The Effect of Proprotein Convertase Subtilisin Kexin Type 9 Inhibitors on Circulating Endothelial Progenitor Cells in Patients with Cardiovascular Disease.

PURPOSE: Circulating endothelial progenitor cells (cEPCs) are vital to vascular repair by re-endothelialization. We aimed to explore the effect of proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) on cEPCs hypothesizing a possible pleiotropic effect. METHODS: Patients with cardiovascular disease (CVD) were sampled for cEPCs at baseline and following the initiation of PCSK9i. cEPCs were assessed using flow cytometry by the expression of CD34(+)/CD133(+) and vascular endothelial growth factor receptor (VEGFR)-2(+), and by the formation of colony-forming units (CFUs) and production of VEGF. RESULTS: Our cohort included 26 patients (median age 68 (IQR 63, 73) years; 69% male). Following 3 months of treatment with PCSK9i and a decline in low-density lipoprotein cholesterol levels (153 (IQR 116, 176) to 56 (IQR 28, 72) mg/dl), p < 0.001), there was an increase in CD34(+)/CD133(+) and VEGFR-2(+) cell levels (0.98% (IQR 0.37, 1.55) to 1.43% (IQR 0.90, 4.51), p = 0.002 and 0.66% (IQR 0.22, 0.99) to 1.53% (IQR 0.73, 2.70), p = 0.05, respectively). Functionally, increase in EPCs-CFUs was microscopically evident following treatment with PCSK9i (1 CFUs (IQR 0.0, 1.0) to 2.5 (IQR 1.5, 3), p < 0.001) with a concomitant increase in EPC's viability as demonstrated by an MTT assay (0.15 (IQR 0.11, 0.19) to 0.21 (IQR 0.18, 0.23), p < 0.001). VEGF levels increased following PCSK9i treatment (57 (IQR 18, 24) to 105 (IQR 43, 245), p = 0.006). CONCLUSIONS: Patients with CVD treated with PCSK9i demonstrate higher levels of active cEPCs, reflecting the promotion of endothelial repair. These findings may represent a novel mechanism of action of PCSK9i.

Clinical significance of myocardial involvement in acute idiopathic pericarditis.

BACKGROUND: Acute idiopathic pericarditis (AIP) is frequently accompanied by myocardial involvement (AIPM). Although in acute myocarditis, the myocardial inflammation can lead to life-threatening complications, the outcome of patients with AIPM has been described as good. It remains unclear if a good prognosis of patients with AIPM reflects mild myocardial involvement or good medical management. METHODS: A retrospective analysis of life-threatening complications and life-saving interventions in a cohort of 248 consecutive patients admitted to a single medical center between 2006 and 2017 with AIP (n = 169) or AIPM (n = 79). Major adverse cardiac events (MACE) included cardiac tamponade, cardiogenic shock, ventricular tachycardia, pericardiocentesis, pericardiectomy, large pericardial effusion and death. RESULTS: Patients with AIPM were younger than patients with AIP (p < 0.001), and more often had left ventricular dysfunction (31.6% vs. 1.2%, p < 0.001) and less often had large pericardial effusion (1.3% vs. 13.6%, p = 0.002), and MACE (5.1% vs. 14.8%, p = 0.014). Cardiac tamponade occurred in 5.3% of the patients with AIP as opposed to 1.3% of the patients with AIPM (p = 0.176). Severe left ventricular dysfunction with cardiogenic shock occurred exclusively among patients with AIPM but the rate was low (2.5%). Life-saving interventions were used in both groups at comparable rates (2.5% vs. 5.3%, p = 0.510). There were no in-hospital deaths. CONCLUSIONS: Myocardial involvement in acute pericarditis is associated with a low rate of severe left ventricular dysfunction and cardiogenic shock and a reduced rate of large pericardial effusion, resulting in a lower rate of MACE. Life-saving interventions were used at comparable rates in patients with and without myocardial involvement having excellent survival rates.

Do Colchicine and Prednisone Affect the Rate of Recurrence of Post-Pericardiotomy Syndrome.

BACKGROUND: Post-pericardiotomy syndrome (PPS) is a major cause of pericarditis, yet data on the risk of recurrence are limited, and the impact of steroids and colchicine in this context is unknown. OBJECTIVES: To examine the effect of prednisone and colchicine on the rate of recurrence of PPS. METHODS: Medical files of patients diagnosed with PPS were reviewed to extract demographic, echocardiographic, X-ray imaging, and follow-up data. RESULTS: The study comprised 132 patients (57% men), aged 27-86 years. Medical treatment included prednisone in 80 patients, non-steroidal anti-inflammatory agents in 41 patients, colchicine monotherapy in 2 patients, and no anti-inflammatory therapy in 9 patients. Fifty-nine patients were given colchicine for prevention of recurrence. The patients were followed for 5-110 months (median 64 months). Recurrent episodes occurred in 15 patients (11.4%), 10 patients had a single episode, 4 patients had two episodes, and one patient had three episodes. The rate of recurrence was lower in patients receiving colchicine compared to patients who did not (8.5% vs. 13.7%), and in patients not receiving vs. receiving prednisone (7.7% vs. 13.8%) but the differences were non-significant. Twenty-three patients died and there were no recurrence-related deaths. CONCLUSIONS: The rate of recurrence after PPS is low and multiple recurrences are rare. The survival of patients with recurrent PPS is excellent. Prednisone pre-treatment was associated with a numerically higher rate of recurrence and colchicine treatment with a numerically lower rate, but the differences were non-significant.

Prognostic and Diagnostic Significance of Serum High-Sensitivity C-Reactive Protein Level in Patients with Acute Idiopathic Pericarditis.

BACKGROUND: The frequency of increased high-sensitivity C-reactive protein (hs-CRP) and the time course of evolution of their levels in patients with acute idiopathic pericarditis (AIP) are not well established. OBJECTIVES: To assess the time course of evolution of hs-CRP levels and the possible clinical significance of maximal hs-CRP levels in patients with AIP. METHODS: We retrospectively reviewed the medical files of 241 patients admitted to the hospital with a diagnosis of AIP between March 2006 and March 2017. Data on demographics, time of symptom onset, laboratory and imaging findings, and outcome were collected. RESULTS: Data on serum hs-CRP levels were available for 225 patients (age 18-89 years, 181 men). Fever, pleural effusion, and age were independently associated with hs-CRP levels. Major cardiac complications (MCC) (death, cardiac tamponade, cardiogenic shock, large pericardial effusion, ventricular tachycardia, pericardiocentesis, or pericardiectomy) were more common in patients with hs-CRP levels above the median compared to those below (21.2% vs. 4.5%, respectively, P < 0.001). Hs-CRP levels were independently associated with MCC (odds ratio [OR] 1.071, 95% confidence interval [95%CI] 1.016-1.130, P = 0.011). Hs-CRP levels were elevated in 76.0%, 92.3% and 96.0% of the patients tested <6 hours, 7-12 hours, and >12 hours of symptom onset, respectively (P = 0.003). The frequency of elevated hs-CRP among patients tested > 24 hours was 98.1%. CONCLUSIONS: Hs-CRP levels rise rapidly among patients with AIP. Maximal hs-CRP levels are associated with MCC. A normal hs-CRP level is rare among patients tested > 24 hours of symptom onset.

Prodromal symptoms predict myocardial involvement in patients with acute idiopathic pericarditis.

BACKGROUND: Myocardial involvement is common in acute idiopathic pericarditis and can, in some cases, lead to life-threatening complications. Acute idiopathic pericarditis is often preceded by various prodromal symptoms, but whether these symptoms can predict myocardial involvement is unclear. The aim of the study was to examine the value of different prodromal symptoms of acute idiopathic pericarditis for predicting myocardial involvement. METHODS AND RESULTS: Patients diagnosed with acute idiopathic pericarditis in 2007-2017 at our hospital were identified by database search. Demographic parameters, levels of plasma cardiac troponin and creatine kinase, and findings on echocardiography, magnetic resonance imaging, cardiac computed tomography and coronary angiography and data on prodromal symptoms were extracted from the medical files. The final cohort included 239 patients (73.2% males) aged 18-89 years. The most common prodromal symptoms were fever, chills, cough, sore throat, abdominal pain, and diarrhea. Myocardial involvement was observed in 83 patients (34.7%), leading to cardiogenic shock in 4 (4.8%). Patients with myocardial involvement more often had prodromal diarrhea, fever, sore throat, vomiting, atypical chest pain, and pharyngitis. On multivariate analysis, diarrhea, sore throat and fever were strong independent predictors of myocardial involvement (OR, 14.257, 95% CI, 3.920-51.782, p < 0.001, OR, 9.6, 95% CI, 2.934-31.982, p < 0.001 and OR, 2.445, 95% CI, 1.077-5.550, p = 0.025). Diarrhea was associated with left ventricular dysfunction as well. CONCLUSIONS: In acute idiopathic pericarditis, prodromal diarrhea, sore throat and fever strongly predict myocardial involvement, resulting in life-threatening hemodynamic compromise in a minority of the patients.

Incidence and Prognosis of Pericarditis After ST-Elevation Myocardial Infarction (from the Acute Coronary Syndrome Israeli Survey 2000 to 2013 Registry Database).

There are scarce contemporary data regarding the incidence and prognosis of early postmyocardial infarction pericarditis (PMIP). Thus, we retrospectively analyzed 6,282 patients with ST-segment elevation myocardial infarction (STEMI) enrolled with known PMIP status in the Acute Coronary Syndrome Israeli Survey 2000 to 2013 registry. The primary outcome was the composite of all-cause mortality, nonfatal myocardial infarction, cerebrovascular event, stent thrombosis, or revascularization. The secondary outcomes were mortality and length of stay during the acute hospitalization. Overall, 76 patients with STEMI had PMIP (1.2%). PMIP incidence gradually decreased from 170 per 10,000 in 2000 to 110 per 10,000 in 2013, respectively (35% reduction, p for trend = 0.035). Patients with PMIP were younger (median 58.0 vs 61.0; p = 0.045), had less hypertension, higher cardiac biomarkers, and more frequently reduced left ventricular ejection fraction (87.0% vs 67.0%; p = 0.001). Patients with PMIP had longer time to reperfusion (225 minutes vs 183 minutes; p = 0.016) and length of stay (7.0 vs 5.0 days; p < 0.001). The composite end point occurred similarly in patients with and without PMIP (10.5% vs 13.2%, respectively). There was no significant difference in 30-day, 1-year, and 5-year survival. In conclusion, PMIP is a relatively rare complication of STEMI in the coronary reperfusion era, portends worse short-term but not long-term outcomes, and is associated with bigger infarct size.

Does colchicine decrease the rate of recurrence of acute idiopathic pericarditis treated with glucocorticoids?

BACKGROUND: The traditional treatment of acute pericarditis includes non-steroidal anti-inflammatory agents (NSAIDs) or glucocorticoids. The addition of colchicine has been found to reduce the rate of recurrences. Glucocorticoids, however, may attenuate this effect, although the available data are limited. We examined the impact of colchicine on the rate of recurrence of acute idiopathic pericarditis pretreated with prednisone. METHODS: The frequency of recurrence in patients hospitalized for acute idiopathic pericarditis in a tertiary medical center in 2004-2014 who were treated with glucocorticoids or with non-steroidal therapy was assessed from the computerized hospital database. A retrospective design was used. RESULTS: The cohort included 199 patients aged 18-86 years. Sixty-two (31%) were treated with prednisone, 42 with colchicine and 20 without, and 133 with non-steroidal therapy; in 4 patients, therapy was not detailed. Follow-up ranged from 13 to 147 months (median, 48 months). Fifty-three patients (26.6%) experienced at least one recurrence of pericarditis. The recurrence rate was significantly higher in patients who received prednisone and colchicine (17/42, 40.5%) than in patients who received NSAIDs or aspirin and colchicine (8/44, 18.2%, p=0.03) or any non-steroidal therapy (30/133, 22.6%, p=0.03). There was no difference between the rate of recurrence in patients who were treated with prednisone alone (5/20, 25%) and those treated with NSAIDs or aspirin and colchicine or with any non-steroidal therapy (p=NS). Baseline characteristics and duration of follow-up were similar in patients with and without recurrence. Hospital stay was longer in patients treated with prednisone alone as compared to patients treated with prednisone and colchicine. There were no other differences in baseline characteristics between these groups. CONCLUSIONS: The addition of colchicine to prednisone in patients admitted for acute idiopathic pericarditis does not reduce the risk of recurrence. This finding suggests that prednisone blunts the salutary effects of colchicine.

Seasonal patterns of acute and recurrent idiopathic pericarditis.

BACKGROUND: Idiopathic pericarditis is presumed to result from viral infection. The incidence rates of some viral infections have typical seasonal patterns. The data in the literature on a possible seasonal pattern of acute pericarditis are very limited. The mechanism and possible seasonality of recurrent episodes are not well established . HYPOTHESIS: The incidence of acute idiopathic pericarditis has a seasonal pattern. METHODS: The computerized database of a tertiary, university-affiliated hospital was searched for all patients admitted with a first episode of acute idiopathic pericarditis between January 1, 2010 and December 31, 2015. Patients for whom a nonviral etiology for the pericarditis was identified were excluded. RESULTS: The final cohort included 175 patients (75% male) ages 19 to 86 years (median = 50.0 ± 18.2 years). The incidence of the disease was twice as high during the colder half of the year (October-March) than the warmer half, peaking in the first quarter (January-March, P = 0.001). This first-quarter peak was observed in each of the 6 years examined. Comparison of the patients who acquired pericarditis during peak and nonpeak quarters yielded no differences in baseline characteristics, peak body temperature, white blood cell count, C-reactive protein level, or frequency of myocardial involvement or liver enzyme elevation. No seasonal pattern was identified for recurrent episodes of pericarditis (n = 57). CONCLUSIONS: Acute idiopathic pericarditis appears to have a seasonal pattern with a distinct late winter peak. No seasonal pattern was identified for recurrent episodes.

Prevalence of Carotid Artery Disease among Ambulatory Patients with Coronary Artery Disease.

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.

The effect of dabigatran and rivaroxaban on platelet reactivity and inflammatory markers.

The new oral anticoagulants (NOACs) reduce stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), but dabigatran may increase risk of coronary ischemic events for unclear reasons. Thus, this study assessed the effects of dabigatran and rivaroxaban on platelet reactivity and inflammatory markers in patients with non-valvular AF. Patients with non-valvular AF planned to begin treatment with NOACs were included. Seventeen patients were prescribed dabigatran and ten rivaroxaban. Platelet function (as assessed by multiple-electrode aggregometry, Impact-R shear-induced platelet deposition, P-selectin expression and plasma RANTES levels) and high-sensitivity C-reactive protein (hs-CRP) were measured at enrollment (prior to initiation of NOAC treatment) and at least 7 days into treatment with either dabigratran or rivaroxaban. Seventeen patients treated with dabigatran (mean age 69 ± 7 years, 35 % women, mean CHADS2 score 2.6 ± 1.2), and ten patients treated with rivaroxaban (mean age 73 ± 9 years, 20 % women, mean CHADS2 score 2.7 ± 1.6) completed the study. In both groups, there were no significant differences in platelet reactivity between the baseline and on-anticoagulant treatment time-points, as measured by each of the platelet-specific assays. There was a trend towards increased platelet reactivity in response to arachidonic acid from baseline to on-treatment in both groups, probably as a result of aspirin discontinuation in 33 % of patients. No significant differences were noted between baseline and on-treatment in hs-CRP in both anticoagulant groups. Treatment with dabigatran and rivaroxaban does not appear to be associated with changes in markers of platelet reactivity or systemic inflammation.

Low plasma vitamin D levels and muscle-related adverse effects in statin users.

BACKGROUND: Treatment with HMG-CoA reductase inhibitors (statins) is often complicated by muscle-related adverse effects (MAEs). Studies of the association between low plasma vitamin D levels and MAEs have yielded conflicting results. OBJECTIVES: To determine if low plasma vitamin D level is a risk factorfor MAEs in statin users. METHODS: Plasma levels of 25(OH) vitamin D were measured as part of the routine evaluation of unselected statin-treated patients attending the coronary and lipid clinics at our hospital during the period 2007-2010. Medical data on muscle complaints and statin use were retrieved from the medical files. Creatine kinase (CK) levels were derived from the hospital laboratory database. RESULTS: The sample included 272 patients (141 men) aged 33-89 years. Mean vitamin D level was 48.04 nmol/L. Levels were higher in men (51.0 +/- 20.5 versus 44.7 +/- 18.9 nmol/L, P = 0.001) and were unaffected by age. MAEs were observed in 106 patients (39%): myalgia in 95 (35%) and CK elevation in 20 (7%); 9 patients (3%) had both. There was no difference in plasma vitamin D levels between patients with and without myalgia (46.3 +/- 17.7 versus 48.9 +/- 21.0 nmol/L, P = 0.31), with and without CK elevation (50.2 +/- 14.6 versus 47.8 +/- 20.3 nmol/L, P = 0.60), or with or without any MAE (50.4 +/- 15.0 versus 47.8 +/- 10.2 nmol/L, P = 0.27). These findings were consistent when analyzed by patient gender and presence/absence of coronary artery disease, and when using a lower vitamin D cutoff (< 25 nmol/L). CONCLUSIONS: There is apparently no relationship between plasma vitamin D level and risk of MAEs in statin users.

Long-term outcome of patients with antiphospholipid syndrome who undergo percutaneous coronary intervention.

OBJECTIVES: Patients with antiphospholipid antibody syndrome (APS) have an increased risk of atherothrombotic complications. There are limited data regarding the outcome of patients with APS who undergo percutaneous coronary intervention (PCI). Accordingly, we aimed to assess the long-term outcomes of these patients. METHODS: Nineteen APS patients who underwent PCI between the years 2003 and 2008 were compared to 380 patients who had undergone PCI during the same period (PCI group) and were matched by age (±5 years), gender, diabetes and hypertension. In addition, APS patients were compared to 1,458 patients with ST segment elevation myocardial infarction (MI) who were treated with PCI during the same period. Six-month to 4-year clinical outcomes were evaluated. RESULTS: The indication for PCI in the APS group was acute coronary syndrome in 52.6% of patients. After 1 year of follow-up, patients with APS had higher rates of target vessel revascularization than the other two groups, which translated to higher rates of major adverse cardiac events. There were no differences in MI or mortality rates between the groups. CONCLUSIONS: Patients with APS who undergo PCI have worse long-term clinical outcomes, driven by higher rates of revascularization, than other patients undergoing PCI. Further study is warranted to examine the mechanisms underlying these findings.

Use of intravenous morphine for acute decompensated heart failure in patients with and without acute coronary syndromes.

BACKGROUND: Current guidelines regarding the use of intravenous morphine (IM) in the management of patients with acute decompensated heart failure (ADHF) are discordant; whereas the American guidelines reserve IM for terminal patients, the European guidelines recommend its use in the early stage of treatment. Our aim was to determine the impact of IM on outcomes of ADHF patients. METHODS: Stepwise logistic regression and propensity score analysis of ADHF patients with and without use of IM was performed in a national heart failure survey. RESULTS: Of the 4102 enrolled patients, we identified 2336 ADHF patients, of whom 218 (9.3%) received IM. IM patients were more likely to have acute coronary syndromes, acute rather than exacerbation of chronic heart failure, and diabetes mellitus and dyslipidemia. They had higher heart rate, were less likely to receive diuretics and more likely to receive aspirin and statins. Unadjusted in-hospital mortality rates were 11.5% versus 5.0% for patients who did or did not receive IM, and the adjusted odds ratio (OR) for in-hospital death was: 2.0 (1.1 ­ 3.5, P = 0.02). Using propensity analysis, we identified 218 matched pairs of patients who did or did not receive IM. In multivariable analysis accounting for the propensity score (c-statistic 0.82), IM was not associated with increased in-hospital death (OR: 1.2 (0.6 ­ 2.4), P = 0.55). CONCLUSION: IM was used sparingly in our ADHF cohort, and was independently associated with increased in-hospital death in multivariable analysis, but not in propensity score analysis. Thus, IM may be used in ADHF, but with caution. Further randomized trials are warranted.

Outcomes of acute heart failure associated with acute coronary syndrome versus other causes.

BACKGROUND: By and large, prior registries and randomized trials have not distinguished between acute heart failure (AHF) associated with acute coronary syndrome (ACS) versus other causes. AIMS: To examine whether the treatments and outcomes of ACS-associated AHF are different from non-ACS-associated AHF. METHODS: We examined in a prospective, nationwide hospital-based survey the adjusted outcomes of AHF patients with and without ACS as its principal cause. RESULTS: Of the 4102 patients in our national heart failure survey, 2336 (56.9%) had AHF, of whom 923 (39.5%) had ACS-associated AHF. These patients were more likely to receive intravenous inotropes and vasodilators and to undergo coronary angiography and revascularization, but less likely to receive intravenous diuretics. The unadjusted in-hospital, 30-day, one-year, and four-year mortality rates for AHF patients with or without ACS were 6.5% versus 5.0% (P = 0.13), 10.3% versus 7.5% (P = 0.02), 26.6% versus 31.0% (P = 0.02), and 55.3% versus 63.3% (P = 0.0001), respectively. In the multivariate analysis, the adjusted mortality risk for patients with ACS at the respective time points were 1.46 (0.99-2.10), 1.67 (1.22-2.30), 1.02 (0.86-1.20), and 0.93 (0.82-1.04). CONCLUSIONS: Patients with ACS-associated AHF seem to have a unique clinical course and perhaps should be distinguished from other AHF patients in future trials and registries.

The ratio of contrast volume to glomerular filtration rate predicts outcomes after percutaneous coronary intervention for ST-segment elevation acute myocardial infarction.

OBJECTIVE: To assess the value of the ratio between contrast medium volume and glomerular filtration rate (CMGFRr) for prediction of development of contrast-induced nephropathy (CIN) and mortality in patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: Renal function is a strong predictor of outcome in patients with STEMI. CIN may complicate the course of primary PCI in these patients. METHODS: The study population included all 871 consecutive patients with STEMI without cardiogenic shock who underwent primary PCI at our center from January 1, 2001, to October 30, 2006. CIN was defined as an absolute increase in serum creatinine > 0.5 mg/dL or a relative increase >25% within 48 hr after PCI. RESULTS: In-hospital CIN developed in 72 (8.3%) patients. On linear regression analysis, the following variables were independently associated with CIN: male sex (odds ratio [OR] = 0.42, 95% confidence interval [CI], 0.18-0.97, P = 0.04), GFR < 60 (OR = 3.6, 95% CI, 2.79-4.78, P < 0.0001), multivessel coronary artery disease (OR = 1.67, 95% CI, 1.08-2.58, P = 0.02), CMGFRr (OR = 1.53, 95% CI, 1.01-2.31, P = 0.04, for upper tertile vs. lower two tertiles), and Killip class > 1 (OR = 1.35, 95% CI, 1.03-1.76, P = 0.03). CMGFRr > 3.7 was a strong independent predictor of CIN (OR = 3.87, 95% CI, 1.72-8.68, P = 0.001). Twenty-six (2.9%) patients died at 1 month after PCI. The following variables were independently predictive of 1-month mortality: CMGFRr > 3.7 (OR = 3.3, 95% CI, 1.22-9.04, P = 0.018) and multivessel coronary artery disease (OR = 2.3, 95% CI, 1.28-4.07, P = 0.005). CONCLUSION: The contrast medium-to-GFR ratio is a strong predictor of CIN and of 1-month mortality in patients undergoing primary PCI for STEMI.

Circulating endothelial progenitor cell levels and function in patients who experienced late coronary stent thrombosis.

AIMS: The pathogenesis of late coronary stent thrombosis may be related to impaired arterial healing. Endothelial progenitor cells (EPCs) have been shown to play an important role in repair and re-endothelialization following vascular injury. We hypothesized that patients who develop late stent thrombosis may have reduced or dysfunctional EPCs, and aimed to compare EPC level and function in patients who experienced stent thrombosis vs. matched controls. METHODS AND RESULTS: Patients who developed late (> 30 days) stent thrombosis within the past 3 years were compared with matched patients who underwent stenting and did not develop stent thrombosis. All patients had blood samples taken ≥ 3 months from the stent thrombosis or index procedure. The proportion of peripheral mononuclear cells (PMNCs) expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34 was evaluated by flow cytometry. Endothelial progenitor cell colony forming units (CFUs) were grown from PMNCs, characterized and counted following 7 days of culture. The two groups (n = 30 each) were well-matched (93.3% men, mean age 60-62 years, 33.3% diabetes, 73-80% DESs). The proportion of cells co-expressing VEGFR-2, CD133, and CD34 was lower in the stent thrombosis group compared with the control [VEGFR-2(+)CD133(+): 0.18% (0.03-0.41%) vs. 0.47% (0.16-0.66%), P = 0.01; VEGFR-2(+)CD34(+): 0.32% (0.22-0.70%) vs. 0.66% (0.24-1.1%), P = 0.03]. The number of EPC CFUs was also lower in the stent thrombosis group [3.9% (3.2-5.5%) vs. 8.3% (6.5-13.4%) colonies/well, respectively, P < 0.0001]. CONCLUSION: Patients who suffered late coronary stent thrombosis appear to have reduced levels of circulating EPCs and impaired functional properties of the cells. These findings require validation by further studies, but may contribute to understanding the pathogenesis of late stent thrombosis.

Nutrigenetic impact of daily folate intake on plasma homocysteine and folate levels in patients with different methylenetetrahydrofolate reductase genotypes.

BACKGROUND: Elevated plasma homocysteine level is associated with coronary artery disease (CAD). Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is typically but inconsistently associated with hyperhomocysteinemia. We examined the impact of daily intake of folate, a co-factor in homocysteine metabolism, on plasma homocysteine and folate levels in CAD patients in relation with MTHFR genotypes. METHODS: Daily folate intake was assessed from 3-day food records in 99 patients with CAD: 35 with the T/T (homozygous mutant) genotype and 64 with the C/C or C/T (non-T/T) genotypes. RESULTS: Patients with the T/T genotype had higher fasting plasma homocysteine levels (18.4±1.9 vs. 12.6±0.6 µmol/l, P=0.01) and lower plasma folate levels (17.8±1.7 vs. 20.8±1.0 nmol/l, P=0.02). There were no differences between the genotype groups in energy-adjusted folate intake. In patients with the non-T/T genotypes, higher folate intake was associated with higher plasma folate levels and lower plasma homocysteine levels. In T/T homozygotes this association was weaker. Linear regression analysis showed that folate intake, the MTHFR genotype, plasma vitamin B12 levels, and the interaction between plasma folate level and MTHFR genotype, predicted homocysteine elevation. (folate intake, P=0.04, MTHFR genotype, P=0.03, plasma folate, P=0.02, and plasma B12 level, P=0.004). The model explained only 29% of the variance in log-transformed plasma homocysteine levels. CONCLUSION: T/T homozygotes are more sensitive to the combination of low folate intake, low plasma folate and vitamin B12 level, than patients with non-T/T genotypes. The variability in plasma homocysteine in T/T homozygotes is only partly explained by these variables.

Effect of narcotic treatment on outcomes of acute coronary syndromes.

Current guidelines have recommended intravenous narcotics (IVNs) for patients with ST-segment elevation acute coronary syndromes (STEACS) and patients with non-STEACS (NSTEACS), although the safety of IVNs has been challenged. We performed a retrospective analysis of the 30-day outcomes stratified by IVN use among patients enrolled in a national survey, using logistic regression and propensity score analysis. Of the 765 patients with STEACS and 993 patients with NSTEACS, 261 (34.1%) and 97 (9.8%) had received IVNs, respectively. The patients with STEACS who received IVNs were more likely to undergo reperfusion (79.7% vs 55.2%, p <0.0001), received it more rapidly (median 59 minutes vs 70 minutes, p = 0.02), and were more likely to undergo coronary angiography and revascularization. No difference was found in hemodynamic status. The patients with NSTEACS who received IVNs were more likely to present with Killip class II-IV (39.2% vs 10.0%, p <0.001) and to have left ventricular systolic dysfunction (39.0% vs 17.0%, p <0.001). No difference was found in the use of invasive procedures. Using propensity score analysis, of 249 matched STEACS pairs, the rate of 30-day death was lower in the group that had received IVNs (2.4% vs 6.2%, p = 0.04), and this trend persisted after logistic regression analysis (odds ratio 0.40, 95% confidence interval 0.14 to 1.14, p = 0.09). Using propensity score analysis, of 95 matched NSTEACS pairs, no difference was found in the 30-day death rate (2.2% for patients receiving IVNs vs 6.3%, p = 0.16), even after logistic regression analysis (odds ratio 0.56, 95% confidence interval 0.14 to 2.33, p = 0.43). In conclusion, IVNs were commonly used in different scenarios-patients with STEACS were more likely to receive IVNs in the context of prompt reperfusion, and patients with NSTEACS were more likely to receive IVNs in the context of heart failure. In both scenarios, IVN use did not adversely affect the outcomes.

Treatment of aspirin-resistant patients with omega-3 fatty acids versus aspirin dose escalation.

OBJECTIVES: The aim of this study was to evaluate whether addition of omega-3 fatty acids or increase in aspirin dose improves response to low-dose aspirin among patients who are aspirin resistant. BACKGROUND: Low response to aspirin has been associated with adverse cardiovascular events. However, there is no established therapeutic approach to overcome aspirin resistance. Omega-3 fatty acids decrease the availability of platelet arachidonic acid (AA) and indirectly thromboxane A2 formation. METHODS: Patients (n = 485) with stable coronary artery disease taking low-dose aspirin (75 to 162 mg) for at least 1 week were screened for aspirin response with the VerifyNow Aspirin assay (Accumetrics, San Diego, California). Further testing was performed by platelet aggregation. Aspirin resistance was defined by > or =2 of 3 criteria: VerifyNow score > or =550, 0.5-mg/ml AA-induced aggregation > or =20%, and 10-micromol/l adenosine diphosphate (ADP)-induced aggregation > or =70%. Thirty patients (6.2%) were found to be aspirin resistant and randomized to receive either low-dose aspirin + omega-3 fatty acids (4 capsules daily) or aspirin 325 mg daily. After 30 days of treatment patients were re-tested. RESULTS: Both groups (n = 15 each) had similar clinical characteristics. After treatment significant reductions in AA- and ADP-induced aggregation and the VerifyNow score were observed in both groups. Plasma levels of thromboxane B2 were also reduced in both groups (56.8% reduction in the omega-3 fatty acids group, and 39.6% decrease in the aspirin group). Twelve patients (80%) who received omega-3 fatty acids and 11 patients (73%) who received aspirin 325 mg were no longer aspirin resistant after treatment. CONCLUSIONS: Treatment of aspirin-resistant patients by adding omega-3 fatty acids or increasing the aspirin dose seems to improve response to aspirin and effectively reduces platelet reactivity.