Significant Reduction In C-reactive Protein Levels Research Articles

STAR VaS - Short Term Atorvastatin Regime for Vasculopathic Subjects: a randomized placebo-controlled trial evaluating perioperative atorvastatin therapy in noncardiac surgery

Evidence suggests that statins reduce cardiovascular complications in patients undergoing noncardiac surgery, although questions remain regarding the mechanism of benefit and the preferred dosing strategy. In this trial, we evaluated the perioperative effects on C-reactive protein (CRP) that resulted from starting atorvastatin within seven days of noncardiac surgery. The objective was to identify anti-inflammatory effects of atorvastatin prior to conducting a large randomized trial with clinical end points. In a single centre, parallel group, placebo-controlled trial, sixty high cardiac risk participants over age 45 yr undergoing noncardiac surgery were assigned randomly to one of three groups to receive atorvastatin 80 mg (A) and/or placebo (P). Group AA (n = 26) received atorvastatin seven days before surgery, the day of surgery, and for seven days post surgery. Group PA (n = 17) received placebo seven days before surgery, atorvastatin on the day of surgery, and atorvastatin for seven days post surgery. Group PP (n = 17) received placebo at all times. All participants, health care professionals, research assistants, and outcome adjudicators were masked to treatment allocation. Analyses were by intention to treat. The primary outcome was the C-reactive protein level at 48 hr. Fifty-six participants completed the 30-day follow-up. The mean (standard deviation) changes in CRP levels from baseline at 48 hr in Groups AA, PA, and PP were 141.0 (72.4), 153.5 (42.2), and 111.2 (84.6), respectively. The mean differences (95% confidence interval) at 48 hr for AA vs PA, AA vs PP, and PA vs PP were: -20.1 (-81.2 to 41.1), 22.7 (-31.7 to 77.2), and 42.8 (-20.0 to 105.7), respectively, adjusting for baseline CRP, type of procedure, presence of coronary artery disease, use of medications, and for multiple comparisons using Tukey's method. Administration of atorvastatin, initiated within seven days preoperatively, was not associated with clinically significant reductions in CRP levels.

Review of the Relationship between C-Reactive Protein and Exercise

C-reactive protein (CRP), an acute phase reactant, is associated with systemic inflammation. Many studies have demonstrated that CRP levels have important prognostic implications for patients. For example, individuals with elevated CRP levels have an increased risk of cardiovascular events. The JUPITER study showed that reducing CRP levels can mitigate this risk. Various trials have investigated the effect of lifestyle modifications on serum CRP levels. Specifically, the impact of different exercise-based protocols on CRP levels has been researched. This review article evaluates the response of CRP levels to aerobic-based, resistance-based, and combination exercise protocols. Furthermore, it examines the impact of such regimens in children, adults, and the elderly. No definitive answers exist regarding the relationship between exercise and CRP levels. Significant reductions in CRP levels were noted in 11 of 25 trials of aerobic-based regimens, two of five studies of combination protocols, and neither of two trials of resistance-based regimens. Similar findings were seen across all age groups. There were significant CRP reductions in nine of 18 adult studies, four of ten child studies, and one of three elderly studies. Mixed results reflect uncertainty about the ability of exercise to reduce inflammation. Various mechanisms, including increased protein synthesis and fat loss, have been proposed to explain the potential anti-inflammatory effects of exercise. While exercise-based regimens have produced inconsistent results, lifestyle modifications do appear to have significant anti-inflammatory effects. This was particularly evident in studies that utilized combined diet/exercise programs. Significant CRP reductions were seen in five of seven such trials. Interestingly, both studies with failed combination protocols achieved substantial CRP reductions in their diet-only groups. These findings suggest that weight loss is important in reducing inflammation. Additionally, they indicate that combined diet/exercise protocols should be part of any lifestyle intervention program. Further research will be needed to identify optimal regimens for achieving anti-inflammatory benefits.

C‐reactive protein evolution in obstructive sleep apnoea patients under CPAP therapy

C-reactive protein (CRP) is recognized as a potential factor implicated in atherogenesis and associated cardiovascular morbidity. The aim of our study was to assess the CRP evolution during 1-year follow-up period in obstructive sleep apnoea (OSA) patients under CPAP treatment. Five hundred and twenty-eight patients with newly diagnosed moderate to severe OSA were included. CRP was assessed before CPAP initiation and at the 3rd, 6th and 12th month of the follow-up period. Patients were divided into good and poor CPAP compliance groups. A significant reduction in CRP levels was observed after CPAP therapy (0·74±0·62mgdL(-1) vs. 0·31±0·29mgdL(-1) , P<0·001) in the whole patient group. The evolution of CRP values showed a gradual decrease at 3months with a steep decline at 6months, reaching a plateau after this time point. When the patients were divided into those with good and poor compliance with CPAP therapy, the above CRP evolution pattern was observed only in the former group. Good CPAP compliance results in a significant CRP reduction. To achieve the best positive impact on cardiovascular morbidity and mortality, a time period of at least 6months of CPAP use is required.

Beneficial effect of atorvastatin on erythropoietin responsiveness in maintenance haemodialysis patients

To evaluate the effect of atorvastatin on erythropoietin responsiveness and whether this effect is mediated by C-reactive protein (CRP) reduction in prevalent dyslipidemic, haemodialysis patients. We studied prospectively 33 stable, iron-repleted haemodialysis patients with low-density lipoprotein cholesterol (LDL) > or =2.58 mmol/L, who received 20 mg atorvastatin aiming to achieve the target of LDL <2.58 mmol/L, over a period of 9 months. Twenty-five patients completed the study, 15 men, with mean age 66.1 +/- 8.2 years. The duration of haemodialysis was 56.6 +/- 63.1 months and 5/25 patients were diabetics. Total serum cholesterol, triglycerides, high-density lipoprotein cholesterol, LDL, haemoglobin, albumin, intact parathyroid hormone, serum iron, ferritin, total iron binding capacity, CRP and weekly dose of erythropoietin/body weight/haemoglobin were analysed. Twenty of the 25 patients (80%) achieved the goal of LDL <2.58 mmol/L. There was a significant decrease in total cholesterol (5.77 +/- 0.88 to 4.16 +/- 0.96 mmol/L, P < 0.001) and LDL (3.59 +/- 0.77 to 1.94 +/- 0.77 mmol/L, P < 0.001). Haemoglobin increased from 121 +/- 11 to 126 +/- 7 g/L (P < 0.05), while weekly dose of erythropoietin/body weight/haemoglobin decreased significantly from 8.34 +/- 3.70 to 7.87 +/- 3.11 IU/kg per haemoglobin (P < 0.05). CRP decreased not significantly from 7.0 +/- 6.1 to 4.5 +/- 2.2 mg/L. Dyslipidemia of haemodialysis patients was treated safely and effectively with atorvastatin, but a fifth of the patients failed to achieve the therapeutic target. Statin therapy resulted in a significant increase of haemoglobin levels and improvement of erythropoietin responsiveness without a significant reduction in CRP levels, suggesting that the beneficial effect of statins on erythropoietin responsiveness may be driven by a mechanism other than CRP reduction.

Appropriate Use of Nasal Continuous Positive Airway Pressure Decreases Elevated C-Reactive Protein in Patients With Obstructive Sleep Apnea

C-reactive protein (CRP) is an important risk factor for cardiovascular disease. Furthermore, it has been reported that levels of CRP are increased in patients with obstructive sleep apnea (OSA). The aim of this study was to examine the effects of long-term therapy with nasal continuous positive airway pressure (nCPAP) on CRP levels and to investigate whether compliance with nCPAP therapy more effectively attenuated markers of systemic inflammation in patients with OSA. Fifty-five patients (mean [+/- SEM] age, 55 +/- 2 years; 44 male patients, 11 female patients) with newly diagnosed moderate-to-severe OSA (apnea-hypopnea index > 20 events/h) were studied before and after 6 months of nCPAP treatment. There was a significant reduction in CRP levels after nCPAP therapy (before nCPAP therapy, 0.23 +/- 0.03 mg/dL; after nCPAP therapy, 0.17 +/- 0.02 mg/dL; p < 0.01). Additionally, we divided these patients into two groups based on adherence to nCPAP therapy. A group of patients using nCPAP > 4 h/d and > 5 d/wk were designated as the good compliance group. The decrease in CRP concentration was significant (before nCPAP therapy, 0.23 +/- 0.04 mg/dL; after nCPAP therapy, 0.16 +/- 0.03 mg/dL; p < 0.05) in the good compliance group but not in the poor compliance group (before nCPAP therapy, 0.24 +/- 0.05 mg/dL; after nCPAP therapy, 0.20 +/- 0.05 mg/dL; p = 0.21). Furthermore, we divided those patients into a high CRP group (>/= 0.2 mg/dL) and a normal CRP group (< 0.2 mg/dL) before nCPAP therapy. The significant decrease in CRP levels in the good compliance group was evident only in those patients with an initially elevated CRP level (before nCPAP therapy, 0.48 +/- 0.08 mg/dL; after nCPAP therapy, 0.29 +/- 0.06 mg/dL; p < 0.05). Appropriate use of nCPAP in patients with OSA may be required to decrease elevated CRP levels, with possible implications for cardiovascular morbidity and mortality.

C-reactive protein in patients on chronic hemodialysis with different techniques and different membranes

In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and cardiovascular mortality. The aim of the present study was to evaluate CRP levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities and dialyzed with different membranes, at baseline and after 6 months. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 3 months and were prospectively followed in their initial dialytic modality for 6 months. Patients were treated with conventional bicarbonate dialysis (N=127) or hemodiafiltration (N=120). Patients treated with conventional bicarbonate dialysis were dialyzed with different membranes: Cuprophane (N=51), low-flux cellulose modified membrane (N=37) and synthetic membranes (N = 39). Hemodiafiltration was performed in post-dilution mode with polysulfone (N=66) and polyacrylonitrile (N = 54) membranes. Analysis of baseline CRP values in the clinically stable patients showed that an unexpectedly high proportion (47%) of the patients had CRP values higher than 5 mg/l (upper limit in normal subjects). The mean ± S.D. CRP values were significantly higher (P<0.05) in hemodiafiltration with infusion volumes<10 l per session (14.6±3.1 mg/l) than in standard hemodialysis (5.1±2.1 mg/l) and hemodiafiltration with infusion volumes>20 l per session (4.9±2.1 mg/l). These values did not significantly change after 6 months of follow-up. Concerning the membranes, the highest levels of CRP were observed in patients dialyzed with Cuprophane with a significant increase from 15.1±3.6 to 21.2±3.1 mg/l after 6 months (P<0.05); a significant reduction of CRP levels was observed in patients dialyzed with polysulfone in the same follow-up period (from 13.5±2.9 to 8.1±2.4 mg/l; P<0.05).The CRP increase following low volume HDF can be related to back-filtration of bacterial derived contaminants.; moreover, an important effect on CRP of the hemodialysis membrane is observed and new synthetic membranes can be used to decrease these levels.

Dialysis water treated by reverse osmosis decreases the levels of C-reactive protein in uremic patients

Atherosclerosis is a major complication of chronic renal failure. Microinflammation is involved in atherogenesis and is associated with uremia and dialysis. The role of dialysate water contamination in inducing inflammation has been debated. Our aim was to study inflammatory markers in patients on chronic dialysis, before and 3 to 6 months after switching the water purification system from deionization to reverse osmosis. Patients had demographic, clinical and nutritional information collected and blood drawn for determination of albumin, ferritin, C-reactive protein (CRP), interleukin-6, and tumor necrosis factor-alpha in both situations. Acceptable levels of water purity were less than 200 colony-forming units of bacteria and less than 1 ng/ml of endotoxin. Sixteen patients died. They had higher median CRP (26.6 vs 11.2 mg/dl, P = 0.007) and lower median albumin levels (3.1 vs 3.9 g/l, P < 0.05) compared to the 31 survivors. Eight patients were excluded because of obvious inflammatory conditions. From the 23 remaining patients (mean age +/- SD: 51.3 +/- 13.9 years), 18 had a decrease in CRP after the water treatment system was changed. Overall, median CRP was lower with reverse osmosis than with deionization (13.2 vs 4.5 mg/l, P = 0.022, N = 23). There was no difference in albumin, cytokines, subjective global evaluation, or clinical and biochemical parameters. In conclusion, uremic patients presented a clinically significant reduction in CRP levels when dialysate water purification system switched from deionization to reverse osmosis. It is possible that better water treatments induce less inflammation and eventually less atherosclerosis in hemodialysis patients.

HMG-CoA reductase inhibitors for lowering elevated levels of C-reactive protein

Clinical trials evaluating the effectiveness of therapy with hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors for reducing elevated C-reactive protein (CRP) levels and associated coronary events are reviewed. Atherosclerotic plaque growth may be attenuated with therapy aimed at minimizing inflammation. Because increased levels of CRP have been associated with arterial-wall inflammation, statins can prevent ischemia by both inhibiting deposition of lipids and decreasing inflammation. Evaluation of recent clinical trials, including WOSCOPS, PRINCE, AFCAPS/ TexCAPS, MIRACL, CURVES, REVERSAL, and JUPITER, demonstrated the correlation of statin therapy with decreased levels of CRP. WOSCOPS found that patients with CRP values of > 4.59 mg/L at baseline were at the highest risk of coronary events. The PRINCE trial evaluated the antiinflammatory effects of pravastatin and found a mean 16.9% reduction in CRP levels after 24 weeks of therapy. AFCAPS/TexCAPS researchers found that lovastatin provded a 14.8% reduction in the median levels of CRP (p < 0.001). The MIRACL study showed that atorvastatin reduced CRP levels by 83% (p < 0.001). Researchers in the CURVES study found a significant reduction in CRP levels with pravastatin, simvastatin, and atorvastatin compared with baseline (p < 0.025). Results of the REVERSAL study linked atorvastatin with a 36.4% decrease in CRP levels, while pravastatin was associated with a 5.2% decrease (p < 0.0001). JUPITER is ongoing and will determine whether long-term use of rosuvastatin can reduce the rate of coronary events. The lowering of elevated CRP levels by statins may reduce the risk of coronary events independently of the effect of statins on lipid levels.

Elevated concentrations of C-reactive protein in subjects with Type 2 diabetes mellitus are moderately influenced by glycemic control

The aim of this study was to establish whether glycemic control results in decrease of C-reactive protein (CRP) in Type 2 diabetic subjects. Newly diagnosed Type 2 diabetic subjects were recruited and followed-up by 6-month intensive medical management. All the participants were carefully interviewed, clinically examined, and laboratory tested to exclude conditions likely to provoke an inflammatory response, which was an exclusion criterium. CRP was measured by automated microparticle enzyme immunoassay (IMx, Abbott Laboratories, USA). Two-hundred and forty-eight patients were included in the analysis of data. At baseline, average CRP levels were of 9.6 +/- 6.2 mg/l. Only 14 (5.7%) patients showed a fasting glucose equal or lower than 6.1 mmo/l (5.6 +/- 0.4 mmo/l); of them, 6 (42.8%) had elevated CRP levels (8.8 +/- 6.7 mg/l). The fasting glucose in the 234 (94.3%) non-controlled subjects was 13.1 +/- 4.8 mmol/l; of them 179 (76.5%) subjects showed elevated CRP levels (10.9 +/- 6.5 mg/I). At the end of the 6-month follow-up, the average fasting glucose and HbA1c in the overall group decreased from 12.5 +/- 5.0 to 9.0 +/- 1.6 mmol/l, p < 0.00001, and 13.0 +/- 4.9 to 8.9 +/- 2.9%, p < 0.00001, which resulted in a significant reduction of CRP levels (9.6 +/- 6.2 to 6.3 +/- 3.0 mg/l, p < 0.00001). Seventy-one (28.6%) patients reached glycemic control; however, only 29 (40.8%) of them reduced the CRP levels to 3 mg/l or less (1.3 +/- 1.9 mg/l), and the remaining 42 controlled patients maintained high CRP concentration (4.2 +/- 1.2 mg/I), p < 0.00001. Concentration of CRP is moderately influenced by glycemic control in the Type 2 diabetic subjects.