Involvement of APOE in Incidence of Revascularization in Patients Affected by Peripheral Arterial Disease: A Prospective Study from Southern Italy.

INTRODUCTION: Atherosclerosis is a complex multifactorial disease and apolipoprotein E (APOE) polymorphism has been associated with cardiovascular events. The APOE gene, located on chromosome 19q13.2, has an important role in lipid metabolism, in particular on circulating cholesterol levels, implying further pleiotropic effects; from its polymorphism are derived three alleles (ε2, ε3 and ε4), which induce different phenotypes, while its impact on carotid and femoral atherosclerosis is still controversial. OBJECTIVES: The aim of the study is to investigate the relationship between APOE genotypes and peripheral revascularization in a cohort of patients affected by advanced peripheral arterial disease (PAD) at a prolonged follow-up. MATERIALS AND METHODS: Some 332 patients (259 males and 73 females; mean age 70.86 ± 7.95 years) with severe PAD were enrolled in a longitudinal study, with a 90.75 ± 32.25 month follow-up, assessing major adverse cardiovascular events (MACE). RESULTS: As compared with ε3/ε3, in ε4 patients we observed a significant higher incidence of carotid (13.2% vs. 5.6%; HR = 2.485, 95% CI 1.062-5.814; p = 0.036) and lower limb (11.8% vs. 4.3%; HR = 2.765, 95% CI 1.091-7.008; p = 0.032) revascularizations and, accordingly, a higher incidence of total peripheral revascularizations (13.5% vs. 9.5%; HR = 2.705, 95% CI 1.420-5.151; p = 0.002). HR remained statistically significant even when adjusted for classic cardiovascular risk factors. CONCLUSIONS: In our observational study, we confirm that the ε4 allele is associated with higher total peripheral revascularization in patients with advanced atherosclerotic vascular disease at prolonged follow-up.

Timing of clopidogrel loading dose on peripheral blood endothelial progenitor cells, SDF-1α and neointimal hyperplasia in carotid stenting.

BACKGROUND: Carotid stenting stimulates intimal proliferation through platelet and stem cell activation. OBJECTIVE: The aim of this study is to evaluate whether the administration before or after carotid stenting of clopidogrel loading dose may play a role on circulating endothelial progenitor cells, stromal cell-derived factor-1α (SDF-1α) and neointimal hyperplasia. METHODS: We recruited 13 patients (aged 74.52±7.23) with indication of carotid revascularization and in therapy with salicylic acid and statin. We blindly randomized them in two groups: pre-carotid angioplasty with stent (Pre-CAS group) receiving 300 mg of clopidogrel before stenting, and post-carotid angioplasty with stent (Post-CAS group) receiving 300 mg after stenting. At the admission, we valued endothelial progenitor cells, SDF-1α and prospectively we repeated blood samples and measured intima-media thickness to estimate neointimal hyperplasia on the stent at 3, 6 and 12 months. RESULTS: In the days following the CAS, we found a lower, statistically not significant, trend of endothelial progenitor cells in Pre-CAS group. The SDF-1α concentration tended to be lower at baseline in the pre-CAS group than in the post-CAS group and it did not show an increase in the observed time. On the contrary, in the Post-CAS group we observed a peak at six hours with a significant reduction (p < 0.001) at one day after stenting.The intima-media thickness was significantly lower in the Pre-CAS group than the Post-CAS group both at six months and 12 months after stenting. CONCLUSIONS: Pre-stenting clopidogrel loading dose leaded to short-time modification of endothelial progenitor cells and platelets and to long-term a minor neointimal hyperplasia.

Role of the APOE polymorphism in carotid and lower limb revascularization: A prospective study from Southern Italy.

BACKGROUND: Atherosclerosis is a complex multifactorial disease and the apolipoprotein E (APOE) polymorphism has been associated to vascular complications of atherosclerosis. OBJECTIVES: To investigate the relationship between the APOE genotypes and advanced peripheral vascular disease. MATERIALS AND METHODS: 258 consecutive patients (201 males and 57 females, mean age 70.83 ± 7.89 years) with severe PVD were enrolled in a 42-months longitudinal study (mean 31.65 ± 21.11 months) for major adverse cardiovascular events. At follow-up genotypes of the APOE polymorphism were investigated in blinded fashion. RESULTS: As compared with ε3/ε3, in ε4-carriers a significant higher incidence of major adverse cardiovascular events (35.58% vs. 20.79%; p = 0.025) and total peripheral revascularization (22.64% vs. 5.06%; p < 0.001) was observed. Prospective analysis, showed that ε4-carriers have an increased hazard ratio for major adverse cardiovascular events (adjusted HR 1.829, 95% CI 1.017-3.287; p = 0.044) and total peripheral revascularization (adjusted HR = 5.916, 95% CI 2.405-14.554, p <0.001). CONCLUSIONS: The ε4 allele seems to be risk factor for major adverse cardiovascular events, and in particular for total peripheral revascularization in patients with advanced atherosclerotic vascular disease.

Serum uric acid as a prognostic marker in the setting of advanced vascular disease: a prospective study in the elderly.

BACKGROUND: Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid (SUA) levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. METHODS: Two hundred and seventy six elderly patients affected by advanced atherosclerosis (217 males and 59 females; aged 71.2 ± 7.8 years) were included. All patients were assessed for history of cardiovascular disease, cancer, obesity and traditional risk factors. Patients were followed for approximately 31 ± 11 months. Major events were recorded during follow-up, defined as myocardial infarction, cerebral ischemia, myocardial and/or peripheral revascularization and death. RESULTS: Mean SUA level was 5.47 ± 1.43 mg/dL; then we further divided the population in two groups, according to the median value (5.36 mg/dL). During a median follow up of 31 months (5 to 49 months), 66 cardiovascular events, 9 fatal cardiovascular events and 14 cancer-related deaths have occurred. The patients with increased SUA level presented a higher significant incidence of total cardiovascular events (HR: 1.867, P = 0.014, 95% CI: 1.134-3.074). The same patients showed a significant increased risk of cancer-related death (HR: 4.335, P = 0.025, 95% CI: 1.204-15.606). CONCLUSIONS: Increased SUA levels are independently and significantly associated with risk of cardiovascular events and cancer related death in a population of mainly elderly patients affected by peripheral vasculopathy.

Residual shunt after percutaneous closure of patent foramen ovale with AMPLATZER occluder devices - influence of anatomic features: a transcranial Doppler and intracardiac echocardiography study.

AIMS: To evaluate the relationship between the anatomic features of the fossa ovalis (FO) and residual right-to-left shunt (RLS) after percutaneous patent foramen ovale (PFO) closure with AMPLATZER PFO occluder devices. METHODS AND RESULTS: FO anatomic features were assessed by intracardiac echocardiography in 127 patients with large RLS at contrast-enhanced transcranial colour Doppler (TCCD) undergoing percutaneous PFO closure with an AMPLATZER device. Residual RLS was evaluated by TCCD three and 12 months after the procedure. PFO closure was successful in all but two patients. At TCCD, a significant residual RLS (grade ≥2) was observed in 27 (21.6%) and 17 (13.6%) patients at three and 12 months, respectively. Larger baseline RLS, presence of atrial septal aneurysm, greater longitudinal and transverse FO dimensions, and use of larger devices were associated with significant residual RLS. At multivariate analysis, the presence of atrial septal aneurysm (OR 7.6; 95% CI: 1.38-42.35; p=0.02) and longitudinal FO dimension >20.8 mm (OR 8.5; 95% CI: 1.55-46.95; p=0.014) were identified as independent predictors of significant residual RLS at 12 months. CONCLUSIONS: Our study suggests that a large FO and the presence of atrial septal aneurysm are independent predictors of persistent residual RLS after PFO closure with AMPLATZER devices.

Echocardiographic guidance of percutaneous patent foramen ovale closure: head-to-head comparison of transesophageal versus rotational intracardiac echocardiography.

BACKGROUND: Transesophageal (TEE) and intracardiac (ICE) echocardiography are commonly used to guide percutaneous patent foramen ovale (PFO) closure. The study aim was to perform a head-to-head comparison between TEE and rotational ICE echocardiography in the measurement of the fossa ovalis and device selection. METHODS: In 45 patients with cryptogenic stroke or peripheral embolism and PFO with large right-to-left shunt, fossa ovalis dimensions were assessed preoperatively by TEE and intraoperatively by rotational ICE. The Amplatzer devices, deployed on the basis of ICE, were compared with those that would have been selected by TEE. RESULTS: A good correlation between TEE and rotational ICE was observed for both longitudinal and transverse fossa ovalis dimensions (TEE four-chamber vs. ICE four-chamber: r = 0.75; TEE bicaval vs. ICE four-chamber: r = 0.77; TEE aorta vs. ICE aorta: r = 0.59; P < 0.001 for all). However, no such correlation was found in 13 patients with atrial septal aneurysm (ASA) (TEE four-chamber vs. ICE four-chamber: r = 0.33; TEE bicaval vs. ICE four-chamber: r = 0.49; TEE aorta vs. ICE aorta: r = 0.05; P = NS for all). At Bland-Altman analysis, slight systematic differences with wide limits of agreement for each comparison were observed, particularly in patients with ASA, suggesting that the two imaging modalities cannot be used interchangeably. As regards device selection, a moderate agreement was found between TEE- and ICE-guided device size (72%, κ = 0.53, P < 0.001), except in patients with ASA (36%, κ = 0.02, P = NS). CONCLUSIONS: Our study suggests a significant disagreement between TEE and rotational ICE in measuring fossa ovalis and selecting the device for PFO closure, particularly in patients with ASA.

Improvement of migraine after patent foramen ovale percutaneous closure in patients with subclinical brain lesions: a case-control study.

OBJECTIVES: We sought to evaluate the benefits on frequency and severity of migraine recurrence after patent foramen ovale (PFO) closure in patients with subclinical brain lesions at magnetic resonance imaging (MRI). BACKGROUND: Migraine improvement has been reported after PFO closure in patients with cerebrovascular symptomatic events. Subclinical brain MRI lesions are detectable in patients with PFO and in migraineurs. METHODS: A total of 82 patients with moderate/severe migraine, PFO, large right-to-left shunt, and subclinical brain MRI lesions were prospectively examined for a 6-month period. Patients were subdivided into closure (n = 53) and control (n = 29) group according to their consent to undergo percutaneous PFO closure. In controls, therapy for migraine was optimized. Six-month frequency and severity of migraine recurrence were compared with baseline. RESULTS: The number of total attacks decreased more in the closure group (32 +/- 9 to 7 +/- 7, p < 0.001) than in the control group (36 +/- 13 to 30 +/- 21, p = NS) (p < 0.001). A significant reduction in disabling attacks was observed only in the closure group (20 +/- 12 to 2 +/- 2, p < 0.001; controls: 15 +/- 12 to 12 +/- 12, p = NS). Migraine disappeared in 34% of the closure group patients and 7% of controls (p = 0.007); >50% reduction of attacks was reported by 87% and 21%, respectively (p < 0.001). Disabling attacks disappeared in 53% of closure group patients and 7% of controls (p < 0.001); >50% reduction occurred in 89% and 17%, respectively (p < 0.001). CONCLUSIONS: In migraineurs with a large PFO and subclinical brain MRI lesions, a significant reduction in frequency and severity of migraine recurrence can be obtained by PFO closure when compared with frequency and severity in controls.