Relative validity of the 10-year cardiovascular risk estimate in a population cohort of the REGICOR study

Introduction and objectives

Cardiovascular risk screening requires accurate risk functions. The relative validity of the Framingham-based REGICOR adapted function is analyzed and the population distribution of cardiovascular 10-year cardiovascular events is described by risk group.

Methods

A population cohort of 3856 participants recruited between 1995 and 2000, aged 35 to 74 years from Girona without symptoms of cardiovascular diseases, was followed between 2006 and 2009. Standardized laboratory and blood pressure measurements, questionnaires, and case definitions were used. The follow-up combined cross-linkage of our databases with our regional mortality registry, reexamination, and telephone contact with participants. Coronary disease endpoints alone were considered.

Results

A total of 27 487 person-years were obtained (mean follow-up 7.1 years), and the follow-up was achieved in 97% of participants (120 coronary disease events). Validity was good: the regression coefficients estimated with the cohort data did not differ from those obtained in the original Framingham function. Function calibration was good: the observed incidence of cardiovascular events in the decile groups of risk did not differ from the function prediction (P = .127 in women, and P = .054 in men). The C statistic (discrimination) was 0.82 (95% confidence interval, 0.76-0.88) in women, and 0.78 (95% confidence interval, 0.73-0.83) in men. More than 50% of cardiovascular events occurred in participants whose 10-year risk was 5% to 14.9%.

Conclusions

The studied function accurately predicts coronary disease events at 10 years. Risk stratification could be simplified in 4 groups: low (<5%), moderate (5%-9.9%), high (10%-14.9%) and very high (≥15%).Full English text available from: www.revespcardiol.org     

Remnant-like lipoproteins, hormone therapy, and angiographic and clinical outcomes: the Women's Angiographic Vitamin & Estrogen Trial

Background

Little is known about the impact of post-menopausal hormone therapy on remnant-like particle (RLP) concentrations and about the relationship between RLP concentration and angiographic progression of coronary artery disease and clinical events in women.

Methods

RLP cholesterol and triglyceride levels were measured at baseline and 3 months after randomization in 397 post-menopausal women enrolled in The Women's Angiographic Vitamin & Estrogen (WAVE) trial. Correlates of baseline RLP levels and changes in levels with post-menopausal hormone therapy were determined with multiple linear regression. Coronary angiography was performed at baseline and after a mean of 2.9 years. Changes in minimal and average luminal diameter were modeled with multivariate linear regression, clinical outcomes (non-fatal myocardial infarction, stroke, or cardiovascular death) with multiple logistic regression.

Results

The mean subject age was 65 years, 66% of subjects were white, 18% of subjects smoked, most subjects were overweight or obese, and 35% of subjects had diabetes mellitus. RLP cholesterol (0.277 ± 0.254 mmol/L) and triglyceride (0.386 ± 0.552 mmol/L) levels corresponded approximately to the 90th percentile in women in the Framingham study. RLP levels did not change significantly with hormone therapy. RLP levels at baseline, changes in RLP levels, and on treatment RLP levels did not relate to angiographic changes or clinical outcomes (non-fatal myocardial infarction, stroke, or cardiovascular death).

Conclusions

RLP levels were high among post-menopausal women enrolled in the WAVE study, were not affected by hormone therapy, and did not relate to angiographic progression of coronary artery disease or clinical outcomes.     

Coronary ischemic events after first atrial fibrillation: risk and survival

Purpose

We aimed to determine the long-term, gender-specific incidence and mortality risk of coronary ischemic events after first atrial fibrillation (AF).

Methods

In this longitudinal cohort study, adult residents of Olmsted County, Minnesota, with an electrocardiogram-confirmed AF first documented in 1980 to 2000 and without prior coronary heart disease, were followed to 2004. The primary outcome was first coronary events (angina with angiographic confirmation, unstable angina, nonfatal myocardial infarction, or coronary death). Sex-specific incidence of coronary ischemic events and survival after development of such events were assessed using Cox proportional hazards modeling. Kaplan-Meier estimates of risks for coronary ischemic events were compared with those predicted by the Framingham equation.

Results

Of the 2768 subjects (mean age 71 years, 48% were men), 463 (17%) had a first coronary event during a follow-up of 6.0 ± 5.2 years. The unadjusted incidence was 31 per 1000 person-years, and there was no difference between men and women. The incidence was higher in men (hazard ratio 1.32, P = .004) after adjusting for age. The 10-year event estimates were 22% and 19% in men and women, respectively, by our Kaplan-Meier analyses, and 21% and 11%, respectively, by Framingham risk equation. The mortality risk after coronary events was higher in women (hazard ratio 2.99 vs 2.33; P = .044), even after multiple adjustment.

Conclusions

First AF marks a high risk for new coronary ischemic events in both men and women. AF conferred additional risk for coronary events beyond conventional risk prediction in women only. The excess mortality risk associated with the development of coronary events was significantly greater in women.     

Impact of Gender on Risk Stratification by Stress Echocardiography

Objective

To compare the prognostic value of stress echocardiography results in men and women with known and suspected coronary artery disease.

Methods

We analyzed the data of 8737 patients (5529 men and 3208 women) who underwent stress echocardiography (exercise in 523 patients, dipyridamole in 6227 patients, dobutamine in 1987) for evaluating known (n = 3857) or suspected (n = 4880) coronary artery disease. Patients were followed up for the occurrence of overall mortality or nonfatal myocardial infarction.

Results

During a median follow-up of 25 months, 1218 cardiac events (693 deaths and 525 infarctions) occurred. Moreover, 2263 patients (1731 men [31%] and 532 women [17%]; P < .0001) underwent coronary revascularization and were censored. Stress echocardiography results added prognostic information to that of clinical findings and resting wall motion score index in men and women with both known and suspected coronary artery disease. In patients with known coronary artery disease, women had a higher (P = .01) event rate than men in the presence of ischemia. The annual event rate was worse for nondiabetic women (P = .007) but not diabetic women; age had a neutral prognostic effect in the 2 sexes. In patients with suspected coronary artery disease, men without ischemia had a higher (P < .0001) event rate than women. The annual event rate was worse in men aged less than 65 years (P < .0001) or more than 65 years (P = .04), and those with (P = .03) or without (P < .0001) diabetes.

Conclusion

Prognosis is at least comparable in men and women with ischemia and in those with coronary artery disease and no ischemia at stress echocardiography. In these clinical settings, availability for major procedures should be similar for both genders.     

Impaired fasting glucose and recurrent cardiovascular disease among survivors of a first acute myocardial infarction: Evidence of a sex difference? The Western New York experience

Background and aims

There is little epidemiological evidence regarding the association of impaired glucose metabolism with recurrent cardiovascular events. We therefore examined potential sex differences in the effect of impaired fasting glucose (IFG) on recurrent cardiovascular disease (CVD) in a community-based study of survivors of a first acute myocardial infarction (MI).

Methods and results

This report focuses on 1226 incident MI cases (28.4% women) discharged alive from area hospitals in the Western New York Acute MI Study (1996-2004). Deaths and underlying cause of death were determined via query of the National Death Index (Plus) Retrieval Program with follow-up through December 31, 2004. Outcomes reported included fatal or non-fatal coronary heart disease (CHD) or coronary revascularization surgery and total stroke. Traditional CHD risk factors and other explanatory variables were determined by clinical examination after the first acute event. Impaired fasting glucose was defined as fasting blood glucose between 100 and 125 mg/dl. During a mean follow-up of 4.5 years, there were 91 recurrent events (26.1%) in women and 173 recurrent events (19.7%) in men. After multivariable adjustment, the hazard ratios for recurrent cardiovascular events were 1.96 (95% CI: 1.15-3.16) and 2.59 (1.56-4.30) in women with IFG and with diabetes, respectively, compared to normoglycemic women. Among men, neither IFG nor diabetes was independently related to risk of recurrence.

Conclusions

In this study, IFG was a strong risk factor for recurrent cardiovascular events only among women. These results suggest that increased cardiovascular risk in MI survivors begins at lower glucose levels in women than men.     

Metabolic syndrome and coronary angiographic disease progression: the Women's Angiographic Vitamin & Estrogen trial

Background

The metabolic syndrome is a cluster of clinical characteristics thought to be associated with increased coronary risk. This analysis evaluates angiographic progression of coronary disease in women who are postmenopausal with and without the metabolic syndrome enrolled in the Women’s Angiographic Vitamin & Estrogen (WAVE) trial, a randomized, controlled trial of hormone therapy and antioxidant vitamins.

Methods

A total of 425 women who are postmenopausal and have angiographic coronary disease were enrolled at 7 clinics between July 1997 and August 1999. Women were categorized as having the metabolic syndrome when they met the National Cholesterol Education Program Adult Treatment Panel III definition. Coronary angiograms were performed at baseline and after 2.8 ± 0.9 years (mean ± SD). Quantitative coronary angiographic analysis was performed at a core laboratory.

Results

Women with the metabolic syndrome (177/294, 60%) were more likely to be taking cholesterol-lowering medication (65% vs 51%, P = .01) and had higher body mass index (33 ± 6 vs 28 ± 6 kg/m², P <.001). The mean reduction in minimum lumen diameter was greater (−0.041 ± 0.151 vs −0.023 ± 0.148 mm/year, P = .33) and new lesions were more frequent (34% vs 23%, P = .054) in women with the metabolic syndrome. In multivariate analysis, the metabolic syndrome was not an independent predictor of angiographic disease progression. However, clinical events (myocardial infarction, stroke, or coronary death) were more frequent among women with the metabolic syndrome (P = .02).

Conclusion

The metabolic syndrome was prevalent among postmenopausal women with coronary disease enrolled in the WAVE trial. Having the metabolic syndrome was not independently associated with changes in minimum lumen diameter or the development of new or progressing coronary lesions, but did confer an increased risk of clinical cardiovascular events.     

Mediterranean diet and the incidence of cardiovascular disease: A Spanish cohort

Background and aim

The Mediterranean diet is considered a model for healthy eating. However, prospective evidence in Mediterranean countries evaluating the relationship between this dietary pattern and non-fatal cardiovascular events is scarce. The aim of the present study was to evaluate the association between the adherence to the Mediterranean diet and the incidence of fatal and non-fatal cardiovascular events among initially healthy middle-aged adults from the Mediterranean area.

Methods and results

We followed-up 13,609 participants (60 percent women, mean age: 38 years) initially free of cardiovascular disease (CVD) during 4.9 years. Participants were part of a prospective cohort study of university graduates from all regions of Spain. Baseline diet was assessed using a validated 136-item food-frequency questionnaire. A 9-point score was used to appraise adherence to the Mediterranean diet. Incident clinical events were confirmed by a review of medical records. We observed 100 incident cases of CVD. In multivariate analyses, participants with the highest adherence to the Mediterranean diet (score > 6) exhibited a lower cardiovascular risk (hazard ratio = 0.41, 95% confidence interval [CI]: 0.18-0.95) compared to those with the lowest score (<3). For each 2-point increment in the score, the adjusted hazard ratios were 0.80 (95% CI: 0.62-1.02) for total CVD and 0.74 (0.55-0.99) for coronary heart disease.

Conclusions

There is an inverse association between adherence to the Mediterranean diet and the incidence of fatal and non-fatal CVD in initially healthy middle-aged adults.     

Change of multiple complex coronary plaques in patients with acute myocardial infarction: a study with coronary angiography

Background

Patients with acute myocardial infarction (AMI) may have multiple complex coronary plaques that are not limited to the culprit lesions. However, it is unknown whether they tend to progress in severity, regress, or remain stable. The aim of this angiographic study is to evaluate the natural history of these lesions.

Methods

We consecutively enrolled 229 patients who underwent coronary angiography at the time of their hospitalization to treat AMI with primary angioplasty. Baseline and follow-up (mean follow-up duration, 192 ± 33 days) coronary angiographic data in patients with multiple complex coronary plaques characterized by thrombus, ulceration, plaque irregularity, and impaired flow were compared.

Results

Single complex coronary plaques were identified in 167 patients (73%), and multiple complex plaques were identified in the other 62 patients (27%). Among the patients with multiple complex plaques (62 patients, 83 non-culprit complex plaques), the angiographic examinations were reviewed simultaneously in 43.5% (27 patients, 35 non-culprit complex plaques). Of 35 non-culprit complex lesions, 29 lesions (82%) remained complex without changing into smooth lesions, 1 lesion became totally occluded, and 4 lesions regressed. The severity of non-culprit complex lesions between baseline and follow-up angiography is equal (maximal diameter stenosis, 74% ± 15% vs 72% ± 15%, P = .4). Long-term cardiac events after discharge were more likely to develop in patients with multiple complex plaques than in patients with single complex plaques (24% vs 10%, respectively; P <.01).

Conclusions

In patients with AMI, little angiographic change occurred during 6 months of follow-up in the non-culprit complex plaques.     

Differences in the clinical features and outcomes in African Americans and whites with myocardial infarction

Purpose

Less is known about the differences in clinical and angiographic features and the outcomes of African Americans with ST-elevation myocardial infarction compared with whites with ST-elevation myocardial infarction. Accordingly, the current study examines the relationship of African American race to patient-related clinical factors, angiographic findings, and clinical events.

Methods

We evaluated data from 32 419 patients with ST-elevation myocardial infarction who received fibrinolysis. The primary outcomes of interest were 30-day and 5-year mortality.

Results

African Americans comprised 5.1% of the study population (1664/32 419). Compared with white patients, black patients were younger, were more likely female, had a higher prevalence of coronary risk factors, and were more likely to have higher presenting heart rate, blood pressure, and Killip Class. Coronary angiography rates were similar in the two groups, but blacks were less likely to undergo coronary revascularization. The patency of the infarct-related artery after thrombolysis or mechanical reperfusion was higher in blacks, who were more likely to have no significant coronary artery disease and less likely to have disease in two or more vessels. In-hospital stroke (adjusted odds ratio 1.75, 95% confidence interval [CI] 1.19-2.59) and major bleeding (adjusted odds ratio 1.32, 95% CI 1.13-1.55) were higher among African Americans. Although no differences were observed in the 30-day mortality between the two groups, African Americans who survived to 30 days had higher 5-year mortality than whites (17% vs 12.5%, adjusted hazard ratio 1.63, 95% CI 1.41-1.90).

Conclusions

Although 30-day survival was similar between African Americans and whites with ST-elevation myocardial infarction, in-hospital stroke and bleeding and 5-year mortality among 30-day survivors were significantly higher among blacks despite their younger age.     

Short- and long-term prognostic value of the corrected QT interval in the non-ST-elevation acute coronary syndrome

Background and purpose

Myocardial ischemia prolongs the QTc interval. Very little data exists about its prognostic implications in the non-ST-elevation acute coronary syndromes (NST-ACS).

Methods

This is and observational and prospective study in which we evaluated the prognostic implications of the QTc obtained at admission (AQTc) in the short- and long-term of the NST-ACS. The median of the follow-up was 17 months.

Results

AQTc correlated adequately with the incidence of adverse events in the short- and long-term (P < .001), with the best cut-off point in 450 milliseconds. Patients with AQTc ≥450 presented higher frequency of in-hospital death: 8.8% vs 1.2%; P = .001, and MACE (death, recurrent ischemia, or urgent coronary revascularization): 72% vs 25%; P < .001. In a Cox regression analysis, we found 3 independent predictors of cardiovascular death after discharge: AQTc ≥450 (14.7% vs 2.1%; P < .0001), age >65 years and left ventricular ejection fraction <40%. Coronary revascularization reduced the risk of posthospitalary cardiovascular death in AQTc ≥450 milliseconds (5% vs 24%; P < .0001) but had no significant effect in AQTc<450 milliseconds.

Conclusion

These findings provide a new evidence supporting the prognostic value of the AQTc in predicting unfavorable events in the short- and long-term of the NST-ACS.     

Serum antimüllerian hormone is not predictive of oocyte quality in vitro fertilization

Objectives

The assessment of the ovarian reserve is mandatory in women undergoing assisted reproduction. Antimüllerian hormone (AMH) produced by granulosa cells from preantral and early antral follicles, is a promising indicator of ovarian reserve. However, few studies have evaluated the predictive value of AMH on oocyte quality.

Material and methods

A retrospective study was undertaken at the Bretonneau University Hospital of Tours. A total of 559 women undergoing in vitro fertilization treatment between January 2007 and December 2007 were included in the study. Serum AMH levels were determined by using an ultrasensitive ELISA test. Total number of oocytes, rate of mature oocytes, fertilization rate, embryo quality and clinical pregnancy rate were recorded.

Results

Serum AMH was significantly lower in groups of patients with few oocytes collected. However, serum AMH was not predictive of nuclear maturity of oocytes, fertilization rate and quality of early embryos. Additionally, low levels of AMH do not preclude clinical pregnancy, in in vitro fertilization.

Conclusion

At the moment, serum AMH is a relatively predictive indicator of the ovarian reserve, in terms of quantity but not in terms of quality. Moreover, it is still not possible to determine serum AMH cut-off value to predict clinical pregnancy in IVF programmes.     

Plasma asymmetric dimethylarginine predicts death and major adverse cardiovascular events in individuals referred for coronary angiography

Background

Elevated plasma level of asymmetric dimethylarginine (ADMA) was reported to be associated with endothelial dysfunction and atherosclerotic risk factors. We assessed the prognostic value of plasma ADMA levels in 997 consecutive individuals referred for coronary angiography from July 2006 to June 2009.

Methods

ADMA was measured by high performance liquid chromatography. All subjects were followed for a median period of 2.4 years for the occurrence of all-cause mortality, major adverse cardiovascular events (MACE, defined as cardiovascular death, non-fatal myocardial infarction and stroke), and MACE plus clinically-driven target vessel revascularization (TVR).

Results

Plasma ADMA levels were significantly higher in patients with significant coronary artery disease (CAD) (≥ 50% stenosis, n = 655) than those with insignificant CAD (20-50% stenosis, n = 272) and normal coronary artery (< 20% stenosis, n = 70) (0.47 ± 0.10 μmol/l vs 0.44 ± 0.10 μmol/l vs 0.42 ± 0.08 μmol/l, p < 0.001). By multivariate analysis, plasma ADMA level was identified as a significant independent risk factor of significant CAD (OR: 1.29, 95% CI: 1.10−1.50; p = 0.002). Moreover, multivariate Cox regression analysis showed that, comparing with the ADMA tertile I, the highest ADMA tertile was a significant independent predictor for all adverse long-term clinical outcomes. Notably, plasma ADMA level remained associated with the long-term outcomes in non-diabetic individuals, but not in those with diabetes (interaction p = 0.04 for MACE plus TVR).

Conclusions

Our findings suggest that elevated plasma ADMA level might be a risk factor of significant CAD, and might predict worse long-term clinical outcomes in subjects referred for cardiac catheterization, especially in non-diabetic individuals.     

Epidemiology of mitral annular calcification and its predictive value for coronary events in African Americans: the Jackson Cohort of the Atherosclerotic Risk in Communities Study

Background

Despite the potential link between mitral annular calcification (MAC) and atherosclerosis, there is limited data regarding the prevalence of MAC in African Americans and its relationship with coronary heart disease (CHD)events in this high-risk population.

Methods

The study population included 2409 African American participants of the Artherosclerotic Risk in Communities study (ARIC) undergoing echo examinations between 1993-1996. The primary outcome was incident CHD events [defined as fatal coronary event, hospitalized myocardial infarction or cardiac procedure]. MAC was considered a binary variable (yes/no). The Cox proportional hazard model was used for the analysis and the model was adjusted for gender, age, body mass index, hypertension, diabetes, smoking status, renal function (based on serum creatinine), high LDL and low HDL.

Results

Of the 2409 in the study population, 1549 (64%) were women and the mean age was 59.2 ± 5.8 years (range 49-75). MAC was positively associated with age and renal function. The overall prevalence of MAC was 4.6% for women and 5.6% for men. In participants aged ≥ 70, the prevalence of MAC was 10% in women and 15.2% in men. During a median follow-up of 4.8 years, there were 237 total incident CHD events recorded. After adjustment, the hazard ratio for CHD events among the MAC subgroup was 2.32 (95% CI, 1.11-4.87).

Conclusions

In this relatively young population of middle-aged African Americans, the prevalence of MAC is low; however, the presence of MAC incurs a significant risk for coronary events.     

Relation of admission QRS duration with development of angiographic no-reflow in patients with acute ST-segment elevation myocardial infarction treated with primary percutaneous interventions

Background

Although QRS-complex changes during ischemia have been described previously, their relation with no-reflow is not clear.

Purpose

To evaluate relation of admission QRS duration with angiographic no-reflow, we studied 162 patients who underwent primary angioplasty.

Methods

Twelve-lead electrocardiogram with a paper speed of 50 mm/s was recorded on admission and repeated after angioplasty. Patients were divided into reflow and no-reflow groups based on postangioplasty coronary thrombolysis in myocardial infarction flow grade.

Results

Patients in the no-reflow group (26 patients) were older (P = .001) and had significantly longer pain-to-balloon interval (P = .007). The patients in the no-reflow group had significantly longer QRS duration on admission electrocardiogram compared with patients in the reflow group (interquartile range, 80-93 [median, 84] milliseconds vs 60-80 [median, 76] milliseconds, respectively; P < .001). After adjusting all variables, QRS duration on admission was found to be independently related to angiographic no-reflow (odds ratio, 1.07; 95% confidence interval, 1.02-1.12; P = .003).

Conclusion

QRS duration on admission may be valuable in predicting no-reflow.     

Risk of mortality with vitamin E supplements: the Cache County study

Purpose

A recent meta-analysis reported increased mortality in clinical trial participants randomized to high-dose vitamin E. We sought to determine whether these mortality risks with vitamin E reflect adverse consequences of its use in the presence of cardiovascular disease.

Methods

In a defined population aged 65 years or older, baseline interviews captured self- or proxy-reported history of cardiovascular illness. A medicine cabinet inventory verified nutritional supplement and medication use. Three sources identified subsequent deaths. Cox proportional hazards methods examined the association between vitamin E use and mortality.

Results

After adjustment for age and sex, there was no association in this population between vitamin E use and mortality (adjusted hazard ratio [aHR] 0.93; 95% confidence interval [CI], 0.74-1.15). Predictably, deaths were more frequent with a history of diabetes, stroke, coronary artery bypass graft surgery, or myocardial infarction, and with the use of warfarin, nitrates, or diuretics. None of these conditions or treatments altered the null main effect with vitamin E, but mortality was increased in vitamin E users who had a history of stroke (aHR 3.64; CI, 1.73-7.68), coronary bypass graft surgery (aHR 4.40; CI, 2.83-6.83), or myocardial infarction (aHR 1.95; CI, 1.29-2.95) and, independently, in those taking nitrates (aHR 3.95; CI, 2.04-7.65), warfarin (aHR 3.71; CI, 2.22-6.21), or diuretics (aHR 1.83; CI, 1.35-2.49). Although not definitive, a consistent trend toward reduced mortality was seen in vitamin E users without these conditions or treatments.

Conclusions

In this population-based study, vitamin E use was unrelated to mortality, but this apparently null finding seems to represent a combination of increased mortality in those with severe cardiovascular disease and a possible protective effect in those without.     

C-reactive protein is released in the coronary circulation and causes endothelial dysfunction in patients with acute coronary syndromes

Background

C-reactive protein (CRP) plasma levels correlate with cardiovascular events. Although a direct role for CRP in atherothrombosis has been suggested, at the moment little is known about its involvement in the pathophysiology of acute coronary syndromes (ACS). Thus, the aim of this study was to determine whether CRP is produced in the culprit lesion and released within the coronary circulation of patients with ACS and whether it may affect coronary endothelial function.

Methods

Blood samples were simultaneously obtained from the aorta (Ao) and the coronary sinus (CS) of patients with normal coronary artery (n = 16), stable angina (n = 30), and ACS (n = 29) for later measurement of plasma CRP levels. Endothelium-dependent and -independent coronary vasodilation were evaluated by means of a Doppler Flow Wire in response to the increasing intracoronary doses of acetylcholine and adenosine, respectively.

Results

CRP plasma levels were significantly higher across the coronary circulation only in ACS patients with the culprit lesion located in the left coronary artery, while no differences between CS and Ao CRP plasma levels were observed in all other groups. Transcardiac CRP levels were correlated with impairment in coronary endothelium-dependent vasodilation. In six additional patients (SA = 3 and ACS = 3), subjected to coronary atherectomy, real-time quantitative PCR revealed presence of CRP mRNA only in unstable plaques.

Conclusions

Thus, CRP is produced and released within the coronary circulation of patients with ACS; this is associated with impairment of endothelial function, suggesting a new pathophysiological link between CRP and ACS.     

Tratamiento y control de los factores de riesgo según el riesgo coronario en la población española del estudio DARIOS

Introduction and objectives

The treatment and control of cardiovascular risk factors both play key roles in primary prevention. The aim of the present study is to analyze the proportion of primary prevention patients aged 35-74 years being treated and controlled in relation to their level of coronary risk.

Methods

Pooled analysis with individual data from 11 studies conducted in the first decade of the 21st century. We used standardized questionnaires and blood pressure measures, glycohemoglobin and lipid profiles. We defined optimal risk factor control as blood pressure <140/90 mmHg and glycohemoglobin <7%. In hypercholesterolemia, we applied both the European Societies and Health Prevention and Promotion Activities Programme criteria.

Results

We enrolled 27 903 participants (54% women). Drug treatments were being administered to 68% of men and 73% of women with a history of hypertension (P < .001), 66% and 69% respectively, of patients with diabetes (P = .03), and 39% and 42% respectively, of those with hypercholesterolemia (P < .001). Control was good in 34% of men and 42% of women with hypertension (P < .001); 65% and 63% respectively, of those with diabetes (P = .626); 2% and 3% respectively, of patients with hypercholesterolemia according to European Societies criteria (P = .092) and 46% and 52% respectively, of those with hypercholesterolemia according to Health Prevention and Promotion Activities Programme criteria (P < .001). The proportion of uncontrolled participants increased with coronary risk (P < .001), except in men with diabetes. Lipid-lowering treatments were more often administered to women with ≥10% coronary risk than to men (59% vs. 50%, P = .024).

Conclusions

The proportion of well-controlled participants was 65% at best. The European Societies criteria for hypercholesterolemia were vaguely reached. Lipid-lowering treatment is not prioritized in patients at high coronary risk.Full English text available from: www.revespcardiol.org     

Biomarkers to predict recurrent cardiovascular disease: the Heart and Soul Study

Purpose

The study purpose was to evaluate the ability of 6 biomarkers to improve the prediction of cardiovascular events among persons with established coronary artery disease.

Background

Cardiovascular risk algorithms are designed to predict the initial onset of coronary artery disease but are less effective in persons with preexisting coronary artery disease.

Methods

We examined the association of N-terminal prohormone brain natriuretic peptide (Nt-proBNP), cystatin C, albuminuria, C-reactive protein (CRP), interleukin-6, and fibrinogen with cardiovascular events in 979 Heart and Soul Study participants with coronary artery disease after adjusting for demographic, lifestyle, and behavior variables; cardiovascular risk factors; cardiovascular disease severity; medication use; and left ventricular ejection fraction. The outcome was a composite of stroke, myocardial infarction, and coronary heart disease death during an average of 3.5 years of follow-up.

Results

During follow-up, 142 participants (15%) developed cardiovascular events. The highest quartiles (vs lower 3 quartiles) of 5 biomarkers were individually associated with cardiovascular risk after multivariate analysis: Nt-proBNP hazard ratio (HR) = 2.13 (95% confidence interval [CI], 1.43-3.18); cystatin C HR = 1.72 (95% CI, 1.10-2.70); albuminuria HR = 1.71 (95% CI, 1.15-2.54); CRP HR = 2.00 (95% CI, 1.40-2.85); and interleukin-6 HR = 1.76 (95% CI, 1.22-2.53). When all biomarkers were included in the multivariable analysis, only Nt-proBNP, albuminuria, and CRP remained significant predictors of events: HR = 1.88 (95% CI, 1.23-2.85), HR = 1.63 (95% CI, 1.09-2.43), and HR = 1.82 (95% CI, 1.24-2.67), respectively. The area under the receiver operator curve for clinical predictors alone was 0.73 (95% CI, 0.68-0.78); adding Nt-proBNP, albuminuria, and CRP significantly increased the area under the receiver operator curve to 0.77 (95% CI, 0.73-0.82, P <.005).

Conclusion

Among persons with prevalent coronary artery disease, biomarkers reflecting hemodynamic stress, kidney damage, and inflammation added significant risk discrimination for cardiovascular events.     

Effect of aggressive versus moderate lipid-lowering therapy on myocardial ischemia: the rationale, design, and baseline characteristics of the Study Assessing Goals in the Elderly (SAGE)

Background

Patients with stable CHD who experience episodes of ischemia during routine daily activities are at increased risk of coronary events. Older patients are at a particularly high risk. Few trials have specifically investigated the effects of lipid-lowering therapy with statins in older patients.

Methods

The SAGE trial is a prospective, randomized, double-blind, parallel-arm study enrolling men and women with stable CHD at 192 centers worldwide. Qualifying participants (aged 65-85 years; low-density lipoprotein cholesterol 100-250 mg/dL) have had at least 1 episode of myocardial ischemia with total ischemia duration ≥3 minutes on 48-hour ambulatory electrocardiographic (AECG) monitoring performed during routine daily activities. Participants have been randomized to either atorvastatin 80 mg/day (aggressive lipid lowering) or pravastatin 40 mg/day (moderate lipid lowering). The primary efficacy measure is the absolute change in the total duration of myocardial ischemic events on 48-hour AECG monitoring from baseline to month 12.

Results

SAGE is fully enrolled and 893 patients have been randomized. The majority of the study participants are white (97%) men (69%). The mean age of the participants is 72 years. Most participants (94%) have a history of angina. Other high-risk patient groups included in the study are patients with hypertension (65%), patients with diabetes (23%), and patients with peripheral vascular disease (12%).

Conclusions

SAGE will evaluate the effect of aggressive versus moderate lipid lowering on the total duration of myocardial ischemia in older ambulatory patients with CHD. It is likely to provide valuable data on the benefits of statins in this patient population.     

Effects of low-dose angiotensin II receptor blocker candesartan on cardiovascular events in patients with coronary artery disease

Objectives

The purpose of this study was to investigate the effects of angiotensin II receptor blockers on the prevention of cardiovascular events in patients with coronary artery disease (CAD).

Background

Angiotensin II may contribute to the pathogenesis of CAD. Long-term clinical trials have shown that blockade of the renin-angiotensin system can reduce cardiovascular events in patients with acute myocardial infarction complicated by heart failure.

Methods

Patients with a history of coronary intervention and no significant coronary stenosis on follow-up angiography 6 months after intervention were randomly assigned into a candesartan group (n = 203; baseline treatment plus candesartan 4 mg/d) or a control group (n = 203; baseline treatment alone). The primary end point was a composite of revascularization, nonfatal myocardial infarction, or cardiovascular death. The secondary end point was hospitalization for cardiovascular causes.

Results

There were no changes in blood pressure and in other coronary risk factors in either group during a mean follow-up of 24 months. Primary end point risk was significantly lower in the candesartan group (n = 12) than in control group patients (n = 25) (P = .03). Candesartan treatment reduced primary end point risk (5.9% vs 12.3% for control subjects; relative risk, 0.47; 95% CI, 0.24 to 0.93). The incidence of all events including secondary end points and noncardiovascular death was significantly lower in the candesartan group than in control group patients (23 vs 40 cases) (P = .02).

Conclusions

Relatively low-dose candesartan, which did not alter blood pressure levels, reduces cardiovascular risk in high-risk patients with CAD.