APpropriAteness of percutaneous Coronary interventions in patients with ischaemic HEart disease in Italy: the APACHE pilot study.

OBJECTIVES: To first explore in Italy appropriateness of indication, adherence to guideline recommendations and mode of selection for coronary revascularisation. DESIGN: Retrospective, pilot study. SETTING: 22 percutaneous coronary intervention (PCI)-performing hospitals (20 patients per site), 13 (59%) with on-site cardiac surgery. PARTICIPANTS: 440 patients who received PCI for stable coronary artery disease (CAD) or non-ST elevation acute coronary syndrome were independently selected in a 4:1 ratio with half diabetics. PRIMARY AND SECONDARY OUTCOME MEASURES: Proportion of patients who received appropriate PCI using validated appropriate use scores (ie, AUS≥7). Also, in patients with stable CAD, we examined adherence to the following European Society of Cardiology recommendations: (A) per cent of patients with complex coronary anatomy treated after heart team discussion; (B) per cent of fractional flow reserve-guided PCI for borderline stenoses in patients without documented ischaemia; (C) per cent of patients receiving guideline-directed medical therapy at the time of PCI as well as use of provocative test of ischaemia according to pretest probability (PTP) of CAD. RESULTS: Of the 401 mappable PCIs (91%), 38.7% (95% CI 33.9 to 43.6) were classified as appropriate, 47.6% (95% CI 42.7 to 52.6) as uncertain and 13.7% (95% CI 10.5% to 17.5%) as inappropriate. Median PTP in patients with stable CAD without known coronary anatomy was 69% (78% intermediate PTP, 22% high PTP). Ischaemia testing use was similar (p=0.71) in patients with intermediate (n=140, 63%) and with high PTP (n=40, 66%). In patients with stable CAD (n=352) guideline adherence to the three recommendations explored was: (A) 11%; (B) 25%; (C) 23%. AUS was higher in patients evaluated by the heart team as compared with patients who were not (7 (6.8) vs 5 (4.7); p=0.001). CONCLUSIONS: Use of heart team approaches and adherence to guideline recommendations on coronary revascularisation in a real-world setting is limited. This pilot study documents the feasibility of measuring appropriateness and guideline adherence in clinical practice and identifies substantial opportunities for quality improvement. TRIAL REGISTRATION NUMBER: NCT02748603.

Clinically apparent long-term electric disturbances in the acute and very long-term of patent foramen ovale device-based closure.

BACKGROUND/PURPOSE: Incidence of electrical disturbances in patients submitted to transcatheter patent foramen ovale (PFO) closure has not been fully clarified in a large population. The aim of the study is to assess the incidence of atrial fibrillation, supraventricular tachi-arrhythmias, and atrio-ventricular block in the acute and very long-term follow-up. METHODS/MATERIALS: We reviewed the medical and instrumental data of 1000 consecutive patients (mean age 47.3±17.1years) prospectively enrolled in two centers over a 13-year period (February 1999 to February 2012) for right-to-left (R-to-L) shunt ICE-aided catheter-based closure using different devices. RESULTS: Successful transcatheter PFO closure was achieved in 99.8% of the patients. Implanted devices were: Amplatzer PFO Occluder in 463 patients (46.3%), Amplatzer ASD Cribriform Occluder in 420 patients (42.0%), Premere Occlusion System in 95 patients (9.5%), and Biostar Occluder in 22 patients (2.2%). Postprocedural electrical complications occurred in 5.9% of patients. The only independent predictors of electrophysiological complications were female gender (OR 2.3, 0.5-5.1 [95% CI], p<0.001) and device disk >30mm (OR 5.0, 1.2-7.2 [95% CI], p<0.001). On a mean follow-up of 12 .3±0.6years (minimum 4- maximum 17years), electrical complications occurred in 1.4% of patients including one only case of complete AVB and 5 cases of permanent AF. The only independent predictors were female gender (OR 2.3, 0.5-5.1 [95% CI], p<0.001) and device disk >30mm (OR 5.0, 1.2-7.2 [95% CI], p<0.001). CONCLUSION: Device-based closure of PFO using different devices, appeared very safe from an electrophysiological point of view with low incidence of electrical disturbances even in the very long-term follow-up.

Long-Term Outcomes and Complications of Intracardiac Echocardiography-Assisted Patent Foramen Ovale Closure in 1,000 Consecutive Patients.

BACKGROUNDS: Long-term fate of patients submitted to patent foramen ovale (PFO) closure is still unclear. The aim of the study was to evaluate the incidence of atrial fibrillation (AF), aortic or atrial free wall erosion, device thrombosis (DT), new onset or worsening of mitral valve regurgitation (MVR), and recurrent cerebral ischemic events in the long-term follow up after intracardiac echocardiography (ICE)-aided PFO closure in a large population. METHODS: We reviewed the medical and instrumental data of 1,000 consecutive patients (mean age 47.3 ± 17.1 years, females) prospectively enrolled in 2 centres over a 13 years period (February 1999-February 2012) for R-to-L shunt ICE-aided catheter-based closure using different devices. RESULTS: Immediate success was 99.8%. Implanted devices were Amplatzer PFO Occluder in 463 patients (46.3%), Amplatzer ASD Cribriform Occluder in 420 patients (42.0%), Premere Occlusion System in 95 patients (9.5%), and Biostar Occluder in 22 patients (2.2%). On a mean follow-up of 12.3 ± 0.6 years (minimum 4- maximum 17 years), permanent AF occurred in 0.5%, DT was apparent in 0.5%, new onset or worsening of MVR was observed in 0.2%, whereas recurrent cerebral ischemic events were 0.8%. Occlusion rate was 93.8%. No aortic or atrial free wall erosion has been observed. CONCLUSION: ICE-aided closure of PFO using different devices, appeared very safe and effective on very long-term follow up with low incidence of erosion, DT, recurrent ischemic events, MVR new onset or worsening, and permanent AF.

Galectin-3 predicts long-term cardiovascular death in high-risk patients with coronary artery disease.

OBJECTIVE: Galectin-3 (Gal-3) can affect atherogenesis by multiple mechanisms, but it remains scarcely known whether plasma Gal-3 levels predict cardiovascular events in patients with coronary artery disease. Therefore, we investigated if Gal-3 predicts cardiovascular death in patients with coronary artery disease of the Genetic and ENvironmental factors In Coronary Artery disease study. APPROACH AND RESULTS: In a prospective cohort study, we measured the plasma levels of Gal-3 in 1013 randomly selected patients who underwent coronary angiography and long-term follow-up to assess incident cardiovascular events. The primary end points were (1) cardiovascular death and (2) a composite of cardiovascular death, acute coronary syndrome, and stroke. Secondary end points entailed (1) acute myocardial infarction, (2) stroke, and (3) a composite fatal ischemic event including fatal myocardial infarction and stroke. The effect of Gal-3 on prognosis was assessed using Kaplan-Meier analysis and multivariate Cox's regression. During long-term follow-up (median, 7.2 years), 115 cardiovascular deaths occurred (15.2%), more commonly in the high Gal-3 tertile (25.2%) than in the intermediate and the low tertiles (13.6% versus 7.5%, respectively; P<0.001). The adverse prognostic effect of high Gal-3 was confirmed in subgroup analysis of the patients with angiographically documented coronary artery disease and also of those with a normal left ventricular ejection fraction. At multivariate analysis, Gal-3 was a predictor of cardiovascular mortality (hazard ratio, 1.79; 95% confidence interval, 1.10-2.93; P=0.020) along with age, left ventricular ejection fraction, and coronary atherosclerotic burden. CONCLUSIONS: In high cardiovascular risk patients referred for coronary angiography Gal-3 is a strong independent predictor of cardiovascular death.

Lipoprotein-associated phospholipase A2 single-nucleotide polymorphisms and cardiovascular events in patients with coronary artery disease.

AIMS: We tested the hypothesis that variations in the PLA2G7 gene encoding the lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme deemed to have proatherogenic activity, affect the Lp-PLA2 levels and predicts cardiovascular events. METHODS: Using a prospective cohort study design, we investigated incident cardiovascular events as a function of the PLA2G7 gene for rs1805017, rs1805018, and rs1051931 single-nucleotide polymorphisms (SNPs) in 643 randomly selected white patients from the GENICA Study, who at baseline underwent coronary angiography, measurement of Lp-PLA2 mass and activity. Cardiovascular event-free survival was compared across the genotypes by Cox regression, propensity score matching, and haplotype analysis. RESULTS: The rs1805018 SNP did not follow the Hardy-Weinberg equilibrium and was not further explored. The rs1805017 GG genotype had a lower Lp-PLA2 mass and a higher Lp-PLA2 activity, thus suggesting that this SNP is functional. Long-term follow-up (median 7.8 years) was obtained in 75% of the cohort and allowed recording of incident cardiovascular events in 25.8% of the patients. On Cox regression analysis, the common rs1805017 GG genotype predicted acute myocardial infarction (AMI) [hazard ratio 1.75, 95% confidence interval (CI) 1.03-2.99, P = 0.041]; this finding was confirmed on propensity score matching (82.6% AMI-free survival in GG vs. 94.4% in GA + AA, P = 0.003). The rs1805017 and rs1051931 G/G haplotype was also associated with AMI (52.7 vs. 42.2%, P = 0.026) and cardiovascular event incidence (49.5 vs. 41.7%, P = 0.025). CONCLUSION: In high-risk coronary artery disease patients of European ancestry, the PLA2G7 rs1805017 GG genotype is associated with increased Lp-PLA2 plasma activity and AMI.

A new management for limb graft occlusion after endovascular aneurysm repair adding a vollmar ring stripper: the unclogging technique.

BACKGROUND: Lower extremity ischemia for limb thrombosis is a well-known adverse event after endovascular abdominal aortic aneurysm repair (EVAR), ranging from 2.6-7.4%. We report our experience in the management of graft limb occlusion that occurred in patients who underwent EVAR in our institution. In cases in which balloon catheter thrombectomy is not useful or is risky, it is important to take into consideration the use of a Vollmar ring stripper (Aesculap, San Jose, CA) to avoid dislodging or disrupting the sealing zones. This technique has taken from thromboendarterectomy the principle of detaching plaque from adventitia and transformed it in a less traumatic way for dissecting thromboses from endografts. METHODS: Between September 1999 and December 2011, 608 patients underwent EVAR in our institution. In cases of severe claudication or critical ischemia, we tried to remove the thrombus using mild Fogarty balloon traction; in cases of progressive and old stratification, we added the Vollmar ring stripper. After recanalization, if there was a stenosis, an angioplasty was performed and in most patients an adequately size Cheatham platinum stent was positioned. If the endovascular approach failed, bypass procedures were considered. RESULTS: In 608 patients over a mean follow-up time of 72 months, there were 23 cases of limb thrombosis. Fifteen of the 23 limb occlusions were identified within 6 months after aneurysm repair. The mean time to occlusion was 8.2 ± 4.3 months (range: 20 days-25 months). Presenting symptoms were mild to moderate claudication (Rutherford classification I) in 3 patients (13%), medium severe claudication (Rutherford classification IIA) in 18 patients (78.3%), and paresthesia and rest pain (Rutherford classification IIB) in 2 patients (8.7%; 1 of those patients had a loss of motor function). Four (17.4%) were stable during follow-up, and in 1 of these cases we tried thrombolysis without thrombosis resolution. In 13 (56.5%) cases, we performed balloon catheter thrombectomy with a LeMaitre over the wire embolectomy catheter (LeMaitre Vascular, Burlington, MA). In 8 of 13 (61.5%) patients with certain thrombosis characteristics, we decided to add to the balloon catheter a Vollmar ring stripper for mechanical catheter thrombectomy. In all 13 thrombectomy cases, blood flow was restored through the limb with the endograft itself. There were no episodes of graft dislocation, disruption of the sealing zones, or recurrences. In 5 (21.7%) cases, a femorofemoral crossover was performed, and in 1 (4.3%) case, an axillofemoral bypass was performed. During the follow-up period, 2 of the 5 femorofemoral crossovers closed after 6 and 8 months, respectively. CONCLUSIONS: This unclogging technique, alone or associated with Vollmar ring stripper, proves to be simple, safe, and effective in the treatment of graft limb occlusion. Additional research will help confirm the role of Vollmar ring stripper.

Antibodies to malondialdehyde oxidized low-density lipoproteins predict long term cardiovascular mortality in high risk patients.

AIMS: Antibodies to oxidized low-density lipoproteins (oxLDLAbs) are detectable in the serum of patients with and without atherosclerosis, but it is unclear if they play a pathogenic or a protective role in atherogenesis or if they are simply a marker of atherosclerosis. Therefore, in a prospective cohort study we investigated if oxLDLAbs titer predicts cardiovascular (CV) events in high-risk coronary artery disease patients. METHODS AND RESULTS: The titer of IgG antibodies to malondialdehyde modified oxidized low-density lipoproteins was measured in 748 randomly selected patients of the GENICA study who underwent coronary angiography and assessment of incident CV events at follow-up. Patients were classified by oxLDLAbs into a low and a high titer group, corresponding to the first three and the last quartile, respectively. Cardiovascular event-free survival was compared between oxLDLAbs groups by Kaplan-Meier and multivariate technique including propensity score matching analysis. During long-term follow-up (median 7.2 years) CV deaths were observed in 65 patients (11.6%), more commonly in the high than in the low oxLDLAbs group (patients free from CV death 83.1% vs. 89% respectively, p=0.025). The incidence of CV events was also higher in the former than in latter (event-free survival 69.2% vs. 77.7% respectively, p=0.030). CONCLUSIONS: An oxLDLAbs titer above the 75th percentile is a marker of LDL oxidation which predicts a worse CV prognosis at long term follow-up in high-risk Caucasian patients referred for coronary angiography.

Lipoprotein-associated phospholipase A2 activity predicts cardiovascular events in high risk coronary artery disease patients.

OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is deemed to play a role in atherosclerosis and plaque destabilization as demonstrated in animal models and in prospective clinical studies. However, most of the literature is either focused on high-risk, apparently healthy patients, or is based on cross sectional studies. Therefore, we tested the hypothesis that serum Lp-PLA2 mass and activity are useful for predicting cardiovascular (CV) events over the coronary atherosclerotic burden and conventional risk factors in high-risk coronary artery disease patients. METHODS AND RESULTS: In a prospective cohort study of 712 Caucasian patients, who underwent coronary angiography and measurement of both Lp-PLA2 mass and activity at baseline, we determined incident CV events at follow-up after splitting the patients into a high and a low Lp-PLA2 mass and activity groups based on ROC analysis and Youden index. Kaplan-Meier and propensity score matching analysis were used to compare CV event-free survival between groups. Follow-up data were obtained in 75% of the cohort after a median of 7.2 years (range 1-12.7 years) during which 129 (25.5%) CV events were observed. The high Lp-PLA2 activity patients showed worse CV event-free survival (66.7% vs. 79.5%, p = 0.023) and acute coronary syndrome-free survival (75.4% vs. 85.6%, p = 0.04) than those in low Lp-PLA2 group. CONCLUSIONS: A high Lp-PLA2 activity implies a worse CV prognosis at long term follow up in high-risk Caucasian patients referred for coronary angiography.

Exon 11 deletion in the myocyte enhancer factor (MEF)2A and early onset coronary artery disease gene in a Sicilian family.

AIMS: We investigated the prevalence of the myocyte enhancer factor (MEF)2A exon 11 deletion, a putative coronary artery disease (CAD) susceptibility gene, in patients referred for coronary angiography. METHODS AND RESULTS: In total, 1079 consecutive patients referred for coronary angiography in the GENICA Study were genotyped and 301 low-risk subjects were used as controls. One patient with early onset three vessels CAD, carrying the MEF2A deletion was found in the GENICA Study cohort and none in the control group. CONCLUSION: In a cohort of patients undergoing coronary angiography for suspected CAD the MEF2A exon 11 deletion occurred in 0.09%.

Use of the Amplatzer ASD Occluder for closing a persistent left vertical vein.

We report the case of a very large anomalous connection of the veins draining the upper lobe of the left lung to both the left-sided vertical vein and the left atrium, associated with mild rheumatic mitral valve stenosis, in which the atrial septum was intact and the remaining venous system, including the coronary sinus, was otherwise normal (a variant of Lutembacher's syndrome). In order to abolish the left-to-right shunting, a transcatheter approach to close this venous structure was successfully attempted using an Amplatzer ASD Occluder device. The technical aspects and the alternative options of performing a procedure with a device for a purpose outside the scope of its approved label are discussed.

Strut fracture: a further concern with drug-eluting stents.

A potential cause of drug-eluting stent restenosis is strut fracture. To date, few cases have been reported in the available literature and a best treatment method has not been established. We describe two cases of sirolimus-eluting stent fracture combined with focal restenosis and also review those previously reported.

Plasma adiponectin for prediction of cardiovascular events and mortality in high-risk patients.

CONTEXT: The prognostic value of plasma levels of adiponectin, an adipocytokine with antiatherogenic, antiinflammatory, and insulin-sensitizing effects, is contentious. OBJECTIVE: The objective of the study was to investigate whether plasma adiponectin levels predict cardiovascular (CV) events and mortality in high-risk coronary artery disease (CAD) patients. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURE: We measured plasma adiponectin and examined its impact on the incidence of CV deaths and events at follow-up in the context of all potentially relevant background covariates in 712 high-risk patients of the Genetic and ENvironmental factors in Coronary Atherosclerosis study who underwent coronary angiography for suspected CAD. Based on the population plasma adiponectin median (6.38 microg/ml, interquartile range 4.2-10.2), we split the patients in a high- and a low-plasma adiponectin subgroup. After a median follow-up of 3.8 years (interquartile range 3.3-4.3 yr), outcome data were obtained in 100% of the patients and 45 CV deaths (6.4%) were recorded. Kaplan-Meier analysis unexpectedly showed a higher CV death rate in high-plasma adiponectin than low-plasma adiponectin patients. By contrast, multivariate Cox regression analysis, in which potential confounders, including ongoing medical treatment, were considered, showed no impact of plasma adiponectin on CV death. Similar negative results were obtained using the propensity score that considered all relevant covariables and medical treatment rate, which differed between the high- and low-plasma adiponectin group. CONCLUSIONS: In high-risk CAD patients, plasma adiponectin above the median (6.38 microg/ml) implies a paradoxical higher risk of CV death. However, when relevant covariates that differ between high- and low-plasma adiponectin groups are considered, this association wanes, indicating that the clustering of plasma adiponectin with other covariates can abolish its impact on CV prognosis.

Randomized study comparing mechanical with electronic 2-dimensional intracardiac ultrasound monitoring (MEDIUM) during percutaneous closure of patent foramen ovale in adult patients with cryptogenic stroke.

BACKGROUND: Previous studies have shown that mechanical and electronic intracardiac echocardiography (ICE) improves ultrasound monitoring during transcatheter patent foramen ovale (PFO) interventional closure. OBJECTIVES: This study sought to compare the procedural data, clinical imaging quality, and effectiveness PFO closure by using two different ICE monitoring modalities. METHODS: Patients referred for PFO closure (n = 82) were randomly assigned to mechanical (group 1) or electronic (group 2) ICE monitoring of Amplatzer device implantation. The digital ICE images were evaluated offline by means of absolute visual grading analysis score (VGAS(abs)), and the residual shunting at follow-up were assessed by means of contrast echocardiographic studies, all blinded regarding the ICE closure monitoring modality. RESULTS: The two groups were comparable with respect to clinical baseline characteristics, intracardiac fossa ovalis measurements, and procedural data (fluoroscopy time, procedure time and measurement of the amount of radiation that the patients absorbed). The total VGAS(abs) ranked the mechanical clinical images in a higher order than the electronic ones (3.78 +/- 0.09 vs 3.58 +/- 0.12, P = 0.005); additionally, three patients (7.3%) of group 2 needed to cross over to mechanical ICE monitoring because a right-convex atrial septal aneurysm configured itself incompletely. No differences in rates of residual shunting were observed at 12 months follow-up between the two groups (97.5% vs 94.7%, P = 0.951). CONCLUSIONS: Electronic monitoring of PFO closure performed a less diagnostic impact than the mechanical one while maintaining comparable procedural data and clinical outcome. These results represent an important step in validating these new intracardiac ultrasound imaging modalities.

Intraoperative intrasac thrombin injection to prevent type II endoleak after endovascular abdominal aortic aneurysm repair.

PURPOSE: To report a prospective, nonrandomized pilot study to determine whether fibrin glue aneurysm sac embolization at the time of endovascular aneurysm repair (EVAR) is a safe and effective procedure to primarily prevent type II endoleaks. METHODS: Between June 2003 and December 2005, 84 consecutive patients (79 men; mean age 73.8+/-7.8 years, range 64-86) with degenerative infrarenal abdominal aortic aneurysm underwent EVAR with bifurcated stent-grafts and fibrin glue injection into the aneurysm sac at the conclusion of the endovascular procedure. A total of 424 imaging studies and 348 visits were recorded during the study period and reviewed. RESULTS: Selective catheterization of the aneurysm sac and fibrin glue injection immediately after initial stent-graft deployment was successful in 83 (99%) of 84 cases; there was one failure to access the excluded aneurysm sac due to severe iliac artery calcification. The estimated primary and assisted clinical success rates at 2 years were 91.3% and 98.8%, respectively, but the major findings were the low rate of delayed type II endoleak (2.4%) and the statistically significant decrease in the maximum transverse aneurysm diameter (50.40+/-6.70 versus 42.03+/-6.50 mm, p = 0.0001) at follow-up. In addition, of 31 patients available for 24-month follow-up, 14 (45.2%) patients showed a reduction in maximum transverse aneurysm diameter by >or=5 mm; 16 (51.6%) patients had no significant changes, whereas only 1 patient showed a >5-mm enlargement. CONCLUSION: This clot engineering approach to aneurysm sac embolization at the time of endografting appears to be safe and may spare the patient a repeated catheter-based intervention or surgical procedure.

Funnel technique for first-line endovascular treatment of an abdominal aortic aneurysm with an ectatic proximal neck.

PURPOSE: To describe a novel endovascular technique for proximal stent-graft fixation in an abdominal aortic aneurysm (AAA) with an ectatic aortic neck. CASE REPORT: An 84-year-old man with multiple comorbidities and an asymptomatic 7-cm infrarenal AAA with a 38-mm aortic neck diameter was treated with a 3-component Talent-LPS stent-graft system. After the left internal iliac artery was embolized with coils, a 34 x 16 x 170-mm Talent bifurcated stent-graft was placed in the lower part of the AAA. A 44-mm-diameter, 90-mm-long free-flow thoracic tube endograft (6-mm oversizing) was delivered to the proximal neck through the bifurcated device and deployed with at least 30 mm of overlap, leaving more than 40 mm extending into the infrarenal aorta to ensure expansion to its nominal diameter as well as an adequate seal. An iliac extension was deployed into the left external iliac artery, and 2 sequential iliac extensions were inserted from the bifurcated stent-graft limb to the right common iliac artery in a bell-bottom configuration. Serial computed tomographic angiograms at up to 18 months have documented the intact 3-component stent-graft, with no endoleak or migration and no increase in aneurysm sac diameter. CONCLUSION: This case illustrates the feasibility of placing a straight thoracic endograft as a proximal extension of a bifurcated aortic endograft into a dilated proximal aortic neck. This endograft configuration appears secure and effective, with no type I endoleak or migration over a midterm follow-up.

The T(-786)C endothelial nitric oxide synthase genotype predicts cardiovascular mortality in high-risk patients.

OBJECTIVES: This study sought to investigate the impact of a common T(-786)C single-nucleotide polymorphism (SNP) in the promoter of the endothelial nitric oxide synthase (eNOS, NOS3) gene on cardiovascular (CV) death in a prospective cohort study. BACKGROUND: The T(-786)C SNP eNOS gene implies a blunted endothelium-dependent vasodilation in hypertensive patients and was associated with multivessel coronary artery disease in cross-sectional studies, but it remained unsettled whether it carried prognostic information. METHODS: In consecutive white patients of the GENICA (Genetic and Environmental Factors in Coronary Atherosclerosis) study, who underwent coronary angiography between 1999 and 2001, we determined the incidence of CV death at follow-up. The eNOS T(-786)C and the exon 7 G(894)T SNPs were determined by melting curve analysis of amplicons from allele-specific fluorescence resonance energy transfer probes. Plasma levels of nitrate/nitrite, nitrotyrosine, and myeloperoxidase were also measured. The Kaplan-Meier and Cox regression analyses were used to assess the impact of SNPs on event-free survival. RESULTS: Complete follow-up data were obtained in 1,086 (98%) patients. After a median follow-up of 1,296 days (range 4 to 2,057 days), we observed 85 (8.2%) CV deaths. There was a significant impact of the T(-786)C eNOS genotype on CV death-free (p = 0.0102) survival, but no differences in CV death rates across G(894)T genotypes. The TT individuals, who showed a lower survival, exhibited higher plasma myeloperoxidase (p < 0.0001) and lower levels of nitrotyrosine (p < 0.0001) than CC patients. CONCLUSIONS: The T(-786)C SNP in the promoter of eNOS bears independent prognostic information and is associated with changes in markers of oxidant stress in high-risk white patients referred for coronary angiography.

Hyperhomocysteinemia predicts total and cardiovascular mortality in high-risk women.

OBJECTIVE: The impact of homocysteine on cardiovascular disease can be more detrimental in women than in men, but it is unknown whether this applies to high-risk women. We therefore investigated the association of hyperhomocysteinemia with coronary artery disease (CAD) and cardiovascular mortality in high-risk women referred for CAD, both in the total population and in the hypertensive and normotensive cohorts. DESIGN: A prospective study cohort. SETTING: A tertiary centre. INCLUSION CRITERIA: 262 consecutive Caucasian postmenopausal women referred for coronary angiography. EXCLUSION CRITERIA: acute myocardial infarction and vitamin supplementation. MAIN OUTCOME MEASURE(S): We assessed total plasma homocysteine (tHcy), folate levels, and the MTHFR677C-->T polymorphism. CAD was defined as a modified Duke Index score greater than 0; hyperhomocysteinemia as tHcy levels of 15 micromol/l or greater. The primary study outcome was cardiovascular mortality at follow-up. RESULTS: Mild/moderate and severe hyperhomocysteinemia was found in 15.1 and 1.6% of women, respectively, without differences between CAD and non-CAD women. By the ATPIII criteria, 92.2% of the women were in the highest risk class and 55% had CAD; however, no association of tHcy with the CAD score was found. After a median follow-up of 3.6 years, 23 women (9.1%) had died, 15 (6%) of cardiovascular causes. Women with high tHcy levels showed the worst all-cause and cardiovascular death-free survival at Kaplan-Meier and Cox regression analysis. Moreover, in the hypertensive cohort only women with hyperhomocysteinemia showed increased cardiovascular mortality. CONCLUSION: Hyperhomocysteinemia is common in high-risk women and adversely affects their prognosis, although it is unrelated to the CAD atherosclerotic burden.