Differential leucocyte count and the risk of future coronary artery disease in healthy men and women: the EPIC-Norfolk Prospective Population Study

Abstract. Rana JS, Boekholdt SM, Ridker PM, Jukema JW, Luben R, Bingham SA, Day NE, Wareham NJ, Kastelein JJP, Khaw K‐T. (Academic Medical Center, Amsterdam, The Netherlands; University of Pittsburgh, Pittsburgh, PA, USA; Leiden University Medical Center, The Netherlands; and Institute of Public Health, University of Cambridge, Cambridge, UK). Differential leucocyte count and the risk of future coronary artery disease in healthy men and women: the EPIC‐Norfolk Prospective Population Study. J Intern Med 2007; 262 : 678–689. Background: We examined the relationship between granulocyte, lymphocyte and monocyte counts and risk of coronary heart disease (CHD) and cardiovascular disease (CVD) in men and women. There is paucity of data on the differential leucocyte count and its relationship with the risk of CHD and CVD. Methods: This prospective study comprised 7073 men and 9035 women who were 45–79 years of age and were residents of Norfolk. United Kingdom. Results: During an average of 8 years of follow‐up we identified 857 incident CHD events and 2581 CVD incident events. Increased total leucocyte count was associated with increased risk for both CHD and CVD. The highest quartile of granulocyte count was associated with increased risk when compared to lowest quartile for CHD (men HR 1.70 95% CI: 1.30–2.21; women HR 1.24 95% CI: 0.91–1.69) and for CVD (men HR 1.46 95% CI: 1.24–1.71; women HR 1.20 95% CI: 1.02–1.42). The association remained unchanged when the analyses were restricted to nonsmokers and when risk was assessed for every 1000 cells L^?1 increase in cell count. In multivariable models, despite adjusting for C‐reactive protein (CRP), the granulocyte count remained an independent predictor of CHD and CVD risk, especially amongst men. Lymphocyte or monocyte counts were not significantly associated with increased risk. In all analyses, additionally adjusting for CRP did not affect the results materially. Conclusions: In conclusion, we found that the higher risk for CHD and CVD associated with increased total leucocyte count seems to be accounted for by the increased granulocyte count.     

Increased Plasma Concentrations of Soluble ST2 Independently Predict Mortality but not Cardiovascular Events in Stable Coronary Heart Disease Patients: 13-Year Follow-up of the KAROLA Study

Purpose

sST2 (soluble suppression of tumorigenicity 2), a member of the interleukin-1 family, has been suggested to play a role in cardiac remodeling and inflammatory signaling. We assessed the association between sST2 in patients with stable coronary heart disease (CHD) with multiple cardiovascular outcomes and total mortality, simultaneously controlling for a large number of potential confounders.

Methods

Plasma concentrations of sST2 (ELISA, Critical Diagnostics) were measured at baseline in a cohort of 1081 patients. The Cox-proportional hazards model was used to determine the prognostic value of sST2 on a combined cardiovascular disease (CVD) endpoint, on cardiovascular death, and on total mortality after adjustment for covariates.

Results

The median sST2 level was 28.9 ng/mL (IQR 23.8, 35.1) (mean age at baseline 58.9 years, 84.6% male). sST2 concentration was positively correlated with inflammatory markers and emerging risk factors, e.g., cystatin C, N-terminal probrainnatriuretic peptide (NT-proBNP), high-sensitivity (hs)-Troponin T and I, mid-regional pro-atrial natriuretic peptide (MR-proANP), and growth differentiation factor 15 (GDF-15). Results after short- and long-term (4.5 and 12.3 years, respectively) follow-up (FU) displayed no statistically significant association with the combined endpoint of non-fatal and fatal CVD events when the top quartile (Q4) of sST2 concentration was compared to the bottom quartile (Q1). A relationship during long-term FU was seen with CVD mortality even after multivariable adjustments including clinical risk variables (HR 1.65; 95% CI 1.02–2.86), but not in a fully adjusted model whereas, in contrast, it was still highly significant after short-term FU (HR (5.97 (95%CI 1.32–27.06)). In addition, the sST2 concentration was still strongly associated with total mortality in the fully adjusted model including clinical variables and cystatin C based estimated glomerular filtration rate, NT-proBNP, hsCRP and hs-TnI comparing Q4 vs Q1 during long-term FU (HR of 1.48 (95% CI 1.03–2.13)) and short-term FU (HR 3.06 (95% CI 1.29–7.24)).

Conclusions

Elevated levels of sST2 concentration in stable CHD patients may independently predict short- and long-term risk for fatal CVD events and total mortality but not non-fatal CVD events.

     

Dietary fiber intake and reduced risk of coronary heart disease in US men and women: the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study

BACKGROUND: Prospective studies suggest that dietary fiber intake, especially water-soluble fiber, may be inversely associated with the risk of coronary heart disease (CHD). METHODS: We examined the relationship between total and soluble dietary fiber intake and the risk of CHD and cardiovascular disease (CVD) in 9776 adults who participated in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study and were free of CVD at baseline. A 24-hour dietary recall was conducted at the baseline examination, and nutrient intakes were calculated using Food Processor software. Incidence and mortality data for CHD and CVD were obtained from medical records and death certificates during follow-up. RESULTS: During an average of 19 years of follow-up, 1843 incident cases of CHD and 3762 incident cases of CVD were documented. Compared with the lowest quartile of dietary fiber intake (median, 5.9 g/d), participants in the highest quartile (median, 20.7 g/d) had an adjusted relative risk of 0.88 (95% confidence interval [CI], 0.74-1.04; P =.05 for trend) for CHD events and of 0.89 (95% CI, 0.80-0.99; P =.01 for trend) for CVD events. The relative risks for those in the highest (median, 5.9 g/d) compared with those in the lowest (median, 0.9 g/d) quartile of water-soluble dietary fiber intake were 0.85 (95% CI, 0.74-0.98; P =.004 for trend) for CHD events and 0.90 (95% CI, 0.82-0.99; P =.01 for trend) for CVD events. CONCLUSION: A higher intake of dietary fiber, particularly water-soluble fiber, reduces the risk of CHD.     

Erratum to “The growing interest of fibrin imaging in atherosclerosis” [Atherosclerosis 222 (1) (2012) 22–25]

ObjectiveHigh-density lipoprotein cholesterol (HDL) and physical fitness (PF) have both been shown to predict cardiovascular disease (CVD), particularly coronary heart disease (CHD). Increased PF is associated with increased HDL and may partly explain the benefit of HDL. We tested the hypothesis that PF influences the prognostic impact of HDL for CHD and also for CHD-, CVD- and all-cause death.MethodsHDL was measured 1979–1982 in 1357 healthy men aged 44–69 years followed up to 28 years. PF was measured using bicycle exercise test. Hazard ratios (HRs) adjusted for age, smoking, systolic blood pressure, and total cholesterol and further for PF between HDL quartiles were calculated using Cox proportional survival model.ResultsThe highest HDL quartile was associated with lower risk of CHD (HR: 0.57, 95% confidence interval [CI]: 0.43–0.74), fatal CHD (HR: 0.56, CI: 0.36–0.86), fatal CVD (HR: 0.64, CI: 0.46–0.88) and all-cause death (HR: 0.80, CI: 0.65–0.99) compared to the lowest quartile. Adjustments for PF or changes in PF over 8.6 years did not change the results except for all-cause death, which was not significantly different between HDL quartiles. We found no interaction between HDL and PF.ConclusionsHDL is a strong predictor of long term risk of CHD, fatal CHD and fatal CVD in healthy middle-aged men. Physical fitness or its changes had no impact on the ability of HDL to predict CHD.     

Usefulness of clinical and NT-proBNP monitoring for prognostic guidance in destabilized heart failure outpatients.

AIMS: To study the relative prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) monitoring in addition to clinical disease severity scores (CDSSs) in outpatients with destabilized heart failure (HF). METHODS AND RESULTS: Seventy-one outpatients with recently destabilized HF were recruited. At baseline, and at all following visits, a CDSS based on Framingham criteria was obtained, and NT-proBNP levels were measured in a blind fashion. CDSS did not correlate with NT-proBNP levels at any time (P > 0.1), although their relative changes correlated during follow-up (P < 0.001). Forty patients (56%) had clinical events (cardiovascular death and/or HF hospitalization) within 1 year of follow-up. Changes in CDSS from baseline were not predictive of subsequent events (P > 0.1 for all visits), whereas changes in NT-proBNP levels were predictive at several time points: week 2 (P = 0.005), week 3 (P = 0.037), week 4 (P = 0.015), and 6 months (P = 0.026). A change in NT-proBNP levels at follow-up week 2 (%) added independent prognostic information (P < 0.001, HR 0.982, 95% CI 0.972-0.992) to baseline CDSS (P = 0.002, HR 2.05, 95% CI 1.290-3.266), age (P = 0.007, HR 1.034, 95% CI 1.009-1.059), and left ventricular ejection fraction (P = 0.013, HR 0.942, 95% CI 0.898-0.987). CONCLUSION: Serial monitoring for per cent change in NT-proBNP concentrations offers superior prognostic information to clinical assessment among outpatients with recent destabilized HF.     

High dietary glycemic load and glycemic index increase risk of cardiovascular disease among middle-aged women: a population-based follow-up study.

OBJECTIVES: The goal of this work was to assess whether high dietary glycemic load and glycemic index are associated with an increased risk of cardiovascular disease (CVD). BACKGROUND: The associations of dietary glycemic index and glycemic load with risk of CVD are not well established, particularly in populations consuming modest glycemic load diets. Moreover, risk may differ between lean and overweight subjects. METHODS: Associations of glycemic index and glycemic load with incident CVD were examined in a prospective cohort of 15,714 Dutch women age 49 to 70 years without diabetes or CVD. Dietary glycemic index and glycemic load were calculated using the glycemic index, carbohydrate content, and frequency of intake of individual foods. RESULTS: During 9 +/- 2 years of follow-up, 556 cases of coronary heart disease (CHD) and 243 cases of cerebrovascular accident (CVA) occurred. Dietary glycemic load (mean = 100; SD = 17) was associated with increased risk of CVD, adjusted for CVD risk factors and dietary variables, with a hazard ratio (HR) for the highest against lowest quartile of 1.47 (95% confidence interval [CI] 1.04 to 2.09; p(trend) = 0.03). Similar results were observed for dietary glycemic index with a corresponding HR of 1.33 (95% CI 1.07 to 1.67; p(trend) = 0.02). Glycemic load tended to be associated with both CHD (HR 1.44; 95% CI 0.95 to 2.19; p(trend) = 0.14) and CVA (HR 1.55; 95% CI 0.81 to 2.97; p(trend) = 0.10), but glycemic index only with CHD (HR 1.44; 95% CI 1.10 to 1.89; p(trend) = 0.01). Among overweight women (body mass index >25 kg/m2), glycemic load was associated with CVD (1.78; 95% CI 1.11 to 2.85; p(trend) = 0.04), but not among normal weight women (p(interaction) = 0.19). Body mass index did not modify the association of glycemic index with CVD. CONCLUSIONS: Among women consuming modest glycemic load diets, high dietary glycemic load and glycemic index increase the risk of CVD, particularly for overweight women.     

The prognostic value of estimated creatinine clearance alongside functional capacity in ambulatory patients with chronic congestive heart failure

OBJECTIVES: The goal of this study was to determine the prognostic significance of estimated creatinine clearance (CrCl) in relation to 6-min walk distance in ambulatory patients with congestive heart failure (HF). BACKGROUND: Although measurement of renal function is integral to the management of chronic congestive HF, its prognostic implications are not well described and have not been formally evaluated relative to measures of functional capacity. METHODS: We analyzed outcomes of the 585 participants of the 6-min walk substudy of the Digitalis Investigation Group (DIG) trial. The CrCl was estimated using the Cockcroft-Gault equation. Predictors of all-cause mortality were identified using semiparametric Cox proportional hazards regression and completely parametric hazard analyses. RESULTS: Most subjects (85%) were New York Heart Association functional class II and III. Mean age was 65 (+/-12) years and mean ejection fraction (EF) 35% (+/-13%). There were 153 (26%) deaths during a median of 2.6 years of follow-up. Mortality by increasing quartiles of estimated CrCl was 37% (18 to 48 ml/min), 29% (47 to 64 ml/min), 18% (64 to 86 ml/min), and 21% (86 to 194 ml/min) with corresponding hazard ratios (HRs) relative to the top quartile of 2.1 (95% confidence interval [CI], 1.4 to 3.3), 1.6 (95% CI, 1.0 to 2.5), and 0.9 (95% CI, 0.5 to 1.5), respectively. In Cox regression analyses, independent predictors of mortality were estimated CrCl (adjusted HR [quartile 1:quartile 4] 1.5; 95% CI, 1.1 to 2.1), 6-min walk distance < or =262 m [adjusted HR, 1.63; 95% CI, 1.12 to 2.27]), EF, recent hospitalization for worsening HF, and need for diuretic treatment. Parametric (hazard) analysis confirmed consistent effects of estimated CrCl on mortality in several subgroups including that of patients with EF >45%. CONCLUSION: In ambulatory patients with congestive HF, estimated CrCl predicts all-cause mortality independently of established prognostic variables.     

NT-proBNP on admission for early risk stratification in STEMI patients submitted to PCI. Relation with extension of STEMI and inflammatory markers

The prognostic implications of NT-proBNP measured on admission in patients with the ST-elevation myocardial infarction (STEMI) are not so far well elucidated. The present investigation, performed in 198 STEMI patients submitted to percutaneous coronary intervention (PCI), was aimed at assessing the prognostic value of NT-proBNP measured on admission to Intensive Cardiac Care Unit (ICCU) and its relation with the extension of myocardial infarction (indicated by cardiac biomarkers and ejection fraction) and inflammatory markers (C-reactive protein - CRP, erythrocyte sedimentation rate - ESR, leucocytes, fibrinogen). All patients who died during ICCU stay had increased values of NT-proBNP. Each quartile of NT-proBNP resulted directly correlated with age, heart rate, peak Tn I, admission creatinine serum levels, ESR, fibrinogen, and inversely correlated with ejection fraction. At backward logistic regression analysis, NT-proBNP values showed a significative correlation with peak Tn I (OR 1.013; 95% CI 1.001-1.025; p=0.036), and CRP positive (OR 6.450; 95% CI 1.714-24.272; p=0.006); age was close to reaching statistical significance (OR 1.043; 95% CI 0.999-1.089; p=0.055). At long term-follow-up NT-proBNP lacks any prognostic role in predicting adverse events such as hospitalization for rePCI, re-infarction and heart failure. Kaplan-Meier curves showed that all patients dead at follow-up were in the highest NT-proBNP quartiles.     

C-reactive protein and electrocardiographic ST-segment depression additively predict mortality: the Strong Heart Study

OBJECTIVES: This study was designed to examine whether high-sensitivity C-reactive protein (CRP) and electrocardiographic (ECG) ST-segment depression (STD) have additive utility for predicting cardiovascular disease (CVD) death and all-cause death (ACD). BACKGROUND: C-reactive protein, a marker of systemic inflammation, and ECG STD, an index of myocardial ischemia and hypertrophy, independently predict mortality. METHODS: Electrocardiograms and CRP levels were examined in 2,155 American Indian participants in the second Strong Heart Study examination. ST-segment depression >/=50 microV (n = 127) and CRP >7.0 mg/l (defining the upper quartile of CRP levels, n = 540) were considered abnormal. RESULTS: After 5.2 +/- 1.2 years follow-up there were 95 CVD deaths and 310 ACD. In univariate Cox analyses, the combination of CRP and ECG STD improved risk stratification compared to either alone, with the presence of both CRP >7.0 and ECG STD associated with a 7.7-fold increased risk of CVD death (95% confidence interval [CI] 3.3 to 18.2) and a 6.5-fold increased risk of ACD (95% CI 4.1 to 10.3). After adjustment for age, gender, and relevant risk factors, the combination of high CRP and STD remained predictive of CVD death and ACD, with the presence of both abnormal CRP and STD associated with the highest risks of CVD death (hazard ratio [HR] 3.2, 95% CI 1.1 to 10.5) and ACD (HR 3.9, 95% CI 2.1 to 7.2) and the presence of either high CRP or abnormal STD associated with intermediate risks of CVD death (HR 2.2, 95% CI 1.4 to 3.4) and ACD (HR 1.5, 95% CI 1.2 to 2.0). CONCLUSIONS: The combination of ECG STD and CRP increases the risk of mortality, demonstrating the additive impacts of active inflammation and preclinical CVD on prognosis.     

Risk factors for primary prevention of cardiovascular disease and risk reduction by lipid control: the OMEGA study risk factor sub-analysis

To identify risk factors for cardiovascular disease (CVD) in hypertensive patients with no history of CVD being treated with antihypertensive drugs, we examined subgroup data (n?=?13?052) from the prospective, observational Olmesartan Mega Study to Determine the Relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement (OMEGA) study. Risk factors for CVD, stroke and coronary heart disease (CHD) were examined using a Cox proportional hazards model. In addition, the effect of statin therapy at baseline on CHD prevention was analyzed in dyslipidemic patients. The factors significantly related to CVD were female (hazard ratio [HR]?=?0.637, 95% confidence interval [CI] 0.428–0.948), older age (65–69 years: HR?=?2.165, 95% CI 1.214–3.861; 70–74 years: HR?=?2.324, 95% CI 1.294–4.174; ≥75 years: HR?=?2.448, 95% CI 1.309–4.578), family history of CHD (HR?=?1.993, 95% CI 1.249–3.179), diabetes (HR?=?2.287, 95% CI 1.700–3.078), current smoking (HR?=?2.289, 95% CI 1.512–3.466) and alcohol drinking socially (HR?=?0.589, 95% CI 0.379–0.913). Diabetes was a risk factor for both stroke and CHD, while age, family history of CHD, and sodium intake score were risk factors for stroke alone. Sex, dyslipidemia, smoking and exercise habits were risk factors for CHD alone. The risk of CHD in dyslipidemic patients on statin treatment was comparable to the risk in patients without dyslipidemia (HR?=?1.134, 95% CI 0.604–2.126). However, in dyslipidemic patients not on statin treatment, the HR increased to 1.807 (95% CI 1.156–2.825). In conclusion, some risk factors for CVD in hypertensive patients being treated with antihypertensive drugs with no history of CVD differed between CHD and stroke. These results suggest the importance of managing dyslipidemia with a statin for primary prevention of CHD, as well as the importance of hypertension therapy.     

Early inflammation and risk of long-term development of heart failure and mortality in survivors of acute myocardial infarction predictive role of C-reactive protein.

OBJECTIVES: We aimed to study the relationship between C-reactive-protein (CRP), obtained within 12 to 24 h of symptoms onset, and long-term risk of death and heart failure (HF) in survivors of acute myocardial infarction (MI). BACKGROUND: A robust inflammatory response is an integral component of the response to tissue injury during MI. The magnitude of the early inflammatory response to ischemic injury might be an important determinant of long-term outcome. METHODS: We prospectively studied 1,044 patients admitted with acute MI and discharged from hospital in stable condition. RESULTS: During a median follow-up of 23 months (range, 6 to 42 months), 113 patients died and 112 developed HF. In a multivariable Cox regression model adjusting for clinical variables and predischarge ejection fraction, compared with patients in the first CRP quartile, the adjusted hazard ratios (HRs) for death progressively increased with higher quartiles of CRP (second quartile 1.4 [95% confidence interval (CI) 0.6 to 2.9]; third quartile 2.3 [95% CI 1.2 to 4.6]; fourth quartile 3.0 [95% CI 1.5 to 5.7]; for trend, p = 0.0002). Compared with patients in the first CRP quartile, the adjusted HRs for HF were: second quartile, 1.1 (95% CI 0.5 to 2.3); third quartile, 1.9 (95% CI 1.0 to 3.6); and fourth quartile, 2.1 (95% CI 1.2 to 3.9) (for trend, p = 0.005). CONCLUSIONS: C-reactive-protein is a marker of long-term development of HF and mortality in patients with acute MI and provides prognostic information beyond that provided by conventional risk factors and the degree of left ventricular systolic dysfunction.     

Amino terminal B-type natriuretic peptide, renal function, and prognosis in acute heart failure: a hospital cohort study

BackgroundAmino-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable diagnostic and prognostic test in heart failure (HF). Limited information is available concerning its use in patients with renal failure, in whom dependence on renal clearance may negatively affect its performance.Methods and ResultsWe evaluated influence of renal function on NT-proBNP levels and on its prognostic value after hospital discharge in 283 acute HF patients. Admission and discharge NT-proBNP levels were higher in patients with decreased estimated glomerular filtration rate (eGFR). In these patients discharge NT-proBNP above median was associated to occurrence of death or readmission at 6 months (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.27–5.03); in patients with normal eGFR, a trend to this association was found (HR 1.64, CI 0.98–2.76). Decrease in NT-proBNP less than 30% of baseline was associated to outcome in patients with normal eGFR (HR 2.68, CI 1.54–4.68) and decreased eGFR (HR 2.54, CI 1.49–4.33).ConclusionsAcute HF patients with renal failure have higher NT-proBNP levels than those with normal renal function. Discharge NT-proBNP has long-term prognostic value in HF patients with renal dysfunction. NT-proBNP variations during hospitalization provide additional prognostic information either in patients with normal or reduced eGFR.     

Plasma N-terminal fragments of natriuretic propeptides predict the risk of cardiovascular events and mortality in middle-aged men.

AIMS: The prognostic significance of N-terminal pro-A-type (NT-proANP) and pro-B-type natriuretic peptides (NT-proBNP) is not well documented in population-based prospective studies. We, therefore, studied if both NT-proANP and NT-proBNP are predictive for overall death, cardiovascular events, and atrial fibrillation (AF) among middle-aged men without heart failure or AF at baseline. METHODS AND RESULTS: Plasma NT-proANP and NT-proBNP were measured in a representative population-based sample of 905 men (age 46-65 years) from eastern Finland. There were 110 deaths [58 cardiovascular and 40 coronary heart disease (CHD)] and 59 cases of AF during a follow-up of 10 years. The multivariable adjusted risk for overall was 1.35-fold (95% CI 1.15-1.57) and 1.52-fold (95% CI 1.21-1.91) for CHD death for each SD (160.8 pmol/L) increment in NT-proANP. The respective risks were 1.26-fold (95% CI 1.12-1.42) and 1.44-fold (95% CI 1.22-1.60) for each SD (58.9 pmol/L) increment in NT-proBNP. The adjusted risks for future AF were 1.46 (P<0.001) and 1.72-fold (P<0.001) for each SD increment in NT-proANP and NT-proBNP, respectively. CONCLUSION: The main finding of the present study is that NT-proANP and NT-proBNP are strong predictors of death from cardiovascular and other causes including AF. These natriuretic peptides add to the prognostic value of conventional risk factors and provide a non-invasive measure for identifying men with high risk of death and its co-morbidities.     

Higher Level of Systemic C-Reactive Protein Is Independently Predictive of Coronary Heart Disease in Older Community-Dwelling Adults: The Three-City Study

OBJECTIVES: To assess the association between systemic C-reactive protein (CRP) and incident coronary heart disease (CHD) in community-dwelling elderly people.
DESIGN: A French population-based multicenter prospective cohort study.
SETTING: Three cities in France: Bordeaux in the southwest, Dijon in the northeast, and Montpellier in the southeast.
PARTICIPANTS: After 4 years of follow-up, a case–cohort study was designed including 1,004 subjects randomly selected from the initial cohort of 9,294 subjects free of CHD at baseline and 174 subjects who developed first CHD events during follow-up.
MEASUREMENTS: Hazard ratios (HRs) were estimated using a Cox proportional hazard model adapted for the case–cohort design using a CRP level less than 1 mg/L as the reference category.
RESULTS: Of the random sample, 24.3% had a CRP level less than 1.0 mg/L, 45.8% had a CRP level of 1.0 to 2.9 mg/L, and 29.9% had a CRP level of 3.0 to 10.0 mg/L. The HRs for CHD, adjusted for age, sex, and study center, were 1.69 (95% confidence interval (CI)=1.04–2.75) for CRP from 1.0 to 2.9 mg/L and 2.32 (95% CI=1.41–3.82) for CRP from 3.0 to 10.0 mg/L ( P for trend <.001). After additional adjustment for smoking, body mass index, diabetes mellitus, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, statin use, and antihypertensive treatment, a baseline CRP of 3.0 to 10.0 mg/L remained associated with risk of CHD (HR=1.87, 95% CI=1.09–3.25), although CRP did not improve the discriminative ability of a predicting model based on traditional risk factors (receiver operating characteristic curves from 0.740 to 0.749).
CONCLUSION: CRP is an independent CHD risk marker but does not improve CHD risk prediction in community-dwelling elderly people.     

Estimated glomerular filtration rate, inflammation, and cardiovascular events after an acute coronary syndrome

Both renal dysfunction and elevated levels of high-sensitivity C-reactive protein (CRP) are associated with a higher risk of cardiovascular (CV) outcomes. However, it remains to be established whether the prognostic value of impaired estimated glomerular filtration rate (GFR) remains after accounting for markers of inflammation. METHODS AND RESULTS: Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation in 4178 patients with non-ST or ST-elevation acute coronary syndromes, participating in the A to Z trial. The mean estimated GFR was 68 mL/min, with a median baseline CRP of 20.2 mg/L. Both an estimated GFR <60 mL/min (HR 2.13, 95% CI 1.7-2.6) and a CRP in the fourth quartile (HR 1.7, 95% CI 1.4-2.2) were strong univariate predictors of a CV event (composite of CV death, recurrent myocardial infarction, heart failure, or stroke). After adjusting for baseline CRP, GFR <60 mL/min remained a strong multivariate predictor for CV death (HR 1.82, 95% CI 1.1-2.97). Randomization to high-dose statin therapy was associated with a reduction in the CV composite (adjusted HR 0.69, 95% CI 0.5-0.95) irrespective of baseline renal function. CONCLUSIONS: In a population of patients without overt renal disease, moderate reductions in estimated GFR remain an important prognostic marker. This increased CV hazard associated with an estimated GFR <60 mL/min is independent and additive to markers of inflammation.     

C-reactive protein, diastolic dysfunction, and risk of heart failure in patients with coronary disease: Heart and Soul Study

BACKGROUND: High-sensitivity C-reactive protein (CRP) is an inflammatory marker that predicts coronary heart disease (CHD) and, in recent studies, incident heart failure (HF). Whether the association of inflammation with incident HF is explained by worse baseline left ventricular dysfunction or by underlying CHD is unknown. METHODS AND RESULTS: Serum CRP was measured in a cohort of 985 outpatients with established CHD from the Heart and Soul Study. During 3 years of follow-up, 15% of the participants with elevated CRP levels (>3 mg/L) were hospitalised for HF, compared with 7% of those with CRP 相似文献   

B-Type Natriuretic Peptides Improve Cardiovascular Disease Risk Prediction in a Cohort of Women

Background

Although N-terminal pro–B-type natriuretic peptide (NT-proBNP) has a strong relationship with incident cardiovascular disease (CVD), few studies have examined whether NT-proBNP adds to risk prediction algorithms, particularly in women.

Objectives

This study sought to evaluate the relationship between NT-proBNP and incident CVD in women.

Methods

Using a prospective case-cohort within the WHI (Women’s Health Initiative) observational study, we selected 1,821 incident cases of CVD (746 myocardial infarctions, 754 ischemic strokes, 160 hemorrhagic strokes, and 161 other cardiovascular [CV] deaths) and a randomly selected reference cohort of 1,992 women without CVD at baseline.

Results

Median levels of NT-proBNP were higher at study entry among incident cases (120.3 ng/l [interquartile range (IQR): 68.1 to 219.5 ng/l]) than among control subjects (100.4 ng/l [IQR: 59.7 to 172.6 ng/l]; p < 0.0001). Women in the highest quartile of NT-proBNP (≥140.8 ng/l) were at 53% increased risk of CVD versus those in the lowest quartile after adjusting for traditional risk factors (1.53 [95% confidence interval (CI): 1.21 to 1.94]; p for trend <0.0001). Similar associations were observed after adjustment for Reynolds Risk Score covariables (1.53 [95% CI: 1.20 to 1.95]; p for trend <0.0001); the association remained in separate analyses of CV death (2.66 [95% CI: 1.48 to 4.81]; p for trend <0.0001), myocardial infarction (1.39 [95% CI: 1.02 to 1.88]; p for trend = 0.008), and stroke (1.60 [95% CI: 1.22 to 2.11]; p for trend <0.0001). When added to traditional risk covariables, NT-proBNP improved the c-statistic (0.765 to 0.774; p = 0.0003), categorical net reclassification (0.08; p < 0.0001), and integrated discrimination (0.0105; p < 0.0001). Similar results were observed when NT-proBNP was added to the Reynolds Risk Score.

Conclusions

In this multiethnic cohort of women with numerous CV events, NT-proBNP modestly improved measures of CVD risk prediction.     

Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (The Framingham Heart Study)

A delayed heart rate (HR) recovery after graded exercise testing has been associated with increased all-cause mortality in clinic-based samples. No prior study has examined the association of HR recovery after exercise with the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) events. We evaluated 2,967 Framingham study subjects (1,400 men, mean age 43 years) who were free of CVD and underwent a treadmill exercise test (Bruce protocol) at a routine examination. We examined the relations of HR recovery indexes (decrease in HR from peak exercise) to the incidence of a first CHD or CVD event and all-cause mortality, adjusting for established CVD risk factors. During follow-up (mean 15 years), 214 subjects experienced a CHD event (156 men), 312 developed a CVD event (207 men), and 167 died (105 men). In multivariable models, continuous HR recovery indexes were not associated with the incidence of CHD or CVD events, or with all-cause mortality. However, in models evaluating quintile-based cut points, the top quintile of HR recovery (greatest decline in HR) at 1-minute after exercise was associated with a lower risk of CHD (hazards ratio vs bottom 4 quintiles 0.54, 95% confidence interval [CI], 0.32 to 0.93) and CVD (hazards ratio 0.61, 95% CI 0.41 to 0.93), but not all-cause mortality (hazards ratio 0.99, 95% CI 0.60 to 1.62). In our community-based sample, HR recovery indexes were not associated with all-cause mortality. A very rapid HR recovery immediately after exercise was associated with lower risk of CHD and CVD events. These findings should be confirmed in other settings.     

Lipoprotein particles, insulin, adiponectin, C-reactive protein and risk of coronary heart disease among men with metabolic syndrome

We tested the hypotheses whether nuclear magnetic resonance (NMR) determined lipoprotein particles, insulin and adiponectin, and C-reactive protein (CRP) and white blood cell (WBC) count as markers of inflammation predicted risk of coronary heart disease (CHD) death among 428 men age 35-57 years with metabolic syndrome (MetSyn) in a matched case control study within the multiple risk factor intervention trial. Blood samples collected at entry into the study and stored at -60 degrees C were obtained from central storage for blood analyte analysis. Two hundred and fourteen men with MetSyn who died of CHD were matched with 214 men with MetSyn who did not die of CHD during 18 years of follow-up. Cases were matched to controls on age, study group, number of factors present in the MetSyn, and presence or absence of a nonfatal CVD event during the trial. Mortality follow-up was determined using the National Death Index. Higher levels of high density lipoprotein particles (HDL-P), especially medium-sized HDL-P [hazard ratio (95% confidence interval) 0.45 (0.25-0.83, P<0.01), quartile 1 as compared to quartile 4], were associated with lower risk of CHD death. Low density lipoprotein (LDL) particles were not associated with increased risk of CHD. Elevated LDL cholesterol (LDL-C), smoking and WBC count were, but levels of adiponectin, insulin and CRP were not significantly related to CHD death. In multivariate models adjusting for smoking and LDL-C, medium HDL-P and WBC count remained independent predictors of CHD death. Number of HDL particles, especially medium-sized HDL particles and WBC count were independent predictors of CHD death among men with MetSyn.     

Diabetes,plasma insulin,and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT)

BACKGROUND: Diabetes mellitus, impaired fasting glucose level, or insulin resistance are associated with increased risk of cardiovascular disease. OBJECTIVES: To determine the efficacy of gemfibrozil in subjects with varying levels of glucose tolerance or hyperinsulinemia and to examine the association between diabetes status and glucose and insulin levels and risk of cardiovascular outcomes. METHODS: Subgroup analyses from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, a randomized controlled trial that enrolled 2531 men with coronary heart disease (CHD), a high-density lipoprotein cholesterol level of 40 mg/dL or less (/=271 pmol/L) was associated with a 31% increased risk of events (P =.03). Gemfibrozil was effective in persons with diabetes (risk reduction for composite end point, 32%; P =.004). The reduction in CHD death was 41% (HR, 0.59; 95% CI, 0.39-0.91; P =.02). Among individuals without diabetes, gemfibrozil was most efficacious for those in the highest fasting plasma insulin level quartile (risk reduction, 35%; P =.04). CONCLUSION: In men with CHD and a low high-density lipoprotein cholesterol level, gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level.