Risk factors related to the occurrence of silent myocardial ischemia in Mexicans

BACKGROUND: Silent myocardial ischemia is a growing world health problem. It has been related to factors that promote an increase in myocardial oxygen demand or affect coronary vasomotor tone. Coronary artery disease has shown an increasing trend in Mexico in this century. HYPOTHESIS: The aim of the study was to estimate the strength of the association between some risk factors and the occurrence of silent myocardial ischemia. METHODS: A cross-sectional study was conducted and 249 individuals were screened by 24-h Holter electrocardiogram. Silent myocardial ischemia was diagnosed in patients with painless transient ST-segment depression. All subjects were interviewed for coronary risk factors and total serum cholesterol was measured. RESULTS: Silent ischemia was diagnosed in 115 patients (46%), who were older (59 +/- 9 vs. 57 +/- 11 years; p = 0.01). In a logistic regression analysis, a lower risk for silent ischemia was found in patients with thrombolysis [odds ratio (OR) 0.28; 95% confidence interval (CI 95%) 0.14-0.53], or those who followed their medical treatment (OR 0.16; CI 95% 0.04-0.68). The major risk factors were hypercholesterolemia (OR 1.6; CI 95% 0.9-2.9) and more severe coronary artery disease (OR 2.5; CI 95% 1.1-5.7). CONCLUSIONS: Some coronary risk factors are related to silent ischemia. It is still important to diagnose this entity, but modification of its related risk factors should be kept in mind to diminish its occurrence and its severe consequences.     

Predictive value of differential pulse pressure in the diagnosis of silent myocardial ischemia in patients with type-2 diabetes

Silent myocardial ischemia occurs more frequently in diabetics. Differential arterial pulse pressure is a valuable predictor of cardiovascular disease. We studied 48 consecutive male patients with type-2 diabetes and no known history of ischemic heart disease. Ambulatory monitoring of arterial pressure was carried out and the presence of silent myocardial ischemia was studied using a protocol that involved: resting ECG, echocardiography, 24-hour Holter ECG, conventional exercise stress testing, and exercise testing with nuclear scanning. Nine patients (19%) had silent myocardial ischemia. Differential pulse pressure had good discriminative ability in identifying the presence of silent ischemia: the area under the receiver operating characteristic (ROC) curve was 0.83 (95% confidence interval [CI], 0.71-0.96; P=.002). This predictive ability was also observed on adjusted logistic regression modeling (odds ratio [OR], 1.24, 95% CI = 1.02-1.49). We found that the OR for the risk of silent ischemia for every 10-mmHg increase in differential pulse pressure was 8.5 (95% CI 1.7-31.2). Age and differential pulse pressure were the only independent predictors of silent myocardial ischemia found in this study.     

Significance of silent ischemia and microalbuminuria in predicting coronary events in asymptomatic patients with type 2 diabetes

OBJECTIVES: The aim of this study was to investigate the relationships between future coronary heart disease (CHD) events and baseline silent myocardial ischemia (SMI) and microalbuminuria (MA) in subjects with type 2 diabetes (T2D) free from known CHD. BACKGROUND: Coronary heart disease is often asymptomatic in subjects with diabetes. There is limited information on the prognostic value of SMI and MA in this group. METHODS: Eighty-six patients with T2D and no history of CHD were studied (43 with MA individually matched with 43 normoalbuminuric patients; mean [SD] age 62 [+/-7] years, 62 men). Metabolic assessment, three timed overnight urine collections for albumin excretion rate, a treadmill exercise test and ankle brachial index (ABI) were performed at baseline. Patients were followed for 2.8 years. RESULTS: Forty-five (52%) patients had SMI during treadmill testing. At review, there had been 23 coronary (CHD) events in 15 patients. Univariate Cox regression analysis showed that CHD events were significantly related to baseline ABI (p = 0.014), SMI (p = 0.020), MA (p = 0.046), 10-year Framingham CHD risk >30% (p = 0.035) and fibrinogen (p = 0.026). In multivariate analysis, SMI was the strongest independent predictor of CHD events (p = 0.008); risk ratio (95% confidence interval) for SMI: 21 (2 to 204). In the prediction of CHD events, SMI showed higher sensitivity and positive predictive value than MA or Framingham calculated CHD risk. CONCLUSIONS: The presence of baseline SMI and MA are associated with future CHD events in asymptomatic patients with T2D and may be of practical use in risk stratification.     

Primary risk factors influence risk of recurrent myocardial infarction/death from coronary heart disease: results from the Stockholm Heart Epidemiology Program (SHEEP).

BACKGROUND: Prognosis after a first myocardial infarction (MI) is influenced by primary risk factors as well as secondary risk factors. There is still a lack of follow-up studies of well-characterized patient cohorts assessing the relative importance of these factors. DESIGN: A cohort of 1635 patients (aged 45-70 years) surviving at least 28 days after a first MI were followed for 6-9 years with regard to recurrent MI/fatal coronary heart disease (CHD). Data were collected through questionnaires, physical examinations, and medical records. METHODS: Hazard ratios (HR) with 95% confidence intervals (CI) for different risk factors were calculated using the Cox proportional hazard model. RESULTS: Of the primary risk factors, diabetes in both sexes was the most important predictor of recurrent MI/fatal CHD, multivariate-adjusted HR in men 1.6 (95% CI; 1.0-2.4) and in women 2.5 (95% CI; 0.9-6.9). Other primary risk factors with prognostic influence were job strain, HR 1.5 (95% CI; 1.0-2.1), and central obesity, HR 1.4 (95% CI; 1.0-2.0), in men and a low level of apolipoprotein A1, HR 2.3 (95% CI; 1.1-5.0), and high-density lipoprotein cholesterol, HR 1.9 (95% CI; 0.9-4.1), in women. The secondary risk factors most detrimental for prognosis were heart failure in men, HR 2.2 (95% CI; 1.2-4.0), and a high peak acute cardiac enzyme level in women, HR 4.4 (95% CI; 2.0-9.7). CONCLUSIONS: Long-term follow-up of patients who survived at least 28 days after a first MI shows that several primary cardiovascular risk factors, particularly diabetes, contribute to the increased risk of recurrent MI/fatal CHD.     

Contemporary management of silent ischemia: the role of ambulatory monitoring

Silent ischemia is highly prevalent among patients with ischemic heart disease and is associated with a poor prognosis in moderate/high risk outpatients who either exhibit exercise- or pharmacological-induced myocardial ischemia, or in those patients who demonstrate silent ischemia following an acute coronary syndrome. Pharmacotherapy, including beta-blockers, angiotensin-converting enzyme inhibitors, statins, calcium channel antagonists and antiplatelet agents, have all demonstrated a reduction in silent ischemia and an improvement in cardiac prognosis. The management of patients with ischemic heart disease is currently based on patients' report of anginal symptoms: documentation of silent ischemia, usually using ambulatory electrocardiography, is not incorporated into the routine management of coronary artery disease. Yet studies comparing ambulatory electrocardiography with exercise testing have shown these tests to be complementary. We review the evidence concerning the prognostic value of ambulatory electrocardiography for monitoring silent ischemia and the prognostic value of attenuating silent ischemia. Mitigation of silent ischemia improves cardiac prognosis and ambulatory electrocardiographic monitoring before and after treatment of silent ischemia can play a valuable role in the management of coronary artery disease.     

Silent Ischemia Is Associated With Subclinical Atherosclerosis in African Males: The Sympathetic Activity and Ambulatory Blood Pressure in Africans Study

Silent myocardial ischemia is a predictor of subclinical atherosclerosis driven by increased cardiovascular risk markers, although still unknown in Africans. The aim of this study was to assess if cardiovascular risk markers will be associated with subclinical atherosclerosis. African men were stratified into (i) 24-hour silent ischemia (SI, n = 38) and (ii) without (nSI, n = 40) groups. Ambulatory blood pressure (BP), SI, 12-lead resting electrocardiogram, ultrasound carotid intima-media thickness (CIMT) measurements, and fasting blood samples were obtained. Above-normal cardiovascular risk markers, that is, glucose level, heart rate, BP, and CIMT, were evident in men with SI. Hypertension prevalence was 89% in the African SI men as opposed to 64% in the nSI men. Regression analyses revealed that only SI events in SI men explained 35% (95% confidence interval [CI]: 0.22;0.52) of the variance in CIMT, while in all African men it explained 29% (95% CI: 0.19;0.39). In conclusion, SI was associated with structural vascular disease in African men. This could imply that SI is not necessarily driven by hypertension in African men but through other possible mechanisms such as increased sympathetic nervous system activity.     

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.     

Sex differences in risk for coronary heart disease mortality associated with diabetes and established coronary heart disease

BACKGROUND: The sex-specific independent effect of diabetes mellitus and established coronary heart disease (CHD) on subsequent CHD mortality is not known. METHODS: This is an analysis of pooled data (n = 5243) from the Framingham Heart Study and the Framingham Offspring Study with follow-up of 20 years. At baseline (1971-1975), 134 men and 95 women had diabetes, while 222 men and 129 women had CHD. Risk for CHD death was analyzed by proportional hazards models, adjusting for age, hypertension, serum cholesterol levels, smoking, and body mass index. The comparative effect of established CHD vs diabetes on the risk of CHD mortality was tested by testing the difference in log hazards. RESULTS: The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for death from CHD were 2.1 (95% CI, 1.3-3.3) in men with diabetes only, and 4.2 (95% CI, 3.2-5.6) in men with CHD only compared with men without diabetes or CHD. The HR for CHD death was 3.8 (95% CI, 2.2-6.6) in women with diabetes, and 1.9 (95% CI, 1.1-3.4) in women with CHD. The difference between the CHD and the diabetes log hazards was +0.73 (95% CI, 0.72-0.75) in men and -0.65 (95% CI, -0.68 to -0.63) in women. CONCLUSIONS: In men, established CHD signifies a higher risk for CHD mortality than diabetes. This is reversed in women, with diabetes being associated with greater risk for CHD mortality. Current treatment recommendations for women with diabetes may need to be more aggressive to match CHD mortality risk.     

Prognostic value of systolic and diastolic blood pressure in treated hypertensive men

BACKGROUND: The aim of this study was to assess the cardiovascular risk in hypertensive subjects according to systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels. METHODS: The study sample consisted of 4714 hypertensive men, treated by their physician, who had a standard health checkup at the d'Investigations Préventives et Cliniques Center, Paris, France, between 1972 and 1988. Cardiovascular disease (CVD) and coronary heart disease (CHD) mortality were assessed for a mean period of 14 years. RESULTS: Among treated subjects, 85.5% presented uncontrolled values for SBP (> or = 40 mm Hg) and/or DBP (> or = 90 mm Hg). After adjustment for age and associated risk factors, these subjects presented an increased risk for CVD mortality (risk ratio [RR], 1.66; 95% confidence interval [CI], 1.04-2.64) and for CHD mortality (RR, 2.35; 95% CI, 1.03-5.35) compared with controlled subjects. After adjustment for age, associated risk factors, and DBP, and compared with subjects with SBP under 140 mm Hg, the RR for CVD mortality was 1.81 (95% CI, 1.04-3.13) in subjects with SBP between 140 and 160 mm Hg and 1.94 (95% CI, 1.10-3.43) in subjects with SBP over 160 mm Hg. By contrast, after adjustment for SBP levels, CVD risk was not associated with DBP. Compared with subjects with DBP under 90 mm Hg, RR for CVD mortality was 1.17 (95% CI, 0.80-1.70) in subjects with DBP between 90 and 99 mm Hg and 1.03 (95% CI, 0.67-1.56) in subjects with DBP over 100 mm Hg. Similar results were observed for CHD mortality. CONCLUSIONS: In hypertensive men treated in clinical practice, SBP is a good predictor of CVD and CHD risk. Diastolic blood pressure, which remains the main criterion used by most physicians to determine drug efficacy, appears to be of little value in determining cardiovascular risk. Evaluation of risk in treated individuals should take SBP rather than DBP values into account.     

Symptom-limited exercise testing, ST depressions and long-term coronary heart disease mortality in apparently healthy middle-aged men.

BACKGROUND: Previous studies have shown that ST depressions > or =1.0 mm during or post-exercise increase long-term risk of dying from coronary heart disease (CHD), the need for coronary artery bypass grafting (CABG) or the development of acute myocardial infarction (AMI) in healthy men. In the present prospective cohort study we investigate whether less marked ST depressions may influence CHD mortality, incidence of AMI, the need for a CABG or having a non-fatal stroke. METHODS: During 1972-75, 2014 men aged 40-59 years, free from somatic diseases and not using any drugs, underwent an examination programme including case history, clinical examination, various blood tests and a symptom-limited exercise ECG-test. ECG was registered during exercise and at 30 s, 1, 2, 3 and 5 min post-exercise. The possible prognostic impact of ST-changes of 0.50-0.99 mm and > or =1.00 mm compared with normal ST-segments were studied separately and combined. Horizontal, down-sloping and slowly up-sloping ST-segment patterns were combined. RESULTS: After adjustment for age, smoking, blood pressure, cholesterol, maximal heart rate, left ventricular hypertrophy and physical fitness ST depressions > or =0.50 mm--during and/or post-exercise--were associated with a 1.47-fold [95% confidence interval (CI) 1.10-1.95], and 1.54-fold (95% CI of 1.17-2.04) increased 26 years risk of CHD-mortality, respectively. The same ST-changes also increased 22 years risk of developing non-fatal AMI or needing CABG but not developing non-fatal stroke. CONCLUSIONS: Even an ST depression > or =0.50 mm during and/or after exercise increases the long-term risk of CHD-death, developing an AMI or needing CABG. No association was found between ST-changes and incidence of non-fatal strokes.     

Upper-body adiposity and risk of myocardial infarction.

BACKGROUND: The relation between obesity and coronary heart disease (CHD) has long been studied, but no convincing conclusion has been drawn. OBJECTIVE: To estimate the relative risk associated with upper-body adiposity which is at present believed to be a better predictor of CHD. DESIGN: This was a community-based case-control study. METHODS: We studied 338 consecutively admitted patients who had had their first acute myocardial infarction (AMI) and 662 community controls who had not suffered AMI selected as a random sample of adults living in the catchment area of the hospital. We defined three classes of body mass index (BMI) and waist: hip circumference ratio on the basis of tertiles of distribution for controls. Odds ratios (OR) were estimated using unconditional logistic regression. Separate models were built for men and women. RESULTS: In univariate analysis we found a higher risk of AMI for men and women with hypertension, dyslipidaemia, diabetes and lower levels of education, for older women, for male smokers and for men with family histories of CHD. Both for men and for women a higher BMI was associated with a slightly higher risk, whereas the adjusted risk of AMI increased with increasing waist: hip circumference ratio [for men OR (second tertile)= 2.5, 95% confidence interval (CI) 1.3-4.9 and OR (third tertile)= 11.1, 95% CI 6.0-20.6; for women OR (second tertile) = 3.0, 95% CI 0.6-14.8 and OR (third tertile) = 14.1,95% CI 3.2-62.7]. This relation held for each BMI class and was stronger for classes of lower BMI. CONCLUSIONS: Distribution of body fat rather than BMI is a strong marker of risk for AMI and there is a clear interaction between these two variables.     

Diabetes and all-cause and coronary heart disease mortality among US male physicians

BACKGROUND: While diabetes has long been associated with increased risk of coronary heart disease (CHD), the magnitude of risk of diabetes-related CHD is uncertain. OBJECTIVE: To evaluate the impact of diabetes and prior CHD on all-cause and CHD mortality. METHODS: In a prospective cohort study of 91 285 US male physicians aged 40 to 84 years, participants were divided into 4 groups: (1) a reference group of 82 247 men free of both diabetes and CHD (previous myocardial infarction and/or angina) at baseline, (2) 2317 men with a history of diabetes but not CHD, (3) 5906 men with a history of CHD but not diabetes, and (4) 815 men with a history of both diabetes and CHD. Rates of all-cause and CHD mortality were compared in these groups. RESULTS: Over 5 years (49 7952 person-years of follow-up), 3627 deaths from all causes were documented, including 1242 deaths from CHD. Compared with men with no diabetes or CHD, the age-adjusted relative risk of death from any cause was 2.3 (95% confidence interval [CI], 2.0-2.6) among men with diabetes and without CHD, 2.2 (95% CI, 2.0-2.4) among men with CHD and without diabetes, and 4.7 (95% CI, 4.0-5.4) among men with both diabetes and CHD. The relative risk of CHD death was 3.3 (95% CI, 2.6-4.1) among men with diabetes and without CHD, 5.6 (95% CI, 4.9-6.3) among men with CHD and without diabetes, and 12.0 (95% CI, 9.9-14.6) among men with both diabetes and CHD. Multivariate adjustment for body mass index, smoking status, alcohol intake, and physical activity as well as stratification by these variables did not materially alter these associations. CONCLUSIONS: These prospective data indicate that diabetes is associated with a substantial increase in all-cause and CHD mortality. For all-cause mortality, the magnitude of excess risk conferred by diabetes is similar to that conferred by a history of CHD; for mortality from CHD, a history of CHD is a more potent predictor of death. The presence of both diabetes and CHD, however, identifies a particularly high-risk group.     

Clinical importance of silent ischemia]

Objective signs of myocardial ischemia without angina pectoris or its equivalents define the syndrome of silent myocardial ischemia. Its significance lies in the prevalence and prognostic implications. As a prevalence, asymptomatic coronary heart disease can be found in 2.5% of men 40 to 60 years old. Silent myocardial ischemia is frequently found in patients with unstable coronary syndromes. The Framingham Study showed 25% of all myocardial infarctions as unrecognized by patients and physicians. The prognostic implications of silent myocardial ischemia are shown in large studies on prognosis of pathologic exercise-ECG's. Asymptomatic patients with pathologic exercise-ECG have always been recognized as having a significantly increased risk of myocardial infarction and death. Recently, many studies showed a worse prognosis for patients with asymptomatic transient ischemia on Holter-ECG. This can be found in patients with stable angina pectoris, unstable angina pectoris, patients with peripheral arterial disease, and patients after myocardial infarction. It becomes clear that prognosis is not defined by the pain, but by the severity of ischemia. Silent ischemia has to be viewed together with the severity of the underlying coronary heart disease. This synopsis will define the necessary steps for further diagnosis and treatment.     

Reasons for terminating an exercise test provide independent prognostic information: 2014 apparently healthy men followed for 26 years.

AIMS: We wanted to study whether reasons for terminating an exercise test might influence long-term mortality of healthy men, a previously unreported subject. METHODS AND RESULTS: During 1972-75, 2014 men aged 40-59, free from somatic diseases and not using drugs, underwent an examination programme including case history, clinical examination, various blood tests, and a symptom limited exercise ECG-test. The following reasons for test termination were noted: impaired breathing, lower limb fatigue, exhaustion (=combined lower limb fatigue and impaired breathing), high heart rate, abnormal blood pressure response, heart arrhythmias, increasing chest pain during exercise, marked ST-depressions during the test, and refusal to continue. Follow-up was 26 years. When adjusting for age, men who stopped exercising exclusively because of impaired breathing (n=178) had a 1.86-fold increased risk (95% CI 1.34-2.60; P=0.0002) of dying from coronary heart disease (CHD), a 1.64-fold increased risk (95% CI 1.32-2.03; P<0.0001) of dying from any cause, and a 3.47-fold increased risk (95% CI 2.24-5.12; P<0.0001) of dying from pulmonary causes compared with men having defined exhaustion (n=1376). After adjustment for age, smoking, total serum cholesterol, fasting blood glucose, systolic blood pressure, and physical fitness, impaired breathing remained significantly associated to an increased risk of dying from CHD, pulmonary disease, or any causes. CONCLUSION: Healthy men who stop bicycle exercising only because of impaired breathing have a high long-term CHD-, pulmonary-, and total-mortality, and such men may need further diagnostic scrutiny and follow-up.     

Risk of coronary heart disease in subjects with chest discomfort: the Framingham Heart Study

PURPOSE: To examine the risk of coronary heart disease (CHD) events in subjects of the Framingham Study reporting new chest discomfort. SUBJECTS AND METHODS: Original cohort subjects with chest discomfort were classified by their history into three groups: definite angina, possible angina, or nonanginal chest discomfort. Subjects were followed for 2 years for CHD events, including coronary insufficiency, myocardial infarction, or CHD death. RESULTS: Compared to that in subjects without chest discomfort, the relative odds of a CHD event was 3.7 (95% confidence interval [CI] 2.11, 6.60) in men with definite angina and 3.0 (95% CI 1.33, 6.69) in men with possible angina. Comparable increased CHD risk was also observed in women with definite or possible angina, with relative odds of 5.4 (95% CI 3.08, 9.30) and 2.9 (95% CI 1.13, 7.17), respectively. The increase in CHD risk associated with definite or possible angina persisted after adjustment for cardiac risk factor profile. There was no increase in risk associated with nonanginal chest discomfort. CONCLUSION: CHD risk is increased in subjects with new chest discomfort that on the basis of history is consistent with definite or possible angina, whereas CHD risk is not increased in subjects with nonanginal chest discomfort. The presence of chest discomfort and its characteristics facilitate the classification of subjects into meaningful categories that offer prognostic information beyond that provided by traditional CHD risk factors.     

Clinical,exercise electrocardiographic,and pharmacologic stress echocardiographic findings for risk stratification of hypertensive patients with chest pain

Exercise electrocardiography (ECG) is of limited usefulness in hypertensive patients, whereas pharmacologic stress echocardiography can provide diagnostic and prognostic information. The aim of this study was to compare the prognostic value of clinical data, exercise ECG, and pharmacologic stress echocardiography in hypertensive patients with chest pain and to identify the best strategy for their risk stratification. Three hundred sixty-seven hypertensive patients (189 men, age 61 +/- 9 years) with chest pain of unknown origin underwent exercise ECG and pharmacologic stress echocardiography (237 with dipyridamole and 130 with dobutamine) and were followed up for 31 +/- 24 months. Positive exercise ECG (ST-segment shift of > or =1 mm at 80 ms after the J point) and stress echocardiography (new wall motion abnormalities) were found in 130 (35%) and 86 (23%) patients, respectively. During follow-up, there were 13 deaths and 16 myocardial infarctions. Additionally, 43 patients underwent coronary revascularization and were censored accordingly. Of 12 clinical, electrocardiographic, and echocardiographic variables analyzed, a positive result of stress echocardiography was the only multivariate predictor of either death (hazard ratio [HR] 4.7, 95% confidence interval [CI] 1.5 to 14.5, p = 0.007) or hard events (death, myocardial infarction) (HR 4.1, 95% CI 1.8 to 9.3, p = 0.0009). Using an interactive stepwise procedure, stress echocardiography provided additional prognostic information to clinical evaluation and exercise ECG. However, the negative predictive value of the 2 tests was similarly (p = NS) high in assessing 4-year event-free survival. In conclusion, a negative exercise electrocardiographic test identifies low-risk hypertensive patients with chest pain and should be the first-line approach for risk stratification. In contrast, positive exercise ECG is unable to distinguish between patients with different levels of risk. In this case, stress echocardiography provides strong and incremental prognostic power over clinical and exercise electrocardiographic data.     

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.     

Silent myocardial ischemia during daily activities in asymptomatic men with positive exercise test responses

The usefulness of prolonged ambulatory electrocardiographic monitoring (AEM) for detecting ischemia was investigated in 17 asymptomatic men who had ischemic-type ST-segment depression (greater than or equal to 2.0 mm) during treadmill exercise testing. No patient took anti-ischemic medications and all patients underwent coronary angiography. A total of 1,154 hours (range 64 to 72 hours/patient) of high-quality AEM recordings was obtained. Silent ischemia (episodes of asymptomatic ischemic-type ST depression of 60 seconds or longer) occurred in 11 patients during daily activity detected by AEM. In 6 other patients, no myocardial ischemic episodes were found. But 1 of these patients withdrew after only 24 hours of AEM and the remaining 5 had no significant coronary artery disease (CAD). All 11 patients who had silent ischemia had significant CAD (at least 50% stenosis) on angiography. There was wide intrapatient variability in the frequency of silent ischemic episodes. Silent ischemia was identified in 6 of these 11 patients after 24 hours of AEM, in 2 after 48 hours and in 3 after 72 hours. Thus, asymptomatic men with positive exercise test responses and CAD have silent ischemic episodes during daily activity. AEM may be useful in helping to predict which patients with asymptomatic positive exercise test responses have CAD; however, extended AEM periods are required.     

Plasma N-terminal pro-brain natriuretic peptide concentration predicts coronary events in men at work: a report from the BELSTRESS study.

AIMS: Increased levels of neurohormonal markers, including the N-terminal fragment of pro-brain natriuretic peptide (NT-pro-BNP), have been shown to be of prognostic significance in patients with heart failure or coronary heart disease (CHD). The aim of this study was to study the predictive value of NT-pro-BNP for coronary events in a middle-aged population of men at work. METHODS AND RESULTS: A nested case-control study was performed in a large cohort of over 10 000 men at work (aged 35-59) after a median follow-up of 2.66 years. In total, 66 individuals who developed coronary events were matched on a 3-to-1 basis to 198 controls free of coronary events during follow-up. Besides clinical characteristics and conventional cardiac risk factors, NT-pro-BNP (electrochemiluminiscence assay, Roche diagnostics) and serum creatinine levels were determined. In univariable analysis, cases were more frequently current smokers and diabetics, had more frequently a history of CHD, and had higher levels of total cholesterol and systolic blood pressure (SBP), and lower levels of HDL cholesterol. A highly significant difference (P < 0.0001) was noted for NT-pro-BNP levels between cases (median 48.5 pg/mL, interquartile range 26.4-116.6 pg/mL) and controls (30.0 pg/mL, 19.5-47.6 pg/mL). In multivariable conditional logistic regression analysis, NT-pro-BNP remained strongly associated with risk for coronary events [third vs. first tertile, odds ratio (95% CI) 3.24 (1.18-8.85)], independent of body mass index, smoking, diabetes, SBP, total and HDL cholesterol, creatinine, and previous CHD. CONCLUSION: NT-pro-BNP is a strong predictor of coronary events in men at work after a relatively short period, even after adjustment for conventional risk factors.     

Silent ischemia predicts infarction and death during 2 year follow-up of unstable angina

Silent myocardial ischemia as detected on Holter electrocardiographic (ECG) monitoring is present in greater than 50% of patients with unstable angina despite intensive medical therapy. The presence and the extent of silent ischemia have been correlated with an increased risk of early (1 month) unfavorable outcome including myocardial infarction and need for coronary revascularization for persistent symptoms. Seventy patients with unstable angina who had undergone continuous ECG monitoring for silent ischemia were followed up for 2 years; 37 patients (Group I) had Holter ECG evidence of silent ischemia at bed rest in the coronary care unit during medical treatment with nitrates, beta-receptor blockers and calcium channel antagonists; the other 33 patients (Group II) had no ischemic ST segment changes (symptomatic or silent) on Holter monitoring. Over a 2 year follow-up period, myocardial infarction occurred in 10 patients in Group I (in 2 it was fatal) compared with one nonfatal infarction in Group II (p less than 0.01 by Kaplan-Meier analysis); revascularization with either coronary bypass surgery or angioplasty for symptomatic ischemia was performed in 11 Group I and 5 Group II patients (p less than 0.05). Multivariate Cox's hazard analysis demonstrated that the presence of silent ischemia was the best predictor of 2 year outcome. Therefore, persistent silent myocardial ischemia despite medical therapy in patients with unstable angina carries adverse prognostic implications that persist over a 2 year period.