Silent myocardial ischemia: an update

Silent myocardial ischemia is diagnosed by several different techniques and has been documented in all the anginal syndromes. In addition to other factors, its presence may be related to increased pain threshold and increased pain tolerance. Although some patients with painless ischemia may have less extensive coronary artery disease, cumulative evidence indicates that silent myocardial ischemia does not necessarily signify a lesser degree of cardiac ischemia or a less severe coronary abnormality. As judged by ambulatory monitoring studies, it shows circadian variation; occurs more frequently than symptomatic ischemia; and appears to depend, in large part, on activation of the sympathetic nervous system. Frequent silent ischemic events during ambulatory monitoring are worrisome because they reflect the disease "activity" of single or multiple coronary atherosclerotic lesions. Thus, there may be a direct association between the severity of ischemia seen during Holter monitoring, the extent of underlying coronary artery disease or disease activity, and prognosis. When diagnosed by exercise testing, silent myocardial ischemia may be associated with significant coronary involvement. In this regard, patients with three vessel coronary disease, impaired left ventricular function, and silent ischemia during stress testing should benefit from coronary revascularization. Compared with symptomatic patients, other evidence suggests that patients with exercise-induced asymptomatic ischemia have at least the same or perhaps even a worse outlook; this may be related to the lack of symptoms that would prompt evaluation and therapy. Awareness of the possibility of silent myocardial ischemia and use of commonly available tests, both to establish its presence and severity and to guide treatment, are emerging as new clinical goals. Further data, however, are necessary to determine how vigorously this should be pursued in different patient subgroups. In association with unstable angina or post-myocardial infarction, the added risk of silent myocardial ischemia warrants a more aggressive approach.     

Clinical, socioeconomic, and lifestyle parameters associated with erectile dysfunction among diabetic men

OBJECTIVE: Erectile dysfunction is frequently observed in diabetes. The current study aims to assess the association of a comprehensive set of clinical, socioeconomic, and lifestyle parameters with erectile dysfunction in diabetic men. RESEARCH DESIGN AND METHODS: Participants were randomly selected from male patients (age >18 years) treated in 26 diabetes clinics in Israel. Participants completed a self-reported questionnaire on demographic, socioeconomic, and lifestyle characteristics and on erectile function, using the IIEF-15 (International Index of Erectile Function). Information on diabetes type, duration, treatment, and control; microvascular complications and cardiovascular disease; drug therapy; blood pressure; and lipid levels was also obtained. RESULTS: Information on erectile function was obtained in 1,040 patients. Their mean age was 57 years, and their median diabetes duration was 8 years (range <1-50). Normal erectile function was found in 13.5% of the patients and severe erectile dysfunction in 30.1%. The characteristics found to be significantly associated with erectile dysfunction [associations presented as adjusted odds ratio (95% CI)] were: patient's age (5-year increments): 1.38 (1.29-1.48); diabetes duration (5-year increments): 1.16 (1.07-1.26); current HbA(1c) level (1% increment): 1.10 (1.01-1.19); any microvascular disease: 1.43 (1.09-1.88); cardiovascular disease: 1.78 (1.27-2.48); and diuretic treatment: 1.78 (1.09-2.91). Leisure time and work-related physical activity and consumption of small amounts of alcohol were found to be protective: 0.51 (0.36-0.72) and 0.70 (0.51-0.97), respectively. CONCLUSIONS: In diabetic men, erectile dysfunction severity increases with age and diabetes duration, poor glycemic control, presence of microvascular complications, diuretic treatment, and cardiovascular disease. Physical activity and alcohol intake may be protective. These findings can guide clinicians in taking preventive measures and undertaking early screening and treatment in high-risk patients.     

Surgical management of unstable angina and symptomatic coronary artery disease

The treatment of coronary artery disease and, in particular, acute coronary syndromes has evolved from watchful waiting to an early aggressive intervention strategy. Patients are currently receiving either percutaneous or surgical revascularization. Several major clinical trials have identified those patients mostly likely to benefit from surgical intervention. These patients typically include those with left-main coronary artery disease, triple vessel disease with decreased left ventricular function, and other clinical risk factors. As a result of these studies, unique needs and outcomes of special populations have been identified. This article will present an overview of surgical treatment of coronary artery disease with emphasis on patient selection with particular attention to women, older persons, diabetic patients, and innovations in surgical techniques that may improve patient outcomes.     

Ischemia imaging and plaque imaging in diabetes: complementary tools to improve cardiovascular risk management

Cardiovascular disease is the most frequent cause of death and disability in diabetes, and the morbidity and mortality for coronary artery disease (CAD) in this population is two to four times higher than in nondiabetic subjects. Traditional risk factors do not fully explain the level of cardiovascular risk, and coronary disease events are often silent in diabetic patients. Thus, research has recently focused on improving the risk assessment of an individual patient with new tools in an effort to better identify subjects at highest risk and in need of aggressive management. Cardiovascular imaging has proven very helpful in this regard. Traditional methods to assess CAD are based on detection of obstructive luminal disease responsible for myocardial ischemia. However, acute coronary syndromes often occur in the absence of luminal stenoses. Hence, the utilization of imaging methodologies to visualize atherosclerosis in its presymptomatic stages has received mounting attention in recent years. In this article, we review the current literature on the utility of traditional imaging modalities for obstructive CAD (nuclear and echocardiographic stress testing) as well as atherosclerosis plaque imaging with carotid intima-media thickness and coronary artery calcium for risk stratification of diabetic patients.     

Anxiety, panic disorder and coronary artery disease: issues concerning physical exercise and cognitive behavioral therapy

Psychological factors such as stress and depression have already been established as primary and secondary cardiovascular risk factors. More recently, the role of anxiety in increasing cardiac risk has also been studied. The underlying mechanisms of increased cardiac risk in panic disorder patients seem to reflect the direct and indirect effects of autonomic dysfunction, as well as behavioral risk factors associated with an unhealthy lifestyle. Implications of the comorbidity between panic and cardiovascular disease include higher morbidity, functional deficits, increased cardiovascular risk, and poor adherence to cardiac rehabilitation or exercise programs. This article probes the most recent evidence on the association between coronary artery disease, anxiety and panic disorder, and discusses the potential role of incorporating regular physical exercise and cognitive behavioral therapy in the treatment of this condition.     

Viagra and Cardiovascular Disease

BACKGROUND: The introduction of the drug sildenafil (Viagra; Pfizer, New York, NY) into the armamentarium for treatment of erectile dysfunction is a major advance. Many of the patients who will benefit from its use have cardiovascular disease. Erectile dysfunction and cardiovascular disease share common risk factors. Although the metabolic demands of sexual activity are modest and the associated risk for coronary events is low, the clinician caring for cardiac patients needs to be aware of the pharmacology and hemodynamic profile of sildenafil in those with heart disease who use cardioactive drugs. METHODS AND RESULTS: We reviewed the current literature relating to the pharmacology, hemodynamic profile, efficacy, safety, and clinical application of sildenafil in patients with cardiovascular disease. Sildenafil is highly effective in the treatment of erectile dysfunction. The overall incidence of cardiovascular adverse events is low and similar to placebo. Current postmarketing data do not suggest an increase in cardiovascular death in sildenafil users. The drug is contraindicated in those taking organic nitrates. It should be used with caution and on an individual basis in patients who have active coronary ischemia and heart failure with tenous blood pressure and volume status. CONCLUSIONS: When used with discretion, sildenafil is safe, effective, and has the potential to greatly enhance quality of life in the relatively large proportion of the population with heart disease.     

Corifollitropin alfa for female infertility

Cardiovascular disease is the leading cause of death in patients with diabetes mellitus. Attempts to improve this statistic tend to focus primarily on the prevention of coronary artery disease. However, coronary artery disease is not the sole cause of cardiac death in diabetic patients; left ventricular dysfunction (LVD) and left ventricular hypertrophy (LVH) are also implicated and, unlike coronary artery disease, are ideal targets for screening. The treatment of left ventricular abnormalities, even when these are asymptomatic, is associated with prognostic benefit. Prescreening diabetic patients with plasma B-type natriuretic peptide (BNP) may permit identification of those who are likely to have left ventricular abnormalities, so that they may be put forward for echocardiography and receive targeted therapy.     

Screening for treatable left ventricular abnormalities in diabetic patients

Cardiovascular disease is the leading cause of death in patients with diabetes mellitus. Attempts to improve this statistic tend to focus primarily on the prevention of coronary artery disease. However, coronary artery disease is not the sole cause of cardiac death in diabetic patients; left ventricular dysfunction (LVD) and left ventricular hypertrophy (LVH) are also implicated and, unlike coronary artery disease, are ideal targets for screening. The treatment of left ventricular abnormalities, even when these are asymptomatic, is associated with prognostic benefit. Prescreening diabetic patients with plasma B-type natriuretic peptide (BNP) may permit identification of those who are likely to have left ventricular abnormalities, so that they may be put forward for echocardiography and receive targeted therapy.     

Nuclear Cardiology in Heart Failure

Coronary atherosclerosis is a chronic process starting already in teenage years and progressing over years often silently. Once perfusion abnormalities are diagnosed the disease process already has an advanced state. Myocardial infarctions are often due to nonobstructive ruptured plaques and not to high grade stenosis. Therefore risk stratification in an individualized tailored approach is warranted. Routine myocardial perfusion scintigraphy (MPS) is currently not recommended in the general asymptomatic population with low or intermediate cardiovascular risk. Nevertheless high rates of silent ischemia are found in selected patient groups, particularly in asymptomatic diabetic patients. For this reason in carefully selected patients with diabetes, PAVD, chronic kidney disease, or individuals prior to major surgery functional assessment with MPS allows identification of high risk patients and can provide prognostic information and possibly improve outcome. In individuals with positive family history of coronary artery disease anatomical screening with coronary calcium score and computed tomography angiography allows to identify individuals at risk for ischemic events. In this review incidence/prevalence of silent coronary artery disease are summarized, with a focus on patient screening with myocardial perfusion imaging. Possible strategies are provided for decision making in a clinical context.     

Evolution of coronary stents in patients with diabetes: are clinical outcomes still improving?

Diabetic patients are prone to diffuse and accelerated atherosclerosis, which increases the likelihood of requiring myocardial revascularization. Diabetes mellitus is a strong risk factor for restenosis following coronary stenting, with greater need for repeat revascularization and inferior clinical outcomes. Despite the recent advances in drug-eluting stent technology, diabetic patients are still at higher risk of adverse clinical events after coronary angioplasty. The focus of this review is to describe the evolution of the percutaneous management of diabetic patients with coronary artery disease and to define if any real progress has been made in terms of safety and efficacy with the use of the second generation drug-eluting stents in this high-risk population.     

2型糖尿病合并冠心病患者血清 SPARC 水平与冠状动脉病变的关系

目的：探讨2型糖尿病合并冠心病患者血清中富含半胱氨酸的酸性分泌蛋白(SPARC)水平变化及与冠状动脉病变的关系。方法选取120例患者作为研究对象,采用酶联免疫吸附实验(ELISA)检测血清 SPARC 水平,应用 Gensini 积分评价冠状动脉病变程度。A 组为健康对照组40例,根据造影结果和1999年世界卫生组织(WHO)糖尿病诊断标准将患者分为 B、C、D 组：其中 B 组(单纯2型糖尿病组)40例、C 组(单纯冠心病组)40例、D 组(2型糖尿病合并冠心病组)40例。结果①B 组、C 组和 D 组血清 SPARC 水平高于 A 组(4.22±1.19)μg/L、(3.71±1.05)μg/L、(5.96±1.40)μg/L vs (3.60±0.40)μg/L(P 均<0.05),其中 D 组血清 SPARC 水平最高(P <0.05)。②血清 SPARC 水平、胰岛素抵抗指数(HOMA-IR)、糖化血红蛋白(HbA1 c)是冠心病的影响因素。③D 组血清 SPARC 水平与 Gensini 积分呈正相关(r =0.770,P <0.05),C 组 SPARC 水平与 Gensini 积分无相关性(r =0.520,P >0.05)。④ Pearson 相关分析显示：甘油三酯(TG)、FINS、HOMA-IR 与 SPARC 呈显著正相关(r 分别为0.780、0.762、0.891,P 均<0.05)。结论2型糖尿病合并冠心病患者血清 SPARC 水平升高,并且与冠状动脉病变程度显著相关。     

Safe use of sildenafil in patients with coronary artery disease

Despite isolated reports of myocardial infarction and sudden cardiac death in men taking sildenafil for erectile dysfunction, clinical evidence shows the drug to be safe, effective, and well tolerated in most men with coronary artery disease. Nevertheless, caution is advised in specific instances.     

Contraindications and side effects of commonly used medications in coronary CT angiography

For certain clinical applications, coronary CT angiography (CCTA) has become a useful tool for the noninvasive evaluation of coronary artery atherosclerosis. To optimize image quality in CCTA, medications are often given prior to scanning to slow the heart rate or distend the arteries. These medications have side effects and are contraindicated in certain patient populations. Metoprolol is the ß-blocker of choice in CCTA, and it has been shown to be effective in achieving the goal heart rate of less than 65 beats per minute for CCTA and in minimizing variability of heart rate. It is contraindicated in patients with hypotension or high degree AV block, and it must be used with caution in patients with asthma or obstructive pulmonary disease, patients with decompensated heart failure, and those with vasospastic or vasoocclusive disease. Diltiazem, the calcium channel blocker of choice in CCTA, is a reasonable alternative for heart control, particularly in patients with asthma or bronchospastic disease, and patients with orthotopic heart transplants that have been sympathetically denervated. Sublingual nitroglycerin is especially useful in order to dilate distal arteries to improve stenosis visibility. However, it is contraindicated in patients on erectile dysfunction medications and those with severe anemia. It must be used cautiously in patients with aortic stenosis or other preload-dependant cardiac pathologies.     

Thyroid dysfunction in patients with diabetes: clinical implications and screening strategies

Background: Patients with diabetes mellitus are at an increased risk of thyroid disease. The frequency of thyroid dysfunction in diabetic patients is higher than that of the general population and up to a third of patients with type‐1 diabetes (T1DM) ultimately develop thyroid dysfunction. Unrecognised thyroid dysfunction may impair metabolic control and add to cardiovascular disease risk in diabetic patients. Aims: Our aims were to review the current literature on the association between thyroid dysfunction and diabetes mellitus, to highlight relevant clinical implications, and to examine present thyroid disease screening strategies in routine diabetes care. Results: The pleiotropic effects of thyroid hormones on various metabolic processes are now better understood. Uncontrolled hyperthyroidism in diabetic patients may trigger hyperglycaemic emergencies while recurrent hypoglycaemic episodes have been reported in diabetic patients with hypothyroidism. Furthermore, thyroid dysfunction may amplify cardiovascular disease risk in diabetic patients through inter‐relationships with dyslipidaemia, insulin resistance and vascular endothelial dysfunction. However, the significance of subclinical degrees of thyroid dysfunction remains to be clarified. While these developments have implications for diabetic patients a consensus is yet to be reached on optimal thyroid screening strategies in diabetes management. Conclusions: The increased frequency of thyroid dysfunction in diabetic patients and its likely deleterious effects on cardiovascular and metabolic function calls for a systematic approach to thyroid disease screening in diabetes. Routine annual thyroid testing should be targeted at diabetic patients at risk of thyroid dysfunction such as patients with T1DM, positive thyroid autoantibodies or high‐normal TSH concentrations.     

Circulating markers of endothelial function in cardiovascular disease

Endothelial dysfunction is a key event in cardiovascular disease. Measurement of endothelial dysfunction in vivo presents a major challenge, but has important implications since it may identify the clinical need for therapeutic intervention, specifically in primary prevention. Several biological markers have been used as indicators of endothelial dysfunction. The soluble adhesion molecules sICAM-1 and sVCAM-1 lack specificity and are increased in inflammatory processes. Both markers are increased in coronary artery disease. sICAM-1 level predicts the risk for cardiovascular disease or diabetes mellitus in healthy individuals. sE-selectin is specific for the endothelium and is increased in coronary artery disease and diabetes mellitus. sE-selectin is also associated with diabetic risk. The endothelium-specific marker, soluble thrombomodulin, is associated with severity of coronary artery disease, stroke or peripheral occlusive arterial disease and is not increased in healthy or asymptomatic subjects. Interestingly, thrombomodulin decreases during treatment of hypercholesterolemia or hyperhomocysteinemia. In contrast, von Willebrand factor is the best endothelial biomarker and predicts risk for ischemic heart disease or stroke.     

New approaches to the treatment of angina pectoris

Patients with coronary artery disease represent a highly heterogeneous group and require individualized treatment based on severity of symptoms, extent and distribution of coronary artery lesions, and left ventricular function. Patients with left main coronary artery disease or triple-vessel disease and left ventricular dysfunction should be referred for surgery, as should patients satisfying the Veterans Administration high-risk group criteria, as well as those patients with intractable symptoms unsuitable for PTCA. Patients in whom discrete proximal lesions in a single coronary artery have caused recent onset of medically refractory angina should be considered for PTCA. In these patients, PTCA has been proven to be both a safe and effective technique. The procedure will relieve the signs and symptoms of myocardial ischemia in half of these patients. One third of this group will have a recurrence of their symptoms but will return to an asymptomatic state for a prolonged period following a second PTCA procedure. The rate of infarction and death compares favorably with that seen with CABG surgery. What are the relative merits of PTCA vs. CABG surgery or drug regimens in the treatment of ischemic heart disease? To answer this critical question, a well-defined prospective randomized clinical trial is needed. The results of such a trial may usher in a new era in the treatment of ischemic heart disease.     

Sildenafil-associated coronary thrombosis in a patient with angiographically normal coronary arteries: a case report with review of literature

Sildenafil is widely used as a primary pharmacological treatment of erectile dysfunction in men with and without underlying cardiovascular disease. Although initial reports of adverse cardiac events were reported soon after Food and Drug Administration approval of this agent, a large body of data suggests that sildenafil does not significantly increase the risk of nonfatal myocardial infarction, stroke, or cardiovascular deaths in patients with preexisting ischemic heart disease. We report the case of a 66-year-old man who developed thrombotic occlusion of the left anterior descending artery and presented with acute myocardial infarction after the use of sildenafil. The patient had presented with chest pain syndrome and borderline elevation of serum troponin I levels 1 week before sildenafil use, and a coronary angiogram had demonstrated normal coronary arteries. This case emphasizes the potential of precipitating coronary thrombosis in patients with unstable plaque after sildenafil use, even in patients with angiographically normal coronary arteries.     

Osteoprotegerin is associated with silent coronary artery disease in high-risk but asymptomatic type 2 diabetic patients

OBJECTIVE: Osteoprotegerin (OPG) is an inhibitor of osteoclastogenesis, which has been recently involved in atherosclerosis. The relationship between coronary atherosclerosis and OPG has never been studied in asymptomatic type 2 diabetic patients. RESEARCH DESIGN AND METHODS: This is a nested case-control study; 162 asymptomatic type 2 diabetic patients were evaluated for silent myocardial ischemia using stress myocardial perfusion imaging; of 50 patients with positive results, 37 underwent coronary angiography, 20 of whom showed significant coronary artery disease (CAD group). Of 112 patients without silent myocardial ischemia, 20 subjects (NO-CAD group) were selected and matched by age and sex to patients with CAD. OPG, C-reactive protein, adiponectin, lipoprotein(a), albuminuria, and classical risk factors were measured. RESULTS: The percentages of subjects with OPG levels above median and with nephropathy were higher in the CAD group than in the NO-CAD group (70 vs. 25%, P = 0.004 and 50 vs. 5%, P = 0.001, respectively). LDL cholesterol levels were higher and HDL cholesterol levels lower in the CAD compared with the NO-CAD group (P = 0.033 and P = 0.005, respectively). No other variables were associated with CAD. Logistic regression analysis showed that OPG values above median (odds ratio 8.31 [95% CI 1.18-58.68], P = 0.034) and nephropathy (21.98 [1.24-388.36], P = 0.035) were significant independent predictors of asymptomatic CAD in type 2 diabetic patients. CONCLUSIONS: Our investigation reports the first evidence of an independent association of OPG with asymptomatic CAD in type 2 diabetic patients. The results of this nested case- control study with 20 cases need to be confirmed in a larger population.     

Evaluation of the patient with angina pectoris

All patients with chronic stable angina presumed to be due to coronary artery disease should undergo exercise stress testing early in evaluation for evidence of high-risk coronary disease. If the exercise stress test shows early positive findings, patients should undergo cardiac catheterization to exclude left main coronary vessel disease and three-vessel disease with concomitant left ventricular dysfunction. Patients with unstable angina who are subsequently stabilized on medical therapy should undergo a limited exercise stress test before discharge from the hospital to identify those at high risk. An ambulatory ECG is also helpful in evaluating for evidence of silent ischemia in these patients.     

Indications for coronary artery bypass grafting in the DES era

Several treatments for coronary artery disease have been developed. Current techniques for both coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) have improved the outcomes after procedures. However, patients referred for CABG have been changing because of the recent advancement of PCI. The number of patients referred for CABG has decreased; furthermore, those patients have significant comorbid conditions and multiple severe coronary artery disease. Several randomized controlled clinical trials demonstrated the superiority of CABG regarding major adverse cardiac and cerebral events to PCI. The selection of these two invasive therapies including hybrid approach should be done by both patients' clinical condition and anatomical characteristics of coronary artery.