Using CRP to predict anastomotic leakage after open and laparoscopic colorectal surgery: is there a difference?


Original Article found : DOI: 10.1007/s00384-016-2547-0


C-reactive protein (CRP) has proven to be a useful adjunct in early diagnosis of anastomotic leak (AL) after colorectal surgery. It would be of considerable value to examine whether modality of surgery has influence upon postoperative CRP serum levels and their predictive value in the diagnosis of AL.


All patients undergoing elective colorectal surgery with anastomosis were enrolled into a prospective database between 2011 and 2014. AL was defined with strict operative and radiological criteria. Outcomes between open and laparoscopic resections were assessed statistically and Receiver Operating Characteristic (ROC) curve analysis performed.


Seven hundred twenty-seven patients with an intestinal anastomosis were identified including 468 laparoscopic procedures  


CRP levels are higher after open surgery compared with laparoscopic surgery, both with and without AL. AL generates a significant detectable increase in CRP within 2–4 days after surgery.

The association remained statistically significant after adjustment for characteristics such as lifestyle, medication use and cardiac function.

Many women get too little sleep, despite considerable evidence showing the importance of sleep to overall health. Now a new UC San Francisco study has discovered another reason why inadequate sleep may be harmful, especially to women and their hearts.

The study found that poor sleep, particularly waking too early, appears to play a significant role in raising unhealthy levels of inflammation among women with coronary heart disease. The elevated inflammation affected only women, not men, even when adjusted for medical, lifestyle and socio-demographic differences, the authors said.

The findings highlight potentially important gender differences and provide evidence that inflammation may serve as a key biological pathway through which poor sleep contributes to the progression of heart disease in women, the researchers reported.

The study will be published online on June 5, 2013 in the Journal of Psychiatric Research.
"Inflammation is a well-known predictor of cardiovascular health," said lead author Aric Prather, PhD, a clinical health psychologist and assistant professor of psychiatry at UCSF. "Now we have evidence that poor sleep appears to play a bigger role than we had previously thought in driving long-term increases in inflammation levels and may contribute to the negative consequences often associated with poor sleep."

Scientists have documented that poor sleep - generally defined as fewer than six hours a night - is a risk factor in a number of chronic health conditions, including coronary heart disease, and is associated with elevations in markers of inflammation.
The goal of the UCSF study, which began in 2000 and involved nearly 700 people, was to examine the association between self-reported sleep quality and changes in inflammation levels over five years in older people with stable coronary heart disease.

Participants were recruited from UCSF, Veterans Affairs Medical Centers in San Francisco and Palo Alto, and nine public health clinics in the Community Health Network of San Francisco.
The average age of the men was 66 compared to age 64 among women. On average, the women had higher systolic blood pressure, were more likely to be taking antidepressants, and less likely than men to have a history of taking beta-blockers, statins or other medications that treat blood pressure and other coronary-related ailments.

All participants had coronary heart disease, a condition marked by inflammatory activity.
Participants were asked when they first enrolled and five years later: "During the past month, how would you rate your overall sleep quality?" Their choices were "very good," "fairly good," "good," "fairly bad," or "very bad."

Biomarkers, assessed in the study were Interleukin-6, C-reactive protein, and Fibrinogen.
The researchers found that poor sleep quality was significantly associated with five-year increases in the biomarkers in women but not men: Women who reported very poor or fairly poor sleep quality showed a percent increase in markers 2.5 times that of men who said they slept poorly.

The association remained statistically significant after adjustment for characteristics such as lifestyle, medication use and cardiac function.
The women in the study were largely post-menopausal, so the researchers hypothesized that lower levels of estrogen could help explain the inflammatory activity associated with poor sleep.
"It is possible that testosterone, which is at higher levels in men, served to buffer the effects of poor subjective sleep quality," the authors wrote.
The study also measured other self-reported aspects such as difficulty falling asleep or staying asleep, waking frequently and waking too early. Among the findings:
  • Some 81 percent of the women reported that they frequently woke up (78 percent among men);
  • About half the women said they woke too early (nearly 41 percent among men);
  • A third of the women said they had difficulty falling asleep (31 percent among men).
The researchers note that men comprised the majority of the study subjects, but point out that their findings may actually underestimate the real effects given the limited sample size. They say that further investigation is needed to explain the gender-specific associations between poor sleep quality and markers of inflammation which could help clarify gender disparities in coronary heart disease.
The results could add to established evidence of the importance of assessing and treating sleep disturbances in high-risk populations, including those with heart disease, the authors said.
Source: University of California - San Francisco



Just a Biomarker of Inflammation or a Pathophysiological Player in Myocardial Function and Morphology?
bY: Rainer Schulz, Gerd Heusch

In response to inflammatory stress, C-reactive protein (CRP) is predominantly secreted from the liver and adipose tissue(s), and an independent relationship exists between different markers of overweight/obesity and elevated high sensitive (hs) CRP levels

Higher hsCRP levels predict incident myocardial infarction (MI), stroke, peripheral arterial disease, sudden cardiac death, and all-cause mortality in healthy individuals with no history of cardiovascular disease.1,2 hsCRP at admission predicts in-hospital outcome, and hsCRP at discharge predicts 6-month event rate and 30-day mortality (Global Utilization of Strategies To Open occluded arteries [GUSTO] IV) in patients with an acute coronary syndrome. Indeed, adding hsCRP levels to the Global Registry in Acute Coronary Events (GRACE) acute coronary syndrome risk model improves the prediction of 30-day mortality. In patients with non-ST-elevated MI, an increased hsCRP level predicts the death rate even at 20-month follow-up but does not predict stent-related complications.

The question of whether CRP, apart from serving as a biomarker, acts as a causal factor in vascular/coronary artery disease has been addressed in animal models, in which CRP was injected or genetically …


Cross-Sectional Associations of Albuminuria and C-Reactive Protein With Functional Disability in Older Adults With Diabetes

OBJECTIVE To examine the relationship between albuminuria, inflammation, and disability in older adults with diabetes.

RESEARCH DESIGN AND METHODS Data were from 1,729 adults (≥60 years) with diabetes in the National Health and Nutrition Examination Survey, 1999–2008. Disability in activities of daily living (ADL), instrumental activities of daily living (IADL), leisure and social activities (LSA), general physical activities (GPA), and lower-extremity mobility (LEM) was obtained from self-reports. Urinary albumin-to-creatinine ratio (UACR) (mg/g) was categorized into normal (UACR <30 mg/g), microalbuminuria (UACR 30–300 mg/g), and macroalbuminuria (UACR >300 mg/g). C-reactive protein (CRP) levels were quantified by latex-enhanced nephelometry.

RESULTS In the full-adjusted model, microalbuminuria was associated with disability in ADL, LSA, and LEM with corresponding odds ratios (ORs) (95% CIs) of 1.51 (1.16–1.98), 1.62 (1.23–2.14), and 1.34 (1.03–1.74), respectively, compared with participants without albuminuria. Macroalbuminuria was associated with disability in ADL, IADL, and LEM with corresponding ORs (95% CIs) of 1.94 (1.24–3.03), 1.93 (1.23–3.02), and 2.20 (1.38–3.49), respectively, compared with participants without albuminuria. Elevated CRP (>0.3 mg/dL) was associated with increased odds of disability in ADL and LEM, with corresponding ORs (95% CIs) of 1.28 (1.00–1.62) and 1.68 (1.34–2.11), respectively. Subjects with both albuminuria and elevated CRP had higher odds of disability than individuals with no albuminuria and normal CRP.

CONCLUSIONS Albuminuria and inflammation were independent correlates for disability among older adults with diabetes. There was an interaction of albuminuria and elevated CRP on disability, suggesting that the presence of subclinical inflammation may amplify the effect of albuminuria on disability in older adults living with diabetes.

Hsu-Ko Kuo, MD, MPH1, Soham Al Snih, MD, PHD1,2, Yong-Fang Kuo, PHD1,2,3 and Mukaila A. Raji, MD1,2


Changes in C-reactive protein from low-fat diet and/or physical activity in men and women with and without metabolic syndrome

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. The objective of the study was to assess CRP change (ΔCRP) with diet and/or PA in men and women with and without metabolic syndrome. Men (n = 149) and postmenopausal women (n = 125) with elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol were recruited into a 1-year randomized controlled trial.

Treatment groups were as follows: control, diet (reduced total fat, saturated fat, and cholesterol intake), PA (45-60 minutes at 60%-85% maximum heart rate), or 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. Change in CRP was compared between treatments, within sex and metabolic syndrome status, using analysis of covariance, including covariates for baseline CRP and body fat change. For women with metabolic syndrome (n = 39), ΔCRP was greater in diet vs control (-1.2 ± 0.4, P = .009), diet + PA vs control (-1.3 ± 0.4, P = .006), and diet + PA vs PA (-1.1 ± 0.4, P = .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 = .001).

Change in CRP 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). Low-fat diet may be the most effective treatment for reducing CRP in women with metabolic syndrome.

CAMHI Sarah M. (1) ; STEFANICK Marcia L. (2) ; RIDKER Paul M. (3) ; ROHM YOUNG Deborah (4) ;


Increased Consumption of Fatty and Lean Fish Reduces Serum C-Reactive Protein Concentrations but Not Inflammation Markers

Journal of Nutrition, doi:10.3945/jn.109.113472
Vol. 140, No. 2, 371-376, February 2010

Fish consumption is associated with a reduced colorectal cancer risk. A possible mechanism by which fish consumption could decrease colorectal cancer risk is by reducing inflammation. However, thus far, intervention studies investigating both systemic and local gut inflammation markers are lacking. Our objective in this study was to investigate the effects of fatty and lean fish consumption on inflammation markers in serum, feces, and gut. In an intervention study, participants were randomly allocated to receive dietary advice (DA) plus either 300 g of fatty fish (salmon) or 300 g of lean fish (cod) per week for 6 mo, or only DA.

Serum C-reactive protein (CRP) concentrations were measured pre- and postintervention (n = 161). In a subgroup (n = 52), we explored the effects of the fish intervention on fecal calprotectin and a wide range of cytokines and chemokines in fecal water and in colonic biopsies. Serum CRP concentrations were lower in the salmon (–0.5 mg/L; 95% CI –0.9, –0.2) and cod (–0.4 mg/L; 95% CI –0.7, 0.0) groups compared with the DA group. None of the inflammation markers in fecal water and colonic biopsies differed between the DA group and the groups that consumed extra fish.

In conclusion, increasing salmon or cod consumption for 6 mo resulted in lower concentrations of the systemic inflammation marker CRP. However, exploratory analysis of local markers of inflammation in the colon or feces did not reveal an effect of fish consumption.

Gerda K. Pot5, Anouk Geelen5, Gosia Majsak-Newman6, Linda J. Harvey6, Fokko M. Nagengast7, Ben J. M. Witteman8, Paul C. van de Meeberg9, Andrew R. Hart10,11, Gertjan Schaafsma1, Elizabeth K. Lund2, Ger T. Rijkers12,13 and Ellen Kampman5,*

5 Division of Human Nutrition, Wageningen University, Wageningen 6703 HD, The Netherlands; 6 Nutrition and Gastrointestinal Health, Institute of Food Research, Norwich NR4 7UA, UK; 7 UMC St Radboud, Nijmegen 6525 GA, The Netherlands; 8 Gelderse Vallei Hospital, Ede 6716 RP, The Netherlands; 9 Slingeland Hospital, Doetinchem 7000 AD, The Netherlands; 10 Norfolk and Norwich University Hospital NHS Trust, NR4 7UY, UK; 11 University of East Anglia, Norwich NR4 7TJ, UK; 12 Department of Surgery, University Medical Center Utrecht, Utrecht 3508 GA, The Netherlands; 13 Laboratory of Medical Microbiology and Immunology, St. Antonius Hospital, Nieuwegein 3430 EM, The Netherlands


C-Reactive Protein Inhibits Insulin Activation of Endothelial Nitric Oxide Synthase via the Immunoreceptor Tyrosine-Based Inhibition Motif of FcRIIB a

Keiji Tanigaki, Chieko Mineo, Ivan S. Yuhanna, Ken L. Chambliss, Michael J. Quon, Ezio Bonvini, Philip W. Shaul

Insulin promotes the cardiovascular protective functions of the endothelium including NO production by endothelial NO synthase (eNOS), which it stimulates via Akt kinase which phosphorylates eNOS Ser1179. C-reactive protein (CRP) is an acute-phase reactant that is positively correlated with cardiovascular disease risk in patients with type 2 diabetes.

We previously showed that CRP inhibits eNOS activation by insulin by blunting Ser1179 phosphorylation. We now elucidate the underlying molecular mechanisms. We first show in mice that CRP inhibits insulin-induced eNOS phosphorylation, indicating that these processes are operative in vivo. In endothelial cells we find that CRP attenuates insulin-induced Akt phosphorylation, and CRP antagonism of eNOS is negated by expression of constitutively active Akt; the inhibitory effect of CRP on Akt is also observed in vivo.

A requirement for the IgG receptor FcRIIB was demonstrated in vitro using blocking antibody, and reconstitution experiments with wild-type and mutant FcRIIB in NIH3T3IR cells revealed that these processes require the ITIM (immunoreceptor tyrosine-based inhibition motif) of the receptor. Furthermore, we find that endothelium express SHIP-1 (Src homology 2 domain–containing inositol 5'-phosphatase 1), that CRP induces SHIP-1 stimulatory phosphorylation in endothelium in culture and in vivo, and that SHIP-1 knockdown by small interfering RNA prevents CRP antagonism of insulin-induced eNOS activation.

Thus, CRP inhibits eNOS stimulation by insulin via FcRIIB and its ITIM, SHIP-1 activation, and resulting blunted activation of Akt. These findings provide mechanistic linkage among CRP, impaired insulin signaling in endothelium, and greater cardiovascular disease risk in type 2 diabetes.