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1.  Insulin Resistance Is an Independent Determinate of ED in Young Adult Men 
PLoS ONE  2013;8(12):e83951.
Background
Insulin resistance (IR) triggers endothelial dysfunction, which contributes to erectile dysfunction (ED) and cardiovascular disease.
Aim
To evaluate whether IR was related to ED in young adult patients.
Methods
A total of 283 consecutive men complaining of ED at least six months were enrolled, with a full medical history, physical examination, and laboratory tests collected. Quantitative Insulin Sensitivity Check Index (QUICKI) was used to determine IR. The severity of ED was assessed by IIEF-5 questionnaire. Endothelial function was assessed by ultrasonographic examination of brachial artery flow mediated dilation (FMD).
Results
IR was detected in 52% patients. Subjects with IR had significant higher total cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-c), glycated haemoglobin (HBA1c), high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI), but showed significant lower IIEF-5 score, FMD%, high density lipoprotein -cholesterol (HDL-c), testosterone, sex hormone binding globulin (SHBG) levels than patients without IR. Multiple regression analysis showed QUICKI and testosterone were independent predictors of IIEF-5 score. Furthermore, the incidence of IR was correlated with the severity of ED.
Conclusions
Compared with other CVFs, IR was found as the most prevalent in our subjects. Besides, IR was independently associated with ED and its severity, suggesting an adverse effect of insulin resistance on erectile function.
doi:10.1371/journal.pone.0083951
PMCID: PMC3877124  PMID: 24391852
2.  Lipoproteins and their subfractions in psoriatic arthritis: identification of an atherogenic profile with active joint disease 
Annals of the Rheumatic Diseases  2000;59(11):904-909.
OBJECTIVES—(a) To characterise the lipid profile in psoriatic arthritis and investigate whether there are similarities to the dyslipoproteinaemia reported in rheumatoid arthritis and other inflammatory forms of joint disease; (b) to investigate whether there is an atherogenic lipid profile in psoriatic arthritis, which may have a bearing on mortality.
METHODS—Fasting lipids, lipoproteins, and their subfractions were measured in 50 patients with psoriatic arthritis and their age and sex matched controls.
RESULTS—High density lipoprotein cholesterol (HDL cholesterol) and its third subfraction, HDL3 cholesterol, were significantly reduced and the most dense subfraction of low density lipoprotein (LDL), LDL3, was significantly increased in the patients with psoriatic arthritis. Twenty patients with active synovitis had significantly lower total cholesterol, LDL cholesterol, and HDL3 cholesterol than their controls. 25% of the patients with psoriatic arthritis had raised Lp(a) lipoprotein levels (>300 mg/l) compared with 19% of controls, but this was not statistically significant.
CONCLUSION—Raised levels of LDL3 and low levels of HDL cholesterol are associated with coronary artery disease. Such an atherogenic profile in a chronic inflammatory form of arthritis is reported, which may be associated with accelerated mortality.


doi:10.1136/ard.59.11.904
PMCID: PMC1753033  PMID: 11053070
3.  Anti-tumour necrosis factor alpha therapy improves insulin sensitivity in normal-weight but not in obese patients with rheumatoid arthritis 
Arthritis Research & Therapy  2012;14(4):R160.
Introduction
Insulin resistance (IR), a risk factor for the development of cardiovascular disease, is common among patients with rheumatoid arthritis (RA). Inflammation, and especially tumour necrosis factor alpha (TNFα), has been associated with IR, and the administration of anti-TNFα agents is suggested to improve insulin sensitivity. However obesity, a potent contributor to IR, may limit the beneficial effects of anti-TNFα medication on IR. The aim of this study is to compare the effects of anti-TNFα therapy on IR between normal-weight and obese patients with RA.
Methods
Patients who were normal-weight with IR (N+IR) or obese with IR (O+IR) and had embarked on anti-TNFα treatment, participated. Assessments included body mass index (BMI), insulin sensitivity (Homeostasis Model Assessment of insulin resistance, HOMA and the Quantitative Insulin sensitivity Check Index, QUICKI), and RA disease characteristics before and following six months of anti-TNFα treatment. Their results were compared to matched (for age, gender, BMI, disease duration and smoking status) normal-weight patients without IR (N-IR) and obese without IR (N-IR), respectively. In total, 32 patients were assessed for this study, with 8 in each group.
Results
Following six months of treatment, disease activity was significantly reduced in all groups (P < 0.05) to a similar extent (P for differences between groups > 0.05 in all cases). In the total population, changes in HOMA (mean reduction at 6 m = -0.2 ± 0.1; P = 0.088) and QUICKI (mean increase at 6 m = 0.03 ± 0.022; P = 0.092) after treatment were not statistically significant, though a trend towards improvement was observed. However, N+IR patients showed a significant decrease in HOMA (mean reduction at 6 m = -0.54 ± 0.2; P = 0.002) and increase in QUICKI (mean increase at 6 m = 0.046 ± 0.02; P = 0.011). These changes were significantly different compared to the other groups (P < 0.05 in all cases). Multivariable analyses showed that the change in Erythrocyte Sedimentation Rate (ESR), and the change in C-Reactive Protein (CRP) associated with the improvement in HOMA (ESR: F1-7 = 5.143, P = 0.019; CRP: F1-7 = 3.122, P = 0.022) and QUICKI (ESR: F1-7 = 3.814, P = 0.021; CRP: F1-7 = 2.67; P = 0.041) only in the N+IR group.
Conclusions
Anti-TNFα therapy, through controlling inflammation, seems to improve insulin sensitivity in normal-weight RA patients with insulin resistance, but is not sufficient to achieving the same beneficial effect in obese RA patients with insulin resistance.
doi:10.1186/ar3900
PMCID: PMC3580552  PMID: 22765047
4.  Effects of infliximab treatment on insulin resistance in patients with rheumatoid arthritis and ankylosing spondylitis 
Annals of the Rheumatic Diseases  2004;64(5):765-766.
Objective: To assess the effects of infliximab infusions on insulin sensitivity in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS).
Methods: 45 patients (28 with RA, 17 with AS) aged 19–74 years were studied. All patients were treated with intravenous infliximab. A complete biochemical profile was obtained before and after 6 months' treatment with infliximab. The Homoeostasis Model Assessment (HOMA) Index was used to measure insulin resistance and the Quantitative Insulin Sensitivity Check Index (QUICKI) to measure insulin sensitivity.
Results: In the whole study group, no significant changes of the HOMA Index or QUICKI were seen. In the tertile of patients with the highest insulin resistance, a significant decrease of the HOMA Index and increase of the QUICKI was found (p<0.01 for both).
Conclusions: The results suggest that infliximab treatment may have beneficial effects on insulin sensitivity in the most insulin resistant patients with RA and AS.
doi:10.1136/ard.2004.026534
PMCID: PMC1755470  PMID: 15458960
5.  Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis 
Annals of the Rheumatic Diseases  2003;62(9):842-845.
Background: Glucocorticoids induce hypercholesterolaemia, a cardiovascular risk factor, in patients with diseases other than rheumatoid arthritis (RA), but the data in RA are contradictory.
Objective: To determine the effects of antirheumatic treatment, including prednisolone (combination) therapy on total and high density lipoprotein (HDL) cholesterol levels in RA, taking disease activity into account.
Methods: HDL cholesterol and total cholesterol levels were determined in:(a) established RA (b) two cohorts with early active RA, (c) a previously conducted 56 week trial among patients with early RA comparing the value of intensive combination therapy (that included glucocorticoids) with sulfasalazine alone (COBRA trial).
Results: In established RA total cholesterol levels were only slightly raised, irrespective of disease activity. However, HDL cholesterol was significantly higher in patients in remission than in patients with active disease. In contrast, in active early RA at baseline total cholesterol was low normal: between 4.6 and 5.1 mmol/l in the different populations. The level of HDL cholesterol was highly dependent on the duration of storage. In both COBRA groups total cholesterol increased by a mean of 0.6 mmol/l. HDL cholesterol increased by more than 50% after treatment, leading to an improvement of the total cholesterol/HDL ratio (atherogenic index). This increase (and index improvement) was much more rapid in the group receiving combination treatment. A similar pattern was seen in the 2001 cohort with early RA. In all the groups with active disease HDL and total cholesterol levels correlated inversely with disease activity.
Conclusion: In established, but especially in early RA, disease activity is accompanied by atherogenic lipid levels. This dyslipidaemia can be rapidly reversed by aggressive antirheumatic treatment including glucocorticoids.
doi:10.1136/ard.62.9.842
PMCID: PMC1754645  PMID: 12922956
6.  Dyslipidemia and Changes in Lipid Profiles Associated with Rheumatoid Arthritis and Initiation of Anti-TNF Therapy 
Arthritis care & research  2012;64(9):1282-1291.
OBJECTIVE
To investigate the frequency of lipid testing in clinical practice and explore the relationship between rheumatoid arthritis (RA), dyslipidemia, and other cardiovascular (CV) risk factors, with RA treatment.
METHODS
Patients in the retrospective database study were ≥18 years old and had ≥2 physician diagnoses for RA or osteoarthritis (OA) [comparator group] between March 2004-March 2008. Outcomes of interest included the percentage of RA and OA patients receiving lipid tests, lipid profiles (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]) of RA vs. OA patients, and lipid profiles of RA patients before and after initiation with a tumor necrosis factor inhibitor (TNFi). We used multivariable regression to control potential confounders between the cohorts.
RESULTS
Over a median 2+ year follow-up, fewer RA patients than OA patients had at least one lipid test (62% [95% CI, 60-64] vs. 68% [95% CI, 65-71]). Mean TC and LDL-C were each 4 mg/dL lower in the RA cohort (P<0.0001); HDL-C was similar between cohorts. Across the RA cohort, 25.2% of patients had suboptimal LDL-C levels (≥130 mg/dL). Among RA patients not using lipid-lowering therapy who initiated TNFi therapy (n=96), mean TC and LDL-C increased by 5.4 and 4.0 mg/dL, respectively.
CONCLUSION
RA patients were less likely to be tested for hyperlipidemia and had more favorable lipid profiles than OA patients. TNFi therapy modestly increased all lipid parameters. Additional studies are needed to determine the effect of traditional CV risk factors, inflammation, and the impact of biologics on CV outcomes in RA patients.
doi:10.1002/acr.21693
PMCID: PMC3404153  PMID: 22504829
7.  Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis 
Annals of the Rheumatic Diseases  2006;66(2):184-188.
Background
Rheumatoid arthritis is characterised by inflammation and an increased cardiovascular risk. It was recently shown that active early rheumatoid arthritis is associated with dyslipidaemia, which may partially explain the enhanced cardiovascular risk. However, it is unknown when this dyslipidaemia starts.
Objective
To investigate the progression of the lipid profile over time and the influence of inflammatory parameters on this lipid profile, in people who later developed rheumatoid arthritis.
Methods
Levels of total cholesterol, high‐density lipoprotein cholesterol (HDLc), triglycerides, apolipoprotein AI (apo AI), apolipoprotein B (apo B) and lipoprotein(a) (Lp(a)) were determined in 1078 stored, deep‐frozen, serial blood bank samples, collected between 1984 and 1999, of 79 blood donors who later developed rheumatoid arthritis. These samples were compared with 1071 control samples of unselected blood donors, matched for age, sex and storage time.
Results
Samples of patients who later developed rheumatoid arthritis showed, on average, 4% higher total cholesterol, 9% lower HDLc, 17% higher triglyceride and 6% higher apo B levels than matched controls (p⩽0.05).
The magnitude of the differences in lipid levels between groups, explained by C reactive protein (CRP), was limited. For example, only 3.6% of the difference in HDLc levels between the groups was explained by the CRP concentrations.
Conclusion
Patients who later develop rheumatoid arthritis have a considerably more atherogenic lipid profile than matched blood donors at least 10 years before onset of symptoms. As inflammation only marginally explains the differences between the two groups, a modulating effect of lipids on inflammatory processes is hypothesised.
doi:10.1136/ard.2006.051672
PMCID: PMC1798498  PMID: 16760255
8.  Anti-TNFα therapy transiently improves high density lipoprotein cholesterol levels and microvascular endothelial function in patients with rheumatoid arthritis: a Pilot Study 
Background
Rheumatoid arthritis (RA) is associated with increased morbidity and mortality from cardiovascular disease (CVD). This can be only partially attributed to traditional CVD risk factors such as dyslipidaemia and their downstream effects on endothelial function. The most common lipid abnormality in RA is reduced levels of high-density lipoprotein (HDL) cholesterol, probably due to active inflammation. In this longitudinal study we hypothesised that anti-tumor necrosis factor-α (anti-TNFα) therapy in patients with active RA improves HDL cholesterol, microvascular and macrovascular endothelial function.
Methods
Twenty-three RA patients starting on anti-TNFα treatment were assessed for HDL cholesterol level, and endothelial-dependent and -independent function of microvessels and macrovessels at baseline, 2-weeks and 3 months of treatment.
Results
Disease activity (CRP, fibrinogen, DAS28) significantly decreased during the follow-up period. There was an increase in HDL cholesterol levels at 2 weeks (p < 0.05) which was paralleled by a significant increase in microvascular endothelial-dependent function (p < 0.05). However, both parameters returned towards baseline at 12 weeks.
Conclusion
Anti-TNFα therapy in RA patients appears to be accompanied by transient but significant improvements in HDL cholesterol levels, which coexists with an improvement in microvascular endothelial-dependent function.
doi:10.1186/1471-2474-13-127
PMCID: PMC3502606  PMID: 22824166
Dyslipidaemia; Anti-TNFα; Endothelial function; Rheumatoid arthritis; Cardiovascular disease
9.  The Association of the Triglyceride-to-HDL Cholesterol Ratio with Insulin Resistance in White European and South Asian Men and Women 
PLoS ONE  2012;7(12):e50931.
Introduction
There is recent interest surrounding the use of the triglyceride-to-HDL cholesterol ratio as a surrogate marker of insulin resistance in clinical practice, as it may identify people at high risk of developing diabetes or its complications. However, it has been suggested using this lipid ratio may not be appropriate for measuring insulin resistance in African-Americans, particularly women. We investigated if this inconsistency extended to South Asian women in a UK multi-ethnic cohort of White Europeans and South Asians.
Methods
Cross-sectional analysis was done of 729 participants from the ADDITION-Leicester study from 2005 to 2009. The association between tertiles of triglyceride-to-HDL cholesterol ratio to fasting insulin, homeostatic model of assessment for insulin resistance (HOMA1-IR), quantitative insulin sensitivity check index (QUICKI) and glucose: insulin ratio was examined with adjustment for confounding variables.
Results
Incremental tertiles of the triglyceride-to-HDL cholesterol ratio demonstrated a significant positive association with levels of fasting insulin, HOMA1-IR, glucose: insulin ratio and a negative association with QUICKI in White European men (n = 255) and women (n = 250) and South Asian men (n = 124) (all p<0.05), but not South Asian women (n = 100). A significant interaction was demonstrated between sex and triglyceride-to-HDL cholesterol ratio tertiles in South Asians only (p<0.05). The area under the receiver operating characteristic curve for triglyceride-to-HDL cholesterol ratio to detect insulin resistance, defined as the cohort HOMA1-IR≥75th percentile (3.08), was 0.74 (0.67 to 0.81), 0.72 (0.65 to 0.79), 0.75 (0.66 to 0.85) and 0.67 (0.56 to 0.78) in White European men and women, South Asian men and women respectively. The optimal cut-points for detecting insulin resistance were 0.9–1.7 in mmol/l (2.0–3.8 in mg/dl) for the triglyceride-to-HDL ratio.
Conclusion
In South Asian women the triglyceride-to-HDL cholesterol ratio was not associated with insulin resistance; therefore there may be limitations in its use as a surrogate marker in this group.
doi:10.1371/journal.pone.0050931
PMCID: PMC3518473  PMID: 23251403
10.  Unacylated Ghrelin is associated with the isolated low HDL-cholesterol obese phenotype independently of insulin resistance and CRP level 
Background
Low plasma high-density lipoprotein-cholesterol (HDL-c) level is commonly present in obesity and represents an independent cardiovascular risk factor. However, obese patients are a very heterogeneous population and the factors and mechanisms that contribute to low HDL-c remain unclear. The aim of this study was to investigate the association between plasma HDL-c levels and plasma hormonal profiles (insulin, adiponectin, resistin, leptin and ghrelin) in subsets of class II and III obese patients.
Methods
Fasting plasma levels of glucose, total cholesterol, LDL-c, HDL-c, triglycerides, free fatty acids, apoproteins A-I, B-100, B-48, C-II, C-III, insulin, hs-CRP, adipocytokines (adiponectin, resistin, leptin), unacylated ghrelin, body composition (DXA) and resting energy expenditure were measured in three subsets of obese patients: 17 metabolically abnormal obese (MAO) with metabolic syndrome and the typical metabolic dyslipidaemia, 21 metabolically healthy obese (MHO) without metabolic syndrome and with a normal lipid profile, and 21 isolated low HDL-c obese patients (LHO) without metabolic syndrome, compared to 21 healthy lean control subjects.
Results
Insulin resistance (HOMA-IR) increased gradually from MHO to LHO and from LHO to MAO patients (p < 0.05 between MHO and MAO and between LHO and MAO). In multiple regression analysis, serum unacylated ghrelin levels were only positively and independently associated with HDL-c levels in the LHO group (p = 0.032).
Conclusions
These results suggest that, in class II and III obese patients with an isolated low HDL-c phenotype, unacylated ghrelin is positively associated with HDL-c level independently of insulin resistance and CRP levels, and may contribute to the highly prevalent low HDL-c level seen in obesity.
doi:10.1186/1743-7075-9-17
PMCID: PMC3317856  PMID: 22413940
Adiponectin; Apolipoprotein; Cardiovascular risk; Ghrelin; HDL-cholesterol; Inflammation; Insulin resistance; Lipids; Obesity
11.  Hepatitis C Infection Is Associated with Lower Lipids and High-Sensitivity C-Reactive Protein in HIV-Infected Men 
AIDS patient care and STDs  2007;21(7):479-491.
Increased cardiovascular risk has been linked to HIV infection and combination antiretroviral therapy, but the impact of hepatitis C virus (HCV) status on indices of cardiovascular risk has not been routinely assessed in the HIV-infected population. The objective of this study was to analyze associations of HCV, HIV, and combination antiretroviral therapy with lipid levels and C-reactive protein (CRP) among older men. We measured fasting total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and high-sensitivity CRP serum levels in a cross-sectional study of 108 HIV-infected and 74 HIV-uninfected at-risk older men. One hundred ten men (60%) had detectable HCV RNA, with no difference by HIV status (p = 0.25). The majority (88%) of men with HCV infection had a history of injection drug use. Among all men, HCV infection was independently associated with lower total cholesterol (p < 0.001), LDL-C (p < 0.001), triglycerides (p = 0.01), and CRP (p < 0.001). Among HIV-infected men, HCV infection was associated with lower total cholesterol (p < 0.001), LDL-C (p < 0.001), and CRP (p = 0.004). HCV infection was associated with lower triglycerides among men on protease inhibitors (PI) (p = 0.02) and non-PI combination antiretroviral therapy (p = 0.02), but not among antiretroviral-naïve men. These findings demonstrate an association of lower serum lipid and CRP levels with HCV infection and suggest that HCV status should be assessed as an important correlate of cardiovascular risk factors in studies of older men with or at risk for HIV.
doi:10.1089/apc.2006.0150
PMCID: PMC2423809  PMID: 17651029
12.  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
13.  Adiponectin in Women with Polycystic Ovary Syndrome 
Korean Journal of Family Medicine  2011;32(4):243-248.
Background
Though adiponectin has been associated with insulin resistance and cardiovascular risk factors, the relationship between adiponectin and polycystic ovary syndrome (PCOS) remains controversial. The aim of this study was to compare adiponectin level in women with PCOS and without PCOS, and to investigate the relationship between adiponectin level and metabolic variables including insulin resistance.
Methods
60 women with PCOS were enrolled along with a control group of 80 healthy women, matched for age and body mass index (BMI). We measured hormonal and metabolic parameters, as well as the plasma adiponectin concentration of each participant. We estimated the insulin sensitivity according to the quantitative insulin sensitivity check index (QUICKI).
Results
The PCOS group displayed significantly lower level of adiponectin (P < 0.001) after adjustment for age, BMI, mean blood pressure, fasting glucose, fasting insulin, and several metabolic parameters. Adiponectin levels were positively correlated with QUICKI in the PCOS group (P < 0.001) and the control group (P = 0.03). Following step-wise multiple regression analysis, however, adiponectin level was positively correlated with QUICKI in the control group only (P = 0.03). In addition, adiponectin level was found to be independently associated with HDL-cholesterol level (P < 0.001) and BMI (P = 0.02) in the PCOS group and independently associated with HDL-cholesterol (P = 0.02) in the control group.
Conclusion
We report decreased adiponectin level in PCOS patients in relation to controls independently of insulin resistance or other metabolic factors. And adiponectin is associated with both lipid metabolism and obesity, which, in turn, is related to insulin resistance in PCOS. Further studies are needed to clarify the mechanism of adiponectin in PCOS.
doi:10.4082/kjfm.2011.32.4.243
PMCID: PMC3383132  PMID: 22745860
Adiponectin; Polycystic Ovary Syndrome; Insulin Resistance
14.  Lipoprotein (a), C-reactive protein and some metabolic cardiovascular risk factors in type 2 DM 
Background
Lipoprotein (a) (LP (a) is an independent cardiovascular risk factor that is not widely studied in people of sub-Saharan African origin. The aim of this report is to determine the frequency of occurrence of elevated Lp (a) and possible relationship with total cholesterol (TCHOL), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), C reactive protein (CRP) and serum uric acid (SUA).
Methods
This is a cross sectional study carried out in 200 Nigerian patients with type 2 DM and 100 sex and age matched healthy Controls aged between 32-86 years. We determined the frequency of occurrence of elevated Lp (a) levels in the study subjects and compared clinical and biochemical variables between type 2 diabetic patients and non-diabetic patients. Clinical and biochemical parameters were also compared between subjects with type 2 DM who had elevated LP (a) and normal LP (a) levels. Long term glycaemic control using glycosylated haemoglobin was determined and compared in the study subjects. Test statistics used include chi square, correlation coefficient analysis and Student's t test.
Results
The mean Lp(a) concentration differed significantly between type 2 diabetic patients and the Control subjects (18.7 (5.8) mg/dl vs 23 (6.8) mg/dl, 0.00001). Similarly, the prevalence of high LP (a) levels in type 2 DM patients was significantly higher than that of the Control subjects (12.5% vs 4%, p-0.019). The mean levels of the lipid profile parameters (TCHOL, LDL-C, TG, LDL/HDL) and CRP were significantly higher in DM patients than in the Control subjects. The mean LP (a) levels were comparable in both sexes and in DM subjects with and without hypertension. TG was the only parameter that differed significantly between subjects with elevated Lp (a) levels and those with normal Lp (a) levels. There was a significant positive correlation (r) between Lp(a) levels and TG, LDL-C. TCHOL, LDL/HDL and uric acid. No association was found between Lp(a) and clinical parameters such as age and anthropometric indices.
Conclusion
We have showed that Lp (a), CRP and other CVS risk factors cluster more in patients with DM than non DM patients. Serum Lp (a) levels are not associated with anthropometric and glycaemic indices.
doi:10.1186/1758-5996-2-51
PMCID: PMC2919447  PMID: 20663222
15.  Cholesterol efflux by high density lipoproteins is impaired in patients with active rheumatoid arthritis 
Annals of the rheumatic diseases  2012;71(7):1157-1162.
Objectives
Reverse cholesterol transport (RCT) is a major antiatherogenic function of high density lipoprotein (HDL). In the current work, the authors evaluated whether the RCT capacity of HDL from rheumatoid arthritis (RA) patients is impaired when compared to healthy controls.
Methods
HDL was isolated from 40 patients with RA and 40 age and sex matched healthy controls. Assays of cholesterol efflux, HDL’s antioxidant function and paraoxanase-1 (PON-1) activity were performed as described previously. Plasma myeloperoxidase (MPO) activity was assessed by a commercially available assay.
Results
Mean cholesterol efflux capacity of HDL was not significantly different between RA patients (40.2%±11.1%) and controls (39.5%±8.9%); p=0.75. However, HDL from RA patients with high disease activity measured by a disease activity score using 28 joint count (DAS28>5.1), had significantly decreased ability to promote cholesterol efflux compared to HDL from patients with very low disease activity/clinical remission (DAS28<2.6). Significant correlations were noted between cholesterol efflux and the DAS28 (r=−0.39, p=0.01) and erythrocyte sedimentation rate, (r=−0.41, p=0.0009). Higher plasma MPO activity was associated with worse HDL function (r=0.41/p=0.009 (antioxidant capacity); r=0.35, p=0.03 (efflux)). HDL’s ability to promote cholesterol efflux was modestly but significantly correlated with its antioxidant function (r=−0.34, p=0.03).
Conclusions
The cholesterol efflux capacity of HDL is impaired in RA patients with high disease activity and is correlated with systemic inflammation and HDL’s antioxidant capacity. Attenuation of HDL function, independent of HDL cholesterol levels, may suggest a mechanism by which active RA contributes to increased cardiovascular (CV) risk.
doi:10.1136/annrheumdis-2011-200493
PMCID: PMC3428121  PMID: 22267330
16.  Evaluation of heart rate reserve and high-sensitivity C-reactive protein in individuals with and without metabolic syndrome in Isfahan, Iran 
ARYA Atherosclerosis  2012;8(2):70-75.
BACKGROUND
Lack of heart rate increase proportionate to exercise causes poor prognosis. Moreover, inflammatory factors such as C-reactive protein (CRP) are associated with atherosclerosis. The current study compared these two indices in individuals with and without metabolic syndrome in Isfahan, Iran.
METHODS
This study was performed on 203 people without and 123 patients with metabolic syndrome who were randomly selected from the participants of the Isfahan Cohort Study. The demographic data, waist circumference, blood pressure, height, and weight of the participants were recorded. Moreover, serum tr`viglyceride (TG), fasting blood sugar (FBS), total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), and high-sensitivity CRP (hs-CRP) levels were measured. Exercise test was carried out according to the Bruce standard protocol and heart rate reserve (HRR) was determined and recorded. The age-adjusted data was analyzed using generalized linear regression and student's t-test in SPSS15.
RESULTS
The mean ages of participants without and with metabolic syndrome were 54.16 ± 8.61 and 54.29 ± 7.6 years, respectively. The corresponding values for mean LDL levels were 116.17 ± 24.04 and 120.12 ± 29.55 mg/dl. TG levels were 140.38 ± 61.65 and 259.99 ± 184.49 mg/dl for subjects without and with the metabolic syndrome, respectively. The mean FBS levels were 81.81 ± 9.90 mg/dl in the participants without the syndrome and 107.13 ± 48.46 mg/dl in those with metabolic syndrome. The mean systolic blood pressure was 116.06 ± 13.69 mmHg in persons without metabolic syndrome and 130.73 ± 15.15 mmHg in patients with the syndrome. The values for mean diastolic levels in the two groups were 76.52 ± 6.69 and 82.84 ± 8.7 mmHg, respectively. While the two groups were not significantly different in terms of HRR (P = 0.27), hs-CRP levels in the metabolic syndrome group was significantly higher than the other group (P = 0.02).
CONCLUSION
We failed to establish a relationship between HRR and the metabolic syndrome. However, the observed relationship between metabolic syndrome and hs-CRP level, which is an inflammatory factor, indicates elevated levels of hs-CRP in patients with metabolic syndrome.
PMCID: PMC3463992  PMID: 23056106
Metabolic Syndrome; Exercise Test; Heart Rate Reserve; High-Sensitivity C-Reactive Protein
17.  Estimation of insulin resistance in non-diabetic normotensive Saudi adults by QUICKI, HOMA-IR and modified QUICKI: A comparative study 
Annals of Saudi Medicine  2010;30(4):257-264.
BACKGROUND AND OBJECTIVES:
Identification of insulin resistance (IR) in the general population is important for developing strategies to reduce the prevalence of non-insulin-dependent diabetes mellitus (NIDDM). We used the original and a modified version of the Quantitative Insulin Sensitivity Check Index (QUICKI, M-QUICKI), and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) to divide non-diabetic normotensive adults into high- (HIR) and low-insulin-resistant (LIR) subgroups to investigate similarities and differences in their characteristics.
SUBJECTS AND METHODS:
Three hundred fifty-seven healthy adults aged 18-50 years were recruited randomly from health centers in Jeddah in a cross-sectional study design. Anthropometric and demographic information was taken. Insulin, glucose, lipid profile and free fatty acid were determined in fasting blood samples. M-QUICKI, HOMA-IR and QUICKI were calculated. Reported cut-off points were used to identify HIR subjects, who were then matched for age and sex to others in the study population, resulting in 3 HIR and 3 LIR subgroups.
RESULTS:
Two hundred nine subjects satisfied the selection criteria. M-QUICKI correlated significantly (P=.01) with HOMA-IR and QUICKI values. Increased adiposity was the common characteristic of the three HIR subgroups. HIR subgroups identified using M-QUICKI (97 subjects) and HOMA (25 subjects), but not QUICKI (135 subjects), had statistically different biochemical characteristics compared to corresponding LIR sub-groups.
CONCLUSION:
Adiposity, but not sex, is a risk factor for IR in the studied population. Further studies are needed to choose the most appropriate index for detecting IR in community-based surveys.
doi:10.4103/0256-4947.65252
PMCID: PMC2931775  PMID: 20622341
18.  Prevalence of Traditional Modifiable Cardiovascular Risk Factors in Patients with Rheumatoid Arthritis: Comparison with Control Subjects from the Multi-Ethnic Study of Atherosclerosis 
Objective
Despite the recognized risk of accelerated atherosclerosis in patients with rheumatoid arthritis (RA), little is known about cardiovascular risk management in contemporary cohorts of these patients. We tested the hypotheses that major modifiable cardiovascular risk factors were more frequent and rates of treatment, detection, and control were lower in patients with RA than in non-RA controls.
Methods
The prevalence of hypertension, diabetes, elevated low-density lipoprotein (LDL) cholesterol, elevated body mass index, smoking, moderate-high 10-year cardiovascular risk and the rates of underdiagnosis, therapeutic treatment, and recommended management were compared in 197 RA patients and 274 frequency-matched control subjects, and their associations with clinical characteristics were examined.
Results
Eighty percent of RA patients and 81% of control subjects had at least 1 modifiable traditional cardiovascular risk factor. Hypertension was more prevalent in the RA group (57%) than in controls [42%, P =0.001]. There were no statistically significant differences in the frequency of diabetes, elevated body mass index, smoking, intermediate-high 10-year coronary heart disease risk, or elevated LDL in patients with RA versus controls. Rates of newly identified diabetes, hypertension, and hyperlipidemia were similar in RA patients versus controls. Rates of therapeutic interventions were low in both groups but their use was associated with well-controlled blood pressure (OR = 4.55, 95% CI: 1.70, 12.19) and lipid levels (OR = 9.90, 95% CI: 3.30, 29.67).
Conclusions
Hypertension is more common in RA than in controls. Other traditional cardiovascular risk factors are highly prevalent, underdiagnosed, and poorly controlled in patients with RA, as well as controls.
doi:10.1016/j.semarthrit.2011.07.004
PMCID: PMC3538033  PMID: 22340996
rheumatoid arthritis; cardiovascular risk; epidemiology
19.  High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in women with rheumatoid arthritis and may augment the cardiovascular risk of women with RA: a cross-sectional study 
Arthritis Research & Therapy  2012;14(3):R116.
Introduction
Higher levels of high density lipoprotein (HDL) subfractions HDL3-chol and particularly HDL2-chol protect against cardiovascular disease (CVD), but inflammation reduces the HDL level and may impair its anti-atherogenic effect. Changed HDL composition through the impact of inflammation on HDL subfractions may contribute to the excess risk of CVD in rheumatoid arthritis (RA). In this study, we investigated whether HDL2-chol and HDL3-chol concentrations differ between RA patients and healthy controls, and whether these levels are related to the level of RA disease activity.
Methods
Non-fasting blood samples were collected from 45 RA patients and 45 healthy controls. None of the participants had a history of CVD, diabetes, or used lipid-lowering drugs. HDL2-chol and HDL3-chol concentrations were obtained by ultracentrifugation. Regression modeling was used to compare HDL subfraction levels between RA patients and healthy controls, and to analyze the effect of disease activity on HDL2-chol and HDL3-chol.
Results
HDL2-chol and HDL3-chol were significantly lower in RA patients compared to healthy controls (P = 0.01, P = 0.005, respectively). The HDL2:HDL3 ratio was significantly lower in patients compared to controls (P = 0.04). Reduced HDL2-chol and HDL3-chol levels were primarily present in female RA patients and not in male RA patients. A modest effect of the disease activity score in 28 joins ( DAS28) on HDL2-chol concentrations was found, after correction for disease duration, glucocorticosteroid use and body mass index (BMI), with a 0.06 mmol/L decrease with every point increase in DAS28 (P = 0.05). DAS28 did not significantly affect HDL3-chol concentrations (P = 0.186).
Conclusions
Both HDL subfractions but particularly HDL2-chol concentrations were decreased in RA, primarily in women. This seems to be associated with disease activity and is of clinical relevance. The reduction of the HDL subfraction concentrations, particularly the supposedly beneficial HDL2-chol, may negatively impact the cardiovascular risk profile of women with RA.
doi:10.1186/ar3842
PMCID: PMC3446493  PMID: 22584154
20.  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
21.  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
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 
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
23.  The Triglyceride to HDL Ratio and Its Relationship to Insulin Resistance in Pre- and Postpubertal Children: Observation from the Wausau SCHOOL Project 
Cholesterol  2012;2012:794252.
Insulin resistance (IR) is a risk factor for ischemic heart disease and diabetes and raises the triglyceride/high-density lipoprotein (TG/HDL) ratio in adults, but is not well defined in children. Purpose. To investigate the TG/HDL ratios in children as an IR marker. Methods. Wausau SCHOOL Project assessed 99 prepubertal and 118 postpubertal children. The TG/HDL ratio was correlated with numerous risk factors. Results. TG/HDL ratio was significantly correlated with QUICKI, HOMA-IR, zBMI, waist-to hip ratio, systolic and diastolic BP, LDL size and LDL number. A group of 32 IR children (HOMA-IR > 1 SD from the mean, i.e., >2.45) had significantly higher TG/HDL (3.11 ± 1.77) compared to non-IR children (1.86 ± 0.75). A TG/HDL ratio of ≥2.0 identified 32 of the 40 children deemed IR by HOMA-IR (>2.45) with a sensitivity of 0.80 and a specificity of 0.66. Children with TG/HDL ratio ≥3 were heavier and had higher BP, glucose, HOMA-IR, LDL number, and lower HDL level, QUICKI, and LDL size, regardless of pubertal status. Conclusion. The TG/HDL ratio is strongly associated with IR in children, and with higher BMI, waist hip ratio, BP, and more athrogenic lipid profile.
doi:10.1155/2012/794252
PMCID: PMC3395199  PMID: 22811895
24.  Serum Levels of Lipids, Calcium and Magnesium in Women with Hypothyroidism and Cardiovascular Diseases 
Lipid abnormalities in hypothyroidism contribute to the disproportionate increase in cardiovascular risk. A possible relationship between serum level of magnesium (Mg) and calcium (Ca) and cardiovascular disease was recorded. In this work, the possible correlation between lipid profile components and serum cations Ca and Mg was investigated. Matched healthy women were evaluated in a cross-sectional study. All parameters were measured spectrophotometrically. The results showed a significant decrease (P < 0.05) in high-density lipoprotein-cholesterol (HDL-C), total and ionized Mg in hypothyroid patients in comparing with control group. There was a significant increase (P <0.05) in serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and (LDL-C)/(HDL-C) ratio in hypothyroid patients as compared with control group. However, no correlation was found between the cation levels and lipid profile of the studied groups. It can be concluded that patients with hypothyroidism exhibited elevated atherogenic parameters (TC and LDL-C) and high risk of cardiovascular diseases.
doi:10.4103/0974-2727.59698
PMCID: PMC3167967  PMID: 21938249
Calcium; cholesterol; hypothyroidism; lipid; magnesium
25.  Adiponectin and inducible ischemia in patients with stable coronary heart disease: data from the Heart and Soul study 
Atherosclerosis  2008;205(1):233-238.
Objective
Elevated concentrations of adiponectin are associated with a favorable metabolic profile but also with adverse cardiovascular outcomes. This apparent discrepancy has raised questions about whether adiponectin is associated with an increased or decreased risk of coronary heart disease (CHD). We sought to determine whether higher adiponectin levels are associated with exercise-induced ischemia in patients with stable CHD.
Methods and results
We measured total serum adiponectin concentrations and evaluated exercise-induced ischemia by stress echocardiography in a cross-sectional study of 899 outpatients with documented stable CHD. Of these, 217 (24%) had inducible ischemia. Although adiponectin levels correlated negatively with diabetes prevalence, body mass index, serum insulin, fasting glucose, low-density lipoprotein cholesterol, and triglycerides and positively with high-density lipoprotein cholesterol (all P< 0.005), elevated adiponectin concentrations were also associated with a greater risk of inducible ischemia. Each standard deviation (0.08 μg/mL) increase in log adiponectin was associated with a 35% greater odds of inducible ischemia (unadjusted odds ratio 1.35; 95% confidence interval 1.15–1.57; P=0.0002). Although attenuated, this association remained present after multivariable adjustment for traditional cardiovascular risk factors and other measures of cardiac function (adjusted odds ratio 1.21; 95% confidence interval 1.02–1.43; P=0.03).
Conclusions
Elevated concentrations of adiponectin are independently associated with inducible ischemia in patients with stable CHD. These findings raise the possibility that the presence of chronic inducible ischemia may alter the cardio-protective effects afforded by adiponectin secretion in the healthy population.
doi:10.1016/j.atherosclerosis.2008.11.014
PMCID: PMC2779844  PMID: 19111833
Adiponectin; Coronary heart disease (CHD); Ischemia; Adipokine; Reverse epidemiology

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