Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?

Yudkin, John; Kumari, Meena; Humphries, Steve E.; Mohamed‐Ali, Vidya

doi:10.1016/s0021-9150(99)00463-3

Cited by 1,604 publications

(1,145 citation statements)

References 42 publications

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“…This lower predictive accuracy of CRP in obese participants may be affected by the close correlation between CRP and adiposity. Interleukin 6 is the principle cytokine that stimulates CRP release from the liver, and up to one‐third of circulating interleukin 6 is released from adipose tissue 39, 40. Despite these data suggesting a weakened association in obese versus nonobese persons, our data showed that obese participants with elevated levels of CRP have a higher risk of future CHD than obese participants with CRP levels <2 mg/dL, suggesting that CRP adds prognostic information for the obese population, although the presence or absence of cardiometabolic risk factors may influence the predictive value of CRP in abdominally obese persons (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

C‐Reactive Protein Identifies Low‐Risk Metabolically Healthy Obese Persons: The European Prospective Investigation of Cancer–Norfolk Prospective Population Study

Wijk

Boekholdt

Arsenault

et al. 2016

JAHA

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BackgroundConflicting data exist about the cardiovascular risk of metabolically healthy obese persons. The prognostic value of C‐reactive protein (CRP) in this intriguing group is unknown. We assessed the association between CRP levels and the risk of coronary heart disease (CHD) in metabolically healthy persons with abdominal obesity.Methods and ResultsIn the European Prospective Investigation of Cancer–Norfolk prospective cohort, CRP levels and information on metabolic syndrome criteria were available for 7279 participants, of whom 825 (11%) developed CHD during a follow‐up period of 10.9±1.8 years. There was a trend toward a higher multivariable‐adjusted hazard ratio for CHD in metabolically healthy obese participants with CRP levels >2 mg/L compared with <2 mg/L (hazard ratio 1.59, 95% CI 0.97–2.62, P=0.066). Metabolically unhealthy obese participants had significantly higher CHD risk compared with metabolically healthy obese participants with CRP levels <2 mg/L (hazard ratio 1.88, 95% CI 1.20–2.94, P=0.006). Most important, we found that the risk of CHD among metabolically healthy obese persons with CRP levels <2 mg/L was comparable to that of metabolically healthy nonobese persons (hazard ratio 0.91, 95% CI 0.60–1.39, P=0.674).ConclusionsAmong metabolically healthy obese persons, low CRP levels were associated with a CHD risk comparable to that of metabolically healthy nonobese persons. CRP appears to be an easy and widely available method for identifying a low‐risk subpopulation among metabolically healthy obese persons.

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Section: Discussionmentioning

confidence: 99%

C‐Reactive Protein Identifies Low‐Risk Metabolically Healthy Obese Persons: The European Prospective Investigation of Cancer–Norfolk Prospective Population Study

Wijk

Boekholdt

Arsenault

et al. 2016

JAHA

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“…The circulating concentrations are low in healthy people without acute illness and with the high-sensitivity techniques available today, even low levels are predictive for future cardiovascular events including myocardial infarct and stroke. 2,[17][18][19] As mentioned, there are diverging reports regarding the roles of obesity and insulin resistance in influencing the production of CRP. The circulating levels are elevated in obesity, 8,20 particularly when adipose tissue is centrally deposited, 2 as indicated by a high waist-hip ratio.…”

Section: Discussionmentioning

confidence: 99%

“…31 The glycoprotein IL-6 is secreted from numerous cell types, including activated macrophages, monocytes, endothelium, 32 and adipocytes, from which approximately one-third of the serum concentration is derived. 7 IL-6 stimulates the production of acutephase proteins in the liver, 18 as well as having other pro-and anti-inflammatory roles. 33 The levels increase with adiposity, in particular abdominal, 7,34 and omental fat cells secrete 2-3 times more IL-6 than subcutaneous adipocytes.…”

Section: Discussionmentioning

confidence: 99%

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects

et al. 2005

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OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk of cardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent the insulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypass surgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies on the regulation of inflammatory markers. DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects. SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m 2 were studied prior to and 6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery. MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well as markers of glucose and lipid metabolism. RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRP correlated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, when corrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m 2 and lowered CRP, SAA and IL-6 levels by 82, 57 and 50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the change in body weight (r ¼ À0.36, P ¼ 0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA o 4 (insulin sensitive) and HOMA49 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended to parallel the changes in CRP, but were less informative. CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers and improves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulinresistant patients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather than energy supply.

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“…Yet, a relationship seems likely because the products of chronic inflammation are some of the major determinants of WBV. Elevations in interleukin-6, a cytokine characteristic of SLE (23)(24)(25), are associated with higher blood viscosity in the general population and are thought to drive the hepatic production of acute-phase reactants (9,26,27). Several small studies have found that patients with SLE have elevated plasma or blood viscosity compared with healthy controls (28 -30).…”

Section: Introductionmentioning

confidence: 99%

Whole blood viscosity and arterial thrombotic events in patients with systemic lupus erythematosus

Booth¹,

Chohan²,

Curran³

et al. 2007

Arthritis & Rheumatism

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Objective. To determine if whole blood viscosity (WBV), a rheologic variable contributing to risk of myocardial infarction and stroke in the general population, is elevated in patients with systemic lupus erythematosus (SLE), particularly SLE patients with a history of thrombotic or atherothrombotic events. Because the high rates of arterial and venous thrombosis in lupus cannot be explained by traditional risk factors, elevated WBV may be an easily measurable nontraditional risk factor to identify SLE patients at high risk for thrombotic events. Methods. Sixty SLE patients (30 with a history of a thrombotic event) and 20 matched controls were recruited into the study. The thrombosis group was further subdivided into an arterial thrombosis group (n ‫؍‬ 17). WBV values were determined at 9 different shear rates (1, 2, 5, 10, 50, 100, 150, 300, and 1,000 seconds ؊1 ). WBV was then compared between groups by repeated-measures analysis of variance. Results. SLE patients with a history of arterial events had significantly elevated WBV relative to either controls (P ‫؍‬ 0.022) or SLE patients without arterial events (P ‫؍‬ 0.014). WBV in the total SLE group did not differ from controls. Differences in WBV were most prominent at lower shear rates (1, 2, 5, 10, 50, and 100 seconds ؊1 ). Anticoagulation, prednisone dose, and antiphospholipid antibodies did not significantly impact WBV. Conclusion. Our study demonstrated that WBV is selectively elevated in patients with SLE with a history of arterial events. Although this association is striking, longitudinal studies are needed to assess the positive predictive value of WBV for atherothrombotic events in SLE.

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Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?

Cited by 1,604 publications

References 42 publications

C‐Reactive Protein Identifies Low‐Risk Metabolically Healthy Obese Persons: The European Prospective Investigation of Cancer–Norfolk Prospective Population Study

C‐Reactive Protein Identifies Low‐Risk Metabolically Healthy Obese Persons: The European Prospective Investigation of Cancer–Norfolk Prospective Population Study

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects

Whole blood viscosity and arterial thrombotic events in patients with systemic lupus erythematosus

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