ORs, the TC/HDL C ratio underestimated risk in 69.4% of male subjects and overestimated risk in 26.1% of male subjects, whereas in the female subjects, the TC/HDL C ratio underestimated risk in 84.9% of the subjects and overestimated risk in 12.0%. Thus, using the conventional cholesterol ratios rather than the apoB/apoA-I ratio results in frequent and substantial error in the estimation of the lipoprotein-related risk of vascular disease.     

Dialysis Method Alters the Expression of MicroRNA‐33a and Its Target Genes ABCA1, ABCG1 in THP‐1 Macrophages

Atherosclerosis and accompanying cardiovascular disease are the first causes of mortality in patients undergoing maintenance hemodialysis. Anti‐atherosclerotic effects of hemodiafiltration (HDF) have been reported. Our study aimed to investigate the effect of serum derived from a healthy group (n = 23), before and after hemodialysis (HD) therapy (n = 23), and before and after HDF therapy (n = 17) on the expression of microRNA‐33a and its target genes adenosine triphosphate‐binding cassette transporter A1,G1 (ABCA1, ABCG1) in THP‐1 macrophages. Meanwhile, blood lipids and high‐sensitivity C‐reactive protein (hs‐CRP) were measured in these groups. Our data showed that the expression of miRNA‐33a was lower (P < 0.05) and ABCA1 and ABCG1 were higher (P < 0.05) in the healthy group than pre‐HD and pre‐HDF. miR‐33a was significantly decreased (P < 0.05) but ABCA1, ABCG1 was significantly increased (P < 0.05) in post‐HDF compared with pre‐HDF, while these parameters in pre‐ and post‐ HD groups did not show any significant change (P > 0.05). High density lipoprotein cholesterol (HDL‐C) was higher and hs‐CRP was lower in the healthy group than pre‐HD and pre‐HDF groups. Moreover, a significant increase of HDL‐C (P < 0.05) and decrease (P < 0.05) of hs‐CRP was shown in post‐HDF compared with pre‐HDF, but HD appeared to have no significant change in these subjects. HDF therapy can downregulate miR‐33a expression, and then result in ABCA1, ABCG1 upregulation and an increase in circulating HDL‐C, leading to a possible anti‐atherosclerosis effect to some extent.     

Changes of lipid metabolism in plasma, liver and bile during cholesterol gallstone formation in rabbit model

AIM To find out the relationship between the disturbances of lipid metabolism and the formation of cholesterol gallstones by studying the changes of lipid metabolism in plasma, liver tissue and the bile.METHODS Male and female white Japanese rabbits were divided randomly into a control group (Con) and four experimental groups of 10 rabbits each fed with a diet containing 1.2% cholesterol for one, two, three and four weeks (1wk, 2wk, 3wk and 4wk group). The measurement of plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and its subfractions (HDL2-C, HDL3-C), very low and low density lipoprotein cholesterol (VLDL-C, LDL-C) was taken with standard enzymatic techniques. Apolipoprotein (apo) concentrations in plasma were measured by radial immunodiffusion assay for apoA1, apoB100, aopCⅡ and apoCⅢ. Total cholesterol of liver was measured by the enzymatic procedure for each animal. Bile acids, mainly glycocholate (GCA) and glycodeoxycholate (GDCA) were detected by dual wavelength thin layer scanner.RESULTS In all the experimental groups fed with dietary cholesterol, cholesterol crystal was found in the gallbladder in 2/10 cases of the 1wk group, 4/10 of the 2wk group, 6/10 of the 3wk group and 7/10 of the 4wk group respectively. The concentration of plasma total cholesterol (TC), triglyceride (TG), phospholipid (pl), VLDL-C, LDL-C, apoB100, apoCⅡ, apoCⅢ gradually increased (P＜0.05) with the prolonged feeding time of dietary cholesterol. High density lipoprotein cholesterol and its subfractions (HDL-C, HDL2-C, HDL3-C) showed a tendency to decrease, but without statistical significance (P＞ 0.05). ApoA1 was reduced with increased feeding time of dietary cholesterol (P ＜0.05). The hepatic and biliary cholesterol increased 1-1.5 times as compared with the control group (t=5.221 and 3.445, P＜0.05). The GCA gradually decreased beginning from the control group to the 4wk group (P＜0.05).CONCLUSION Owing to the high cholesterol diet, the increased concentrations of plasma TC, TG, VLDL-C, LDL-C, hepatic TC and TG, apoB100, apoCⅡ and apoCⅢ possibly enhanced the secretion of biliary cholesterol into bile; the decreased plasma apoA1 level might reduce the secretion of antinucleating factor into bile. All those factors mentioned above probably contribute to the formation of cholesterol gallstones.     

Egg consumption and high-density-lipoprotein cholesterol

Abstract. Objectives . To examine if increased egg consumption raises serum high-density-lipoprotein (HDL) cholesterol in healthy individuals. Design . A cross-over study. Setting . A private clinic for preventive health examinations in Copenhagen. Subjects . Twenty-four healthy adults, 12 men and 12 women, aged 23–52 (median 40) years. Interventions . After a 1-week control period each person added two bolled eggs to the usual daily diet for 6 weeks. All persons were instructed not to change the lifestyle in other ways during the whole study period. Main outcome measures . Serum HDL cholesterol, total cholesterol and triglycerides were measured before, during and after 6 weeks of extra egg consumption. The corresponding serum Iow-density-lipoprotein (LDL) cholesterol was calculated from the Friedewald formula. Results . After 6 weeks of extra egg consumption serum HDL cholesterol increased by 10% (P < 0.05) and total cholesterol increased 4% (P < 0.05), whereas the ratio total cholesterol/HDL cholesterol did not change significantly. Serum triglycerides and LDL cholesterol were also unchanged. Conclusions . A moderate egg intake should not be rigorously restricted in healthy individuals.     

Improvement in lipids after switch to boosted atazanavir or darunavir in children/adolescents with perinatally acquired HIV on older protease inhibitors: results from the Pediatric HIV/AIDS Cohort Study

Objectives

Dyslipidaemia is common in perinatally HIV‐infected (PHIV) youth receiving protease inhibitors (PIs). Few studies have evaluated longitudinal lipid changes in PHIV youth after switch to newer PIs.

Methods

We compared longitudinal changes in fasting lipids [total cholesterol (TC), triglycerides (TG), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and TC:HDL‐C ratio] in PHIV youth enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) study who switched to atazanavir/ritonavir (ATV/r)‐ or darunavir/ritonavir (DRV/r)‐based antiretroviral therapy (ART) from an older PI‐based ART and those remaining on an older PI. Generalized estimating equation models were fitted to assess the association of a switch to ATV/r‐ or DRV/r‐based ART with the rate of change in lipids, adjusted for potential confounders.

Results

From 2007 to 2014, 47 PHIV children/adolescents switched to ATV/r or DRV/r, while 120 remained on an older PI [primarily lopinavir/r (72%) and nelfinavir (24%)]. Baseline age ranged from 7 to 21 years. After adjustment for age, Tanner stage, race/ethnicity, and HIV RNA level, a switch to ATV/r or DRV/r was associated with a more rapid annual rate of decline in the ratio of TC:HDL‐C. (β = ?0.12; P = 0.039) than remaining on an older PI. On average, TC declined by 4.57 mg/dL/year (P = 0.057) more in the switch group. A switch to ATV/r or DRV/r was not associated with the rate of HDL‐C, LDL‐C, or TG change.

Conclusions

A switch to ATV/r or DRV/r may result in more rapid reduction in TC and the TC:HDL‐C ratio in PHIV youth, potentially impacting long‐term cardiovascular disease risk.