Changes In High-sensitivity C-reactive Protein Research Articles

Behavioural modification of the cholinergic anti‐inflammatory response to C‐reactive protein in patients with hypertension

A central hypothesis of the cholinergic anti-inflammatory reflex model is that innate immune activity is inhibited by the efferent vagus. We evaluated whether changes in markers of tonic or reflex vagal heart rate modulation following behavioural intervention were associated inversely with changes in high-sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6). Subjects diagnosed with hypertension (n = 45, age 35-64 years, 53% women) were randomized to an 8-week protocol of behavioural neurocardiac training (with heart rate variability biofeedback) or autogenic relaxation. Assessments before and after intervention included pro-inflammatory factors (hsCRP, IL-6), markers of vagal heart rate modulation [RR high-frequency (HF) power within 0.15-0.40 Hz, baroreflex sensitivity and RR interval], conventional measures of lipoprotein cholesterol and 24-h ambulatory systolic and diastolic blood pressure. Changes in hsCRP and IL-6 were not associated with changes in lipoprotein cholesterol or blood pressure. After adjusting for anti-inflammatory drugs and confounding factors, changes in hsCRP related inversely to changes in HF power (β = -0.25±0.1, P = 0.02), baroreflex sensitivity (β = -0.33±0.7, P = 0.04) and RR interval (β = -0.001 ± 0.0004, P = 0.02). Statistically significant relationships were not observed for IL-6. Changes in hsCRP were consistent with the inhibitory effect of increased vagal efferent activity on pro-inflammatory factors predicted by the cholinergic anti-inflammatory reflex model. Clinical trials for patients with cardiovascular dysfunction are warranted to assess whether behavioural interventions can contribute independently to the chronic regulation of inflammatory activity and to improved clinical outcomes.

Adaptive servo-ventilation improves renal function in patients with heart failure

Impaired cardiac function and sleep-disordered breathing (SDB) are associated with progression of chronic kidney disease (CKD) in heart failure (HF) patients. Adaptive servo-ventilation (ASV) therapy improves cardiac function in HF patients regardless of the SDB severity through hemodynamic support and prevention of repetitive hypoxic stress. This study was designed to test the hypothesis that ASV therapy improves renal function in HF patients with SDB. Of 59 consecutively enrolled HF patients, 43 with moderate-to-severe SDB underwent ASV therapy. HF patients were divided into the ASV-treated group (n = 27) and the non-ASV-treated group (n = 16). Estimated glomerular filtration rate (eGFR), echocardiographic parameters, and inflammatory biomarkers were measured before and 12 months after ASV initiation. Improvement in the eGFR was found in the ASV-treated group, but not in the non-ASV-treated group. There was a positive correlation between the increases in eGFR and left ventricular ejection fraction (r = 0.488, p = 0.001). The changes in high-sensitivity C-reactive protein were negatively correlated with change in the eGFR (r = -0.416, p = 0.006). ASV therapy could improve renal dysfunction in HF patients through hemodynamic support. Additionally, prevention of SDB with the use of ASV therapy could exert anti-inflammatory effects, which could contribute to the improvement of renal function in HF patients.

High-sensitivity C-reactive protein and clopidogrel treatment in patients at high risk of cardiovascular events: a substudy from the CHARISMA trial

AimsThis study investigated the effect of clopidogrel treatment on inflammatory activity as evidenced by the change in high-sensitivity C-reactive protein (hsCRP) levels in a broad population of patients who are...

Severity of Obstructive Sleep Apnea Syndrome and High‐Sensitivity C‐Reactive Protein Reduced After Relocation Pharyngoplasty

To report improvement of obstructive sleep apnea syndrome (OSAS) and changes of high-sensitivity C-reactive protein (hs-CRP) concentrations after relocation pharyngoplasty (RP), a high variant of uvulopalatopharyngoplasty. Prospective comparative study. Tertiary referral center. Thirty consecutive OSAS patients without a preexisting diagnosis of cardiovascular disease who underwent RP were assessed for body mass index (BMI), Epworth Sleepiness Scale (ESS), sleep apnea-hypopnea index (AHI), and serum levels of hs-CRP at baseline and 6 months postoperatively. Of the subjects, the mean values of age, BMI, ESS, AHI, and hs-CRP were 39.5 ± 7.0 years, 27.5 ± 4.5 kg/m(2), 10.8 ± 4.2, 46.2 ± 22.9 events/hour, and 2.06 ± 1.78 mg/L, respectively. After 6 months postoperatively, RP reduced the ESS (Δ = -4.3 ± 4.5, P < .001) and AHI (Δ = -28.3 ± 21.1, P < .001) and levels of hs-CRP (Δ = -0.67 ± 1.36, P = .012) significantly, whereas BMI measurements were indifferent (Δ = -0.42 ± 1.28, P = .073). Moreover, the changes of AHI and hs-CRP were particularly remarkable in patients with very severe OSAS (AHI ≥60). Although many OSAS patients remain in the mild-moderate category, equivalent improvements in excessive daytime sleepiness and reductions of hs-CRP concentrations indicate that reduction of AHI is not all that matters after RP.

The sPLA 2 Inhibition to Decrease Enzyme Release After Percutaneous Coronary Intervention (SPIDER-PCI) Trial

Secretory phospholipase A(2) (sPLA(2)) may play a role in myonecrosis after elective percutaneous coronary intervention (PCI). Inhibition of this enzyme may have a beneficial effect. The central hypothesis of this study was that treatment with varespladib, a small-molecule inhibitor of sPLA(2) would reduce postprocedural release of cardiac biomarkers after elective percutaneous coronary intervention. Between October 2007 and June 2009, 144 stable patients were randomized in a phase II trial to receive varespladib 500 mg PO BID or placebo 3 to 5 days before and for 5 days after elective percutaneous coronary intervention. The primary end point was elevation of troponin I or creatine kinase-MB above the upper limit of normal at 6 to 8 or 18 to 24 hours after percutaneous coronary intervention. Mean age was 63±10 and 64±10 years, with 38% and 42% with diabetes mellitus and 29% and 28% with prior myocardial infarction for the varespladib and placebo groups, respectively. The primary end point occurred in 75% of varespladib and 63% of placebo patients (P=0.14). Troponin I 3 times the upper limit of normal was observed in 57% and 50% (P=0.39) and creatine kinase-MB 2 times the upper limit of normal in 14% and 3% (P=0.018). Median (first and third quartiles) change in high-sensitivity C-reactive protein in these 2 groups was 0.65 mg/L (-0.18 and 1.48) and 0.70 mg/L (0.00 and 1.50) at 18 to 24 hours (P=0.81) and 0.20 mg/L (-0.70 and 1.40) and 0.60 mg/L (-0.12 and 1.72) at 3 to 5 days (P=0.23), whereas change in sPLA(2) activity at 3 to 5 days in a subset was -2.85 ng/ml (-3.40 and -1.85) and 0.25 ng/ml (-0.20 and 0.85) (P<0.001). Inhibition of sPLA(2) by varespladib administered for 3 to 5 days before the procedure does not reduce periprocedural myonecrosis associated with elective percutaneous coronary intervention. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00533039.

Dynamic Observation on High-sensitivity C-reactive Protein in Acute Myocardial Infarction After Percutaneous Coronary Intervention

Objective To observe the dynamic change of high-sensitivity C-reactive protein(hs-CRP)after percutaneous coronary intervention (PCI)within 6 hours after attack of acute myocardial infarction(AMI).Methods The hs-CRP levels in serum was detected in 60 AMI patients within 6 hours after attack with immunoturbidimetry before PCI, at the opint of operation ,6 h, 12 h ,24 h ,72 h .and 7 d after PCI. 30 healthy examinationer were chosen as normal control. The two groups were compared with statistics. Results The hs-CRP levels were increased gradually with time in AMI patients after PCI. The peak value was at 72 h after PCI and recovered to the level of 12 h after PCI at 7 d after PCI. The hs-CRP levels at 6 h,12 h,24 h,72 h and 7 d were significantly higher than those in the normal group (P ＜ 0. 05) , and hs-CRP at 72 h were significant higher than those at other opints(P ＜ 0. 05). Conclusion The hs-CRP levels in short time after attack of AMI with PCI presented an dynamic changing and it can be one of the indexes on curative effect on AMI with PCI. Key words: Acute Myocardial Infarction; High-sensitivity C-reactive Protein; Percutaneous Coronary Intervention

The Effect of Lipid and Inflammatory Profiles on the Morphological Changes of Lipid-Rich Plaques in Patients With Non–ST-Segment Elevated Acute Coronary Syndrome: Follow-Up Study by Optical Coherence Tomography and Intravascular Ultrasound

The aim of this study was to determine the relationship between the morphological changes of nonculprit lipid-rich plaques and several clinical profiles in patients with non-ST-segment elevated acute coronary syndrome (NSTEACS). Identification of coronary lesion with morphological characteristics of rupture-prone plaques is still difficult. Eighty-two consecutive patients with NSTEACS who underwent percutaneous coronary intervention were enrolled. The changes in total atheroma volume (TAV) of residual nonculprit lipid-rich plaques and the changes in the corresponding fibrous cap thickness (FCT) were assessed by intravascular ultrasound and optical coherence tomography, respectively, at baseline and after 9 months. The percentage changes in TAV (mm(3)) of lipid-rich plaques and in the corresponding FCT (microm) over the 9-month follow-up period were 3.1 +/- 11% and 15 +/- 17%, respectively. There was no significant correlation between the changes in TAV and those in FCT. The change in TAV showed a significant correlation with reduction of the low-density lipoprotein/high-density lipoprotein (LDL/HDL) ratio (r = 0.42, p < 0.01). In contrast, the change in FCT showed no correlation with LDL/HDL ratio but had a significant positive correlation with changes in high-sensitivity C-reactive protein (r = 0.44, p < 0.01). Furthermore, in multivariate logistic analysis, statin use was an independent predictor of changes in well-stabilized plaques that showed both TAV reduction and FCT increase. The changes in TAV and FCT of coronary plaques over a 9-month observation period were related to 2 different independent factors (i.e., reduction of LDL-cholesterol and high-sensitivity C-reactive protein, respectively). Furthermore, lipid-lowering therapy with statin has the potential to stabilize these parameters by both plaque reduction and FCT.

Changes in High-Sensitivity C-Reactive Protein in Serum and Exhaled Breath Condensate after Intensive Exercise in Patients with Allergic Asthma

Background: Exercise-induced bronchoconstriction (EIB) in asthmatics depends on the presence of allergic inflammation. This study was performed to assess the possible association of EIB with low-grade systemic inflammation, whose presence was revealed in asthmatic patients. Methods: The study was conducted in a group of 24 asthmatics (14 with EIB, 10 without EIB) and 8 healthy volunteers. Changes in serum and exhaled breath condensate (EBC) high-sensitivity C-reactive protein (hs-CRP) levels induced by intensive exercise were determined. Moreover, the possible correlation of these measurements with the results of other tests used in the diagnosis of asthma as well as laboratory tests commonly associated with asthma were investigated. Results: In asthmatic patients with EIB, a statistically significant increase in hs-CRP levels both in serum and EBC after an exercise test was observed. Twenty-four hours after the exercise test in the group of asthmatics with EIB, a statistically significant increase in exhaled nitric oxide (F_ENO), serum eosinophil cationic protein (ECP) concentrations and bronchial hyperreactivity to histamine was revealed. A statistically significant correlation between the maximum increase in hs-CRP levels both in serum and EBC after exercise and either baseline F_ENO and an increase in serum ECP or F_ENO 24 h after exercise in the group of asthmatics with EIB was revealed. Conclusions: We show that, as a result of intensive exercise leading to bronchoconstriction, an increase in serum and EBC hs-CRP occurs. Our observations could suggest that in asthmatic patients, as a consequence of exercise-induced bronchoconstriction, an intensification of low-grade systemic inflammation can be observed.

Fat redistribution preferentially reflects the anti-inflammatory benefits of pioglitazone treatment

Thiazoledinedione is known to have an anti-inflammatory effect besides a hypoglycemic effect. We investigated changes in high-sensitivity C-reactive protein (hsCRP), a proinflammatory marker, after pioglitazone treatment in association with the resulting changes in various metabolic and anthropometric parameters. A total of 93 type 2 diabetes mellitus patients (47 men and 46 women; mean age, 50.0 ± 10.8 years) who were being treated with a stable dose of sulfonylurea or metformin were enrolled in the study. Pioglitazone (15 mg/d) was added to their treatment regimen for 12 weeks, and metabolic and anthropometric measurements were taken before and after pioglitazone treatment. Pioglitazone treatment for 12 weeks decreased serum hsCRP levels (0.83 [1.14] to 0.52 [0.82] mg/L, P < .001) and improved glycemic control (fasting glucose, P < .001; glycosylated hemoglobin, P < .001) and lipid profiles (triglyceride, P = .016; high-density lipoprotein cholesterol, P < .001). Between responders and nonresponders to the hsCRP-lowering effect of pioglitazone, there were significant differences in baseline hsCRP levels and changes in the postprandial glucose and the ratio of visceral fat thickness (VFT) to subcutaneous fat thickness (SFT) (P = .004, .011, and .001, respectively). The percentage change in hsCRP levels after treatment was inversely correlated with baseline hsCRP levels (r = −0.497, P < .001) and directly correlated with the change in postprandial glucose (r = 0.251, P = .021), VFT (r = 0.246, P = .030), and VFT/SFT ratio (r = 0.276, P = .015). Logistic regression analysis revealed that the hsCRP-lowering effect of pioglitazone was affected by baseline hsCRP levels (odds ratio [OR] = 7.929, P = .007) as well as changes in postprandial 2-hour glucose (OR = 0.716, P = .025) and VFT/SFT ratio (OR = 0.055, P = .009). In conclusion, treatment with pioglitazone produced an anti-inflammatory effect, decreasing serum hsCRP levels; and a decrease in the VFT/SFT ratio was independently and most strongly associated with the hsCRP-decreasing effect. These results suggest that abdominal fat redistribution preferentially reflects the anti-inflammatory benefits of pioglitazone treatment.

Long-Term Safety and Efficacy of Triple Combination Ezetimibe/Simvastatin Plus Extended-Release Niacin in Patients With Hyperlipidemia

The safety and efficacy of combination ezetimibe/simvastatin (E/S) plus extended-release niacin was assessed in 942 patients with type IIa/IIb hyperlipidemia for 64 weeks in a randomized, double-blind study. Patients received E/S (10/20 mg) plus niacin (to 2 g) or E/S (10/20 mg) for 64 weeks, or niacin (to 2 g) for 24 weeks and then E/S (10/20 mg) plus niacin (2 g) or E/S (10/20 mg) for an additional 40 weeks. The primary end point, the safety of E/S plus niacin, included prespecified adverse events (ie, liver, muscle, discontinuations due to flushing, gallbladder-related, cholecystectomy, fasting glucose changes, new-onset diabetes). The secondary end points included the percentage of change from baseline in high-density lipoprotein (HDL) cholesterol, triglycerides, non-HDL cholesterol, and low-density lipoprotein cholesterol, other lipids, lipoprotein ratios and high-sensitivity C-reactive protein. The anticipated niacin-associated flushing led to a greater rate of study discontinuations with the E/S plus niacin regimen than with E/S alone (0.7%, p <0.001). The rate of liver and muscle adverse events was low (<1%) in both groups. Four patients had gallbladder-related adverse events; 1 patient in the E/S and 1 in the E/S plus niacin group underwent cholecystectomy. The occurrence of new-onset diabetes was 3.1% for the E/S and 4.9% for the E/S plus niacin group. The fasting glucose levels increased to greater than baseline during the first 12 weeks (E/S, 3.2 mg/dl; E/S plus niacin, 7.7 mg/dl) and gradually decreased to pretreatment levels by 64 weeks in both groups. E/S plus niacin significantly improved HDL cholesterol, triglycerides, non-HDL cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and A-I, and lipoprotein ratios compared with E/S (p <or=0.004). The changes in high-sensitivity C-reactive protein were comparable for both groups. In conclusion, the combination of E/S plus niacin was generally well tolerated, aside from niacin-associated flushing, and was significantly superior to E/S alone in improving several lipoprotein parameters during a 64-week trial in patients with hyperlipidemia. E/S plus niacin provided a broad, lipid-altering therapeutic option for these patients, even in the presence of diabetes with glucose monitoring.

Variation of Fasting Serum C-Peptide Level After Admission in Japanese Patients with Type 2 Diabetes Mellitus

The aim of this study was to evaluate the variation of fasting serum C-peptide (S-CPR) levels, as a marker for endogenous insulin secretion after admission in Japanese patients with type 2 diabetes mellitus (T2DM). S-CPR levels together with other metabolic factors were measured in 234 T2DM patients twice: at the beginning and at the end of admission for the control of blood sugar levels. As a result, patients were classified into two groups according to their changes of S-CPR (DeltaS-CPR), which consisted of patients whose S-CPR levels had decreased (group D) and increased (group I) after admission. Patients allocated to group I showed younger age, shorter duration of diabetes, and lower basal S-CPR level compared to group D. Conversely, patients in group D showed higher levels of high-sensitivity C-reactive protein (HS-CRP) and brachial-ankle pulse wave velocity compared to group I, suggesting patients in this group are prone to atherosclerosis. DeltaS-CPR was positively correlated with the change of body mass index, waist circumference, and triglycerides in group D. On the other hand, DeltaS-CPR was negatively correlated with the change of HS-CRP in group I, indicating residual beta-cell function could be recovered by the amelioration of inflammatory status in pancreatic islets. It is plausible that Japanese T2DM patients could be classified according to the variation of S-CPR after admission. Evaluation of basal and the variation of S-CPR could provide advantageous information for the management of diabetes mellitus or related disorders.

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.

Abstract 2508: Different Early Changes of Coronary Plaque Composition according to Plaque Stability following Statin Initiation in Acute Coronary Syndromes: Classification and Analysis with IntraVascular UltraSound-Virtual Histology

Previous trials using intravascular ultrasound(IVUS) have demonstrated that the lipid lowering therapy with statin decrease plaque volume and increase plaque echogenecity in patients with coronary artery disease. The aim of this study was to demonstrate the early effect of statin on plaque composition by IVUS-Virtual Histology(VH) during half a year after coronary event. Thirty six patients with ACS were prospectively enrolled. One target segment was determined in a non-PCI site (&gt;5 mm proximal or distal to the PCI site) with a reproducible index side branch or from the ostium of target vessel. We classified and analyzed the target plaques into two types according to plaque stability: thin-cap fibroatheroma (TCFA, n=10); and non TCFA(n=26) In 6 months after statin therapy, no change was demonstrated in mean percentage of the lipid core(16.9 ± 8.5% to 16.2 ± 10.1%, p=0.67), whereas plaque volume and LDL-cholesterol level were significantly reduced. There was a significant reduction of lipid core percentage in the TCFA type (21.1 ± 7.6 % to 10.9 ± 5.8 %, p= 0.001), but not in the non-TCFA type. The percentage change in lipid core showed a significant relation with the change in high-sensitivity C-reactive protein(r=0.4, p=0.03). Changes in LDL cholesterol and lipid core demonstrated no significant associations. A clear reduction of lipid core was observed only in the TCFA type which suggest that the changes of plaque composition following statin therapy might occur earlier in vulnerable plaque than stable plaque and appears related to their anti-inflammatory effects.

Efficacy and Safety of Ezetimibe Added on to Atorvastatin (40 mg) Compared With Uptitration of Atorvastatin (to 80 mg) in Hypercholesterolemic Patients at High Risk of Coronary Heart Disease

The percentage of change from baseline in low-density lipoprotein (LDL) cholesterol after the addition of ezetimibe 10 mg to atorvastatin 40 mg was compared with uptitration to atorvastatin 80 mg. In this multicenter, double-blind, parallel-group study, adult hypercholesterolemic patients using atorvastatin 40 mg/day were randomly assigned to atorvastatin 40 mg plus ezetimibe 10 mg or uptitration to atorvastatin 80 mg. After 6 weeks of treatment, compared with atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe significantly reduced the primary end point of LDL cholesterol by -27% versus atorvastatin 80 mg by -11% (p <0.001), as well as significantly reduced non-high-density lipoprotein cholesterol, apolipoprotein B, total cholesterol, and triglycerides significantly more than atorvastatin 80 mg (all p <0.001). Percentages of change in high-sensitivity C-reactive protein, high-density lipoprotein cholesterol, and apolipoprotein A-I were similar between groups. Significantly more patients treated with atorvastatin 40 mg plus ezetimibe reached LDL cholesterol <70 mg/dl versus patients treated with atorvastatin 80 mg (74% vs 32%; p <0.001). Safety and tolerability profiles and incidence of liver and muscle adverse experiences were generally similar between groups. In conclusion, these results showed that adding ezetimibe to atorvastatin 40 mg was significantly more effective than uptitrating to atorvastatin 80 mg at lowering LDL cholesterol and other lipid parameters. Both treatments were generally well tolerated (clinical trial no. NCT00276484).

Usefulness of C-Reactive Protein and Interleukin-6 as Predictors of Outcomes in Patients With Chronic Obstructive Pulmonary Disease Receiving Pravastatin

Inflammation is increased in chronic obstructive pulmonary disease (COPD) and plays a role in exercise intolerance. We investigated whether pravastatin administration is effective in improving exercise capacity in patients with COPD, and whether baseline or serial changes in high-sensitivity C-reactive protein (hs-CRP) over time are associated with corresponding changes in exercise capacity. In a randomized, double-blinded, and parallel design, 125 patients with clinically stable COPD were randomly assigned to receive placebo or pravastatin (40 mg/day) over a period of 6 months. Plasma hs-CRP levels were measured before randomization and during follow-up. Baseline characteristics were similar in the 2 groups. Exercise time remained stable throughout the study in the placebo group. Exercise time increased by 54% from 599 +/- 323 seconds at baseline to 922 +/- 328 seconds at the end (p <0.0001) in pravastatin-treated patients. A decrease in hs-CRP over baseline values was observed in 79% of patients (42 of 53) treated with pravastatin. Pravastatin-treated patients with a greater percent decrease in hs-CRP had a significant improvement in exercise time compared with those without hs-CRP decrease. A significant correlation was found in univariate analysis between decrease of log-transformed hs-CRP and increase of exercise time. Baseline hs-CRP and change of hs-CRP were significantly correlated with exercise time, even after adjustment for lipid profiles and hemodynamics. In conclusion, these data reinforce hs-CRP as a significant surrogate marker in COPD and underscore an important guide to the efficacy of treatment in COPD trials.

What Predicts Progression and Regression of Urinary Albumin Excretion in the Nondiabetic Population?

An increase or decrease in urinary albumin excretion (UAE) is associated with, respectively, a higher or lower risk for renal and cardiovascular disease, independent of widely known cardiovascular risk factors. This study aimed to identify factors that are associated with changes in UAE in the nondiabetic population using data of the Prevention of Renal and Vascular End stage Disease (PREVEND) Study, a community-based prospective cohort study. Data of the 6647 nondiabetic participants who completed the first (1997 through 2001) and second (2001 through 2003) screening were used. Change in UAE was categorized as regression (n = 650), stable (n = 5240), or progression (n = 757) on the basis of change in class during follow-up, with classes being a UAE <15, 15 to 30, 30 to 300, and >300 mg/24 h. With the use of stepwise forward multinomial regression analysis changes in BP, fasting glucose concentration, and start of antihypertensive drugs were found to be the most important modifiable variables associated with the risk for progression and regression (P < 0.01 for likelihood ratio test). The odds ratios to develop regression or progression of UAE during follow-up were 0.64 (95% confidence interval [CI] 0.57 to 0.73) and 1.91 (95% CI 1.72 to 2.12), respectively, per 10-mmHg increase in BP during follow-up, 0.89 (95% CI 0.80 to 0.98) and 1.09 (95% CI 1.01 to 1.17), respectively, per 1-mmol/L increase of fasting glucose levels during follow-up, and 1.57 (95% CI 1.21 to 2.06) and 0.70 (95% CI 0.51 to 0.95), respectively, for start of antihypertensive drugs during follow-up. These associations were independent of baseline BP, glucose, body mass index, estimated GFR, and UAE and changes in high-sensitivity C-reactive protein during follow-up. In conclusion, changes in glucose concentration and BP and start of antihypertensive drugs (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in >50% of cases) are associated with progression and regression of UAE in the nondiabetic population. Although associations do not necessarily suggest causality, it is hypothesized that in the general population, the most important ways to reduce UAE are by lowering glucose concentration and BP (including start of antihypertensive medication), even in normotensive, nondiabetic individuals.

The effect of spironolactone on circulating adipocytokines in patients with type 2 diabetes mellitus complicated by diabetic nephropathy

Angiotensin II can influence adipocytokine levels in adipose tissue, but the association between aldosterone, which mediates the effect of angiotensin II, and adipocytokines has yet to be fully elucidated. This study was designed to investigate the effect of spironolactone, a representative aldosterone blocker, on adipocytokines such as adiponectin, visfatin, plasminogen activator inhibitor (PAI)-1 and tumor necrosis factor α in patients with type 2 diabetic nephropathy: the study included 33 patients, 22 of whom were randomly assigned to the spironolactone (50 mg/d) group and 11 to the amlodipine (2.5 mg/d) group. Data were collected at baseline and after 3 months of treatment and compared with baseline data for 25 age-matched healthy subjects. A significant decrease in plasminogen activator inhibitor 1 in the spironolactone group was observed (22.6 ± 13.4 to 19.2 ± 11.3 ng/mL, P =.0323), but this did not occur in the amlodipine group. Adiponectin and visfatin levels did not change in the spironolactone and amlodipine groups, but significant increases in these adipocytokines were found in a subgroup of patients in the spironolactone group with glycated hemoglobin A 1c (HbA 1c) 8.0% or greater (11.8 ± 6.4 to 13.3 ± 7.4 μg/mL, P = .0344; and 1.39 ± 0.92 to 2.26 ± 0.76 ng/mL, P =.0397, respectively). The tumor necrosis factor α level at baseline exceeded the lower detection limit of the assay in only 6 patients in the spironolactone group, and no change occurred in these patients. Moreover, neither spironolactone nor amlodipine therapy caused a change in high-sensitivity C-reactive protein or soluble CD40 ligand, but a significant decrease in the level of brain natriuretic peptide was found in the spironolactone group only. Furthermore, significant increases of HbA 1c, creatinine, potassium, and aldosterone levels and plasma renin activity, and a decrease in urinary albumin excretion were also observed only in the spironolactone group. The number of patients with HbA 1c 8.0% or greater increased after spironolactone treatment. A significant decrease in systolic but not in diastolic blood pressure was observed in both treatment groups. In conclusion, our data suggest that in patients with type 2 diabetes mellitus complicated by diabetic nephropathy, spironolactone can decrease plasminogen activator inhibitor 1 and brain natriuretic peptide levels in addition to urinary albumin excretion, and systolic blood pressure, and that in patients with poor glycemic control, spironolactone can increase the levels of adiponectin and visfatin. However, the significant elevation of HbA 1c levels by spironolactone should be emphasized.

Response of high-sensitivity C-reactive protein to exercise training in an at-risk population

High-sensitivity C-reactive protein (hsCRP) is promoted as an independent predictor of atherosclerotic risk. In addition, cardiorespiratory fitness is inversely related to hsCRP in single-sex cross-sectional analyses. Our objective was to determine if modulating fitness with exercise training imposes changes in high-sensitivity C-reactive protein in a mixed-sex population at risk for cardiovascular disease. We studied baseline and postintervention plasma hsCRP in 193 sedentary, overweight to mildly obese, dyslipidemic men and women who were randomized to 6 months of inactivity or 1 of 3 aerobic exercise groups: low amount-moderate intensity (energy equivalent of approximately 19.3 km/wk at 40%-55% peak VO2), low amount-high intensity (energy equivalent of approximately 19.3 km/wk at 65%-80% peak VO2), or high amount-high intensity (energy equivalent of approximately 32.2 km/wk at 65%-80% peak VO2). At baseline, the study population was at intermediate to high cardiovascular risk as defined by hsCRP. Cardiorespiratory fitness was inversely related to hsCRP (P < .001) even after adjusting for significant and expected sex differences. Fitness, hormone replacement therapy use, and high-density lipoprotein cholesterol accounted for the sex difference in baseline hsCRP. Fitness, high-density lipoprotein cholesterol, fasting insulin, hormone replacement therapy, and visceral adiposity were all independent predictors for baseline hsCRP (r2 = 0.34 for the entire model, P < .0001). However, despite significant improvements in fitness, visceral adiposity, subcutaneous adiposity, and insulin sensitivity, hsCRP did not change in response to exercise training (P > .20). Cardiorespiratory fitness is inversely related to hsCRP independent of sex and accounts for most of the large sex disparity in hsCRP. Nonetheless, in the absence of a significant change in diet, 6 months of aerobic exercise training does not produce a significant change in hsCRP in an at-risk population.

Determinants of Arterial Wall Remodeling During Lipid-Lowering Therapy

Coronary plaque progression and instability are associated with expansive remodeling of the arterial wall. However, the remodeling response during plaque-stabilizing therapy and its relationship to markers of lipid metabolism and inflammation are incompletely understood. Serial intravascular ultrasound (IVUS) data from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial were obtained during 18 months of intensive versus moderate lipid-lowering therapy. In a subgroup of 210 patients, focal coronary lesions with mild luminal narrowing were identified. Lumen area, external elastic membrane (EEM) area, and plaque area were determined at the lesion and proximal reference sites at baseline and during follow-up. The remodeling ratio (RR) was calculated by dividing the lesion EEM area by the reference EEM area. The relationship between the change in remodeling, change in plaque area, lipid profile, and inflammatory markers was examined. At the lesion site, a progression in plaque area (8.9+/-25.7%) and a decrease in the RR (-3.0+/-11.2%) occurred during follow-up. In multivariable analyses, the percentage change in plaque area (P<0.0001), baseline RR (P<0.0001), baseline lesion lumen area (0.019), logarithmic value of the change in high-sensitivity C-reactive protein (P=0.027), and hypertension at baseline (P=0.014) showed a significant, direct relation with the RR at follow-up. Lesion location in the right coronary artery (P=0.006), percentage change in triglyceride levels (P=0.049), and age (P=0.037) demonstrated a significant, inverse relation with the RR at follow-up. Changes in LDL cholesterol, HDL cholesterol, and treatment group demonstrated no significant associations. Constrictive remodeling of the arterial wall was observed during plaque-stabilizing therapy with statin medications and appears related to their antiinflammatory effects.

C‐reactive protein in patients with coexistent periodontal disease and acute coronary syndromes

To evaluate periodontal disease (PD) influence on changes in high-sensitivity C-reactive protein (hsCRP) concentrations in patients with acute coronary syndromes and coexistent PD. Dental examinations were carried out in a group of 50 consecutive patients, less than 60 years old, hospitalized as a result of acute coronary syndromes. The patients were divided into two groups on the basis of own-constructed combined PD score (group 2: more advanced; and group 1: less advanced PD) as well as clinical attachment loss (CAL) - group 4: CAL >3 mm; group 3: CAL <or=3 mm. Blood samples for hsCRP estimation were taken at admission, after 10/12 days and long term after acute coronary syndromes. A statistically significant decrease in hsCRP was observed among three consecutive blood sample examinations in groups 2 and 4, whereas it was only seen between examination 1 and examination 2 in groups 1 and 3. Although no statistically significant difference of hsCRP was found between studied groups, patients with less advanced PD, either estimated with the use of own-constructed combined score or on the basis of CAL, have significantly longer diminution of inflammatory response monitored with hsCRP concentrations.