Israel Medical Association Journal

Background: The extent and impact of obesity as an isolated risk factor for coronary artery disease is not clear since co-morbidities serve as confounders and may mask this association.

Objectives: To examine whether obesity is associated with extensive coronary artery disease among metabolically healthy patients presenting with ST-elevation myocardial infarction (STEMI) and to explore the outcomes according to body mass index (BMI).

Methods: We stratified STEMI patients who had a metabolically healthy phenotype and available weight and height data according to BMI: 18.5–25 kg/m² (lean), 25.01–30 kg/m² (overweight), and > 30 kg/m² (obese).

Results: Overall 381 patients were included, 42% lean, 41% overweight, and 17% obese. Patients with increased BMIs had higher levels of low-density proteins and triglycerides (P < 0.05). Obese patients presented with the lowest rates of multi-vessel disease (12.9% vs. 22.9% for overweight and 28% for lean). In a univariable analysis, obese patients were 60% less likely to be diagnosed with multi-vessel disease (odds ratio 0.4, 95% confidence interval 0.2–0.9, P = 0.021) compared to lean patients. The association remained significant in a multivariable model adjusted for baseline characteristics (P = 0.029). There were no differences in 30-day or long-term mortality (median follow-up 3.2 years) among the groups (P > 0.1 for all comparisons).

Conclusions: Metabolically healthy phenotype obesity was associated with lower rates of multi-vessel disease despite higher levels of triglycerides. However, this association did not translate into increased mortality.

Background: Anti-endothelial cell antibodies (AECA) are a known biomarker of endothelial dysfunction and damage in clinical practice, especially in autoimmune disease.

Objectives: To determine the relation between natural AECA levels and prognosis related to coronary artery disease.

Methods: Candidates for coronary angiography were prospectively enrolled. AECA levels were determined by ELISA assay. Mortality was evaluated after more than 5 years follow-up.

Results: Of a total 857 patients, 445 had high AECA levels (group 1) and 412 had low levels (< 1 OD unit, group 2). Both groups did not differ in age, sex, or presence of diabetes. The median follow up was 2293 days (76 months). Patients with high AECA levels were more likely to have normal coronary arteries on angiography (21.6% vs. 16.9%, P = 0.047) and less likely to have calcified lesions (19.0% vs. 26.6%, P = 0.028) and lower prevalence of abnormal renal functions (71.1 mg/dl vs. 66.5 mg/dl, P = 0.033). Patients with higher AECA levels had lower mortality levels (20.1% vs. 27.6%, P = 0.006). A logistic regression model demonstrated independent association between lower AECA levels and the presence of coronary atherosclerosis based on angiogram.

Conclusions: After a median of more than 6 years, higher natural AECA levels were associated with less coronary artery disease and lower mortality rates in patients undergoing coronary angiography

Background: Low folate levels are associated with megaloblastic anemia, neural tube defects, and an increased risk of cancer. Data are scarce regarding the sex aspect of this deficiency.

Objectives: To assess sex differences in folate levels in a large cohort of patients and to investigate the effect of low folate levels on homocysteine concentrations.

Methods: Data were collected from medical records of patients examined at a screening center in Israel between 2000 and 2014. Cross sectional analysis was conducted on 9214 males and 4336 females.

Results: The average age was 48.4 ± 9.5 years for males and 47.6 ± 9.4 years for females. Average folate levels were 19.2 ± 8.6 and 22.4 ±10.3 nmol/L in males and females, respectively (P < 0.001). The prevalence of folate levels below 12.2 nmol/L was 19.5% in males compared to 11.6% in females (P < 0.001). In patients with low folate levels and normal B12 levels, homocysteine levels above 15 μmol/L were found in 32.4% of males and 11.4% of females (P < 0.001). Males had a significantly higher odds ratio (OR) of having folate levels below 12.2 nmol/L: OR 1.84 (95% confidence interval [95%CI] 1.66–2.05) in a non-adjusted model, and OR 2.02 (95%CI 1.82–2.27) adjusted for age, smoking status, body mass index, kidney function, albumin, and triglycerides levels.

Conclusions: Folate levels are lower in males compared to females, which may contribute to the higher homocysteine levels found in males and thus to their increased risk of developing atherosclerosis and coronary artery disease.

Background: Cardiac rehabilitation (CR) is underutilized globally despite evidence of clinical benefit. Major obstacles for wider adoption include distance from the rehabilitation center, travel time, and interference with daily routine. Tele-cardiac rehabilitation (tele-CR) can potentially address some of these limitations, enabling patients to exercise in their home environment or community.

Objectives: To evaluate the clinical and physiological outcomes as well as adherence to tele-CR in patients with low cardiovascular risk and to assess exercise capacity, determined by an exercise stress test, using a treadmill before and following the 6-month intervention.

Methods: A total of 22 patients with established coronary artery disease participated in a 6-month tele-CR program. Datos Health (Ramat Gan, Israel), a digital health application and care-team dashboard, was used for remote monitoring, communication, and management of the patients.

Results: Following the 6-month tele-CR intervention, there was significant improvement in exercise capacity, assessed by estimated metabolic equivalents with an increase from 10.6 ± 0.5 to 12.3 ± 0.5 (P = 0.002). High-density lipoproteins levels significantly improved, whereas low-density lipoproteins, triglyceride, glycosylated hemoglobin, and systolic and diastolic blood pressure levels were not significantly changed. Exercise adherence was consistent among patients, with more than 63% of patients participating in a moderate intensity exercise program for 150 minutes per week.

Conclusions: Patients who participated in tele-CR adhered to the exercise program and attained clinically significant functional improvement. Tele-CR is a viable option for populations that cannot, or elect not to, participate in center-based CR programs.

Background: Current guidelines for choosing between revascularization modalities may not be appropriate for young patients.

Objectives: To compare outcomes and guide treatment options for patients < 40 years of age, who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) between 2008 and 2018.

Methods: Outcomes were compared for 183 consecutive patients aged < 40 years who underwent PCI or CABG between 2008 and 2018, Outcomes were compared as time to first event and as cumulative events for non-fatal outcomes.

Results: Mean patient age was 36.3 years and 96% were male. Risk factors were similar for both groups. Drug eluting stents were implemented in 71% of PCI patients and total arterial revascularization in 74% of CABG patients. During a median follow-up of 6.5 years, 16 patients (8.6%) died. First cardiovascular events occurred in 35 (38.8%) of the PCI group vs. 29 (31.1%) of the CABG group (log rank P = 0.022), repeat events occurred in 96 vs. 51 (P < 0.01), respectively. After multivariate adjustment, CABG was associated with a significantly reduced risk for first adverse event (hazard ratio [HR] 0.305, P < 0.01) caused by a reduction in repeat revascularization. CABG was also associated with a reduction in overall repeat events (HR 0.293, P < 0.01). There was no difference in overall mortality between CABG and PCI.

Conclusions: Young patients with coronary disease treated by CABG showed a reduction in the risk for non-fatal cardiac events. Mortality was similar with CABG and PCI.

Background: Malignancy is a known risk factor for venous thromboembolism; however, the association with arterial thromboembolic events remains unclear.

Objectives: To examine the association between non-ST-elevation myocardial infarction (NSTEMI) and non-significant coronary artery disease (CAD) and the presence of new or occult malignancy.

Methods: An observational cohort, single-center study was performed 2010–2015. Adult patients with NSTEMI, who underwent coronary angiography and had no significant coronary lesion, were included. Using propensity score matching, we created a 2:1 matched control group of adults with NSTEMI, and significant coronary artery disease. Risk factors for new or occult malignancy were assessed using multivariate backward stepwise logistic regression analysis. The primary outcome was new or occult malignancy, defined as any malignancy diagnosed in the 3 months prior and 6 months following the myocardial infarction (MI).

Results: During the study period, 174 patients who presented with MI with non-obstructive coronary arteries were identified. The matched control group included 348 patients. There was no significant difference in the group demographics, past medical history, or clinical presentation. The incidence of new or occult malignancy in the study group was significantly higher (7/174, 4% vs. 3/348, 0.9%, P = 0.019). NSTEMI with non-significant CAD was an independent risk factor for occult malignancy (odds ratio [OR] 4.6, 95% confidence interval [95%CI] 1.1–18.7). Other risk factors included active smoking (OR 11.2, 95%CI 2.5–49.1) and age (OR 1.1, 95%CI 1.03–1.17).

Conclusions: NSTEMI with non-significant CAD may be a presenting or early marker of malignancy and warrants further investigation.

Background: Contemporary data on clinical profiles and long-term outcomes of young adults with coronary artery disease (CAD) are limited.

Objectives: To determine the risk profile, presentation, and outcomes of young adults undergoing coronary angiography.

Methods: A retrospective analysis (2000–2017) of patients aged ≤ 35 years undergoing angiography for evaluation and/or treatment of CAD was conducted.

Results: Coronary angiography was performed in 108 patients (88% males): 67 acute coronary syndrome (ACS) and 41 non-ACS chest pain syndromes. Risk factors were similar: dyslipidemia (69%), positive family history (64%), smoking (61%), obesity (39%), hypertension (32%), and diabetes (22%). Eight of the ACS patients (12%) and 29 of the non-ACS (71%) had normal coronary arteries without subsequent cardiac events. Of the 71 with angiographic evidence of CAD, long-term outcomes (114 ± 60 months) were similar in ACS compared to non-ACS presentations: revascularization 41% vs. 58%, myocardial infarction 32% vs. 33%, and all-cause death 8.5% vs. 8.3%. Familial hypercholesterolemia (FH) was diagnosed in 25% of those with CAD, with higher rates of myocardial infarction (adjusted hazard ratio [HR] 2.62, 95% confidence interval [95%CI] 1.15–5.99) and revascularization (HR 4.30, 95%CI 2.01–9.18) during follow-up. Only 17% of patients with CAD attained a low-density lipoprotein cholesterol treatment goal < 70 mg/dl.

Conclusions: CAD in young adults is associated with marked burden of traditional risk factors and high rates of future adverse cardiac events, regardless of acuity of presentation, especially in patients with FH, emphasizing the importance of detecting cardiovascular risk factors and addressing atherosclerosis at young age.

Background: Coronary artery disease (CAD) has known risk factors. Individual risks related to specific ethnicities are complex and depend on genetic predisposition and lifestyle.

Objectives: To compare the nature and prevalence of risk factors in Arab and non-Arab ethnic patients with symptomatic obstructive CAD referred for coronary angiography.

Methods: CAD, defined as coronary angiography with a ≥ 50% narrowing in ≥ 1 vessel, was diagnosed in 1029 patients admitted to a medical center between April 2014 and October 2015. Patients were divided into two groups according to ethnic origin: Arab vs. non-Arab. Demographics, clinical presentation, and coronary risk profiles were compared.

Results: The diagnosis of CAD was made during ST-elevation myocardial infarction (STEMI) in 198 patients (19%) who arrived at the clinic, 620 (60%) with unstable angina/non-STEMI, and 211 (21%) with stable angina. Patients with symptomatic CAD and Arab ethnicity were 47% more prevalent than non-Arab patients presenting with CAD. The Arab patients were appoximately 5 years younger, 50% more likely to be active smokers, 25% more likely to be obese, and more likely to have a family history of CAD. Other coronary risk factors were similar between the two groups.

Conclusions: Smoking and obesity, which are potentially modifiable CAD risk factors, stood out as major risk factors, in addition to genetic disposition, among Arab and non-Arab patients with symptomatic CAD. Screening and educational interventions for smoking cessation, obesity control, and compliance to treatment of co-morbidities should be attempted in order to decrease CAD in the Arab population.

Background: Since the introduction of the electrocardiogram (ECG) in 1902, the fundamentals of ECG data acquisition, display, and interpretation in the clinical arena have not changed much.

Objectives: To present a new method to enhance and improve acquisition, analysis, and display of the standard ECG.

Methods: We performed ECG enhancement by superimposition and summation of multiple standard ECG cycles of each lead, by temporal alignment to peak R wave and voltage alignment to an improved baseline, at the T-P segment.

Results: We enhanced ECG recordings of 504 patients who underwent coronary angiograms for routine indications. Several new ECG features were noted on the enhanced recordings. Examination of a subgroup of 152 patients with a normal rest 12-lead ECG led to the discovery of a new observation, which may help to distinguish between patients with and without coronary artery disease (CAD): namely, a spontaneous cycle-to-cycle voltage spread (VS) at the S-T interval, normalized to VS at the T-P interval. The mean normalized VS was significantly greater in those with CAD (n=61, 40%) than without (n=91, 60%), 5.61 ± 3.79 vs. 4.01 ± 2.1 (P < 0.05).

Conclusions: Our novel method of multiple ECG-cycle superimposition enhances the ECG display and improves detection of subtle electrical abnormalities, thus facilitating the standard rest ECG diagnostic power. We describe, for the first time, voltage spread at the S-T interval, an observed phenomenon that can help detect CAD among individuals with normal rest 12-lead ECG.

Background: Catastrophic life events are associated with the occurrence of cardiovascular incidents and worsening of the clinical course following such events.

Objectives: To evaluate the characteristics and long-term prognosis of Holocaust survivors presenting with acute myocardial infarction (AMI) compared to non-Holocaust survivors.

Methods: Israeli Jews who were born before 1941 and had been admitted to a tertiary medical center due to AMI during the period 2002–2012 were studied. Holocaust survivors were compared with non-Holocaust survivor controls using individual age matching.

Results: Overall 305 age-matched pairs were followed for up to 10 years after AMI. We found a higher prevalence of depression (5.9% vs. 3.3%, P = 0.045) yet a similar rate of cardiovascular risk factors, non-cardiovascular co-morbidity, severity of coronary artery disease, and in-hospital complications in survivors compared to controls. Throughout the follow-up period, similar mortality rates (62.95% vs. 63.9%, P = 0.801) and reduced cumulative mortality (0.9 vs. 0.96, HR = 0.780, 95%CI 0.636–0.956, P = 0.016) were found among survivors compared to age-matched controls, respectively. However, in a multivariate analysis survival was not found to be an independent predictor of mortality, although some tendency towards reduced mortality was seen (AdjHR = 0.84, 95%CI 0.68–1.03, P = 0.094). Depression disorder was associated with a 77.9% increase in the risk for mortality. 

Conclusions: Holocaust survivors presenting with AMI were older and had a higher prevalence of depression than controls. No excessive, and possibly even mildly improved, risk of mortality was observed in survivors compared with controls presenting with AMI. Possibly, specific traits that are associated with surviving catastrophic events counter the excess risk of such events following AMI.

 

Background: The role of autoimmune factors in the etiology of coronary artery disease (CAD) was suggested in numerous studies but has not been definitively determined.

Objectives: To assess the possible influence of antiphospholipid and antinuclear antibodies on atherosclerosis development in young patients after myocardial revascularization procedures.

Methods: The study group included 39 patients younger than 45 years with coronary artery disease (CAD) who underwent myocardial revascularization. Serum levels of antiphospholipid (aPL), antinuclear (ANA) and antineutrophil cytoplasmatic (ANCA) antibodies were tested within 1 month after the procedure.

Results: All three types of aPL were significantly higher in CAD patients when compared to healthy controls: anti-β2-glycoprotein I (aβ2GPI), both immunoglobulin (Ig)G and IgM classes (median 4.10 SGU, range 3.45–21.63 vs. 0.76, 0.12–6.01, P < 0.001, and 2.82 SGU, 1.44–11.70 vs. 1.08, 0.44–3.64, P < 0.001, respectively); anticardiolipin antibodies (aCL) both IgG and IgM classes (3.13 GPL, 1.32–14.03 vs. 2.42, 0.96–18.45, P = 0.0037, and 6.94 MPL, 1.90–26.40 vs. 4.32, 1.9–28.73, P < 0.008, respectively); and lupus anticoagulant (LA) (27.7% vs. 0%, P = 0.005). ANA were elevated in one patient and ANCA in 23 (60%). The levels of aPL did not correlate with the presence of a clot in a coronary vessel detected during angiography or with exacerbation of coronary artery atherosclerosis.

Conclusions: In young patients with CAD who underwent myocardial revascularization the levels of aPL were significantly higher than in young healthy subjects. Thus, besides the classic risk factors for CAD, autoimmunity may play an important role in atherosclerotic plaque formation and progression.

Background: Concomitant carotid artery disease (CaAD) in patients with coronary artery disease (CAD) is associated with worse cardiac and neurologic outcomes. The reported prevalence and risk factors for concomitant CaAD in CAD patients varied among previous studies. 

Objectives: To examine these factors in ambulatory patients with CAD and well-documented cholesterol levels treated with cholesterol-lowering medications. 

Methods: We retrospectively analyzed prospectively collected data from 325 unselected patients with CAD (89 women, mean age 68.8 ± 9.9 years) undergoing routine evaluation at the coronary clinic of our hospital. 

Results: The low density lipoprotein-cholesterol (LDL-C) was < 100 mg/dl in 292 patients (90%). Age at onset of CAD symptoms was 59.4 ± 10.8 years. Carotid stenosis ≥ 50% was seen in 83 patients (25.5%) and between 30% and 49% in 55 patients (17%) (duplex method). Carotid stenosis was significantly associated with hypertension (P = 0.032), peripheral arterial disease (P = 0.002) and number of coronary arteries with ≥ 50% stenosis (P = 0.002), and showed a borderline association with age at CAD onset (P = 0.062) and diabetes mellitus (P = 0.053). On linear regression analysis, independent predictors of CaAD were peripheral vascular disease (OR 3.186, 95%CI 1.403–7.236, P = 0.006), number of coronary arteries with ≥ 50% stenosis (OR 1.543, 95%CI 1.136–2.095, P = 0.005), and age at CAD onset (OR 1.028, 95%CI 1.002–1.054, P = 0.003). None of the variables studied predicted freedom from CaAD. 

Conclusions: Carotid atherosclerosis is very common in stable ambulatory patients with CAD regularly taking statins. The risk is higher in patients with peripheral arterial disease, a greater number of involved coronary arteries, and older age at onset of CAD. 

 

Abstract

Background: Heart rate variability (HRV) analysis has been shown to be a predictor of sudden cardiac death and all-cause mortality in patients with cardiac disease.

Objectives: To examine whether newer HRV analysis algorithms, as used by the HeartTrends device, are superior to exercise stress testing (EST) for the detection of myocardial ischemia in patients without known coronary artery disease (CAD).

Methods: We present pilot data of the first 100 subjects enrolled in a clinical trial designed to evaluate the yield of short-term (1 hour) HRV testing for the detection of myocardial ischemia. The study population comprised subjects without known CAD referred to a tertiary medical center for EST with single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). All patients underwent a 1 hour electrocardiographic acquisition for HRV analysis with a HeartTrends device prior to EST with MPI. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were calculated for EST and HRV analysis, using MPI as the gold standard for the non-invasive detection of myocardial ischemia.

Results: In this cohort 15% had a pathologic MPI result. HRV analysis showed superior sensitivity (85%), PPV (50%) and NPV (97%) as compared to standard EST (53%, 42%, 90%, respectively), while the specificity of the two tests was similar (86% and 85%, respectively). The close agreement between HRV and MPI was even more pronounced among patients > 65 years of age.

Conclusions: Our pilot data suggest that the diagnostic yield of the novel HeartTrends HRV algorithm is superior to conventional EST for the non-invasive detection of myocardial ischemia.

Background: The Syntax score (SS) is a helpful tool for determining the optimal revascularization strategy regarding coronary artery bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) in patients with complex coronary disease. While an association between higher SS and mortality was found for PCI patients, no such association was found for CABG patients.

Objectives: To assess whether the SS predicts late mortality in patients undergoing CABG in a real-world setting.

Methods: The study included 406 consecutive patients referred for CABG over a 2 year period. Baseline and clinical characteristics were collected. Angiographic data SS were interpreted by an experienced angiographer. Patients were divided into three groups based on SS tertiles: low ≤ 21 (n=205), intermediate 22–31 (n=138), and high ≥ 32 (n=63). Five year mortality was derived from the National Mortality Database.

Results: Compared with low SS, patients with intermediate and high scores were significantly older (P = 0.02), had lower left ventricular ejection fraction (64% vs. 52% and 48%, P < 0.001) and greater incidence of acute coronary syndrome, left main disease, presence of chronic total occlusion of the left anterior descending and/or right coronary artery, and a higher EuroSCORE (5% vs. 5% and 8%, P < 0.01). Patients with intermediate and high SS had higher 5 year mortality rates (18.1% and 19%, respectively) compared to patients with low score (9.8%, P = 0.04). On multivariate analysis, SS was not an independent predictor of late mortality.

Conclusion: Patients with lower SS had lower mortality after CABG, which is attributable to lower baseline risk. SS is not independently predictive of late mortality in patients with multi-vessel coronary artery disease undergoing CABG.