Detection of high-burden coronary artery disease by exercise-induced changes of the E/E’ ratio

To investigate whether exercise-induced changes of the E/E’ average ratio can detect high-burden coronary artery disease (CAD) in patients with chest pain and normal left ventricular (LV) systolic function. The study population consisted of 359 patients admitted for chest pain (59.8 ± 9.8 years, 75% male). Patients underwent exercise echocardiography, scintigraphy and coronary angiography. The average of the lateral and septal ratios of early diastolic transmitral velocity to early diastolic tissue velocity (E/E’) at baseline and immediately after exercise was calculated. Exercise induced wall motion abnormalities were also calculated. Coronary angiography showed flow limiting CAD in 238 patients (66%). The exercise-induced changes of E/E’ average ratio had a sensitivity of 87.3% and a specificity of 75.2% for detection of flow limiting CAD, whereas myocardial scintigraphy showed 79.2% sensitivity and 80.1% specificity and exercise induced wall motion abnormalities had a sensitivity of 74.3% and a specificity of 66.9%. Likelihood ratio chi square showed an incremental value of the exercise-induced changes of E/E’ average ratio over regional perfusion technique (from 121.37 to 194.15, P < 0.001) and over wall motion abnormalities (from 57.03 to 146.50, P < 0.001). The exercise-induced change of the E/E’ average ratio detects flow limiting CAD in patients with chest pain and normal LV systolic function showing an incremental value over regional perfusion technique and wall motion abnormalities.     

Genetics of coronary artery disease: Short people at risk?

Traditional cardiovascular risk factors have been in the spotlight for coronary artery disease (CAD) management over the past decades. A non-modifiable risk marker is short adult stature. However, a causal role in the etiology of CAD was always questioned, since multiple confounders may also explain the inverse association between height and CAD risk. The assumption that genetic variants affecting height do so without interference of exogenous factors allows for the testing of the association between short stature, that is, genetic markers affecting height, and CAD even without measuring height. Interestingly, these studies suggest a rather multifaceted relationship between the two complex phenotypes. Indeed, investigating 180 height-associated genetic variants in 65,066 patients with CAD and 128,383 healthy controls suggests a causal relationship of short stature and CAD risk. Multiple signaling pathways affecting growth, as well as pleiotropic effects of genetic variants affecting height and lipids, seem to underlie the association between height and CAD risk.     

MEF2A sequence variants and coronary artery disease: a change of heart?

Rare mutations in MEF2A have been proposed as a cause of coronary artery disease (CAD) and myocardial infarction (MI). In this issue of the JCI, Pennacchio and colleagues report sequencing MEF2A in 300 patients with premature CAD and in controls. Only 1 CAD patient was found to carry a missense mutation not found in controls. The specific 21-bp deletion in MEF2A previously proposed as causal for CAD and/or MI was observed in unaffected individuals and did not segregate with CAD in families. These results do not support the hypothesis that mutations in MEF2A are a cause of CAD and/or MI but do illustrate general principles regarding the difficulty of connecting genetic variation to common diseases.     

Chlamydia pneumoniae and coronary artery disease: legitimized linkages?

Chlamydia pneumoniae (Cp) infection in early life may accelerate atherosclerosis over ensuing decades, leading to cardiovascular complications. Cp promotes endothelial dysfunction and may modulate inflammation underlying atherosclerosis. It represents a biologically plausible candidate for the causation of atherosclerosis. Other infections simultaneously occurring with Cp may result in a synergistic effect to promote atherosclerosis. Studies on the treatment of Cp with antibiotics indicates decreased rates of infection, modulation of inflammation and in some settings, fewer cardiovascular complications.     

Depression in coronary artery disease: does treatment help?

Research over the past decade on the link between depression and coronary artery disease (CAD) has moved from establishing the epidemiologic association between depression and CAD to a focus on whether and how treating depression in patients with CAD benefits these patients. Evidence to date indicates that depression therapy does improve depression, albeit somewhat modestly, in CAD patients. The effect of depression therapy on CAD outcomes is less clear, although there is enough positive evidence to encourage further research. The effects of depression treatment on mechanisms mediating increased CAD risk in depressed patients are variable. Future research should perhaps focus on targeting treatment at intermediary mechanisms as well as at depression itself.     

MDCT evaluation of atherosclerotic coronary artery disease: What should radiologists know?

As an important tool for diagnosing acute coronary syndrome and stable angina, coronary CT angiography has been increasingly being performed in patients presenting with atypical chest pain. In order to help treating patients more efficiently, it is crucial for radiologists to have a comprehensive understanding about mechanisms and clinical aspects as well as CT findings of coronary atherosclerosis per se. A thorough understanding and optimal performance of coronary CT angiography may lead to reduction of unjustified downstream testing. This article provides a clinical and radiological overview of coronary atherosclerosis, and a practical guideline about how to interpret degree of stenosis on coronary CT angiography.     

B-type natriuretic peptide: a simple new test to identify coronary artery disease?

A common key question in clinical medicine is whether coronary artery disease (CAD) is present in a patient. This applies not only to patients with symptomatic chest pain, but also to those at high risk of sudden unexpected death due to asymptomatic CAD, such as diabetics. In both groups of patients, it would be of great benefit if a simple blood test could identify those most likely to have CAD. Such individuals could then be selected for more definitive but more invasive tests for CAD, such as angiography, exercise testing, etc. In addition to its established role in diagnosing heart failure, it appears that BNP may fulfil this function of pre-screening for both symptomatic and asymptomatic CAD. We review the evidence for this new prospect, which has the potential to reduce cardiac deaths by using a simple blood test to better target cardioprotective strategies to those who most need them.     

Feasibility,safety and accuracy of regadenoson–atropine (REGAT) stress echocardiography for the diagnosis of coronary artery disease: an angiographic correlative study

Regadenoson (REG), a selective A2A receptor vasodilator, has not been widely evaluated in stress echocardiography (SE). We report results of 45 patients participating in REG + atropine (REGAT) SE protocol conducted in a single-center prospective trial. The REGAT study enrolled subjects before a clinically indicated cardiac catheterization for suspected coronary artery disease (CAD). After rest imaging, a 2 mg Atropine (AT) bolus followed by 400 mcg of REG was given. Standard stress imaging views were obtained and interpreted in blinded fashion. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated using cardiac catheterization >70 % stenosis as gold standard. Additional endpoints included major adverse cardiac events (MACE) and patient questionnaire responses. The mean duration of REGAT was 18 ± 7.2 min. There were no MACE, with only transient side-effects of dry mouth, shortness of breath, and headache. The incidence of significant CAD was 51.1 %. The sensitivity and specificity for significant stenosis was 60.9 and 86.4 %, with a PPV and NPV of 82.4 and 67.9 %. By coronary territories, the sensitivity, specificity, PPV, and NPV were: left anterior descending artery 58.8, 92.9, 83.3, and 78.8 %; left circumflex artery 6.7, 93.3, 33.3, and 67.7 %; and right coronary artery 16.7, 93.9, 50, and 75.6 %. Over 90 % of subjects reported feeling comfortable, with 83 % preferring REGAT as a future stress modality. The REGAT protocol is fast, safe, and well-tolerated with good specificity for CAD detection, but its low sensitivity and NPV precludes it from being an imaging modality for routine use.     

Erectile dysfunction: is there silent obstructive coronary artery disease?

Erectile dysfunction (ED) has long been ascribed to the ageing process. Patients presenting with ED often have their symptoms ignored in terms of both underlying aetiology and treatment. It is now clear that, in many cases, the pathological processes in ED are common to those involved in vascular disease. Men with proven coronary artery disease (CAD) have a high incidence of ED when directly questioned. In some, the onset of ED pre-dates the symptoms and diagnosis of CAD as exemplified in our two cases. Patient 1 developed ED two months before an acute anterior myocardial infarction. Patient 2 had several cardiovascular risk factors but only the presence of ED prompted investigations which eventually led to an angiographic diagnosis of three-vessel disease. The presence of silent co-existing myocardial ischaemia should be considered in men who present with ED, particularly when they have other cardiovascular risk factors.     

Association of estrogen receptor α gene polymorphism with the presence of coronary artery disease documented by coronary angiography

Objectives

To examine the relationship between PvuII and XbaI polymorphisms, with the presence of angiographically determined CAD in an Iranian population.

Design and methods

Patients having angiographic evidence of atherosclerosis (Gensini score > 6) in their epicardial coronary tree (CAD⁺ case group) were compared with Patients with Gensini score ≤ 6 (CAD⁻ control group). The presence of PvuII and XbaI polymorphisms was analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP).

Results

The PvuIΙ genotype distributions were not statistically different in CAD groups, and subgroups stratified by gender. For the XbaI polymorphism, after controlling for age, male sex, cigarette smoking and hyperlipidemia, XbaI GG genotype was not also found to be an independent predictor for CAD occurrence (OR = 1.65; 95% CI: 0.90-3.03; P = 0.10).

Conclusions

We did not observe an association between ESR1 PvuII and XbaI gene polymorphisms with CAD in the risk of CAD in an Iranian population.     

Does off‐pump coronary artery bypass surgery reduce secretion of plasminogen activator inhibitor‐1?

Prior studies showed that postoperative increase in plasminogen activator inhibitor-1 (PAI-1) levels is associated with an increased risk of graft occlusion after coronary artery bypass surgery (CABG). This prospective study aimed to compare the changes of PAI-1 antigen levels after off-pump and on-pump CABG. Forty-four patients admitted for elective CABG were randomised to on-pump (n=22) or off-pump (n=22) surgery. Serum samples were collected for estimation of PAI-1 and tissue plasminogen activator (t-PA) antigen levels preoperatively and 2 h after the operation. The groups were similar in terms of age, weight, gender ratio and extent of coronary disease, left ventricular function and number of grafts per patient. Fibrinogen and t-PA levels increased postoperatively in both the groups when compared with baseline values. After operation, statistical analysis revealed that increase of PAI-1 values was higher in off-pump group (44.1+/-9.1 vs. 25.3+/-6.9) than on-pump group (37.2+/-5.5 vs. 27.3+/-7.8, p=0.002). This study shows that increase in PAI-1 antigen values in patients who undergo off-pump (beating heart) CABG is significantly higher than in those who undergo conventional CABG with cardiopulmonary bypass.     

Is chronic kidney disease comparable to diabetes as a coronary artery disease risk factor?

BACKGROUND: Chronic kidney disease (CKD) is one of the known risk factors for coronary heart disease (CHD). Though electrocardiograms (ECGs) have limited accuracy in determining the true prevalence of CHD, we wondered whether CKD and diabetes mellitus (DM) controlled for hypertension (HTN), had similar prevalences of ECG abnormalities that could reflect underlying coronary heart disease. METHOD: Data were collected for 5,942 men and women aged 30 to 69 years in the Tehran Lipid and Glucose Study (TLGS), a crosssectional phase of a large epidemiologic study first initiated in 1999. ECG findings of all subjects were coded according to Minnesota ECG coding criteria. The Whitehall criteria for abnormal ECG findings that could represent ischemia were utilized. Creatinine clearance (Crcl) was estimated using the Cockroft-Gault equation and diabetes was defined according to the American Diabetic Association (ADA) criteria. Subjects with moderate CKD and without DM were compared with the patients with DM without CKD. HTN prevalence was similar. The analysis was performed for all Whitehall ECG ischemia abnormalities combined, and separately for pathologic Q waves. RESULTS: In spite of an overall similar prevalence of smoking, and a lower incidence of dyslipidemia and HTN, moderate CKD patients had a higher prevalence of Whitehall criteria abnormal ECG findings compared with the patients with DM. Over 19% of patients with CKD had abnormal ECG findings while 14.7% of diabetic patients had abnormal ECGs (P = 0.02). The prevalence of Q waves was 11.5% in patients with CKD and 10.8% in patients with DM. In an age-matched subgroup of patients with DM and no CKD, the prevalence of ECG abnormalities was 19.3%, similar to the patients with moderate CKD and no DM (19.7%) (P = 0.9). The prevalence of pathologic Q waves in an age-matched group was 11.45%, compared with 11.5%, respectively. CONCLUSION: Moderate CKD is a major risk factor for the development of the Whitehall ECG criteria which have been associated with ischemic heart disease. The importance of CKD as a risk factor for ECG abnormalities is comparable with DM. Patients with moderate CKD probably are candidates for aggressive CHD risk modification.     

Diagnostic performance of plasma high sensitive C‐reactive protein in detecting three‐vessel coronary artery disease: modification by apolipoprotein E genotype

Objectives. Plasma high sensitive C‐reactive protein (hsCRP) concentration is an important clinical test of systemic inflammation and, like apoE ε4 allele, an important risk factor of coronary artery disease (CAD). We investigated whether the diagnostic performance of plasma hsCRP in detecting severe 3‐vessel CAD may be modified by apoE ε4 carrier status. Methods. The study population (Angiography and Genes Study) comprised 485 Finnish subjects (336 men and 149 women, mean age 64.0±1.0) undergoing coronary angiography. ApoE genotypes were determined by the PCR‐based method and by hsCRP using an automatic analyser. Results. The diagnostic performance of hsCRP concentration in distinguishing 3‐vessel CAD from its less widespread forms (non‐3‐vessel CAD) was assessed by receiver operating characteristic curve (ROC) analysis separately in apoE ε4 non‐carriers and ε4 carriers. ROC analysis showed that hsCRP predicted 3‐vessel CAD in apoE ε4 non‐carriers (AUC 0.646; SE 0.035; p = 0.0001; 95?% CI 0.578–0.714) but not in ε4 carriers (AUC 0.518; SE 0.049; p = 0.719; 95?% CI 0.422–0.615). Multinomial logistic regression analysis revealed a significant (p<0.05) apoE ε4 group versus hsCRP group (<1.0?mg/L/?1.0?mg/L) interaction in relation to incidence of 3‐vessel CAD. In apoE ε4 non‐carriers, high hsCRP (?1.0?mg/L) was significantly (OR 2.1; 95?% CI 1.233–3.562; p = 0.006) associated with high incidence of 3‐vessel CAD after adjustment for major CAD risk factors. Conclusion. The diagnostic performance of hsCRP in distinguishing 3‐vessel CAD from less extensive forms of coronary atherosclerosis is more accurate in a group of subjects without the apoE ε4 allele than in patients with it.     

Hypertriglyceridemia and low high-density lipoprotein: risks for coronary artery disease?

Elevated total cholesterol and LDL cholesterol have been well established as risk factors for coronary heart disease (CHD). Several large clinical trials have demonstrated that lipid lowering decreases the incidence and mortality that results from CHD. However, a high percentage of subjects in these studies did not receive benefit from LDL lowering. Many experts believe that other lipid disorders may play a significant role in the atherogenic process, including elevated triglyceride levels alone or in association with a low level of HDL. Do elevated triglyceride levels pose an increased risk for CHD? This article describes the research done evaluating this question, as well as the influences of lifestyle changes and pharmacologic interventions on these dyslipidemias.     

Pulmonary artery occlusion pressure estimation by transesophageal echocardiography: is simpler better?

The measurement of pulmonary artery occlusion pressure (PAOP) is important for estimation of left ventricular filling pressure and for distinction between cardiac and non-cardiac etiology of pulmonary edema. Clinical assessment of PAOP, which relies on physical signs of pulmonary congestion, is uncertain. Reliable PAOP measurement can be performed by pulmonary artery catheter, but it is possible also by the use of echocardiography. Several Doppler variables show acceptable correlation with PAOP and can be used for its estimation in cardiac and critically ill patients. Noninvasive PAOP estimation should probably become an integral part of transthoracic and transesophageal echocardiographic evaluation in critically ill patients. However, the limitations of both methods should be taken into consideration, and in specific patients invasive PAOP measurement is still unavoidable, if the exact value of PAOP is needed.