Course of depressive symptoms and medication adherence after acute coronary syndromes: an electronic medication monitoring study.

OBJECTIVES: We tested whether improvements in depressive symptoms precede improved adherence to aspirin in patients with acute coronary syndromes (ACS). BACKGROUND: Depression is associated with medication nonadherence in patients with ACS, but it is unclear whether changes in depression impact on adherence. METHODS: Electronic medication monitoring was used to measure adherence to aspirin during a 3-month period in a consecutive cohort of 172 patients (25 to 85 years) recruited within 1 week of hospitalization for ACS. Depressive symptom severity was assessed using the Beck Depression Inventory (BDI) during hospitalization and at 1 and 3 months after hospitalization. Adherence was defined as the percentage of days aspirin was taken as prescribed. RESULTS: Depression severity in hospital was associated with nonadherence in a gradient fashion: 15% of non-depressed patients (BDI score 0 to 4), 29% of mildly depressed patients (BDI score 10 to 16), and 37% of patients with moderately-to-severely depressive symptoms (BDI score >16) took aspirin less than 80% of the time (p = 0.03). A cross-lagged path analytic model revealed that improvements in depressive symptoms in the first month after the ACS were associated with improvements in adherence rates in the subsequent 2 months (standardized direct effect -0.32, p = 0.016). CONCLUSIONS: Diagnosis and treatment of depressive symptoms may improve medication adherence in patients after ACS.     

Rofecoxib, a COX-2 inhibitor, lowers C-reactive protein and interleukin-6 levels in patients with acute coronary syndromes

BACKGROUND: Patients with acute coronary syndromes (ACS) have high levels of inflammatory mediators such as C-reactive protein (CRP) and interleukin (IL)-6. AIM: To evaluate whether patients with ACS treated with rofecoxib, a COX-2 inhibitor, will have reduced CRP, IL-6, and soluble tumor necrotic factor receptor-1 (sTNF-R1) levels and improved endothelial function. METHODS AND RESULTS: Thirty-four patients hospitalized with ACS were randomized to receive rofecoxib, 25 mg/d plus aspirin 100 mg/d, or placebo plus aspirin, 100 mg/d, for a period of 3 months. Blood samples for CRP, IL-6, and sTNF-R1 levels were drawn prior to randomization, and after 1 month and 3 months. CRP levels in the rofecoxib group (n = 18) were significantly lower both at 1 month and 3 months compared to the baseline levels (p < 0.02). IL-6 levels were significantly lower at 1 month (p < 0.02) in the rofecoxib group, but not at 3 months. There was no change in endothelial function or sTNF-R1 levels. CONCLUSION: Patients recovering from ACS had lower levels of CRP and IL-6 at 1 month and lower CRP levels at 3 months when treated with rofecoxib plus aspirin. Suppression of inflammatory processes may lead to retardation of coronary atherosclerosis and coronary events.     

高敏C-反应蛋白对经皮冠状动脉介入术后对比剂肾病风险预测价值

目的:探讨经皮冠状动脉介入治疗术前高敏C反应蛋白(hs-CRP)水平与患者术后对比剂急性肾损伤(CI-AKI)的发生率及远期预后的关系。方法:连续入选1 820例于我院行择期经皮冠状动脉介入治疗患者,排除急性心肌梗死、近期手术或创伤的患者。根据术前hs-CRP值分为3组:hs-CRP升高组(hs-CRP>3 mg/L,n=546)、hs-CRP轻度升高组(hs-CRP 1～3 mg/L,n=650)和hs-CRP正常组(hs-CRP<1 mg/L,n=624)。结果:中位随访时间为26个月。与hs-CRP正常组相比,hs-CRP升高组术后CI-AKI发生率显著增加(10.9%vs.14.8%vs.23.1%,P<0.0001)。经过Logistic回归校正临床基线资料后,术前hs-CRP水平仍然是对比剂急性肾损伤发生率的独立预测因素。此外,男性OR=0.61;95%CI=0.45～0.82;P=0.001),糖尿病(OR=2.21,95%CI=1.67～2.93;P<0.0001),围手术期水化治疗(OR=0.50,95%CI=0.38～0.65,P<0.0001)也是患者对比剂肾病风险的独立预测因素。结论:术前hs-CRP水平与经皮冠状动脉介入治疗术后CI-AKI发生率显著相关。hs-CRP水平可以为患者术前危险分层提供帮助。     

Persistent depression affects adherence to secondary prevention behaviors after acute coronary syndromes

BACKGROUND: The persistence of depressive symptoms after hospitalization is a strong risk factor for mortality after acute coronary syndromes (ACS). Poor adherence to secondary prevention behaviors may be a mediator of the relationship between depression and increased mortality. OBJECTIVE: To determine whether rates of adherence to risk reducing behaviors were affected by depressive status during hospitalization and 3 months later. DESIGN: Prospective observational cohort study. SETTING: Three university hospitals. PARTICIPANTS: Five hundred and sixty patients were enrolled within 7 days after ACS. Of these, 492 (88%) patients completed 3-month follow-up. MEASUREMENTS: We used the Beck Depression Inventory (BDI) to assess depressive symptoms in the hospital and 3 months after discharge. We assessed adherence to 5 risk-reducing behaviors by patient self-report at 3 months. We used chi2 analysis to compare differences in adherence among 3 groups: persistently nondepressed (BDI < 10 at hospitalization and 3 months); remittent depressed (BDI > or = 10 at hospitalization; < 10 at 3 months); and persistently depressed patients (BDI > or = 10 at hospitalization and 3 months). RESULTS: Compared with persistently nondepressed, persistently depressed patients reported lower rates of adherence to quitting smoking (adjusted odds ratio [OR] 0.23, 95% confidence interval [95% CI] 0.05 to 0.97), taking medications (adjusted OR 0.50, 95% CI 0.27 to 0.95), exercising (adjusted OR 0.57, 95% CI 0.34 to 0.95), and attending cardiac rehabilitation (adjusted OR 0.5, 95% CI 0.27 to 0.91). There were no significant differences between remittent depressed and persistently nondepressed patients. CONCLUSIONS: Persistently depressed patients were less likely to adhere to behaviors that reduce the risk of recurrent ACS. Differences in adherence to these behaviors may explain in part why depression predicts mortality after ACS.     

强化调脂治疗对经皮冠状动脉干预术后患者C反应蛋白的影响

目的　探讨阿托伐他汀 2 0mg/d对经皮冠状动脉干预 (percutaneouscoronaryintervention ,PCI)术后患者外周血C反应蛋白 (C reactiveprotein ,CRP)的降低能力是否强于 10mg/d。方法　连续选择因狭窄性病变行PCI的不稳定性心绞痛患者 4 8例 ,随机分为强化调脂组和常规调脂组 ,术后分别给予阿托伐他汀 2 0mg和 10mg,1次 /d。术前、术后 3d、3个月测定外周静脉血CRP、血脂等。结果　与术前比较 ,3个月后强化调脂组总胆固醇和低密度脂蛋白分别下降 2 1.6 %和 39.3% ,常规调脂组下降 11.6 %和 14 .8% ,阿托伐他汀 2 0mg/d降低总胆固醇和低密度脂蛋白的能力强于 10mg/d。强化调脂组术前 ,术后 3个月CRP中位数分别为 4 .1和 1.1mg/L ;常规调脂组为 7.1和 1.4mg/L。两组CRP的降低程度差异有显著性意义。阿托伐他汀的抗炎作用和术前的CRP水平相关 ,3个月后CRP的下降程度与血脂改变无相关性。结论　阿托伐他汀 2 0mg/d较 10mg/d能使PCI术后CRP进一步下降。     

Depressive symptoms and all-cause mortality in unstable angina pectoris (from the Coronary Psychosocial Evaluation Studies [COPES])

Although depression is clearly associated with increased mortality after acute myocardial infarction, there is a paucity of data examining the impact of depression on patients with unstable angina (UA). We analyzed the relation between depressive symptoms and all-cause mortality in patients with UA who were enrolled in a prospective multicenter study of depression and acute coronary syndrome (ACS). Depressive symptoms were measured with the Beck Depression Inventory (BDI) within 1 week of the ACS event, and patients were selected for a BDI score 0 to 4 or ≥ 10. Our sample included 209 patients with UA, with 104 (50%) having a BDI score ≥ 10. Proportional hazards analyses adjusted for variables including left ventricular ejection fraction, Global Registry of Acute Coronary Events risk score, and Charlson co-morbidity index. In multivariable analyses, a BDI score ≥ 10 was associated with increased risk of 42-month all-cause mortality (hazard ratio 2.04, 95% confidence interval 1.20 to 3.46, p = 0.008) compared to a BDI score 0 to 4. In conclusion, our results confirm and extend previous evidence linking depression to worse outcomes in UA and suggest that interventions that address depression may be worth examining across the spectrum of risk in ACS.     

C-reactive protein elevation predicts pulse pressure reduction in hypertensive subjects

Cross-sectional studies have shown a positive association between increased pulse pressure (PP) and an increased likelihood of a C-reactive protein (CRP) level >3 mg/L. In a retrospective subgroup analysis of the hypertensive subjects of the multicenter double-blind study, REASON (PREterax in Regression of Arterial Stiffness in a ContrOlled Double-BliNd), in which fixed first-line antihypertensive combination therapy with an angiotensin converting enzyme (ACE) inhibitor, perindopril (2 mg), and a diuretic, indapamide (0.625 mg), proved significantly more effective than atenolol in normalizing PP, we sought to determine whether perindopril plus indapamide was also more effective than atenolol in lowering CRP levels and, if so, whether this effect correlated with a preferential reduction in PP. At the final visit (12 months) in the 269 patients studied, the decrease in PP was greater, and the proportion of patients with CRP >3 mg/L lower (17.9% versus 28. 9%, P=0.03; adjusted odds ratio, 1.02 to 4.08, P=0.01), in the perindopril plus indapamide group than in the atenolol group. After adjustment for confounders, patients with a baseline CRP >3 mg/L displaying the greatest decrease in PP were more likely (P=0.04) to have a CRP < or =3 mg/L at 12 months. No such relationship was found with systolic or diastolic blood pressure. Perindopril-indapamide combination therapy is more effective than beta-blockade in lowering elevated CRP in hypertensive subjects. This effect is significantly associated with a more effective PP reduction in patients with baseline CRP >3 mg/L.     

Medicare Coverage Policies: A Macro and Micro Analysis

Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, have been shown to be predictive of cardiovascular disease. In the Physicians Health Study, the magnitude of reduction in the risk of myocardial infarction with aspirin therapy was related to baseline CRP levels, raising the possibility that the protective effect of aspirin may be due to antiinflammatory properties in addition to its antiplatelet effect. We therefore investigated whether aspirin therapy lowers CRP levels. Because heavy physical exertion is a well-known trigger of myocardial infarction, we also investigated the effect of aspirin on CRP levels before and after strenuous exercise. Thirty-two healthy men, aged 29 ± 6 years, were enrolled in a randomized, double-blind, parallel study. Blood samples were obtained immediately before and after maximal treadmill exercise at baseline and following 7 days of aspirin therapy (81 or 325 mg). The levels of CRP, as measured by ELISA, increased by 13% following exercise (P < 0.0001). However, aspirin did not significantly alter CRP levels, either at rest (0.81 ± 0.13 mg/L before aspirin vs. 0.78 ± 0.13 mg/L on aspirin) or following exercise (0.92 ± 0.13 mg/L before aspirin vs. 0.86 ± 0.13 mg/L on aspirin), P = 0.73. When the resting and postexercise data were combined, the levels were 0.87 ± 0.13 mg/L before aspirin and 0.82 ± 0.13 mg/L on aspirin (a nonsignificant 6% reduction, P = 0.20). In conclusion, in healthy male subjects CRP levels were not significantly reduced by short-term aspirin therapy. Our data, taking together with other reports, suggest that aspirin may not affect the levels of inflammatory markers. However, further studies are needed with a longer duration of therapy, among subjects with coronary heart disease, and using additional markers of inflammation besides CRP to determine the long-term effects of aspirin use.     

急性冠状动脉综合征患者C-反应蛋白升高与远期死亡率和心力衰竭的相关性分析

目的评估C-反应蛋白(CRP)与急性冠状动脉综合征(ACS)患者远期预后的相关性。方法收集我院急诊ACS患者的资料并检测其CRP水平。入选患者随访3年,内容包括死亡,因急性心肌梗死(AMI)和充血性心力衰竭(CHF)而再次住院情况。结果共有446名患者入选,CRP升高的患者的死亡率和因CHF的再次住院率均高于CRP正常的患者(P<0.05)。校正心肌肌钙蛋白T(cTnT)水平后,急性期CRP>7.44 mg/L与发病后3年内的死亡率和因CHF再住院的风险增加仍显著相关。结论在胸痛早期就出现CRP升高的ACS患者的晚期死亡率和CHF风险增加。     

Response of high-sensitivity C-reactive protein to percutaneous coronary intervention in patients with acute coronary syndrome

Percutaneous coronary intervention (PCI) provokes an inflammatory reaction, as shown by increased concentrations of plasma C-reactive protein (CRP) after PCI. However, the changes of CRP levels after PCI in patients with acute coronary syndrome (ACS) have not been well evaluated. We evaluated the characteristics of the patients with elevated CRP response after PCI and whether an increase in CRP after PCI predicts long-term prognosis in patients with ACS. We studied consecutive 360 patients with ACS who underwent elective coronary stenting. Inflammatory response to PCI was calculated as the difference between the peak postprocedural hsCRP level and the preprocedural hsCRP level (ΔCRP). Twelve months follow-up data were obtained and clinical outcomes were compared with ΔCRP. In receiver operating characteristics analyses, the cutoff point of ΔCRP for major adverse cardiac events (MACE) was 3.0 mg/l, which yielded sensitivity of 61.7% and specificity of 69.7%. The patients with ΔCRP > 3 mg/l revealed higher incidence of myocardial infarction (37.7 vs 14.6%, P < 0.001), and ACC/AHA type B2/C lesion (81.5 vs 68.7%, P = 0.006) than in patients with low ΔCRP. White blood cell count, low-density lipoprotein cholesterol, peak creatinine kinase-MB, and peak troponin T were significantly elevated in patients with ΔCRP > 3 mg/l than in those with ≤3 mg/l. There was significant correlation between ΔCRP and the changes in troponin T after PCI (r = 0.210, P < 0.001). An increase in hsCRP > 3 mg/l after PCI had a higher predictive value for the occurrence of MACE than low hsCRP elevation (hazard ratio 2.1, P = 0.005). In multivariate analysis, ΔCRP and peak troponin T were independent predictors of MACE (P < 0.001 and P = 0.013, respectively). In conclusion, postprocedural hsCRP elevation >3 mg/l was associated with higher incidence of MACE in patients with ACS. ΔCRP determinations may be of value for risk stratification after PCI.     

Relationship of C-reactive protein to adverse cardiovascular events in patients treated by percutaneous coronary intervention for stable angina pectoris

Low-grade inflammation as detected by increased C-reactive protein (CRP) levels predicts the risk of cardiovascular events. However, there is still controversy over the mid-term predictive value of CRP in patients referred for elective percutaneous coronary revascularization (PCI) for stable angina pectoris. The aim of this study was to assess the relationship between baseline CRP level and mid-term outcome of patients undergoing PCI. Two groups of patients with stable angina pectoris were prospectively studied. Group A consisted of 150 consecutive patients with a CRP level < or = 3 mg/L, and group B consisted of 150 consecutive patients with a CRP level > 3 mg/L undergoing PCI at our institution. Comparing both groups of patients, the analysis confirmed a significant difference between medians of the CRP levels (0.5 versus 8 mg/mL; P < 0.001). A higher level of CRP in group B was associated with a lower presence of male gender (P < 0.05) and history of myocardial infarction (P < 0.05). On the other hand, in group B there was higher occurrence of smoking (P < 0.001), hypertension (P < 0.05), hypertriglyceridemia (P < 0.001), and diabetes mellitus (P < 0.01). The incidence of myocardial infarction based on post-interventional release of TnI > 1.5 ng/mL reached 12% in group A and 14% in group B (P = 0.73). Analyses were repeated with adjustment for significant baseline variables, which did not change our findings. The incidence of adverse cardiovascular events during a six month follow-up was 13% in both groups (NS). Increased CRP serum prior to PCI was not associated with the risk and extent of procedure-related myocardial injury measured by TnI release and does not portend heightened cardiovascular risk at six months after percutaneous revascularization. On the other hand, a CRP level > 3 mg/L was associated with a higher occurrence of cardiovascular risk factors (smoking, hypertension, hypertriglyceridemia, and diabetes mellitus).     

Early use of gemfibrozil in patients with non ST Elevation acute coronary syndrome. Changes of markers of inflammation and von Willebrand factor

It is not known whether PPAR-alpha agonist gemfibrozil is able to exert rapidly its lipid modulating, potential antiinflammatory and antithrombotic effects in patients with non-ST elevation acute coronary syndrome (NSTEACS), as some other lipid lowering drugs e.g. statins do. METHODS: We randomized 44 patients with NSTEACS to open gemfibrozil (n=22, 600 mg b.i.d for 90 days) or no gemfibrozil (controls, n=22) within 24 hours after pain onset. Semiquantitative C-reactive protein (CRP) latex test was used at baseline for exclusion of patients with overt inflammation. All patients received dalteparin or enoxaparin for >48 hours and oral aspirin (125 mg/day) and were treated noninvasively. Lipids, high sensitive CRP, soluble CD40 ligand (CD40L) and von Willebrand factor (vWF) activity were assessed on days 1 (baseline), 4, 7, 14, 30 and (except CD40L) 90. RESULTS: Gemfibrozil use was associated with significant lowering of triglycerides by day 30, however it did not prevent acute significant decline of high density lipoprotein cholesterol (HDL-C), which was similar in both groups. CD40L level significantly increased while CRP levels decreased by day 30 in both groups. Moreover, selection of a subgroup with baseline HDL-C <1.0 mmol/l did not reveal any difference in changes of CRP or CD40L between gemfibrosil treated and control patients. vWF activity did not change in controls and significantly increased in gemfibrozil group by days 7, 14, but from lower baseline level. CONCLUSION: In patients with NSTEACS early administration of gemfibrozil was not associated with positive changes of CRP and CD40L levels or vWF activity compared with control group.     

C-reactive protein kinetics and its prognostic value after transfemoral aortic valve implantation

Transcatheter aortic valve implantation (TAVI) has become an established therapeutic option in high-risk patients with severe aortic valve stenosis. The potential threat of a postinterventional infection is one of several life-threatening complications. We have analyzed C-reactive protein levels in all patients who underwent successful transfemoral aortic valve implantation between July 2009 and January 2011. CRP and leukocyte counts were measured within 24 hours prior to implantation and daily up to 14 days after implantation. Patients with CRP levels above 109 mg/L (75th percentile; normal range <5 mg/L) were additionally analyzed. We performed 215 transfemoral aortic valve implantations (Edwards and CoreValve). The mean CRP increased after TAVI with a 7.5-fold peak on day 3, and was nearly normalized on day 14. Interestingly, mean leukocyte count remained within the normal range. To identify further independent predictors for post-TAVI elevation of CRP above the 75th percentile, multivariate logistic regression analysis was performed. This showed a significant relationship for patients with elevated baseline CRP values above 11.9 mg/L, for a body mass index above 25 kg/m2, for a logistic EuroSCORE ≥22% and for signs of postinterventional infection. Elevated baseline (>6.4 mg/L) and elevated peak (>102 mg/L) CRP values were associated with higher 30-day mortality. In conclusion, CRP elevation after TAVI should be expected to peak on day 3. An infection should be taken into account if CRP increases above 110 mg/L and if patients show other signs of infection. Elevated CRP at baseline and at day 3 is associated with higher 30-day mortality.     

C-reactive protein (CRP) is a predictor of high medical-care expenditures in a community-based elderly population aged 70 years and over: the Tsurugaya project

Because CRP is a strong independent predictor of various diseases, it was hypothesized that CRP may be a useful predictor or treatment target for medical-care expenditures. The aim of this study was to investigate the relationship between CRP and medical-care expenditures in a community-dwelling elderly population. This prospective cohort study was conducted including 925 Japanese subjects aged ≥70 years. A high-sensitivity CRP assay was used by applying the nephelometric method. Hospitalizations, outpatient visits, and expenditures were ascertained through computerized linkage with claims lodged between August 2002 and March 2008 with the Miyagi National Health Insurance (NHI) Association. Since medical-care expenditures were not normally distributed, the category of high medical-care expenditures (>75th percentile of medical-care expenditures: inpatient expenditures >$494/month; outpatient expenditure >$522/month; total expenditures >$1103/month) was used to examine the relation of CRP levels with medical-care expenditures. Multiple logistic regression analysis was used to examine the relationship between CRP cutoff points (low concentrations: <1.0mg/L; intermediate concentrations: 1.0-3.0mg/L; or high concentrations: ≥3.0 mg/L) and medical-care expenditures during 6 year-follow up period. After adjustment for potential confounding factors, a positive association of CRP with hospitalization, and total expenditures (p for trend=0.03 and 0.02, respectively) was found. An elevated baseline CRP level is an independent predictor of increases in prospective medical-care expenditures among community-dwelling elderly. Further study is required to clarify whether reducing CRP by intervention is a cost-effective measure.     

脑利钠肽和C-反应蛋白在急性冠状动脉综合征介入治疗患者的预后价值

目的探讨急性冠状动脉综合征(ACS)行经皮冠状动脉介入治疗术(PCI)患者血浆脑利钠肽(BNP)和C-反应蛋白(CRP)水平与临床预后的关系。方法连续性入选189例行PCI治疗的ACS患者。测定症状发作平均(34·2±16·3)h的血浆BNP和CRP水平,随访患者住院期间,30天,3个月病死率及主要心脏不良事件(MACE)(心原性死亡,再次心肌梗死,再发心绞痛,继发心衰和再入院的复合终点)发生率。结果189例ACS患者根据血浆BNP水平分为四组:≤100ng/L组;>100~≤300ng/L组;>300~≤600ng/L组和>600ng/L组。随血浆BNP水平的升高,各组病死率及MACE发生率呈明显递增趋势。3个月时,各组病死率分别为0%、1·4%、7·7%、48·3%;MACE发生率分别为7·9%、17·1%、57·7%、79·3%。在多变量的logistic回归分析中,BNP独立于年龄、性别、家族史、吸烟、高脂血症、高血压、糖尿病及LVEF等危险因素,预测30天(r=0·8515,P<0·01)和3个月(r=0·9201,P<0·01)病死率及30天(r=0·7066,P<0·01)和3个月(r=0·7090,P<0·01)MACE发生率。其中141例患者根据血浆CRP水平分为三组:≤8·0mg/L组;>8·0~≤32·0mg/L组;>32·0mg/L组。随着血浆CRP水平的升高,各组死亡事件及MACE发生率亦呈明显递增趋势。3个月时,病死率分别为2·7%、7·7%、28·6%;MACE发生率分别为28·4%、41·0%、60·7%。在多变量的logistic回归分析中,CRP独立于年龄等其他冠心病危险因素,预测30天(r=0·5882,P=0·0044)和3个月(r=0·5235,P=0·0038)病死率。经年龄因素校正后,CRP独立于性别等其他冠心病危险因素,预测30天(r=0·2705,P=0·0380)和3个月(r=0·2290,P=0·0429)MACE发生率。当将CRP、BNP和年龄等其他冠心病危险因素放入同一模型预测ACS的预后时,血浆CRP水平失去了预测效能,而血浆BNP水平升高独立于各因素预测30天和3个月病死率及MACE发生率。结论BNP和CRP能够很好地对ACS患者行PCI治疗后进行危险分层,预测近期病死率和MACE发生率。BNP可能是较CRP更好的预测ACS患者近期临床预后的指标。     

Effect of central obesity, low high-density lipoprotein cholesterol and C-reactive protein polymorphisms on C-reactive protein levels during treatment with Rosuvastatin (10 mg Daily)

Plasma levels of high-sensitivity C-reactive protein (hsCRP) are an important predictor of cardiovascular disease, and achievement of lower targets of hsCRP with rosuvastatin treatment was associated with improved cardiovascular outcomes. The aim of this study was to examine whether hsCRP levels were related to genetic variants and traditional cardiovascular risk factors in Chinese patients treated with rosuvastatin 10 mg/day. The relations were analyzed between on-treatment plasma hsCRP concentrations and cardiovascular risk factors and 14 single-nucleotide polymorphisms in CRP and other candidate genes. In 281 patients with a median plasma hsCRP level of 0.81 mg/L (interquartile range 0.46 to 1.86), higher hsCRP levels were significantly associated with female gender, greater waist circumference (WC), having diabetes, higher triglycerides, and lower high-density lipoprotein (HDL) cholesterol. Three single-nucleotide polymorphisms (rs1205, 3872G>A and rs2808630, 5237A>G in CRP and rs1169288, I27L in HNF1A) were independently associated with hsCRP levels before and after adjustment for other variables. WC and the CRP rs1205 polymorphism showed the strongest relations with hsCRP, and in multiple regression analysis, gender, WC, diabetes, triglycerides, HDL cholesterol, and the 3 genetic variants explained 35.5% of the variance in hsCRP levels. The 2 CRP polymorphisms, female gender, higher WC, and lower HDL cholesterol were associated with risk for having CRP concentrations ≥ 1 mg/L. In conclusion, central obesity, low HDL cholesterol, and CRP polymorphisms are major determinants of higher hsCRP levels in Chinese patients receiving treatment with rosuvastatin.     

不同剂量阿司匹林对急性冠状动脉综合征炎性标志物和预后的影响

目的 观察不同剂量阿司匹林对急性冠状动脉综合征(ACS)患者炎性标志物和临床预后的影响.方法 将ACS患者随机分为不同剂苗阿司匹林治疗组(A组100 mg/d、B组500 mg/d和C组1000 mg/d)治疗和随访1年,检测各时段炎性标志物水平,并记录有关临床事件.结果 共入选312例,A组106例,B组104例,C组102例.所有入选者基线超敏C反应蛋白(hsCRP)、IL-6、TNFα均显著高于正常参考值,应用不同剂量阿司匹林治疗1、6、12个月后,炎性标志物均下降,治疗前后各指标比较差异均有统计学意义,但各组间比较差异无统计学意义.3组急性冠状动脉事件发生率差异无统计学意义,B、C组发生胃肠道不适症状者较A组增加.结论 ACS患者血清炎性标志物升高,应用阿司匹林治疗后炎性标志物水平显著下降,但大剂量阿司匹林(500～1000 mg)未见炎性标志物水平进一步下降和再发心脏事件减少,而胃肠道不良反应有所增加.     

Pre-procedural plasma levels of C-reactive protein and interleukin-6 do not predict late coronary angiographic restenosis after elective stenting.

AIMS: Inflammatory markers may serve as an important prognostic predictor in patients with coronary heart diseases. In patients undergoing coronary interventions, it has been shown that baseline C-reactive protein (CRP) could predict late clinical restenosis. Only a few small studies have examined the possible relationship with angiographic restenosis. In patients with stable angina pectoris,we examined whether baseline CRP and IL-6 predict late coronary angiographic restenosis after stenting. METHODS AND RESULTS: Pre-procedural plasma levels of CRP and IL-6 were measured in 216 patients with stable angina pectoris undergoing elective coronary stenting. Angiographic follow-up was performed in all patients at 6 months. Baseline CRP levels were 6.15 +/- 0.78 mg/L versus 5.24 +/- 1.17 mg/L in the patent and restenosis groups, respectively (P=0.64). IL-6 levels were 0.46 +/- 0.03 ng/L versus 0.40 +/- 0.07 ng/L in the patent and restenosis groups, respectively (P=0.50). CRP levels were obtained again at the time of angiographic follow-up and were found to be similar in both groups (2.89 +/- 0.29 mg/L versus 2.61 +/- 0.63 mg/L, P=0.72). Moreover, in a sub-group of 43 patients, serial blood samples were obtained at several time points after the procedure up to 6 months. Both CRP and IL-6 plasma levels increased significantly in response to the procedure. CRP levels peaked at 3 days (11.27 +/- 1.53 mg/L versus 4.26 +/- 0.72 mg/L at baseline, P<0.0001). IL-6 levels reached maximum values after 24 h (1.08 +/- 0.14 ng/L versus 0.53 +/- 0.08 ng/L at baseline, P<0.0001). However, in this sub-group of patients, neither peak CRP nor IL-6 levels were found to predict late angiographic restenosis. CONCLUSIONS: Coronary stenting is associated with transient increases in both CRP and IL-6 levels. However, pre-procedural CRP and IL-6 levels do not predict late coronary angiographic restenosis.     

C-reactive protein, cardiovascular risk factors, and mortality in a prospective study in the elderly

Serum C-reactive protein (CRP) reflects inflammation and predicts cardiovascular disease in middle-aged individuals. We investigated CRP, risk factors, and 10-year mortality in 3 elderly cohorts (aged 75, 80, and 85 years; n=455) of the population-based Helsinki Ageing Study. Clinical and laboratory examinations were performed at baseline, and in 1998, CRP was measured by a sensitive method (sensitivity 0.3 mg/L) from frozen serum samples. Mortality data were retrieved from national registers. Serum CRP ranged from 0.18 to 170.0 mg/L (interquartile range 0.68 to 4.10 mg/L, median 1.60 mg/L). CRP correlated significantly with body mass index and plasma insulin and was associated with smoking at baseline. An inverse correlation was found with albumin and total and HDL cholesterol. CRP was not associated with diabetes or cardiovascular disease but was significantly (P=0.015) higher in persons with (n=70) than without (n=385) dementia. During the 10-year follow-up, 61% (n=278) of the cohort died; half of the deaths were due to cardiovascular diseases. Mean CRP in survivors and nonsurvivors was 3.16 and 5.22 mg/L (P=0.017), respectively. After controlling for age and sex, baseline CRP (per 10 mg/L) significantly predicted the 10-year total mortality (risk ratio 1.20, 95% CI 1.08 to 1.32) and cardiovascular mortality (risk ratio 1.22, 95% CI 1.10 to 1.35). Predictive value was found in the 75-year-old cohort, but it was clearly attenuated in the 80- and 85-year-old cohorts. The results indicate that CRP is associated with several cardiovascular risk factors in the elderly. CRP alone predicts overall and cardiovascular mortality, but the prediction was significant in only the 75-year-old cohort.     

Effects of high-dose statin administered prior to coronary angioplasty on the incidence of cardiac events in patients with acute coronary syndrome

INTRODUCTION: Statins given after acute coronary syndrome without ST elevation (NSTE-ACS) reduce the incidence of major adverse cardiac events (MACE) in long-term follow-up. AIM: To evaluate the effects of high-dose statin administered in patients with NSTE ACS and increased CRP level prior to percutaneous coronary intervention (PCI) on the incidence of MACE in long-term follow-up. METHODS: The study involved 140 consecutive patients with NSTE ACS and increased CRP level at baseline. Patients from group A (n=54) did not receive statin before PCI, whereas subjects in group B (n=86) were given 80 mg of atorvastatin. Patients in both groups received typical cardiological therapy including aspirin, thienopyridine and low molecular weight heparin. After PCI all patients received 40 mg of atorvastatin. Incidence of MACE (death, myocardial infarction (MI), re-PCI) during long-term followup was evaluated in both groups. RESULTS: Study groups did not differ with respect to demographic parameters and rate of ischaemic heart disease risk factors. Also, no differences occurred regarding CRP level (group A vs. B: hsCRP 10.8+/-1.8 mg/l vs. 8.2+/-2.8 mg/l; p=NS) and TIMI Risk Score (group A vs. B: 4.3+/-0.71 vs. 4.37+/-0.79; p=NS). During long-term follow-up the incidence of MI (9.25% vs. 1.2%, p=0.03), composite endpoint: death + MI (14.8% vs. 2.32%, p=0.013) and death + MI + re PCI (25.9% vs. 8.1%, p=0.006) was significantly higher in group A than group B. CONCLUSIONS: Administration of high-dose statin in NSTE ACS patients before PCI was associated with significant reduction of MACE in long-term follow-up. This effect was observed despite the same therapy given after PCI.