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1.  Exercise electrocardiographic responses and serum cystatin C levels among metabolic syndrome patients without overt diabetes mellitus 
Objectives:
An impaired heart rate response during exercise (chronotropic incompetence) and an impaired heart rate recovery (HRR) after exercise are predictors of cardiovascular risk and mortality. Cystatin C is a novel marker for cardiovascular disease. We aimed to investigate exercise electrocardiographic responses in patients with metabolic syndrome who were without overt diabetes mellitus, in addition to the association of serum cystatin C levels with the exercise electrocardiographic test results.
Method:
Forty-three consecutive patients admitted to a cardiology outpatient clinic without angina pectoris were recruited if they met criteria for metabolic syndrome but did not have overt diabetes mellitus. Serum cystatin C levels were measured, and all participants underwent exercise electrocardiographic testing. Patients who were found to have ischemia had a coronary angiography procedure.
Results:
The mean cystatin C level of patients was higher in metabolic syndrome group than healthy controls (610.1 ± 334.02 vs 337.3 ± 111.01 μg/L; P < 0.001). The percentage of patients with ischemia confirmed by coronary angiography was 13.9% in the metabolic syndrome group. Cystatin C levels in the ischemic patients of the metabolic syndrome group were higher than that in nonischemic patients (957.00 ± 375.6 vs 553.8 ± 295.3 μg/L; P = 0.005). Chronotropic incompetence was observed in 30.2% of the patients with metabolic syndrome compared with 16.7% in the control group (P = 0.186). Chronotropic response indices were 0.8 ± 0.18 versus 0.9 ± 0.10 for the two groups, respectively (P = 0.259). HRR was significantly lower in the metabolic syndrome patients compared with the controls (20.1 ± 8.01 vs 25.2 ± 4.5 per min; P < 0.001), and the ST-segment adjustment relative to heart rate(ST/HR index ratio) was 1.4 ± 1.34 versus 0.4 ± 0.31 μV/beat (P < 0.001), respectively. Cystatin C was negatively correlated with the chronotropic response index (CRI) and HRR and was positively correlated with ST/HR index in the entire study population (R = −0.658, −0.346, 0.388, respectively; P < 0.05).
Conclusions:
A substantial proportion of metabolic syndrome patients without overt diabetes mellitus had silent coronary ischemia in addition to impairment of objective exercise electrocardiographic parameters. In the metabolic syndrome patients without overt diabetes mellitus, cystatin C levels were found to be elevated and the elevation was more pronounced in the subgroup with silent ischemia. Cystatin C was also correlated with HRR and CRI.
doi:10.2147/VHRM.S16638
PMCID: PMC3049540  PMID: 21415918
exercise electrocardiography; metabolic syndrome; silent ischemia; cystatin C
2.  Relationship between heart rate recovery and inflammatory markers in patients with polycystic ovary syndrome: a cross-sectional study 
Background
Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk factors for cardiovascular disease. An abnormal heart rate recovery (HRR), an easily-obtained measure derived from exercise stress test and closely related to an increased risk for cardiovascular mortality, has been recently described in PCOS women. A subclinical increase of the inflammation markers has been also observed in the PCOS. This study was designed to study the relationships between HRR and inflammatory markers in PCOS women.
Methods
Two-hundred forty-three young PCOS patients without known risk factors for cardiovascular risk were enrolled. All patients underwent hormonal and metabolic profile, white blood cells (WBCs) count and C-reactive protein (CRP). HRR was calculated as the difference between heart rate at peak exercise and heart rate at first minute of the cool-down period. Abnormal HRR was defined as ≤18 beats/min for standard exercise testing.
Results
Eighty-nine out of 243 patients presented abnormal HRR. Serum CRP (1.8 ± 0.7 vs. 1.1 ± 0.4 mg/dl, p < 0.001) and WBCs (7.3 ± 1.8 vs. 6.6 ± 1.5 109 cells/l, p < 0.001) concentrations were significantly higher in PCOS patients with abnormal versus normal HRR. HRR was significantly associated with both CRP (r = -0.33, p < 0.001) and WBCs (r = -0.29, p < 0.001), although in a stepwise multiple regression HRR resulted independently associated with CRP (beta = -0.151, p = 0.001) alone. In a logistic multivariate model, the group within the highest quartile of CRP (odds ratio 1.59, 95% CI 1.07–2.33) was more likely to have abnormal HRR than those within the lowest quartile.
Conclusion
Abnormal HRR and inflammatory markers are closely associated in PCOS women acting probably in concert to increase the cardiovascular risk profile of these patients.
doi:10.1186/1757-2215-2-3
PMCID: PMC2646730  PMID: 19187547
3.  Sex based levels of C-reactive protein and white blood cell count in subjects with metabolic syndrome: Isfahan Healthy Heart Program 
Background:
C-reactive protein (CRP) and white blood cell (WBC) are proinflammatory markers. They are major pathophysiological for the development of metabolic syndrome (MetS). This study aimed to address the independent associations between MetS and WBC counts and serum CRP levels and evaluation of their magnitude in relation to the MetS, based on the sex in the Iranian adults.
Materials and Methods:
In this cross-sectional study, subjects who met the MetS criteria, based on the Adult Treatment Panel III were selected from the Isfahan Healthy Heart Program database. A questionnaire containing the demographic data, weight, height, waist, and hip circumference of the respondents was completed for each person. Blood pressure was measured and the anthropometric measurements were done, and fasting blood samples were taken for 2 h postload plasma glucose (2 hpp). Serum [total, high-density lipoprotein (HDL), and low-density lipoprotein] levels of cholesterol, triglyceride, and CRP as well as WBC counts were determined. The univariate analyses were carried out to assess the relation between the CRP levels, WBC counts with the MetS in both sexes the.
Results:
In men with the abdominal obesity, the higher levels of WBC count, high serum triglyceride and blood glucose levels, a low serum HDL level, and raised systolic and diastolic blood pressure were observed. However, the higher serum CRP levels were only observed in those with the low serum HDL-cholesterol levels. The mean values of the WBC counts were statistically different between the men with and without MetS, but the mean values of the CRP levels were similar between the two groups. In women, the mean values of WBC count and CRP levels were statistically different in the subjects with and without a MetS components (except for the low serum HDL levels and high diastolic blood pressure for the WBC measures and abdominal obesity for the CRP measures) and for those with and without MetS. The age and smoking adjusted changes in the CRP levels and WBC counts correlated with the number of Mets components in the women.
Conclusion:
The findings of this study suggest substantial implications for the prevention and management of the MetS and atherosclerotic diseases, as these involve the suppression of inflammatory conditions rather than the incitement of anti-inflammatory conditions.
PMCID: PMC3818614  PMID: 24250693
C-reactive protein level; metabolic syndrome; white blood cell count
4.  Inflammation, Insulin Resistance, and Diabetes—Mendelian Randomization Using CRP Haplotypes Points Upstream 
PLoS Medicine  2008;5(8):e155.
Background
Raised C-reactive protein (CRP) is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables.
Methods and Findings
We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G) in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study). Homeostasis model assessment-insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29–1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p = 0.52–0.92). The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p = 0.007–0.11). Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p = 0.25–0.88). Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls) using three SNPs in tight linkage disequilibrium with our tagging SNPs also demonstrated null associations.
Conclusions
Observed associations between serum CRP and insulin resistance, glycemia, and diabetes are likely to be noncausal. Inflammation may play a causal role via upstream effectors rather than the downstream marker CRP.
Using a Mendelian randomization approach, Eric Brunner and colleagues show that the associations between serum C-reactive protein and insulin resistance, glycemia, and diabetes are likely to be noncausal.
Editors' Summary
Background.
Diabetes—a common, long-term (chronic) disease that causes heart, kidney, nerve, and eye problems and shortens life expectancy—is characterized by high levels of sugar (glucose) in the blood. In people without diabetes, blood sugar levels are controlled by the hormone insulin. Insulin is released by the pancreas after eating and “instructs” insulin-responsive muscle and fat cells to take up the glucose from the bloodstream that is produced by the digestion of food. In the early stages of type 2 diabetes (the commonest type of diabetes), the muscle and fat cells become nonresponsive to insulin (a condition called insulin resistance), and blood sugar levels increase. The pancreas responds by making more insulin—people with insulin resistance have high blood levels of both insulin and glucose. Eventually, however, the insulin-producing cells in the pancreas start to malfunction, insulin secretion decreases, and frank diabetes develops.
Why Was This Study Done?
Globally, about 200 million people have diabetes, but experts believe this number will double by 2030. Ways to prevent or delay the onset of diabetes are, therefore, urgently needed. One major risk factor for insulin resistance and diabetes is being overweight. According to one theory, increased body fat causes mild, chronic tissue inflammation, which leads to insulin resistance. Consistent with this idea, people with higher than normal amounts of the inflammatory protein C-reactive protein (CRP) in their blood have a high risk of developing diabetes. If inflammation does cause diabetes, then drugs that inhibit CRP might prevent diabetes. However, simply measuring CRP and determining whether the people with high levels develop diabetes cannot prove that CRP causes diabetes. Those people with high blood levels of CRP might have other unknown factors in common (confounding factors) that are the real causes of diabetes. In this study, the researchers use “Mendelian randomization” to examine whether increased blood CRP causes diabetes. Some variants of CRP (the gene that encodes CRP) increase the amount of CRP in the blood. Because these variants are inherited randomly, there is no likelihood of confounding factors, and an association between these variants and the development of insulin resistance and diabetes indicates, therefore, that increased CRP levels cause diabetes.
What Did the Researchers Do and Find?
The researchers measured blood CRP levels in more than 5,000 people enrolled in the Whitehall II study, which is investigating factors that affect disease development. They also used the “homeostasis model assessment-insulin resistance” (HOMA-IR) method to estimate insulin sensitivity from blood glucose and insulin measurements, and measured levels of hemoglobin A1c (HbA1c, hemoglobin with sugar attached—a measure of long-term blood sugar control) in these people. Finally, they looked at three “single polynucleotide polymorphisms” (SNPs, single nucleotide changes in a gene's DNA sequence; combinations of SNPs that are inherited as a block are called haplotypes) in CRP in each study participant. Common haplotypes of CRP were related to blood serum CRP levels and, as previously reported, increased blood CRP levels were associated with diabetes and with HOMA-IR and HbA1c values indicative of insulin resistance and poor blood sugar control, respectively. By contrast, CRP haplotypes were not related to HOMA-IR or HbA1c values. Similarly, pooled analysis of CRP haplotypes and diabetes in Whitehall II and another large study on health determinants (the Northwick Park Heart Study II) showed no association between CRP variants and diabetes risk. Finally, data from the Wellcome Trust Case Control Consortium also showed no association between CRP haplotypes and diabetes risk.
What Do These Findings Mean?
Together, these findings suggest that increased blood CRP levels are not responsible for the development of insulin resistance or diabetes, at least in European populations. It may be that there is a causal relationship between CRP levels and diabetes risk in other ethnic populations—further Mendelian randomization studies are needed to discover whether this is the case. For now, though, these findings suggest that drugs targeted against CRP are unlikely to prevent or delay the onset of diabetes. However, they do not discount the possibility that proteins involved earlier in the inflammatory process might cause diabetes and might thus represent good drug targets for diabetes prevention.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050155.
This study is further discussed in a PLoS Medicine Perspective by Bernard Keavney
The MedlinePlus encyclopedia provides information about diabetes and about C-reactive protein (in English and Spanish)
US National Institute of Diabetes and Digestive and Kidney Diseases provides patient information on all aspects of diabetes, including information on insulin resistance (in English and Spanish)
The International Diabetes Federation provides information about diabetes, including information on the global diabetes epidemic
The US Centers for Disease Control and Prevention provides information for the public and professionals on all aspects of diabetes (in English and Spanish)
Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.0050155
PMCID: PMC2504484  PMID: 18700811
5.  The metabolic syndrome in survivors of childhood acute lymphoblastic leukemia in Isfahan, Iran 
BACKGROUND:
To determine the prevalence of metabolic syndrome in survivors of childhood leukemia in Isfahan, Iran.
METHODS:
During a 4-year period (2003 to 2007), 55 children (33 male and 22 female) diagnosed with ALL at Unit of Hematology/ Oncology, Department of Pediatrics, Isfahan University of Medical Science, were enrolled in this cross-sectional study. Metabolic syndrome was defined using the modified version of Adult Treatment Panel (ATP III) crite-ria. Insulin resistance was defined based on the homeostasis model assessment index (HOMA-IR).
RESULTS:
The mean age of participates was 10.4 years (range 6-19 years) and the mean interval since completion of chemotherapy was 35 months. Twenty percent (11/55) of survivors (10 male, 1 female) met criteria for diagnosis of metabolic syndrome. Obesity was observed in one forth of patients and nearly 3/4 of obese patients had metabolic syndrome. High serum insulin levels were found in 16% of participants and in 63% of obese survivors. The mean insulin levels in survivors with metabolic syndrome was three-times more than those without (28.3 mu/l vs. 9.57 mu/l, p = 0.004). Insulin resistance was detected in 72.7% of survivors with metabolic syndrome and it was positively correlated with serum triglycerides (0.543, p ≤ 0.001), systolic and diastolic BP (0.348, p = 0.01 and 0.368, p = 006 respectively), insulin levels (0.914, p < 0.001) and blood sugar (0.398, p = 003).
CONCLUSIONS:
The prevalence of metabolic syndrome in survivors of childhood leukemia in Iran is higher than developed countries. Nearly all of the obese patients had metabolic syndrome. Weight control and regular physical exercise are recommended to the survivors.
PMCID: PMC3129086  PMID: 21772869
Acute lymphoblastic leukemia; metabolic syndrome; obesity; children
6.  Correlates of heart rate recovery over 20 years in a population sample 
Medicine and science in sports and exercise  2012;44(2):10.1249/MSS.0b013e31822cb190.
Introduction
Slow heart rate recovery (HRR) from a graded exercise treadmill test (GXT) is a marker of impaired parasympathetic reactivation that is associated with elevated mortality. Our objective was to test whether demographic, behavioral or coronary heart disease (CHD) risk factors during young adulthood were associated with the development of slow HRR.
Methods
Participants from the Coronary Artery Risk Development in Young Adults study underwent symptom-limited maximal GXT using a modified Balke protocol at baseline (1985–86) and 20-year follow-up (2005–06) examinations. HRR was calculated as the difference between peak heart rate (HR) and HR two-minutes following cessation of the GXT. Slow HRR was defined as 2-minute HRR < 22 beats·min−1.
Results
In 2,730 participants who did not have slow HRR at baseline, mean HRR was 44 beats*min−1 (SD = 11) at baseline and declined to 40 beats·min−1 (SD=12) in 2005–06; slow HRR developed in 5% (n=135) of the sample by 2005–06. Female sex, black race, fewer years of education, obesity, cigarette smoking, higher depressive symptoms, higher fasting glucose, hypertension, metabolic syndrome and physical inactivity and low fitness were each associated with incident slow HRR. In a multivariable model higher BMI, larger waist, low education, fasting glucose and current smoking remained significantly associated with incident slow HRR. Increasing BMI (per SD higher) over follow-up and incident hypertension, diabetes and metabolic syndrome (in the subsets of participants who were free from those conditions at baseline), were each associated with a significantly elevated odds of incident slow HRR.
Conclusions
On average, HRR declines with aging; however, the odds of having slow HRR in early middle age is significantly associated with traditional CHD risk factors.
doi:10.1249/MSS.0b013e31822cb190
PMCID: PMC3838873  PMID: 21796053
Epidemiology; Cardiovascular Disease; Exercise; Autonomic Nervous System
7.  Relationship Between Carotid Intima-Media Thickness with some Inflammatory Biomarkers, Ghrelin and Adiponectin in Iranians with and without Metabolic Syndrome in Isfahan Cohort Study 
ARYA Atherosclerosis  2010;6(2):56-61.
BACKGROUND
Recent studies have confirmed inflammatory factors and metabolic syndrome (MetS) as important cardiovascular disease (CVD) risk factors. Recently measurement of carotid intima-media thickness (IMT) has been used for evaluation of early atherosclerosis. This study was designed to assess the correlation between IMT with some inflammatory biomarkers, ghrelin and adiponectin in people with and without MetS in a cohort sample in Isfahan province.
METHODS
Among participants of Isfahan Cohort Study (ICS) by random sampling, 88 participants were selected and divided into case (with MetS) and control (without MetS) groups. A questionnaire including demographic data and CVD risk factors was completed for all of the participants. Physical examination and blood pressure, height, weight and waist circumference measurements were done for all subjects. Vascular echocardiography was done for evaluation of IMT of each carotid artery of both sides. Interlukin-6 (IL-6), interlukin-10 (IL-10), highly sensitive C-reactive protein (hs-CRP), ghrelin and adiponectin levels were measured using ELIZA method. Data were entered in SPSS15 software and analyzed by t-test, chi square, Pearson correlation and linear regression analyze.
RESULTS
The mean waist circumference, BMI, systolic blood pressure, diastolic blood pressure, hs-CRP and IMT of left carotid artery were significantly higher in participants with Mets. There was significant correlation between left carotid IMT and IL-6 level in all patients (P = 0.03). After adjustment for age and sex, significant relationship in groups with MetS was only reported between the left IMT and IL-6 (P = 0.02). There was no relation between IMT and other inflammatory markers in subjects with and without MetS.
CONCLUSION
Significant correlation between IL-6 and IMT was reported in patients with MetS. While no significant correlation between IL-10, adiponectin and ghrelin with IMT was observed in metabolic syndrome group.
PMCID: PMC3347812  PMID: 22577415
Intima-media thickness (IMT); Carotid artery; hs-CRP; Ghrelin; Adiponectin IL-6; IL-10
8.  Changes in C-Reactive Protein from Low-Fat Diet and/or Physical Activity in Men and Women With and Without Metabolic Syndrome 
Background
Change in high sensitivity C-reactive protein (CRP) from low-fat diet (diet) and physical activity (PA) interventions is relatively unknown for adults with metabolic syndrome.
Objective
To assess CRP change (ΔCRP) with diet and/or PA in men and women with and without metabolic syndrome.
Design
Men (n=149) and postmenopausal women (n=125) with elevated LDL-C and low HDL-C were recruited into a one-year randomized controlled trial. Treatment groups were: control, diet (reduced total fat, saturated fat and cholesterol intake), PA (45-60 minutes at 60-85% maximum heart rate) or diet plus physical activity (diet+PA). Weight loss was not an intervention focus. Metabolic syndrome was defined using the American Heart Association/National Heart, Lung and Blood Institute/ criteria. Stored plasma samples were analyzed for CRP. ΔCRP was compared between treatments, within gender and metabolic syndrome status, using ANCOVA, including covariates for baseline CRP and body fat change.
Results
For women with metabolic syndrome (n=39) ΔCRP was greater in diet vs. control (-1.2 ± 0.4, p = 0.009), diet+PA vs. control (-1.3 ± 0.4,p = 0.006), and diet+PA vs. PA (-1.1 ± 0.4, p = 0.02). Women with metabolic syndrome receiving the diet component (diet or diet+PA) had greater ΔCRP compared with those who did not (control or PA)(p = 0.001). ΔCRP was not significantly different between intervention groups in men overall, women overall, men with (n=47) or without metabolic syndrome (n=102), or women without metabolic syndrome (n=86).
Conclusion
Low-fat diet may be the most effective treatment for reducing CRP in women with metabolic syndrome.
doi:10.1016/j.metabol.2009.07.008
PMCID: PMC2789861  PMID: 19709693
9.  Hepatic Steatosis, Obesity and the Metabolic Syndrome Are Independently and Additively Associated With Increased Systemic Inflammation 
Objective
To assess the independent and collective associations of hepatic steatosis, obesity, and the metabolic syndrome with elevated high-sensitivity CRP (hs-CRP) levels.
Methods and Results
We evaluated 2,388 individuals without clinical cardiovascular disease between December 2004 and December 2006. Hepatic steatosis was diagnosed by ultrasound, and the metabolic syndrome was defined using NHLBI criteria. The cutpoint of ≥ 3 mg/L was used to define “high” hs-CRP. Multivariate logistic regression was used to assess the independent and collective associations of hepatic steatosis, obesity, and the metabolic syndrome with high hs-CRP. Steatosis was detected in 32% of participants, 23% met criteria for metabolic syndrome, and 17% of individuals were obese. After multivariate regression, hepatic steatosis (OR 2.07; 95% CI: 1.68-2.56), obesity (OR 3.00; 95% CI: 2.39-3.80), and the metabolic syndrome (2.39; 95% CI: 1.88-3.04) were all independently associated with high hs-CRP. Combinations of these factors were associated with an additive increase in the odds of high hs-CRP, with individuals with 1, 2, and 3 factors having ORs for high hs-CRP of 1.92 (1.49-2.48), 3.38 (2.50-4.57) and 4.53 (3.23-6.35), respectively.
Conclusion
Hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased odds of high hs-CRP levels.
doi:10.1161/ATVBAHA.111.228262
PMCID: PMC3148106  PMID: 21546603
Hepatic Steatosis; Obesity; Metabolic Syndrome; Inflammation; Cytokines
10.  High-sensitivity C-reactive protein to detect metabolic syndrome in a centrally obese population: a cross-sectional analysis 
Background
People with central obesity have an increased risk for developing the metabolic syndrome, type 2 diabetes and cardiovascular disease. However, a substantial part of obese individuals have no other cardiovascular risk factors, besides their obesity. High sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation and a predictor of type 2 diabetes and cardiovascular disease, is associated with the metabolic syndrome and its separate components. We evaluated the use of hs-CRP to discriminate between centrally obese people with and without the metabolic syndrome.
Methods
1165 people with central obesity but without any previous diagnosis of hypertension, dyslipidemia, diabetes or cardiovascular disease, aged 20-70 years, underwent a physical examination and laboratory assays to determine the presence of the metabolic syndrome (NCEP ATP III criteria). Multivariable linear regression analyses were performed to assess which metabolic syndrome components were independently associated with hs-CRP. A ROC curve was drawn and the area under the curve was calculated to evaluate whether hs-CRP was capable to predict the presence of the metabolic syndrome.
Results
Median hs-CRP levels were significantly higher in individuals with central obesity with the metabolic syndrome (n = 417; 35.8%) compared to individuals with central obesity without the metabolic syndrome (2.2 mg/L (IQR 1.2-4.0) versus 1.7 mg/L (IQR 1.0-3.4); p < 0.001). Median hs-CRP levels increased with an increasing number of metabolic syndrome components present. In multivariable linear regression analyses, waist circumference and triglycerides were the only components that were independently associated with hs-CRP after adjusting for smoking, gender, alcohol consumption and the other metabolic syndrome components. The area under the ROC curve was 0.57 (95%-CI 0.53-0.60).
Conclusions
Hs-CRP has limited capacity to predict the presence of the metabolic syndrome in a population with central obesity.
doi:10.1186/1475-2840-11-25
PMCID: PMC3359236  PMID: 22417460
Abdominal obesity; Metabolic syndrome; Screening; High-sensitivity C-reactive protein
11.  Metabolic Syndrome, Inflammation, and the Incident Heart Failure in the Elderly: the Cardiovascular Health Study 
Circulation. Heart failure  2008;1(4):242-248.
Background
Inflammation markers and MetS are associated with risk of CHF. We evaluated whether combining inflammation markers and metabolic syndrome (MetS) provided additive information for incident congestive heart failure (CHF), and if incorporating inflammation markers to the MetS definition added prognostic information.
Methods and Results
We studied 4017 men and women ≥ 65 years old, without baseline CHF or diabetes, participating in the Cardiovascular Health Study, an observational study with 12.2 years follow-up and 966 cases of incident CHF. Baseline “C-reactive protein (CRP)-MetS” or “interleukin-6 (IL-6)-MetS” were defined as presence of 3 out of 6 components, with elevated CRP (≥3 mg/L) or IL-6 (≥2.21 pg/mL) as a 6th component added to ATPIII criteria. Cox models adjusted for CHF risk factors and incident coronary disease, were used to calculate HRs for CHF. MetS and elevated inflammation markers were independently associated with CHF risk (HRs, 95 % CI: 1.32, 1.16–1.51 for MetS; 1.53, 1.34–1.75 for CRP; 1.37, 1.19–1.55 for IL-6). There was a 20% relative excess risk attributed to the combination of MetS and CRP (95% CI −44% to 88%). CRP-MetS and IL-6-MetS definitions reclassified 18% and 13%, respectively of participants as MetS. Both CRP-MetS and IL-6-MetS increased risk of CHF by 60% compared to those without MetS.
Conclusion
MetS and inflammation markers provided additive information on CHF risk in this elderly cohort. Inflammation-incorporated MetS definitions identified more participants with the same risk level as ATPIII MetS. Considering inflammation markers and MetS together may be useful in clinical and research settings.
doi:10.1161/CIRCHEARTFAILURE.108.785485
PMCID: PMC2762642  PMID: 19808298
heart failure; metabolism; inflammation
12.  The effects of exercise on C-reactive protein, insulin, leptin and some cardiometabolic risk factors in Egyptian children with or without metabolic syndrome 
Background
The prevalence and magnitude of obesity in the children and the adolescents have increased dramatically in the developing countries over the last 20–30 years. The prevalence of metabolic syndrome (MS) in children is increasing. Aim: This study aimed to investigate the changes of C-reactive protein (CRP), leptin, insulin, and blood lipids before and after the exercise therapy in normal and obese children (with or without metabolic syndrome).
Methods
The study covered 49 normal children (control), 32 obese children without metabolic syndrome and 12 obese children with metabolic syndrome. We examined the influence of exercise (3 times/week) for 12 weeks on the levels of serum CRP, leptin, insulin, homeostatic model assessment insulin resistance (HOMA-IR), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in all groups.
Results
There were significant correlations between HOMA-IR and the individual components of the metabolic syndrome. After 12 weeks of exercise, both of the obese children groups, with and without metabolic syndrome, showed reduced body weight, body mass index (BMI), and CRP level, and increased HDL-C level. The percentage of metabolic syndrome decreased from 12.9% before the exercise training to 7.5% after training. Also, there was a significant reduction in BMI (from 47.3 to 32.6%), in systolic blood pressure (from 18.3 to 15.1%) and in HDL-C level (from 18.3 to 9.7%).
Conclusion
Overweight children have multiple risk factors associated with the metabolic syndrome. 12-week exercise may have a positive effect on reducing risk factors for the metabolic syndrome.
doi:10.1186/1758-5996-4-27
PMCID: PMC3536685  PMID: 22691465
Metabolic syndrome; Exercise; Children; Cardiometabolic risk factor; C-reactive protein and insulin
13.  Metabolic syndrome, insulin resistance, fibrinogen, homocysteine, leptin, and C-reactive protein in obese patients with obstructive sleep apnea syndrome 
Annals of Thoracic Medicine  2011;6(3):120-125.
OBJECTIVE:
The prevalence of obstructive sleep apnea syndrome (OSAS) and metabolic syndrome is increasing worldwide, in part linked to epidemic of obesity. The purposes of this study were to establish the rate of metabolic syndrome and to compare fibrinogen, homocysteine, high-sensitivity C-reactive protein (hsCRP), leptin levels, and homeostasis model assessment insulin resistance (HOMA-IR) in the obese patients with and without OSAS.
METHODS:
The study population included 36 consecutive obese patients with OSAS (23 males; mean age, 50.0 ±19.7 years), and 34 obese patients without OSAS (17 males; mean age, 49.7±11.1 years) were enrolled as control group. Metabolic syndrome was investigated; fibrinogen, homocysteine, CRP, and leptin levels were measured, and IR was assessed.
RESULTS:
Metabolic syndrome was found in 17 (47.2%) obese OSAS patients, whereas only 29.4% of obese subjects had metabolic syndrome (P > 0.05). Obese patients with OSAS had significantly higher mean levels of triglyceride (P < 0.001), total-cholesterol (P = 0.003), low-density lipoprotein-cholesterol (P = 0.001), fasting glucose (P = 0.01), HOMA-IR (P <0.001), thyroid-stimulating hormone (P = 0.03), fibrinogen (P < 0.003), hsCRP (P <0.001), and leptin (P = 0.03) than control group . Besides, leptin level was positively correlated with waist (r = 0.512, P = 0.03) and neck circumferences (r = 0.547, P = 0.03), and fasting glucose (r = 0.471, P = 0.04) in OSAS patients, but not in obese subjects.
CONCLUSION:
This study demonstrated that obese OSAS patients may have an increased rate of metabolic syndrome and higher levels of serum lipids, fasting glucose, IR, leptin, fibrinogen, and hsCRP than obese subjects without sleep apnea. Thus, clinicians should be encouraged to systematically evaluate the presence of metabolic abnormalities in OSAS and vice versa.
doi:10.4103/1817-1737.82440
PMCID: PMC3131753  PMID: 21760842
C-reactive protein; fibrinogen; homocysteine; insulin resistance; leptin; metabolic syndrome; obesity; obstructive sleep apnea syndrome
14.  The association of leptin and C-reactive protein with the cardiovascular risk factors and metabolic syndrome score in Taiwanese adults 
Background
Serum C-reactive protein (CRP) and leptin levels have been independently associated with the cardiovascular risk factors. The aim of the present study was to determine if their serum levels were associated with cardiovascular risk factors or metabolic syndrome as well as their correlation in the Taiwanese population.
Methods
This retrospective study included 999 subjects (> 18 y), who underwent a physical examination in Chang-Gung Memorial Hospital-Linkou and Chiayi in Taiwan. The associations between CRP and/or leptin levels and cardiovascular risk factors and metabolic syndrome were determined using independent two sample t-tests to detect gender differences and chi-square tests to evaluate differences in frequencies. To compare the means of the variables measured among the four groups (high and low leptin and high and low CRP), analysis of variance (ANOVA) was used.
Results
Both CRP and leptin levels were independently associated with several cardiovascular risk factors, including diabetes, hypercholesterolemia and metabolic syndrome in both men and women (P < 0.05). In addition, a positive correlation between leptin and CRP levels was observed in both genders. Both high-CRP and high-leptin were associated with high blood glucose, waist circumference and serum triglyceride. Whereas increased metabolic syndrome incidence was observed in males with elevated leptin regardless of CRP levels, females with elevated CRP or leptin had increased incidence of metabolic syndrome.
Conclusion
Both leptin and CRP levels were associated with cardiovascular risk factors as well as metabolic syndrome score in both men and women although gender-specific differences were observed. Thus, CRP and leptin may represent useful biomarkers for predicting the onset of cardiovascular disease or metabolic syndrome in Taiwanese adults.
Trial registration
IRB/CGMH 100-3514B
doi:10.1186/1475-2840-11-40
PMCID: PMC3471043  PMID: 22533665
C-reactive protein; Leptin; Cardiovascular disease; Metabolic syndrome; Taiwan
15.  Blood Pressure and Fasting Plasma Glucose Rather Than Metabolic Syndrome Predict Coronary Artery Calcium Progression 
Diabetes Care  2009;32(1):141-146.
OBJECTIVE—To examine the association of the metabolic syndrome, defined by World Health Organization (WHO) and Adult Treatment Panel III (ATP-III) criteria, and its components with coronary artery calcium (CAC) progression.
RESEARCH DESIGN AND METHODS—Participants were 338 older community-dwelling men and women without known heart disease who had measurements of heart disease risk factors and CAC at two clinic visits within an average interval of 4.5 years. Progression was defined as an increase in total CAC volume score ≥2.5 mm3.
RESULTS—At baseline, mean age was 67.6 years; metabolic syndrome was present in 15.1% by WHO criteria and in 11.8% by ATP-III criteria, and 5.3% met both criteria. Participants with WHO-defined metabolic syndrome had a greater change in total CAC volume score than those without (P = 0.001). There was no significant difference in CAC volume change by ATP-III–defined metabolic syndrome status (P = 0.69). Overall, 46.4% of participants were CAC progressors. In logistic regression analyses adjusted for age, sex, smoking status, and LDL cholesterol, neither WHO–nor ATP-III–defined metabolic syndrome predicted CAC progression. Among metabolic syndrome components, only hypertension was independently associated with CAC progression (odds ratio 2.11 [95% CI 1.33–3.3], P = 0.002). Fasting blood glucose (>100 mg/dl) was an independent predictor of CAC progression, but only for the 118 participants younger than age 65 years (2.3 [1.01–5.5], P = 0.04).
CONCLUSIONS—In older adults without known heart disease, blood pressure levels and fasting plasma glucose were better independent determinants of CAC progression than metabolic syndrome itself.
doi:10.2337/dc08-1360
PMCID: PMC2606850  PMID: 18852333
16.  Non-Alcoholic Fatty Liver Disease Is Closely Associated with Sub-Clinical Inflammation: A Case-Control Study on Asian Indians in North India 
PLoS ONE  2013;8(1):e49286.
Objectives
Association between sub-clinical inflammation and non-alcoholic fatty liver disease (NAFLD) has not been studied in Asian Indians. In this case-control study, we aimed to analyse association of NAFLD with the sub-clinical inflammation and metabolic profile in Asian Indians in north India.
Methods
Ultrasound diagnosed 120 cases of NAFLD were compared to 152 healthy controls without NAFLD. Anthropometric profile [body mass index (BMI), waist circumference (WC), hip circumference (HC)], high-sensitivity C-reactive protein (hs-CRP), metabolic profile [fasting blood glucose (FBG), lipid profile] and hepatic function tests [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] were recorded.
Results
Metabolic parameters [FBG, total cholesterol (TC), serum triglycerides (TG),low-density lipoprotein (LDL-c)], hs-CRP and prevalence of the metabolic syndrome were higher in cases as compared to controls (p-value<0.05 for all). The median (range) of hs-CRP (mg/L) for cases [2.6(0.2–13.4)] were significantly higher than in controls [1.4(0.03–11.4), p = 0.01]. Similarly, higher values of hs-CRP were obtained when subgroups of cases with obesity, abdominal obesity and the metabolic syndrome were compared to controls [2.75 (0.03–14.3) vs. 1.52 (0.04–14.3), p = 0.0010; 2.8 (0.03–14.3) vs. 1.5 (0.06–14.3), p = 0.0014 and 2.7 (0.5–14.3) vs. 1.6 (0.06–8.5), p = 0.0013, respectively. On multivariate logistic regression analysis BMI (p = 0.001), WC (p = 0.001), FBG (p = 0.002), TC (p = 0.008), TG (p = 0.002), blood pressure (p = 0.005), metabolic syndrome (p = 0.001) and hs-CRP (p = 0.003) were significantly and independently associated with NAFLD. After adjusting for significant variables, the association between high hs-CRP and NAFLD remained large and statistically significant [adjusted OR = 1.17, 95% confidence interval (CI) = 1.05–1.29]. An increase in 1 mg/dl of hs-CRP level calculated to increase the risk of developing NAFLD by 1.7 times as compared to controls after adjusting for significant variables associated with NAFLD.
Conclusions
In this cohort of Asian Indians in North India, presence of NAFLD showed independent relationships with sub-clinical inflammation.
doi:10.1371/journal.pone.0049286
PMCID: PMC3543427  PMID: 23326306
17.  Association of High Sensitivity C-Reactive Protein Concentrations and Metabolic Syndrome among Thai Adults 
Objective
To investigate the association of high sensitivity C-reactive protein (hsCRP) concentrations and metabolic syndrome among Thai adults.
Methods
This cross-sectional study is comprised of 467 Thai participants (209 men and 258 women) receiving annual health check-up. Spearman’s rank correlation coefficients were used to assess associations of metabolic parameters (age, waist circumference, blood pressure, triglycerides, HDL-C, fasting plasma glucose, fasting insulin and uric acid) with hsCRP concentrations for men and women, respectively. Multivariable logistic regression procedures were used to estimate the risk (odds ratios [OR] and 95% confidence intervals [95% CI]) of metabolic syndrome according to low, moderate and high hsCRP concentrations (<1.0, 1.0–3.0 and >3.0 mg/l, respectively).
Results
Measures of adiposity and fasting insulin were positively and significantly correlated with hsCRP concentrations among women with and without metabolic syndrome. Similar associations were observed among men without metabolic syndrome. After controlling for confounders, moderately elevated hsCRP concentrations were associated with a 2.38-fold increased risk of metabolic syndrome (OR=2.38, 95% CI: 1.20–4.72) among men. Men with high hsCRP concentrations had a 5.45-fold increased risk of metabolic syndrome (OR=5.45, 95% CI: 2.24–13.27) when compared with those who had low hsCRP concentrations. The corresponding odds ratios for women with moderately elevated and high hsCRP concentrations were 4.92 (OR=4.92, 95% CI: 2.34–10.35) and 11.93 (OR=11.93, 95% CI: 5.54–25.72), respectively.
Conclusions
These findings are consistent with the literature suggesting a role of hsCRP as a biomarker for metabolic syndrome.
PMCID: PMC3255568  PMID: 22241575
C-Reactive Protein; Inflammation; Obesity; Metabolic Syndrome
18.  Relationship of High Sensitivity C-Reactive Protein Levels to Anthropometric and other Metabolic Parameters in Indian Children with Simple Overweight and Obesity 
Context: High senstivity C-reactive protein (hsCRP) levels correlate well other parameters of obesity related metabolic syndrome (MS) and can be used as predictors of future cardiovascular disease risk. There is limited data on hsCRP levels in Indian children with simple obesity.
Aim: To study the relationship of hsCRP levels with various anthropometric as well as metabolic parameters in children with simple overweight and obesity.
Materials and Methods: This case control study was conducted in Paediatric Endocrinology clinic of a tertiary care hospital in Northern India. Levels of hsCRP were estimated in 100 overweight and obese children (BMI between 85th and 95th percentiles according to age & gender specific CDC 2000 growth charts) aged between 6 and 16 years and in 100 nearly age and sex matched healthy controls. These levels were then correlated to various anthropometric (body mass index, BMI; waist circumference, WC; hip circumference, HC; waist hip ratio, WHR; blood pressure) and biochemical (fasting blood glucose, FBG; total cholesterol, TC; high-density lipoprotein-cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; very low-density lipoprotein-cholesterol, VLDL-C; triglycerides, TG) parameters.
Results: Mean levels of hsCRP were significantly higher in the study group (3.92±2.20 versus 2.15±1.05 mg/L) as compared to controls. Significantly more (58% versus 10%) subjects in the study group had hsCRP (>3 mg/L). Of all the parameters studied, only BMI showed a positive correlation with hsCRP levels in the study group. Multiple logistic regression analysis for predicting outcome of high hsCRP showed positive correlation with BMI; with every 1 kg/m2 increase in BMI, odds of high hsCRP level were increased by 37% (OR=1.37; 95% CI 1.23-1.53, p-value <0.0001). Mean values of all the biochemical parameters except HDL-C were significantly higher in the study group.
Conclusion: Levels of hsCRP were significantly elevated in overweight and obese children as compared to non-obese children. In addition, these patients also showed abnormalities of lipid and glucose metabolism.
doi:10.7860/JCDR/2014/8191.4685
PMCID: PMC4190765  PMID: 25300641
Childhood obesity; Subclinical inflammation; Hscrp levels
19.  Cheese consumption in relation to cardiovascular risk factors among Iranian adults- IHHP Study 
Nutrition Research and Practice  2014;8(3):336-341.
BACKGROUND/OBJECTIVE
It is expected that dairy products such as cheeses, which are the main source of cholesterol and saturated fat, may lead to the development or increase the risk of cardiovascular and metabolic diseases; however, the results of different studies are inconsistent. This study was conducted to assess the association between cheese consumption and cardiovascular risk factors in an Iranian adult population.
SUBJECTS/METHODS
Information from the Isfahan Healthy Heart Program (IHHP) was used for this cross-sectional study with a total of 1,752 participants (782 men and 970 women). Weight, height, waist and hip circumference measurement, as well as fasting blood samples were gathered and biochemical assessments were done. To evaluate the dietary intakes of participants a validated food frequency questionnaire, consists of 49 items, was completed by expert technicians. Consumption of cheese was classified as less than 7 times per week and 7-14 times per week.
RESULTS
Higher consumption of cheese was associated with higher C-Reactive Protein (CRP), apolipoprotein A and high density lipoprotein cholesterol (HDL-C) level but not with fasting blood sugar (FBS), total cholesterol, low density lipoprotein cholesterol (LDL-C), triglyceride (TG) and apolipoprotein B. Higher consumption of cheese was positively associated with consumption of liquid and solid oil, grain, pulses, fruit, vegetable, meat and dairy, and negatively associated with Global Dietary Index. After control for other potential confounders the association between cheese intake and metabolic syndrome (OR: 0.81; 96%CI: 0.71-0.94), low HDL-C level (OR: 0.87; 96%CI: 0.79-0.96) and dyslipidemia (OR: 0.88; 96%CI: 0.79-0.98) became negatively significant.
CONCLUSION
This study found an inverse association between the frequency of cheese intake and cardiovascular risk factors; however, further prospective studies are required to confirm the present results and to illustrate its mechanisms.
doi:10.4162/nrp.2014.8.3.336
PMCID: PMC4058569  PMID: 24944780
Cheese consumption; cardiovascular risk factors; food frequency questionnaire
20.  Migraine may be a risk factor for the development of complex regional pain syndrome 
The aim was to assess the relative frequency of migraine and the headache characteristics of complex regional pain syndrome (CRPS) sufferers. CRPS and migraine are chronic, often disabling pain syndromes. Recent studies suggest that headache is associated with the development of CRPS. Consecutive adults fulfilling International Association for the Study of Pain criteria for CRPS at a pain clinic were included. Demographics, medical history, and pain characteristics were obtained. Headache diagnoses were made using International Classification of Headache Disorders, 2nd edn criteria. Migraine and pain characteristics were compared in those with migraine with those without. ANOVA with Tukey post hoc tests was used to determine the significance of continuous variables and Fisher’s exact or χ2 tests for categorical variables. The expected prevalence of migraine and chronic daily headache (CDH) was calculated based on age- and gender-stratified general population estimates. Standardized morbidity ratios (SMR) were calculated by dividing the observed prevalence of migraine by the expected prevalence from the general population. The sample consisted of 124 CRPS participants. The mean age was 45.5 ± 12.0 years. Age-and gender-adjusted SMRs showed that those with CRPS were 3.6 times more likely to have migraine and nearly twice as likely to have CDH as the general population. Aura was reported in 59.7% (74/124) of participants. Of those CRPS sufferers with migraine, 61.2% (41/67) reported the onset of severe headaches before the onset of CRPS symptoms Mean age of onset of CRPS was earlier in those with migraine (34.9 ± 11.1 years) and CDH (32.5 ± 13.4 years) compared with those with no headaches (46.8 ± 14.9 years) and those with tension-type headache (TTH) (39.9 ± 9.9 years), P < 0.05. More extremities were affected by CRPS in participants with migraine (median of four extremities) compared with the combined group of those CRPS sufferers with no headaches or TTH (median 2.0 extremities), P < 0.05. The presence of static, dynamic and deep joint mechanoallodynia together was reported by more CRPS participants with migraine (72.2%) than those with no headaches or TTH (46.2%), P ≤ 0.05. Migraine may be a risk factor for CRPS and the presence of migraine may be associated with a more severe form of CRPS. Specifically: (i) migraine occurs in a greater percentage of CRPS sufferers than expected in the general population; (ii) the onset of CRPS is reported earlier in those with migraine than in those without; and (iii) CRPS symptoms are present in more extremities in those CRPS sufferers with migraine compared with those without. In addition, as we also found that the presence of aura is reported in a higher percentage of those CRPS sufferers with migraine than reported in migraineurs in the general population, further evaluation of the cardiovascular risk profile of CRPS sufferers is warranted.
doi:10.1111/j.1468-2982.2009.01916.x
PMCID: PMC3979276  PMID: 19614690
Migraine; chronic daily headache; complex regional pain syndrome; allodynia; aura
21.  High-sensitivity c-reactive protein and gamma-glutamyl transferase levels are synergistically associated with metabolic syndrome in community-dwelling persons 
Background
Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. Increased high-sensitivity C-reactive protein (hsCRP) levels are associated with MetS and its components. Changes in gamma-glutamyl transferase (GGT) levels in response to oxidative stress are also associated with MetS, and the levels could be modulated by hsCRP.
Methods
From a single community, we recruited 822 men (mean age, 61 ± 14 years) and 1,097 women (63 ± 12 years) during their annual health examination. We investigated whether increased hsCRP and GGT levels are synergistically associated with MetS and insulin resistance evaluated by Homeostasis of model assessment of insulin resistance (HOMA-IR).
Results
Of these subjects, 141 men (17.2%) and 170 women (15.5%) had MetS. Participants with MetS had a higher hsCRP and GGT level than those without MetS in both genders, and the HOMA-IR increased significantly in correlation with an increase in hsCRP and GGT. In men, the adjusted odds ratios (95% confidence interval) for MetS across tertiles of hsCRP and GGT were 1.00, 1.69 (1.01-2.80), and 2.13 (1.29-3.52), and 1.00, 3.26 (1.84-5.78) and 6.11 (3.30-11.3), respectively. In women, the respective corresponding values were 1.00, 1.54 (0.92-2.60), and 3.08 (1.88-5.06), and 1.00, 1.70 (1.04-2.79) and 2.67 (1.66-4.30). The interaction between increased hsCRP and GGT was a significant and independent determinant for MetS and insulin resistance in both genders.
Conclusions
These results suggested that higher CRP and GGT levels were synergistically associated with MetS and insulin resistance, independently of other confounding factor in the general population.
doi:10.1186/1475-2840-9-87
PMCID: PMC3014885  PMID: 21143879
22.  Association between Obesity, hsCRP ≥2 mg/L, and Subclinical Atherosclerosis: Implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis (MESA) 
Objective
High-sensitivity C-reactive protein (hsCRP) levels are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The JUPITER trial has encouraged using hsCRP ≥2 mg/L to guide statin therapy; however the association of hsCRP to atherosclerosis, independent of obesity, remains unknown.
Methods and Results
We studied 6,760 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were stratified into 4 groups: non-obese/low hsCRP, non-obese/high hsCRP, obese/low hsCRP, and obese/high hsCRP. Using multivariable logistic and robust linear regression, we described the association with subclinical atherosclerosis, using coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). Mean BMI was 28.3 ± 5.5 kg/m2, and median hsCRP was 1.9 mg/L (0.84 – 4.26). High hsCRP, in the absence of obesity, was not associated with CAC and was mildly associated with cIMT. Obesity was strongly associated with CAC and cIMT independent of hsCRP. When obesity and high hsCRP were both present, there was no evidence of multiplicative interaction. Similar associations were seen among 2,083 JUPITER-eligible individuals.
Conclusions
High hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with cIMT in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independent of hsCRP status.
doi:10.1161/ATVBAHA.111.223768
PMCID: PMC3130297  PMID: 21474823
obesity; hsCRP; high sensitivity C-reactive protein; subclinical atherosclerosis; coronary artery calcium; carotid intima-media thickness
23.  Evaluation of the relationship between circulating omentin-1 concentrations and components of the metabolic syndrome in adults without type 2 diabetes or cardiovascular disease 
Background
Dysregulation of omentin-1, a beneficial adipokine, is thought to play a role in the development of type 2 diabetes and cardiovascular disease. The objective of this study was to evaluate the relationship between circulating omentin-1 concentrations and components of the metabolic syndrome in adults without type 2 diabetes or cardiovascular disease, and to determine if sex differences influenced the observed relationships.
Methods
Fasting blood samples were obtained from 93 adults, ages 30–60 years, without type 2 diabetes and/or cardiovascular disease. Participants were classified as having the metabolic syndrome according to American Heart Association/National Heart, Lung and Blood Institute criteria. Plasma omentin-1 concentrations were measured using a commercially-available enzyme-linked immunosorbent assay, and relationships between plasma omentin-1 and components of the metabolic syndrome were assessed in the entire study cohort, by metabolic syndrome status, and by sex.
Results
On average, participants were 48 ± 8 years of age, 50.5% were women, 54.8% were Caucasian, and 70% had the metabolic syndrome. Plasma omentin-1 concentrations did not differ significantly between individuals with versus without the metabolic syndrome (145.7 ± 70 versus 157.4 ± 79.3 ng/ml, p = 0.50). However, men with the metabolic syndrome had significantly lower omentin-1 levels than men without the metabolic syndrome (129.9 ± 66 versus 186.3 ± 84.3 ng/ml, p = 0.03). Plasma omentin-1 concentrations were significantly correlated with HDL cholesterol in the entire study cohort (r = 0.26; p = 0.01), which was primarily driven by a correlation in men (r = 0.451, p = 0.002) and participants with the metabolic syndrome (r = 0.36; p = 0.003). Plasma omentin-1 concentrations did not differ significantly between men and women; however men with the metabolic syndrome had 20% lower plasma omentin-1 levels than women with the metabolic syndrome (p = 0.06).
Conclusion
These data demonstrate that circulating omentin-1 levels are associated with HDL cholesterol, primarily in men and in the presence of the metabolic syndrome. In addition, sex appears to influence the relationship between plasma omentin-1 concentrations and components of the metabolic syndrome. Additional studies are needed to explore sexual dimorphism in circulating omentin-1 levels, and the role of omentin-1 in the metabolic syndrome.
doi:10.1186/1758-5996-6-4
PMCID: PMC3901757  PMID: 24428913
Omentin-1; Metabolic syndrome; Adipokine; Sexual dimorphism
24.  High-Sensitivity C-Reactive Protein Levels and Metabolic Disorders in Obese and Overweight Children and Adolescents 
Objective: To compare high-sensitivity C-reactive protein (hsCRP) levels in obese and overweight children and adolescents to normal-weight individuals as well as to compare hsCRP levels in overweight children/adolescents with and without additional metabolic disorders such as metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD), and prediabetes.
Methods: 54 consecutive obese children and adolescents with a body mass index (BMI) ≥95th centile and 50 overweight children and adolescents with BMI values between 85th and 95th centiles were screened for MS, prediabetes and NAFLD. Serum hsCRP levels were measured in all the participants and in 40 age-matched normal-weight individuals (controls).
Results: HsCRP levels were significantly increased in obese and overweight subjects as compared to the control group, (0.61±1.08 vs. 0.05±0.18 mg/dL, p<0.001 and 0.33±0.25 vs. 0.05±0.18 mg/dL, p<0.001, respectively). HsCRP levels were similar between obese and overweight subjects (p=0.109). Obese and overweight children with NAFLD had significantly higher levels of hsCRP compared to their counterparts without NAFLD (0.78±1.4 vs. 0.34±0.31 mg/dL, p=0.016). The levels of hsCRP were comparable in the obese and overweight children/adolescents with and without MS and with or without prediabetes (0.95±1.66 vs. 0.35±0.27 mg/dL, p=0.096 and 0.43±0.34 vs. 0.53±1.0 mg/dL, p=0.589, respectively).
Conclusions: HsCRP is significantly elevated in children and adolescents with excess weight as compared to normal-weight individuals. In addition, children and adolescents with excessive weight and NAFLD show increased levels of hsCRP compared to their counterparts with normal liver.
Conflict of interest:None declared.
doi:10.4274/Jcrpe.789
PMCID: PMC3628392  PMID: 23367494
High-sensitivity C-reactive protein; obesity; metabolic syndrome; impaired glucose tolerance; liver disease
25.  C-Reactive Protein, High-Molecular-Weight Adiponectin and Development of Metabolic Syndrome in the Japanese General Population: A Longitudinal Cohort Study 
PLoS ONE  2013;8(9):e73430.
Aims
To clarify predictive values of C-reactive protein (CRP) and high-molecular-weight (HMW) adiponectin for development of metabolic syndrome.
Research Design and Methods
We conducted a prospective cohort study of Japanese workers who had participated in an annual health checkup in 2007 and 2011. A total of 750 subjects (558 men and 192 women, age 46±8 years) who had not met the criteria of metabolic syndrome and whose CRP and HMW-adiponectin levels had been measured in 2007 were enrolled in this study. Associations between CRP, HMW-adiponectin and development of metabolic syndrome after 4 years were assessed by logistic regression analysis and their predictive values were compared by receiver operating characteristic analysis.
Results
Among 750 subjects, 61 (8.1%) developed metabolic syndrome defined by modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria and 53 (7.1%) developed metabolic syndrome defined by Japan Society for the Study of Obesity (JASSO) in 2011. Although CRP and HMW-adiponectin were both significantly correlated with development of metabolic syndrome, multivariate logistic regression analysis revealed that HMW-adiponectin but not CRP was associated with metabolic syndrome independently of BMI or waist circumference. Adding these biomarkers to BMI or waist circumference did not improve the predictive value for metabolic syndrome.
Conclusion
Our findings indicate that the traditional markers of adiposity such as BMI or waist circumference remain superior markers for predicting metabolic syndrome compared to CRP, HMW-adiponectin, or the combination of both among the Japanese population.
doi:10.1371/journal.pone.0073430
PMCID: PMC3772031  PMID: 24069195

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