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1.  Characterization of lipid parameters in diabetes mellitus – a Nigerian report 
Background
Diabetes mellitus (DM) is a disorder that is often associated with cardiovascular events and underlying lipid abnormalities. Cardiovascular complications are common causes of DM deaths in Nigeria yet dyslipidaemia is one aspect of DM that is underdiagnosed and undertreated in our patients. This report seeks to determine the prevalence and pattern of lipid abnormalities in Nigerians with types I and 2 DM.
Methods
A total of 600 patients with DM aged between 22 – 79 years were evaluated for lipid abnormalities. The anthropometric indices, glycosylated haemoglobin, pattern of DM treatment and co-morbidities were noted. Total cholesterol (TCHOL), triglyceride (TG), high density lipoproteins (HDL-C), low density lipoproteins cholesterol (LDL-C) levels and the atherogenic indices levels were documented. Test statistic used included student's t test and χ2.
Results
Well over half (89%) of the study subjects had lipid abnormalities and there was no statistically significant difference in the proportions of subjects with type 1 and 2 DM with lipid abnormalities. Elevated LDL-C, TCHOL, TG and reduced HDL-C were noted in 74%, 42%, 13%, and 53% respectively of the study subjects. The commonly noted combined lipid abnormalities were elevated TG and reduced HDL-C. Hypertension, significant histories of smoking and alcohol ingestion were found to be potential determinants of the occurrence of dyslipidaemia. Age, sex, type of DM and anthropometric indices were found to be determinants of the the pattern of dyslipidaemia. Only a small proportion – (8%)-of the subjects with dyslipidaemia were on treatment for it.
Conclusion
Having defined the scope of dyslipidaemia in our patients and also highlighting its gross undertreatment, we hope that our data will help sensitize health care practitioners on screening for and treating dyslipidaemia. Elevated LDL-C and reduced HDL-C should be the primary targets of treatment in our patients with dyslipidaemia.
doi:10.1186/1755-7682-2-19
PMCID: PMC2734749  PMID: 19619328
2.  Comparing the effects of insulin glargine and thiazolidinediones on plasma lipids in type 2 diabetes: a patient-level pooled analysis 
Background
The prevalence of dyslipidaemia and the risk of cardiovascular disease are elevated in patients with type 2 diabetes. This analysis compared the effects of insulin glargine versus thiazolidinediones (TZDs) on lipid profiles.
Methods
Patient-level data were pooled from two randomized clinical studies. The population included 552 men and women aged >18 years, diagnosed with type 2 diabetes for at least 6 months, on metformin and/or sulphonylurea, and with A1C ≥7.5% and <12.0% at screening. Lipid outcome measures included change from baseline in lipid levels [low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, triglycerides, and free fatty acids] and attainment of lipid goals for LDL-C, non-HDL-C, and triglycerides.
Results
Both insulin glargine and TZDs improved lipid profiles from baseline values. Compared with TZDs, treatment with insulin glargine led to 7.9% greater reduction in LDL-C (p < 0.0003), 7.5% greater reduction in non-HDL-C (p < 0.0001), and 7.8% greater reduction in total cholesterol (p < 0.0001), whereas the HDL-C increase with TZD was 7.6% greater than that with insulin glargine (p < 0.0001). The percentage of patients attaining the lipid goals was comparable between insulin glargine and pioglitazone, but lower for rosiglitazone. Insulin glargine improved glycaemic control more than TZDs; however, insulin glargine caused more hypoglycaemia. Treatment with TZDs caused more weight gain and peripheral oedema.
Conclusion
These findings suggest that the favourable effects of insulin glargine on plasma lipid profiles should be considered among the advantages of treatment with insulin glargine as they are for TZDs. Copyright © 2011 John Wiley & Sons, Ltd.
doi:10.1002/dmrr.1305
PMCID: PMC3380564  PMID: 22081557
insulin glargine; lipids; thiazolidinediones; type 2 diabetes
3.  Atorvastatin treatment modulates the interaction between leptin and adiponectin, and the clinical parameters in patients with type II diabetes 
The aim of this study was to examine the effect of atorvastatin treatment on levels of leptin, adiponectin and insulin resistance, and their correlation with clinical parameters, in patients with type II diabetes. Patients with diabetes (n=394) were divided into two groups, comprising 161 patients who received 20 mg/day atorvastatin (statin group), and 233 patients who did not receive statins (statin-free group). The results showed that atorvastatin treatment of patients with diabetes was not associated with changes in leptin, adiponectin, the leptin/adiponectin (L/A) ratio or homeostasis model assessment-insulin resistance (HOMA-IR). However, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and total cholesterol (Tchol) were positively correlated with leptin and L/A ratio in the statin group only (P<0.05). By contrast, high-density lipoprotein cholesterol (HDL-C) showed a significant positive correlation with adiponectin in the statin and statin-free groups (P<0.05). Additionally, a positive correlation was found between HOMA-IR and glycated hemoglobin (HbA1c), and TG, in both groups, whereas Tchol was positively correlated with HOMA-IR in the statin group only (P<0.05). When multivariate analysis was performed with HOMA-IR as the dependent variable, and with adjustment for age, body mass index (BMI) and waist circumference, HbA1c was found to be a significant predictor of HOMA-IR or insulin resistance. In conclusion, atorvastatin treatment may have several effects on the interaction between leptin and adiponectin, and on clinical parameters in patients with type II diabetes.
doi:10.3892/etm.2013.1347
PMCID: PMC3829757  PMID: 24255692
adiponectin; leptin; statins; insulin resistance; lipid panel
4.  Lipid Profile of Type 2 Diabetic and Hypertensive Patients in the Jamaican Population 
Aims:
Previous studies have shown that diabetes mellitus (DM) increases the risk of cardiovascular diseases in females to a greater extent than in males. In this cross-sectional study, we evaluated the lipid profiles of type 2 diabetic males and females.
Materials and Methods:
The study included 107 type 2 diabetic patients (41 males and 66 females), and 122 hypertensive type 2 diabetic patients (39 males and 83 females), aged 15 years and older. Total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) and high density lipoprotein-cholesterol (HDL-C) concentrations were assayed for each group using standard biochemical methods.
Results:
The mean TC, TG, VLDL-C, HDL-C and LDL-C concentrations, TG/HDL and LDL/HDL ratios were higher in type 2 diabetic and hypertensive type 2 diabetic patients compared with non-diabetic, and hypertensive non-diabetic control subjects, although these were not significant (P > 0.05). Hypertensive type 2 diabetic females had significantly higher serum TC (7.42 ± 1.63 mmol/L) than hypertensive non-diabetic males (5.76±1.57 mmol/L; P < 0.05). All the other lipid and lipoprotein parameters except HDL-C were non-significantly higher in females with type 2 DM and those with hypertension and type 2 DM, compared with type 2 diabetic and hypertensive type 2 diabetic males, respectively (P > 0.05).
Conclusion:
This study demonstrated that dyslipidemia exists in our type 2 diabetic population with greater TC in hypertensive type 2 diabetic females compared with hypertensive type 2 diabetic males. This suggests that hypertensive type 2 diabetic females are exposed more profoundly to risk factors including atherogenic dyslipidemia compared with males.
doi:10.4103/0974-2727.66709
PMCID: PMC3147082  PMID: 21814403
Females; hypertension; lipids; lipoprotein; males; type 2 diabetes mellitus
5.  Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management 
European Heart Journal  2011;32(11):1345-1361.
Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.
doi:10.1093/eurheartj/ehr112
PMCID: PMC3105250  PMID: 21531743
High-density lipoprotein cholesterol; Triglycerides; Triglyceride-rich lipoproteins; Remnants; Cholesterol; Atherogenic dyslipidaemia; Cardiovascular disease; Atherosclerosis; Guidelines
6.  Impact of dyslipidemic components of metabolic syndrome, adiponectin levels, and anti-diabetes medications on malondialdehyde-modified low-density lipoprotein levels in statin-treated diabetes patients with coronary artery disease 
Background
A residual risk of cardiovascular disease tends to persist despite standard prevention therapy with statins. This may stem partly from increased oxidized low-density lipoprotein (LDL) levels. However, how oxidized LDL can be further reduced beyond statin therapy in high-risk diabetes patients remains unclear. We aimed to clarify the clinical factors associated with oxidized LDL levels in statin-treated high-risk diabetes patients.
Methods
This cross-sectional observational study included 210 diabetes patients with coronary artery diseases (CAD) who were treated with statins. We determined serum malondialdehyde-modified LDL (MDA-LDL), LDL cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), remnant lipoprotein cholesterol, hemoglobin (Hb) A1c, adiponectin, and C-reactive protein (CRP) levels and investigated the factors influencing the MDA-LDL level.
Results
In univariate analysis, the MDA-LDL level was significantly correlated with LDL cholesterol (p < 0.0001), TG (p < 0.0001), HDL cholesterol (p = 0.017), and adiponectin (p = 0.001) levels but not with age, body mass index, waist circumference, blood pressure, or HbA1c levels. Even after adjusting for the LDL cholesterol level, the correlations between the MDA-LDL level and the TG, HDL cholesterol, and adiponectin levels were still significant. Among these significant factors, multivariate analysis revealed that the MDA-LDL level was independently associated with the LDL cholesterol, TG, and HDL cholesterol but not with adiponectin levels. The MDA-LDL level was also significantly associated with the CRP level (p = 0.014) and the remnant lipoprotein cholesterol level (p < 0.0001) independently of the LDL cholesterol level. The number of metabolic syndrome (MS) components was significantly associated with the MDA-LDL/LDL cholesterol ratio (p < 0.0001). Furthermore, the use of metformin and α-glucosidase inhibitors was inversely associated with high MDA-LDL levels (p = 0.033 and 0.018, respectively).
Conclusion
In statin-treated diabetes patients with CAD, the MDA-LDL level was significantly correlated with TG and HDL cholesterol levels. Adiponectin level was also significantly associated with the MDA-LDL level, but not independent of the above-mentioned factors. The management of dyslipidemic MS components, including the use of metformin or α-glucosidase inhibitors, may be important for reducing the oxidized LDL levels beyond statin therapy in high-risk diabetes patients.
doi:10.1186/1758-5996-5-77
PMCID: PMC4029151  PMID: 24314067
MDA-LDL; Metabolic syndrome; Triglycerides; HDL cholesterol; Adiponectin; Diabetes mellitus; Coronary artery disease; Statins
7.  Implications of the obesity epidemic for lipid-lowering therapy: Non-HDL cholesterol should replace LDL cholesterol as the primary therapeutic target 
Obesity, metabolic syndrome and diabetes are conditions with increasing prevalence around the world. Cardiovascular risk in diabetics is often so high as to overlap with event rates observed in those with established coronary disease and this has lead to diabetes being classified as a coronary risk equivalent. However, despite the elevated risk of cardiovascular events associated with diabetes and the metabolic syndrome, these patients often have normal low density lipoprotein (LDL) cholesterol despite frequent increases in apolipoprotein B, triglycerides and nonhigh density lipoprotein (HDL) cholesterol. In contrast to LDL cholesterol, non-HDL cholesterol represents cardiovascular risk across all patient populations but is currently only recommended as a secondary target of therapy by the ATP III report for patients with hypertriglyceridemia. This article provides an overview of the studies that shown non-HDL cholesterol to be superior to LDL cholesterol in predicting cardiovascular events and presents the case for non-HDL cholesterol being the more appropriate primary target of therapy in the context of the obesity pandemic. Adopting non-HDL cholesterol as the primary therapeutic target for all patients will conceivably lead to an appropriate intensification of therapy for high risk patients with low LDL cholesterol.
PMCID: PMC2464759  PMID: 18629364
obesity; coronary artery disease; non-HDL cholesterol; LDL cholesterol; metabolic syndrome; diabetes
8.  HDL Revisited: New Opportunities for Managing Dyslipoproteinaemia and Cardiovascular Disease 
Low concentrations of high-density lipoprotein (HDL) cholesterol constitute a risk factor for coronary heart disease (CHD). There is increasing evidence that increasing HDL-cholesterol levels reduces cardiovascular risk. The phenotype of low HDL cholesterol with or without elevated triglycerides is common and it is characteristic of patients with central obesity, insulin resistance, hypertension and type 2 diabetes mellitus; conditions associated with increased cardiovascular risk and are part of the rubric of the metabolic syndrome. Epidemiological, experimental and clinical trial evidence suggests that there is a good rationale for raising HDL-cholesterol in these and other high-risk patients. The protective effect of HDL-cholesterol against atherosclerosis and cardiovascular disease is mediated by both enhanced reverse cholesterol transport (RCT) and by direct anti-atherosclerotic mechanisms. Recent studies have elucidated mechanisms whereby HDL acts to reduce cardiovascular risk, supporting the rationale for targeting of HDL with lipid-modifying therapy. Ongoing investigation of mechanisms by which HDL acts to reduce the risk of atherosclerosis will provide opportunities for the development of new therapeutic strategies to decrease the risk of atherosclerosis.
PMCID: PMC1853365  PMID: 18516209
9.  Risk factors of type 2 diabetes in population of Jammu and Kashmir, India 
Journal of Biomedical Research  2013;27(5):372-379.
We sought to identify risk factors for type 2 diabetes (T2D) in Jammu and Kashmir populations, India. A total of 424 diabetic and 226 non-diabetic subjects from Jammu, and 161 diabetic and 100 non-diabetic subjects from Kashmir were screened for various parameters including fasting blood glucose level, 2 hour glucose level, urea, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL-C), uric acid, systolic and diastolic blood pressure level. We found that subjects aged 40-49 years had the highest rate of diabetes, with family income playing not much of a role. Kashmiri migrants or populations with rapid cultural, environmental, social or lifestyle change along with reduced physical activity, obesity and unhealthy lifestyle (smoking and alcohol consumption) were found to have higher rates of diabetes. High blood glucose, triglycerides and low HDL-C levels were found to be contributing to disease outcome. High blood pressure also contributed to a higher risk of developing T2D. Our study supports earlier reports confirming the contribution of comfortable life style, Western dietary habits and rapid life style change along with many other factors to the prevalence of diabetes. This may contribute to the epidemic proportion of diabetes in Jammu and Kashmir. Early diagnosis and routine screening for undiagnosed diabetes in obese subjects and subjects with parental diabetes history is expected to decrease the burden of chronic diabetic complications worldwide.
doi:10.7555/JBR.27.20130043
PMCID: PMC3783822  PMID: 24086170
type 2 diabetes; north India; life style; kashmiri migrants; body mass index
10.  Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches 
Nutrients  2013;5(3):928-948.
Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk.
doi:10.3390/nu5030928
PMCID: PMC3705327  PMID: 23507795
lipoproteins; small dense low density lipoprotein; obesity; metabolic syndrome; obesity treatment; anti-obesity drugs; lipid-lowering drugs
11.  Treatment of dyslipidemia in patients with type 2 diabetes 
Type 2 diabetes is associated with significant cardiovascular morbidity and mortality. Although low-density lipoprotein cholesterol levels may be normal in patients with type 2 diabetes, insulin resistance drives a number of changes in lipid metabolism and lipoprotein composition that render low-density lipoprotein cholesterol and other lipoproteins more pathogenic than species found in patients without type 2 diabetes. Dyslipidemia, which affects almost 50% of patients with type 2 diabetes, is a cardiovascular risk factor characterized by elevated triglyceride levels, low high-density lipoprotein cholesterol levels, and a preponderance of small, dense, low-density lipoprotein particles. Early, aggressive pharmacological management is advocated to reduce low-density lipoprotein cholesterol levels, regardless of baseline levels. A number of lipid-lowering agents, including statins, fibrates, niacin, and bile acid sequestrants, are available to target normalization of the entire lipid profile. Despite use of combination and high-dose lipid-lowering agents, many patients with type 2 diabetes do not achieve lipid targets. This review outlines the characteristics and prevalence of dyslipidemia in patients with type 2 diabetes and discusses strategies that may reduce the risk of cardiovascular disease in this population.
doi:10.1186/1476-511X-9-144
PMCID: PMC3022752  PMID: 21172030
12.  Plasma lipids, lipoproteins, and apolipoproteins in Nigerian diabetes mellitus, essential hypertension, and hypertensive-diabetic patients. 
Plasma lipids, lipoproteins, and apolipoproteins were assessed in three groups of Nigerians at increased risk for atherosclerotic heart disease. The three patient groups, diabetes mellitus (n = 15), essential hypertension (n = 12), and hypertensive-diabetes mellitus (n = 11), were compared with age-matched, apparently healthy controls (n = 14). In subjects with diabetes mellitus, triglyceride and its related apolipoproteins CIII and CIII:NonB were significantly higher than controls. High-density lipoprotein cholesterol (HDL-C) was significantly lower; its related ratios, total/HDL-C and low-density lipoprotein cholesterol (LDL-C)/HDL-C were significantly higher than those for controls. Subjects with hypertension and hypertensive-diabetes mellitus had significantly higher values than controls for those lipids and lipid fractions considered atherogenic (total cholesterol, LDL-C, triglyceride, and the total/HDL-C and LDL-C/HDL-C ratios) as well as apolipoproteins B, CIII, and lipoprotein particles Lp(a) and CIII:NonB. Only hypertensive-diabetes mellitus subjects had lower HDL-C levels, while hypertension patients had significantly higher apolipoprotein AI and LpAI concentrations than controls. Subjects with hypertensive-diabetes mellitus had significantly worse lipid, lipoprotein, and apolipoprotein profiles both in terms of increased atherogenic and reduced anti-atherogenic parameters compared with subjects with diabetes mellitus or hypertension only. These studies suggest that Nigerians with diabetes, hypertension, and especially both hypertension and diabetes need to be fully evaluated from a lipid and lipoprotein standpoint, and any abnormalities detected need to be taken into consideration during therapy of this group of high-risk patients.
PMCID: PMC2607772  PMID: 7897682
13.  New Markers of Early Cardiovascular Risk in Multiple Sclerosis Patients: Oxidized-LDL Correlates with Clinical Staging 
Disease markers  2013;34(5):341-348.
OBJECTIVES: This study aimed to characterize a population of multiple sclerosis (MS) patients in terms of traditional and new cardiovascular risk factors and assess their putative correlation with clinical disease activity (evaluated by the Expanded Disability Status Scale [EDSS]).
METHODS: Thirty relapsing MS patients and 66 subjects, matched by age and sex, were enrolled in this cross-sectional study. For each subject, anthropometric data were collected and classical biochemical (including lipid profile, glucose and C reactive protein [CRP] levels) and novel markers (paraoxonase 1 [PON1] enzyme activity and contents of high-density lipoprotein [HDL] cholesterol, oxidized low-density lipoprotein [Ox-LDL], tumor necrosis factor [TNF]-alfa, vascular endothelial growth factor [VEGF] and adiponectin) were studied.
RESULTS: In patients group, 23 women and 7 men were included, aged 35.00 (28.25–40.25) years and scoring a median of 2.00 (1.50–3.13) in EDSS. Comparing with controls, the most relevant differences encountered were: increased serum triglycerides (P < 0.001), Ox-LDL (P < 0.001) as well as Ox-LDL/LDL ratio and reduced small HDL (P = 0.040), accompanied by a trend to increased VEGF concentration. LDL content, especially Ox-LDL, showed positive and significant correlation with EDSS (r = 0.458; P = 0.011) and VEGF (r = 0.453; P = 0.014).
CONCLUSIONS: MS patients presented a profile of early CV risk, being Ox-LDL contents a putative good marker and having correlation with the clinical activity of the disease.
doi:10.3233/DMA-130979
PMCID: PMC3809749  PMID: 23478275
Multiple sclerosis; early cardiovascular risk; EDSS; oxidized-LDL; small HDL; VEGF
14.  Heat-shock protein 60 kDa and atherogenic dyslipidemia in patients with untreated mild periodontitis: a pilot study 
Cell Stress & Chaperones  2012;17(3):399-407.
Identification of predictors of cardiovascular risk can help in the prevention of pathologic episodes and the management of patients at all stages of illness. Here, we investigated the relationships between serum levels of Hsp60 and dyslipidemia in patients with periodontitis by performing a cross-sectional study of 22 patients with mild periodontitis without any prior treatment for it (i.e., drug naïve) and 22 healthy controls, matched for age and body mass index (BMI). All subjects were evaluated for periodontal status, gingival inflammation, and oral hygiene. Levels of circulating Hsp60, C-reactive protein (CRP), and plasma lipids were measured, and small, dense low-density lipoproteins (LDL) were indirectly assessed by determining the triglycerides/high-density lipoproteins (HDL) cholesterol ratio. We also assessed by immunohistochemistry Hsp60 levels in oral mucosa of patients and controls. No difference was found in CRP levels or plasma lipids between the two groups, but subjects with periodontitis showed, in comparison to controls, higher levels of small, dense LDL (p  = 0.0355) and circulating Hsp60 concentrations (p < 0.0001). However, levels of mucosal Hsp60 did not change significantly between groups. Correlation analysis revealed that circulating Hsp60 inversely correlated with HDL-cholesterol (r  = −0.589, p  = 0.0039), and positively with triglycerides (r  = +0.877, p < 0.0001), and small, dense LDL (r  = +0.925, p < 0.0001). Serum Hsp60 significantly correlated with the degree of periodontal disease (r  = +0.403, p  = 0.0434). In brief, untreated patients with mild periodontitis had increased small, dense LDL and serum Hsp60 concentrations, in comparison to age- and BMI-matched controls and both parameters showed a strong positive correlation. Our data indicate that atherogenic dyslipidemia and elevated circulating Hsp60 tend to be linked and associated to periodontal pathology. Thus, the road is open to investigate the potential value of elevated levels of circulating Hsp60 as predictor of risk for cardiovascular disease when associated to dyslipidemia in periodontitis patients.
doi:10.1007/s12192-011-0315-1
PMCID: PMC3312963  PMID: 22215516
Periodontitis; Hsp60; Small, dense LDL; Risk factors; Cardiovascular disease
15.  Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia 
Although statins reduce cardiovascular morbidity and mortality further risk reduction is needed. In this respect low HDL-cholesterol concentrations and/or elevated triglyceride concentrations may be potential treatment targets. Niacin (nicotinic acid) is an effective drug which increases the plasma concentration of high-density lipoprotein (HDL)-cholesterol and decreases the concentration of low-density lipoprotein (LDL)-cholesterol, triglycerides and lipoprotein(a). Clinical studies indicate that niacin can significantly reduce the risk for cardiovascular events. However, niacin is not very commonly used because of significant side effects (especially flushing). Laropiprant is a potent selective antagonist of PGD2-receptor subtype-1 and can thus reduce niacin-induced flushing. Although the addition of laropiprant will reduce the frequency of flushing, it will not completely eliminate this side effect. Laropiprant does not change the effect of niacin on lipids or other side effects of niacin (ie, gastro-intestinal problems, glucose elevation). The combination of niacin with laropiprant may therefore enable use of niacin at higher doses and therefore exploit the full potential of the drug. Endpoint studies that will be published over the next few years will show whether this treatment modality also translates into clinical effect in patients treated with statins. Until publication of these studies niacin/laropiprant should be used only in high-risk patients not achieving lipid goals on statins.
PMCID: PMC2788595  PMID: 20016845
nicotinic acid; flushing; hyperlipidemia; dyslipoproteinemia
16.  The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: Baseline characteristics of study participants. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH) trial 
American heart journal  2011;161(3):538-543.
Objectives
The study aims to report the baseline characteristics of the fully randomized AIM-HIGH study population.
Background
Residual risk persists despite aggressive low-density lipoprotein cholesterol (LDL-C) reduction in patients with atherosclerotic cardiovascular (CV) disease, many of whom have atherogenic dyslipidemia (low levels of high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, and small dense LDL particles).
Methods
All study participants had established CV disease and atherogenic dyslipidemia. Participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain LDL-C at 40 - 80 mg/dL (1.03-2.07 mmol/L) and were randomized to receive extended-release niacin or matching placebo. The primary end point is time to the first occurrence of coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome or symptom-driven coronary or cerebral revascularization with average follow-up of 4.1 years.
Results
Between 2006 and 2010, 8,162 individuals signed consent to be screened, 4,275 began study drug run-in, and 3,414 were randomized to treatment. Mean age at entry was 64 ± 9 years, 85% were men, and 92% were white. As expected, risk factors were prevalent with 34% having diabetes; 71%, hypertension; and 81%, metabolic syndrome. Most participants had coronary artery disease (92%), whereas 11% had peripheral arterial disease; and 12%, cerebrovascular disease. Previous coronary revascularization occurred in 82%, and 54% reported a prior myocardial infarction. Among participants on a statin at entry (94%), mean baseline LDL-C was 71 mg/dL (1.84 mmol/L); mean HDL-C, 34.9 mg/dL (0.90 mmol/L); and median triglycerides, 161 mg/dL (1.82 mmol/L).
Summary
AIM-HIGH enrolled a high-risk group of patients with established atherosclerotic CV disease and atherogenic dyslipidemia. This study should determine whether there is incremental clinical benefit of niacin in reducing cardiovascular events in patients who have attained optimal on-treatment levels of LDL-C with a statin.
doi:10.1016/j.ahj.2010.12.007
PMCID: PMC3120223  PMID: 21392609
17.  Metabolic effects of fluvastatin extended release 80 mg and atorvastatin 20 mg in patients with type 2 diabetes mellitus and low serum high-density lipoprotein cholesterol levels: a 4-month, prospective, open-label, randomized, blinded—end point (probe) trial 
Background
Diabetic dyslipidemia is characterized by greater triglyceridation of all lipoproteins and low levels of plasma high-density lipoprotein cholesterol (HDL-C). In this condition, the serum level of low-density lipoprotein cholesterol (LDL-C) is only slightly elevated. The central role of decreased serum HDL-C level in diabetic cardiovascular disease has prompted the establishment of a target of ≥50 mg/dL in patients with diabetes mellitus (DM).
Objective
The aim of the study was to assess the effects of once-daily administration of fluvastatin extended release (XL) 80 mg or atorvastatin 20 mg on serum HDL-C levels in patients with type 2 DM and low levels of serum HDL-C.
Methods
This 4-month, prospective, open-label, randomized, blinded—end point (PROBE) trial was conducted at Endocrinology and Diabetology Service, L. Sacco-Polo University Hospital (Milan, Italy). Patients aged 45 to 71 years with type 2 DM receiving standard oral antidiabetic therapy, with serum HDL-C levels <50 mg/dL, and with moderately high serum levels of LDL-C and triglycerides (TG) were enrolled. After 1 month of lifestyle modification and dietary intervention, patients who were still showing a decreased HDL-C level were randomized, using a 1:1 ratio, to receive fluvastatin XL 80-mg tablets or atorvastatin 20-mg tablets, for 3 months. Lipoprotein metabolism was assessed by measuring serum levels of LDL-C, HDL-C, TG, apolipoprotein (apo) A-I (the lipoprotein that carries HDL), and apo B (the lipoprotein that binds very low-density lipoprotein cholesterol, intermediate-density lipoprotein, and LDL on a molar basis). Patients were assessed every 2 weeks for treatment compliance and subjective adverse events. Serum creatine phosphokinase and liver enzymes were assessed before the run-in period, at the start of the trial, and at 1 and 3 months during the study.
Results
One hundred patients were enrolled (50 patients per treatment group; fluvastatin XL group: 33 men, 17 women; mean [SD] age, 58 [12] years; atorvastatin group: 39 men, 11 women; mean [SD] age, 59 [11] years). In the fluvastatin group after 3 months of treatment, mean (SD) LDL-C decreased from 149 (33) to 95 (25) mg/dL (36%; P < 0.01), TG decreased from 437 (287) to 261 (164) mg/dL (40%; P < 0.01), and HDL-C increased from 41 (7) to 46 (10) mg/dL (12%; P < 0.05). In addition, apo A-I increased from 118 (18) to 124 (15) mg/dL (5%; P < 0.05) and apo B decreased from 139 (27) to 97 (19) mg/dL (30%; P < 0.05). In the atorvastatin group, LDL-C decreased from 141 (25) to 84 (23) mg/dL (40%; P < 0.01) and TG decreased from 411 (271) to 221 (87) mg/dL (46%; P < 0.01). Neither HDL-C (41 [7] vs 40 [6] mg/dL; 2%) nor apo A-I (117 [19] vs 114 [19] mg/dL; 3%) changed significantly. However, apo B decreased significantly, from 131 (20) to 92 (17) mg/dL (30%; P < 0.05). Mean changes in HDL-C (+5 [8] vs −1 [2] mg/dL; P < 0.01) and apo A-I (+6 [18] mg/dL vs −3 [21] mg/dL; P < 0.01) were significantly greater in the fluvastatin group than in the atorvastatin group, respectively. However, the decreases in LDL-C (54 [31] vs 57 [32] mg/ dL), TG (177 [219] vs 190 [65] mg/dL), and apo B (42 [26] vs 39 [14] mg/dL) were not significantly different between the fluvastatin and atorvastatin groups, respectively. No severe adverse events were reported.
Conclusions
Fluvastatin XL 80 mg and atorvastatin 20 mg achieved mean serum LDL-C (≤ 100 mg/dL) and apo B target levels (≤ 100 mg/dL) in the majority of this population of patients with type 2 DM, but mean serum HDL-C level was increased significantly only with fluvastatin—16 patients (32%) in the fluvastatin group compared with none in the atorvastatin group achieved HDL-C levels ≥50 mg/dL. The increase in HDL-C in the fluvastatin-treated patients was associated with an increase in apo A-I, suggesting a potential pleiotropic and selective effect in patients with low HDL-C levels.
doi:10.1016/j.curtheres.2004.06.004
PMCID: PMC3964538  PMID: 24672088
fluvastatin XL; atorvastatin; type 2 DM; HDL; LDL; triglycerides; apo A-I; apo B
18.  Pitavastatin in cardiometabolic disease: therapeutic profile 
Cardiovascular Diabetology  2013;12(Suppl 1):S2.
Statins effectively lower low-density lipoprotein-cholesterol (LDL-C) and reduce cardiovascular risk in people with dyslipidemia and cardiometabolic diseases such as Metabolic syndrome (MetS) or type 2 diabetes (T2D). In addition to elevated levels of LDL-C, people with these conditions often have other lipid-related risk factors, such as high levels of triglycerides, low levels of high-density lipoprotein-cholesterol (HDL-C), and a preponderance of highly atherogenic, small, dense low-density lipoprotein particles. The optimal management of dyslipidemia in people with MetS or T2D should therefore address each of these risk factors in addition to LDL-C. Although statins typically have similar effects on LDL-C levels, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects, adverse event profiles and drug-drug interactions. The choice of statin should therefore depend on the characteristics and needs of the individual patient. Compared with other statins, pitavastatin has distinct pharmacological features that translate into a broad range of actions on both apolipoprotein-B-containing and apolipoprotein-A-containing lipoproteins. Studies show that pitavastatin 1 to 4 mg is well tolerated and significantly improves LDL-C and triglyceride levels to a similar or greater degree than comparable doses of atorvastatin, simvastatin or pravastatin, irrespective of diabetic status. Moreover, whereas most statins show inconsistent effects on HDL-C levels, pitavastatin-treated patients routinely experience clinically significant elevations in HDL-C that are maintained and even increased over the long term. In addition to increasing high-density lipoprotein quantity, pitavastatin appears to improve high-density lipoprotein function and to slow the progression of atherosclerotic plaques by modifying high-density lipoprotein-related inflammation and oxidation, both of which are common in patients with MetS and T2D. When choosing a statin, it is important to note that patients with MetS have an increased risk of developing T2D and that some statins can exacerbate this risk via adverse effects on glucose regulation. Unlike many statins, pitavastatin appears to have a neutral and even beneficial effect on glucose regulation, making it a useful treatment option in this high-risk group of patients. Together with pitavastatin’s beneficial effects on the cardiometabolic lipid profile and its low potential for drug-drug interactions, this suggests that pitavastatin might be a useful lipid-lowering option for people with cardiometabolic disease.
doi:10.1186/1475-2840-12-S1-S2
PMCID: PMC3668168  PMID: 23819752
19.  Relationship between adipocytokines and cardiovascular risk factors in patients with type 2 diabetes mellitus 
The aim of this study was to explore the relationship between serum profiles of adiponectin, leptin, resistin and visfatin and traditional and non-traditional cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). A total of 85 patients with T2DM and 30 non-diabetic controls were enrolled in the study. Levels of adipocytokines (adiponectin, leptin, resistin and visfatin), lipids (total cholesterol, triglycerides), lipoproteins [HDL-cholesterol, LDL-cholesterol, lipoprotein (a)], apolipoproteins (Apo-A1 and Apo-B), non-traditional cardiovascular risk markers [asymmetric dimethylarginine (ADMA), homocysteine] and the inflammatory marker hs-CRP were measured, and anthropometric variables were determined. Serum adiponectin levels were decreased and leptin, resistin and visfatin levels were increased in T2DM patients compared to controls. They were associated with obesity (BMI), insulin resistance (HOMA-IR) and various markers of glucose/lipid profile, inflammation and endothelial dysfunction markers. These results suggest that decreased serum adiponectin and increased leptin, resistin and visfatin levels in T2DM may be novel biochemical risk factors for cardiovascular complications.
doi:10.3892/etm.2012.557
PMCID: PMC3460256  PMID: 23060933
adipocytokines; cardiovascular risk markers; type 2 diabetes mellitus
20.  Evaluation of Tumour Necrosis Factor Alpha, Interleukin-2 Soluble Receptor, Nitric Oxide Metabolites, and Lipids as Inflammatory Markers in Type 2 Diabetes Mellitus 
Mediators of Inflammation  2006;2006(1):39062.
This study compared the results of tumour necrosis factor alpha (TNF-α), interleukin-2 soluble receptor (sIL-2R), nitric oxide metabolites (NOx), C-reactive protein (CRP), and lipids (total cholesterol, high-density lipoprotein (HDL-cholesterol), lowdensity lipoprotein (LDL-cholesterol), and triglycerides) between control group (nondiabetic subjects) and overweight type 2 DM subjects. To restrict the influence of variables that could interfere in the interpretation of data, subjects with obesity and/or acute or chronic inflammatory disease, haemoglobinopathies, recent use of antibiotics, antiinflammatory drugs, and trauma were excluded. Type 2 DM patients (n = 39; age 53.3 ± 9.0 years; median glycated haemoglobin A1c < 8%) presented higher levels of TNF-α, triglycerides (P < .01), NOx and sIL-2R (P < .05) than control group (n = 28; age 39.7 ± 14.1 years). CRP, LDL-cholesterol, total cholesterol, and HDL-cholesterol did not differ among groups. Diabetic women (n = 21) had higher levels of TNF-α, total cholesterol, LDL-cholesterol, and HDL-cholesterol than diabetic men (n = 18) (P < .05), but there were no differences among sexes in the control group. This study indicates that increased level of proinflammatory markers occurs in type 2 DM even in the absence of obesity and marked hyperglycaemia, confirming that the inflammation course of the atherosclerotic process is more severe in diabetic patients than in nondiabetic subjects.
doi:10.1155/MI/2006/39062
PMCID: PMC1570394  PMID: 16864902
21.  Plasma lipid, lipoprotein and apolipoprotein profiles in Nigerian university athletes and non-athletes. 
The fasting plasma lipid, lipoprotein and apolipoprotein profiles were determined in 14 healthy Nigerian male athletes and controls matched for sex and anthropometric parameters. The mean levels of total cholesterol (P < 0.05), low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) AII and E were significantly lower (P < 0.01) in the athletes than in the controls. However, there were no statistically significant differences (P > 0.05) between the mean values of the plasma triglycerides, high-density lipoprotein (HDL), very low-density lipoprotein (VLDL) cholesterol, apo AI, B, Lp(a), LpA1 and CIII:NonB respectively for the athletes and controls. A priori, the potential effect on cardiovascular disease (CVD) risk was also compared using three predictor ratios - total cholesterol: HDL cholesterol (TC:HDL), LDL cholesterol: HDL cholesterol and apo B:AI. The mean of the three ratios was lower in the athletes than in the controls; however, the differences were not statistically significant (P > 0.05). Based on our data, exercise appears to decrease the TC:HDL ratio in the athletes by lowering LDL-cholesterol, while the HDL-cholesterol is unaffected. We conclude that physical activity has salutary effects on the lipid, lipoprotein and apolipoprotein profiles of healthy Nigerian men.
PMCID: PMC1332019  PMID: 8130968
22.  Ability Among Adolescents for the Metabolic Syndrome to Predict Elevations in Factors Associated with Type 2 Diabetes and Cardiovascular Disease: Data from the National Health and Nutrition Examination Survey 1999–2006 
Objective
The aim of this study was to compare currently proposed sets of pediatric metabolic syndrome criteria for the ability to predict elevations in “surrogate” factors that are associated with metabolic syndrome and with future cardiovascular disease and type 2 diabetes mellitus. These surrogate factors were fasting insulin, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (hsCRP), and uric acid.
Methods
Waist circumference (WC), blood pressure, triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting glucose, fasting insulin, HbA1c, hsCRP, and uric acid measurements were obtained from 2,624 adolescent (12–18 years old) participants of the 1999–2006 National Health and Nutrition Examination Surveys. We identified children with metabolic syndrome as defined by six commonly used sets of pediatric metabolic syndrome criteria. We then defined elevations in the surrogate factors as values in the top 5% for the cohort and calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each set of metabolic syndrome criteria and for each surrogate factor.
Results
Current pediatric metabolic syndrome criteria exhibited variable sensitivity and specificity for surrogate predictions. Metabolic syndrome criteria had the highest sensitivity for predicting fasting insulin (40–70%), followed by uric acid (31–54%), hsCRP (13–31%), and HbA1c (7–21%). The criteria of de Ferranti (which includes children with WC >75 th percentile, compared to all other sets including children with WC >90 th percentile) exhibited the highest sensitivity for predicting each of the surrogates, with only modest decrease in specificity compared to the other sets of criteria. However, the de Ferranti criteria also exhibited the lowest PPV values. Conversely, the pediatric International Diabetes Federation criteria exhibited the lowest sensitivity and the highest specificity.
Conclusions
Pediatric metabolic syndrome criteria exhibit moderate sensitivity for detecting elevations in surrogate factors associated with metabolic syndrome and with risk for future disease. Inclusion of children with more modestly elevated WC improved sensitivity.
doi:10.1089/met.2010.0008
PMCID: PMC3046372  PMID: 20698802
23.  Ability Among Adolescents for the Metabolic Syndrome to Predict Elevations in Factors Associated with Type 2 Diabetes and Cardiovascular Disease: Data from the National Health and Nutrition Examination Survey 1999–2006 
Abstract
Objective
The aim of this study was to compare currently proposed sets of pediatric metabolic syndrome criteria for the ability to predict elevations in “surrogate” factors that are associated with metabolic syndrome and with future cardiovascular disease and type 2 diabetes mellitus. These surrogate factors were fasting insulin, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (hsCRP), and uric acid.
Methods
Waist circumference (WC), blood pressure, triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting glucose, fasting insulin, HbA1c, hsCRP, and uric acid measurements were obtained from 2,624 adolescent (12–18 years old) participants of the 1999–2006 National Health and Nutrition Examination Surveys. We identified children with metabolic syndrome as defined by six commonly used sets of pediatric metabolic syndrome criteria. We then defined elevations in the surrogate factors as values in the top 5% for the cohort and calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each set of metabolic syndrome criteria and for each surrogate factor.
Results
Current pediatric metabolic syndrome criteria exhibited variable sensitivity and specificity for surrogate predictions. Metabolic syndrome criteria had the highest sensitivity for predicting fasting insulin (40–70%), followed by uric acid (31–54%), hsCRP (13–31%), and HbA1c (7–21%). The criteria of de Ferranti (which includes children with WC >75th percentile, compared to all other sets including children with WC >90th percentile) exhibited the highest sensitivity for predicting each of the surrogates, with only modest decrease in specificity compared to the other sets of criteria. However, the de Ferranti criteria also exhibited the lowest PPV values. Conversely, the pediatric International Diabetes Federation criteria exhibited the lowest sensitivity and the highest specificity.
Conclusions
Pediatric metabolic syndrome criteria exhibit moderate sensitivity for detecting elevations in surrogate factors associated with metabolic syndrome and with risk for future disease. Inclusion of children with more modestly elevated WC improved sensitivity.
doi:10.1089/met.2010.0008
PMCID: PMC3046372  PMID: 20698802
24.  Relation of Uric Acid to Serum Levels of High-Sensitivity C-Reactive Protein, Triglycerides, and High-Density Lipoprotein Cholesterol and to Hepatic Steatosis 
The American journal of cardiology  2012;110(12):1787-1792.
Increased uric acid (UA) is strongly linked to cardiovascular disease. However, the independent role of UA is still debated because it is associated with several cardiovascular risk factors including obesity and metabolic syndrome. This study assessed the association of UA with increased high-sensitivity C-reactive protein (hs-CRP), increased ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL), sonographically detected hepatic steatosis, and their clustering in the presence and absence of obesity and metabolic syndrome. We evaluated 3,518 employed subjects without clinical cardiovascular disease from November 2008 through July 2010. Prevalence of hs-CRP ≥3 mg/L was 19%, that of TG/HDL ≥3 was 44%, and that of hepatic steatosis was 43%. In multivariable logistic regression after adjusting for traditional cardiovascular risk factors and confounders, highest versus lowest UA quartile was associated with hs-CRP ≥3 mg/L (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.01 to 2.28, p = 0.04), TG/HDL ≥3 (OR 3.29, 95% CI 2.36 to 4.60, p <0.001), and hepatic steatosis (OR 3.10, 95% CI 2.22 to 4.32, p <0.001) independently of obesity and metabolic syndrome. Association of UA with hs-CRP ≥3 mg/L became nonsignificant in analyses stratified by obesity. Ascending UA quartiles compared to the lowest UA quartile demonstrated a graded increase in the odds of having 2 or 3 of these risk conditions and a successive decrease in the odds of having none. In conclusion, high UA levels were associated with increased TG/HDL and hepatic steatosis independently of metabolic syndrome and obesity and with increased hs-CRP independently of metabolic syndrome.
doi:10.1016/j.amjcard.2012.08.012
PMCID: PMC3766845  PMID: 22975466
25.  Association of body mass index and abdominal adiposity with atherogenic lipid profile in Nigerians with type 2 diabetes and/or hypertension 
Background:
We explored the relationship between anthropometric indices (obesity and abdominal adiposity) and the presence of an atherogenic lipid profile in Nigerians with major cardiovascular risk factors (type 2 diabetes mellitus-T2DM, hypertension-HBP, and concomitant disease).
Materials and Methods:
Using a prospective design, 278 patients with T2DM, HBP, or concomitant disease, attending out-patient diabetes and hypertension clinics at a tertiary institution in Nigeria were evaluated. All patients were cholesterol-lowering oral medication naοve. Demographic and clinical data and anthropometric measurements were documented. Fasting lipid profiles were measured in all cases. The cut-off points for defining dyslipidaemia were: Elevated total cholesterol (TC) (mg/dL) ≥200, elevated low-density lipoprotein cholestrol (LDL-C) (mg/dL) ≥100, low high-density lipoprotein cholesterol (HDL-C) (mg/dL) <40 for men and <50 for women, and high triglycerides (TG) (mg/dL) ≥150 mg/dL.
Results:
We found a significantly higher mean BMI (kg/m2) in the HBP group (30.5 ± 6.0) compared to T2DM (28.1 ± 5.9) and concomitant HBP and T2DM groups (29.4 ± 5.2) (ANOVA; P = 0.02). The most frequent dyslipidaemia was elevated LDL-C in 92 (96.8%) HBP, 73 (85.9%) T2DM and 79 (80.6%) concomitant disease. The frequency of low HDL-C was highest in T2DM (68.2%) compared to the other 2 groups (P = 0.03).
Conclusions:
Only TG levels were found to relate with any anthropometric index (waist circumference (WC) in this case) in Nigerians with major cardiovascular risk factors in this study. Routine anthropometric indices do not appear to be reliable surrogates for atherogenicity measured by abnormalities in TC, LDL-C and HDL-C.
doi:10.4103/0300-1652.126296
PMCID: PMC3948963  PMID: 24665155
Atherogenic profile; blacks; diabetes; hypertension; metabolic syndrome; Nigerians

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