Stable Coronary Disease Patients Research Articles

The diagnostic role of myocardial work indices in stable coronary disease - global wasted work as a novel important non-invasive parameter?

Abstract Introduction Although the non-invasive diagnostic tools for stable coronary artery disease (CAD) have developed significantly over the past years, there is no resting parameter available to recognize functionally significant CAD. The role of the novel myocardial work index (myocardial work index - MWI) calculated by the pressure-strain loop created with the help of speckle-tracking analysis and blood pressure measurement in the diagnosis of ischemic heart disease is not yet fully clarified. In our research, we examined the parameters of myocardial work analysis in stable coronary disease patients. Purpose Clarification of the diagnostic role of the myocardial work analysis, in patients with stable coronary artery disease. Methods In our prospective, single-center study, we examined 13 patients who had at least moderate stenosis (≥50%) in one main coronary branch detected on coronary CTA. A fractional flow reserve (FFR) test was performed for functional coronary assessment. Based on this measurement, we divided our patients into FFRneg (FFR value>0.8) and FFRpos groups. Echocardiography was performed before coronary angiography in all patients. In addition to the standard echocardiographic parameters, global myocardial work index (GWI), global constructive work (GCW) and global wasted work (GWW) were calculated. In the case of the FFRpos group, we performed the above examination both before and after revascularization (2 months). Results Our results show that neither the standard parameters (GLS, EF), nor the GWI and GCW showed any difference between the FFRpos and FFRneg groups. However, there was a significant difference regarding GWW (172.3±21.8 FFRneg vs. 258.2±38.4 FFRpos, p=0.048) at baseline. In the case of the FFRpos group, the analysis of our data showed that there was no significant difference in EF, GLS, GWI and GWE parameters before and after revascularization. However, global wasted work (GWW) showed a significant improvement after revascularization (preGWW 258.2±38.4 vs. postGWW 139.5±14.5, p=0.041). NT-proBNP levels were normal in our patient population and we could not detect. Conclusion Based on our results, the GWW may be suitable for non-invasive assessment of the functional significance of stable coronary disease, as it showed a significant difference in the case of functionally significant and non-significant stenosis and improved after revascularization in patients with single-vessel CAD.

Impact of the eicosapentaenoic acid to arachidonic acid ratio on plaque characteristics in statin-treated patients with coronary artery disease

BackgroundA low eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is associated with an increased risk of cardiovascular events in patients with coronary artery disease (CAD). ObjectiveTo clarify the impact of the EPA/AA ratio on the characteristics of non-culprit coronary plaques in statin-treated patients with CAD. MethodsA total of 370 consecutive stable coronary disease patients treated with statins, who underwent percutaneous coronary intervention for the culprit lesion and optical coherence tomography (OCT) imaging of the non-culprit plaque in a culprit vessel were included. The characteristics of non-culprit plaques assessed using OCT were compared between the lower EPA/AA group (EPA/AA <0.4, n = 255) and the higher EPA/AA group (EPA/AA ≥0.4, n = 115). ResultsThe prevalence of lipid-rich plaque (58.8 vs. 41.7%, p = 0.003) and plaque with macrophages (56.5 vs. 31.3%, p <0.001) was significantly higher in the lower EPA/AA group than in the higher EPA/AA group. This association was observed even if the LDL-C level was <100 mg/dL. The prevalence of thin-cap fibroatheroma was significantly higher in patients with lower EPA/AA and higher LDL-C (≥100 mg/dL) than in those with higher EPA/AA and lower LDL-C (<100 mg/dL) (odds ratio: 2.750, 95% confidence interval: 1.182-6.988, p = 0.024). An EPA/AA <0.4 was independently associated with a higher prevalence of lipid-rich plaque, plaque with macrophages, and cholesterol crystals. ConclusionLower EPA/AA ratio was associated with higher prevalence of vulnerable characteristics in non-culprit plaques. The present results suggest the importance of EPA/AA ratio on the secondary prevention of CAD.

Gender-Based Outcomes After Surgical Revascularization in Stable Coronary Disease Patients: Decades Later and Questions Remain

Gender-Based Outcomes After Surgical Revascularization in Stable Coronary Disease Patients: Decades Later and Questions Remain

Oxidative stress and kidney injury in trans-radial catheterization.

Oxidative stress is linked to coronary artery disease and is a major mechanism in contrast-induced nephropathy. Trans-radial approach in coronary angiography (CA) with minimized peri-procedural bleeding is expected to reduce acute kidney injury incidence. In the present study, oxidative stress patterns observed in radial CA and their associations with early manifestations of kidney injury are described. A total of 20 stable coronary disease patients submitted to CA and 17 sex-matched patients undergoing computed tomography for myoskeletal reasons were enrolled. Reduced glutathione, catalase, thiobarbituric acid reactive species (TBARS) levels and total anti-oxidant status were measured at various time points postangiography. In ischemic patients baseline TBARS levels were 2-fold lower compared to controls, while carbonyls levels were 35% higher. Glutathione was almost 4-fold lower than the control group. Glutathione and lipid peroxidation in ischemic patients gradually increased after contrast medium administration and reached 180% (P<0.001) and 20% (P=0.021) after 4–6 h, respectively. Four patients presented early evidence of contrast-induced nephropathy postangiography, while no control patient developed acute kidney injury. In the multiple logistic regression analysis, only the creatinine levels at baseline influenced the frequency of early contrast-induced nephropathy development (β =0.36, 95% CI: 0.285–0.438, P=0.01). Glutathione low levels were dominant in the baseline values of ischemic patients who developed contrast-induced nephropathy. Glutathione levels rapidly increased while protein oxidation decreased at the expense of lipid peroxidation. In conclusion, early oxidative stress changes occur in trans-radial CA patients with a mild profile, sufficient to mobilize patient antioxidant defenses.

Quality-of-Life Outcomes With a Disodium EDTA Chelation Regimen for Coronary Disease

The National Institutes of Health.funded Trial to Assess Chelation Therapy (TACT) randomized 1708 stablecoronary disease patients aged .50 years who were .6 months post.myocardial infarction (2003.2010) to 40 infusions ofa multicomponent EDTA chelation solution or placebo. Chelation reduced the primary composite end point of mortality,recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina (hazard ratio, 0.82; 95%confidence interval, 0.69.0.99; P=0.035). In a randomly selected subset of 911 patients, we prospectively collected a battery of quality-of-life(QOL) instruments at baseline and at 6, 12, and 24 months after randomization. The prespecified primary QOL measures were the Duke Activity Status Index (Table I in the Data Supplement) and the Medical Outcomes Study Short-Form 36 Mental Health Inventory-5. All comparisons were by intention to treat. Baseline clinical and QOL variables were well balanced in the 451 patients randomized to chelation and in the 460 patients randomized to placebo. The Duke Activity Status Index improved in both groups during the first 6 months of therapy, but we found no evidence for a treatment-related difference (mean difference [chelation.placebo] during follow-up, 0.9 [95% confidence interval, .0.7 to 2.6; P=0.27]).There was no statistically significant evidence of a treatment-related difference in the Mental Health Inventory-5 during follow-up (mean difference, 1.0; 95% confidence interval, .0.1 to 2.0; P=0.08). None of the secondary QOL measures showed a consistent treatment-related difference. In stable, predominantly asymptomatic coronary disease patients with a history of myocardial infarction,EDTA chelation therapy did not have a detectable effect on QOL during 2 years of follow-up. URL: http://clinicaltrials.gov. Unique identifier: NCT00044213.

All-cause readmission and repeat revascularization after percutaneous coronary intervention

Percutaneous coronary intervention (PCI) is one of the most frequently performed cardiac interventions. However, there is limited data regarding the cause of recurrent hospitalization and repeat revascularization. The aim of this study was to assess re-hospitalization and repeat revascularization within 30 days of the initial hospitalization for PCI, using data from Opolskie Voivodeship, National Health Fund (NHF) Registry. The study population consisted of all PCI patients treated in three interventional cardiology laboratories in Opolskie Voivodeship in Poland between 1 July 2008 and 30 June 2009. All PCI patients who died during the initial hospitalization or who were transferred to other units were excluded from the analysis. The study end-point comprised 30 day all-cause readmission and repeat revascularization. A total of 2,039 PCI patients were included in the analysis. The all-cause 30-day readmission rate was 14.6%. The 30-day readmission rate of acute coronary syndrome (ACS) patients was significantly higher compared to the stable coronary disease patients (ACS 15.8%, non-ACS 10.7%, p = 0.008). The 30-day readmission rate did not differ between the three cardiac laboratories. Approximately half (46.2%) of all readmitted patients underwent a repeat revascularization procedure, mainly in the form of PCI. The overall all-cause 30-day mortality rate was 0.8%. Compared to the PCI patients who did not require readmission, the readmitted patients had a significantly higher all-cause 30-day mortality rate (3.6% vs 0.3%, p < 0.001). Almost one in seven PCI patients requires readmission within 30 days of hospital discharge. Approximately 50% of all readmitted PCI patients resulted in a repeat revascularization procedure. PCI patients who were readmitted within 30 days of an index PCI procedure had a significantly higher all-cause 30-day mortality rate.

Can resistance to aspirin be reversed after an additional dose?

Aspirin resistance or aspirin non-responsiveness is a recently described phenomenon which has been consistently associated with an increased risk of cardiovascular events. This study was designed to determine the effects of an additional dose of 100mg of aspirin on platelet function and proportion of aspirin non-responders using the platelet function analyzer-100 (PFA-100), in a well characterized population of stable coronary heart disease patients already on long-term aspirin treatment. Platelet function was assessed using PFA-100 in 141 patients (64.8±10.1years, 87.9% men) on long-term aspirin treatment (100mg/day) before and 1h after "in site" oral aspirin administration (100mg). Prevalence of aspirin non-responders using PFA-100 was 50.7% (95% confidence interval 42.4-59). One hour after 100mg of oral aspirin, reassessment of aspirin effects showed a prevalence of non-responders using PFA of 35.0% (95% CI 27.3-43.2) (P<0.001 vs. pre-dose proportion). Using the PFA-100 system, reassessment of platelet function following oral administration of daily aspirin dosage significantly reduces the number of stable coronary disease patients considered to be non-responders to such treatment.

Pregnancy associated plasma protein-A as a marker for myocardial infarction and death in patients with stable coronary artery disease: A prognostic study within the CLARICOR Trial

ObjectivePregnancy associated plasma protein-A (PAPP-A) is a potential new marker for vulnerable plaques in the coronary arteries only examined in stable coronary disease (CAD) in patients undergoing coronary angiography. Here we address the prognostic value of serum PAPP-A in unselected stable CAD patients. MethodBlood samples were drawn at study entry. Serum PAPP-A values ≥4mIU/L were considered elevated. Mortality and non-fatal myocardial infarction was prospectively registered. The primary outcome was the composite outcome of myocardial infarction and all-cause mortality, secondary outcomes were all-cause mortality and myocardial infarction. ResultsPatients (n=4243) were followed for a median of 2.8 years. In a Cox analysis, elevated PAPP-A was significantly related to the composite outcome of myocardial infarction and death (HR 1.99, 95% CI 1.62–2.45, p<0.0005), all-cause mortality (HR 2.42, 1.92–3.06, p<0.0005), and myocardial infarction (HR 1.40, 1.01–1.94, p=0.046). After Holm's correction, the latter significance disappeared. After adjustment for risk factors and medication at entry, elevated PAPP-A remained significantly related to the composite outcome (HR 1.51, 1.22–1.86, p<0.0005) and all-cause mortality (HR 1.68, 1.32–2.13, p<0.0005). ConclusionIn patients with stable CAD elevated serum PAPP-A seems promising as aid in identifying patients at high risk for death.

Does the Holy Grail escape us again?

We have read with interest the recent article,1 in which the authors aimed to compare four test to assess inhibition of platelet function by clopidogrel in stable coronary disease patients. They demonstrate that the results of each test are not equivalent, being highly test-specific. The identification of patients with insufficient platelet inhibition varied greatly and correlations between the tests were poor. The idea of tailoring antiplatelet therapy is a promising tool to improve the outcomes of patients but we must not forget that …

Analysis of platelet α2-adrenergic receptor activity in stable coronary artery disease patients on dual antiplatelet therapy

Combined antiplatelet therapy reduces recurrent atherothrombotic events in stable coronary disease patients; however, high residual platelet reactivity measured ex vivo still raises concerns as a condition related to treatment failure. Alpha-2 adrenoceptor enhances platelet reactivity and might contribute to this phenomenon. For the present study, 121 stable angina patients on standard dual antiplatelet therapy (75 mg clopidogrel and 100 mg acetylsalicylic acid) were recruited. Born aggregometry was performed with adenosine diphosphate (ADP), collagen and epinephrine. To verify platelet adrenergic activity, potentiation by low-dose epinephrine and inhibition by selective alpha-2 receptor blocker atipamezole were determined. To assess the P2Y(12)-specific residual activity, cangrelor was used. Plasma norepinephrine, soluble CD40-ligand, high-sensitivity-C-reactive protein (hsCRP) - and in 24 subjects platelet P-selectin positivity were measured. Epinephrine - at very low concentration (10(-9)g/ml) - significantly potentiates (1.25 microM ADP: 26.5% vs. 43%; 5 microM ADP: 53% vs. 64.5%; collagen: 17% vs 42%, p < 0.001) while atipamezole inhibits ADP- and collagen-induced platelet aggregations (1.25 microM ADP: 26.5% vs. 23%; 5 microM ADP: 53% vs. 47%; collagen: 17% vs. 11%, p < 0.001). Patients with high adrenergic activity have significantly increased baseline ADP- and collagen-induced platelet aggregation. Based on cangrelor's efficacy, these patients have significantly more residual P2Y(12) activity as well. HsCRP and soluble CD40-ligand levels were similar. In conclusion, stable coronary heart disease patients with prominent adrenoceptor activity in vitro have significantly increased platelet aggregability and more functional P2Y(12) receptor, indicating poor inhibitory response to thienopyridines. Therefore, platelet adrenergic receptor represents a considerable, dynamic factor of high residual platelet reactivity and might contribute to cardiovascular events indicating failure of antiplatelet therapy.

Anti-inflammatory effect of virgin olive oil in stable coronary disease patients: a randomized, crossover, controlled trial

To assess the effect of two similar olive oils, but with differences in their phenolic compounds (powerful antioxidant compounds), on inflammatory markers in stable coronary heart disease patients. Placebo-controlled, crossover, randomized trial. Cardiology Department of Hospital del Mar and Institut Municipal d'Investigació Mèdica (Barcelona). Twenty-eight stable coronary heart disease patients. A raw daily dose of 50 ml of virgin and refined olive oil (ROO) was sequentially administered over two periods of 3-weeks, preceded by 2-week washout periods in which ROO was used. Interleukin-6 (P<0.002) and C-reactive protein (P=0.024) decreased after virgin olive oil intervention. No changes were observed in soluble intercellular and vascular adhesion molecules, glucose and lipid profile. Consumption of virgin olive oil, could provide beneficial effects in stable coronary heart disease patients as an additional intervention to the pharmacological treatment.

Prevention of cardiovascular events in end-stage renal disease: Results of a randomized trial of fosinopril and implications for future studies

Cardiovascular events (CVEs) are the leading cause of death in chronic hemodialysis patients. Results of trials in non-end-stage renal disease (ESRD) patients cannot be extrapolated to patients with ESRD. It is critical to test cardiovascular therapies in these high-risk patients who are usually excluded from major cardiovascular trials. The study objective was to evaluate the effect of fosinopril on CVEs in patients with ESRD. Eligible patients were randomized to fosinopril 5 mg titrated to 20 mg daily (n=196) or placebo (n=201) plus conventional therapy for 24 months. The primary end point was combined fatal and nonfatal first major CVEs (cardiovascular death, resuscitated death, nonfatal stroke, heart failure, myocardial infarction, or revascularization). No significant benefit for fosinopril was observed in the intent to treat analysis (n=397) after adjusting for independent predictors of CVEs (RR=0.93, 95% confidence interval (CI) 0.68-1.26, P=0.35). The per protocol secondary supportive analysis (n=380) found a trend towards benefit for fosinopril (adjusted RR=0.79 (95% CI 0.59-1.1, P=0.099)). In the patients who were hypertensive at baseline, systolic and diastolic blood pressures were significantly decreased in the fosinopril as compared to the placebo group. After adjustment for risk factors, trends were observed suggesting fosinopril may be associated with a lower risk of CVEs. These trends may have become statistically significant had the sample size been larger, and these findings warrant further study.

INVITED COMMENTARY: Commentaries on Jackson et al. “Successful Withdrawal of Oral Long‐Acting Nitrates to Facilitate Phosphodiesterase Type 5 Inhibitor Use in Stable Coronary Disease Patients with Erectile Dysfunction”

The risk factors for erectile dysfunction (ED) and coronary artery disease are often the same and ED is present in a high percentage of coronary artery disease patients. In one study from our research group, 75% of men with chronic stable angina pectoris had some degree of ED [1]; it was severe in about a quarter of men with ED. Organic nitrates, including the use of the commonly used antianginal agents (nitroglycerin, isosorbide mononitrate, isosorbide dinitrate), remain the one absolute contraindication for the use of the phosphodiesterase type 5 inhibitors.

ORIGINAL RESEARCH—PHARMACOTHERAPY: Successful Withdrawal of Oral Long‐Acting Nitrates to Facilitate Phosphodiesterase Type 5 Inhibitor Use in Stable Coronary Disease Patients with Erectile Dysfunction

Vascular disease is the most common cause of male erectile dysfunction (ED). Phosphodiesterase type 5 (PDE5) inhibitors are effective in up to 80% of men but are contraindicated in the presence of oral nitrates, because of a potentially severe hypotensive interaction. To see if stable coronary disease patients with ED could have their oral nitrates discontinued to allow safe use of a PDE5 inhibitor. Prospective study of 425 men with ED and cardiac disease conducted in an outpatient cardiac sexual advice clinic. Discontinuation of oral nitrates to facilitate subsequent use of PDE5 therapy. Oral nitrates were being used by 88 (21%) coronary artery disease patients all of whom were clinically stable. Fifty-five (63%) of these men with a good exercise ability had their nitrates discontinued in the presence of continuing beta-blockade or calcium antagonist therapy. They were reviewed 1 week later. Only three restarted their nitrate therapy because of an increase in symptoms. Forty-nine of the 52 men no longer taking nitrates were treated with a PDE5 inhibitor which was effective in 22 out of 26 (85%) patients who have completed follow-up. Fifteen patients are currently undergoing clinic follow-up in order to optimize treatment, and nine patients have continued therapy with their family doctors. Importantly, there have been no adverse cardiac events. Oral nitrates can be discontinued in the presence of continuing beta-blockade and/or calcium antagonist therapy in stable coronary disease patients with ED to allow for the safe use of PDE5 inhibitors.

The stratification of platelet reactivity and activation in patients with stable coronary artery disease on aspirin therapy

Condensed abstract: Heightened platelet reactivity may affect the occurrence of ischemic events in patients with coronary artery disease on aspirin therapy. However, a definition to stratify platelet reactivity in this group of patients has not been previously reported. We studied platelet reactivity and activation by measuring platelet aggregation and the expression of p-selectin, total GP IIb/IIIa and active GP IIb/IIIa ( n=96). Patients were divided into quartiles by each of the markers; correlations were made between the markers; and a definition of heightened platelet reactivity was proposed. Marked variability in activation and reactivity were observed despite aspirin therapy. Background: Heightened platelet reactivity and activation may affect the occurrence of ischemic events in patients with coronary artery disease on aspirin therapy. However, a definition to stratify platelet reactivity has not been previously reported. Methods and results: Platelet aggregation (5 and 20 μmol/l ADP), total GP IIb/IIIa, active GP IIb/IIIa and the expression of maximally stimulated p-selectin were measured in patients about to undergo elective coronary stenting ( n=96). All patients had received aspirin (325 mg). There was marked variability in platelet reactivity and activation as measured by all markers. The highest quartile was defined by 77±1% and 98±1% aggregation by 5 and 20 μmol/l ADP, respectively; 65±2% p-selectin positivity; 508±15 MFI for total GP IIb/IIIa; and 23.0±1.8 MFI for active GP IIb/IIIa. Conclusions: There is a wide range in platelet reactivity and activation as measured by multiple markers in stable coronary disease patients on aspirin therapy. From these indices, we can define those patients at the extremes of reactivity and activation and thus, the greatest potential risk of thrombosis and bleeding. These indices will serve as a guide to future studies investigating the relationships of platelet reactivity, activation, drug-induced inhibition and clinical outcomes.

Factors Influencing Clinical Outcomes After Revascularization in the Asymptomatic Cardiac Ischemia Pilot (ACIP)

Abstract Background and Aim The Asymptomatic Cardiac Ischemia Pilot is the first randomized trial where revascularization involved choice of either coronary bypass or angioplasty used in an early or a delayed symptom‐driven approach. One‐year outcomes were favorable (reduced recurrent ischemia and adverse outcomes) for an early revascularization strategy (within 4 weeks), compared with an early medical strategy when revascularization was delayed until symptom‐driven. This ancillary study examined variables influencing outcomes after these 2 revascularization approaches (early vs. delayed until symptom‐driven). Methods: Participants were clinically stable coronary disease patients with stress‐induced and daily life ischemia who underwent revascvularization. Characteristics associated with clinical outcomes occurring within the year following revascularization were examined using Cox regression analysis. Results: A total of 262 patients received revascularization; 170 in the early approach and 92 in the delayed symptom‐driven approach. Thirty‐three patients had adverse outcomes (death, nonfatal myocardial infarction, or repeat revascularization) during l‐year follow‐up. The most important independent predictor of improved outcome during the follow‐up year was attempted revascularization of ≥ 66% of vessels with significant stenosis for the early (risk ratio [RR] 0.25, 95% confidence interval [CI] 0.09–0.67) and the delayed (RR 0.21, CI 0.08–0.58) approaches. Factors such as age, stress test results, and coronary angiographic findings did not predict clinical outcome. Conclusions: Our findings are important in the planning of a large trial with longer follow‐up.