Prognostic interaction between age and sex on outcomes following carotid endarterectomy.

Background: The aim of this study was to assess the prognostic interaction between age and sex on peri-operative and follow-up outcomes following elective carotid endarterectomy (CEA) for asymptomatic and symptomatic carotid stenosis. Patients and methods: A retrospective review of all patients admitted to a single vascular unit who underwent elective CEA between January, 2015 and December, 2019 was performed. The primary endpoints of the study were overall survival (from index operation) and cumulative stroke rate at thirty days. Results: A total of 383 consecutive patients were included in this study; of these 254 (66.4%) were males. At baseline, males were younger (mean age 73.4±11 vs. 76.3±10 years, p=.01) and with lower proportion of octogenarians (20.4% vs. 28.7%, p=.05). The rate of stroke in symptomatic and asymptomatic patients (males vs. females) were as follows: a) whole cohort 1.9% vs. 2% (p=1.00) and 2.7% vs. 1.3% (p=.66), respectively; b) ≥80 years old 3.7% vs. 0% (p=1.00) and 4% vs. 5.9% (p=1.00), respectively; c) <80 years old 1.2% vs. 3.3% (p=.47) and 2.5% vs. 0% (p=.55), respectively. The 3-year survival estimates were significantly lower for males (84% vs. 92%, p=.03). After stratification by age groups, males maintained inferior survival rates in the strata aged <80 years (85% vs. 97%, p=.005), while no differences were seen in the strata aged ≥80 years (82% vs. 79%, p=.92). Using multivariate Cox proportional hazards, age (HR: 2.1, 95% CI: 1.29-3.3, p=.002) and male gender (HR: 2.5, 95% CI: 1.16-5.5, p=.02) were associated with increased hazards of all-cause mortality. Conclusions: In this study of elective CEA for asymptomatic and symptomatic carotid stenosis, similar peri-operative neurologic outcomes were found in both males and females irrespective of age. Despite being usually older, females have superior long-term survival rates.

Contrast Enhanced Ultrasound (CEUS) Is Not Able to Identify Vulnerable Plaques in Asymptomatic Carotid Atherosclerotic Disease.

OBJECTIVES: Contrast enhanced ultrasound (CEUS) has been suggested as an imaging tool for detection of asymptomatic carotid atherosclerotic disease (ACAD) at high risk of cerebral embolisation. The objective of this study was to evaluate CEUS and immunohistochemical (IHC) patterns in ACAD (i.e., without any neurologic symptoms in the last 6 months) and their correlations with histology. METHODS: CEUS analysis was classified on a semiquantitative basis using a three-point classification scale. Plaque morphology was assessed using the American Heart Association (AHA) classification of atherosclerotic plaques, then accordingly assigned as non-vulnerable (AHA Type IV/V) or vulnerable (AHA Type VI). IHC analysis for intra-plaque neo-angiogenesis (IPN) was identified by CD34/VEGF immunostaining and classified on a semiquantitative basis using a four-point classification scale. Both CEUS and IHC analyses were performed and scored by single observers. RESULTS: Fifty-eight consecutive asymptomatic patients (mean age 73 years, 33 males) undergoing carotid endarterectomy were included in the final analysis. Nineteen had AHA Class IV/V plaques, and the remaining 39 had AHA Class VI plaques. There were two main findings of the study: (a) histologically proven vulnerable plaques compared with histologically proven non-vulnerable plaques had denser IPN (p = .004), but did not show more pronounced contrast enhancement; (b) the correlation between IHC analysis and CEUS analysis was significant for both vulnerable and non-vulnerable plaques (p = .04 and p = .01, respectively), but it was direct for AHA Type IV/V plaques and inverse for AHA Type VI plaques. CONCLUSIONS: The main findings of the study were that histologically proven vulnerable plaques (i.e., AHA Class VI) as compared with histologically proven non-vulnerable plaques (i.e., AHA Class IV/V) had denser neo-vascularisation, but not more pronounced contrast enhancement.

Are aortic coarctation and rheumatoid arthritis different models of aortic stiffness? Data from an echocardiographic study.

BACKGROUND: Patients who underwent a successful repair of the aortic coarctation (CoA) show high risk for cardiovascular (CV) events. Mechanical and structural abnormalities in the ascending aorta (Ao) might have a role in the prognosis of CoA patients. We analyzed the elastic properties of Ao measured as aortic stiffness index (AoSI) in CoA patients in the long-term period and we compared AoSI with a cohort of 38 patients with rheumatoid arthritis (RA) and 38 non-RA matched controls. METHODS: Data from 19 CoA patients were analyzed 28 ± 13 years after surgery. Abnormally high AoSI was diagnosed if AoSI > 6.07% (95th percentile of the AoSI detected in our reference healthy population). AoSI was assessed at the level of the aortic root by two-dimensional guided M-mode evaluation. RESULTS: CoA patients showed more than two-fold higher AoSI compared to RA and controls (9.8 ± 12.6 vs 4.8 ± 2.5% and 3.1 ± 2.0%, respectively; all p < 0.05 and in 5 of 19 patients with CoA (26%) AoSI was exceptionally high. The 5 patients with abnormally high AoSI were older with higher BP, LV mass and prevalence of LV diastolic dysfunction. Multiple linear regression analysis revealed that AoSI was independently related to the presence of LV hypertrophy and higher LV relative wall thickness. CONCLUSIONS: CoA patients have higher AoSI levels than RA patients and non-RA matched controls. AoSI levels are abnormally high in a small sub-group of CoA patients who show a very high-risk clinical profile for adverse CV events.

Echocardiographic markers of inducible myocardial ischemia at baseline evaluation preparatory to exercise stress echocardiography.

BACKGROUND: Tissue Doppler Imaging (TDI) is a sensible and feasible method to detect longitudinal left ventricular (LV) systolic dysfunction (LVSD) in patients with diabetes mellitus, hypertension or ischemic heart disease. In this study, we hypothesized that longitudinal LVSD assessed by TDI predicted inducible myocardial ischemia independently of other echocardiographic variables (assessed as coexisting potential markers) in patients at increased cardiovascular (CV) risk. METHODS: Two hundred one patients at high CV risk defined according to the ESC Guidelines 2012 underwent exercise stress echocardiography (ExSEcho) for primary prevention. Echocardiographic parameters were measured at rest and peak exercise. RESULTS: ExSEcho classified 168 (83.6 %) patients as non-ischemic and 33 (16,4 %) as ischemic. Baseline clinical characteristics were similar between the groups, but ischemic had higher blood pressure, received more frequently beta-blockers and antiplatelet agents than non-ischemic patients. The former had greater LV size, lower relative wall thickness and higher left atrial systolic force (LASF) than the latter. LV systolic longitudinal function (measure as peak S') was significantly lower in ischemic than non-ischemic patients (8.7 ± 2.1 vs 9.7 ± 2.7 cm/sec, p = 0.001). The factors independently related to myocardial ischemia at multivariate logistic analysis were: lower peak S', higher LV circumferential end-systolic stress and LASF. CONCLUSIONS: In asymptomatic patients at increased risk for adverse CV events baseline longitudinal LVSD together with higher LV circumferential end-systolic stress and LASF were the factors associated with myocardial ischemia induced by ExSEcho. The assessment of these factors at standard echocardiography might help the physicians for improving the risk stratification among these patients for ExSEcho.

Clinical profile and outcome of patients with rheumatoid arthritis and abnormally high aortic stiffness.

OBJECTIVES: Ascending aorta has an increased stiffness (AoSI) in rheumatoid arthritis (RA) patients due to their chronic inflammatory status. We assessed prevalence and factors associated with increased AoSI and its prognostic role in a large cohort of RA patients. METHODS: We prospectively analysed 226 RA patients without overt cardiac disease compared with 226 non-RA patients matched for cardiovascular risk factors (non-RA controls). Abnormally high AoSI was diagnosed if AoSI > 6.07% (95th percentile of the AoSI detected in our reference healthy population). AoSI was assessed at the level of the aortic root by two-dimensional guided M-mode evaluation as part of a thorough echocardiography performed in all patients. RESULTS: AoSI was significantly higher in the RA patients than non-RA controls (6.3 ± 4.5% vs. 4.6 ± 3.5%, p < 0.001); it was related to older age, higher systolic blood pressure and RA disease. Predictors of AoSI in RA patients were older age, higher systolic blood pressure and the non-prescription of non-steroidal anti-inflammatory drug and/or immunomodulatory/anti-cytotoxic agents. Abnormally high AoSI was diagnosed in 41% RA patients and 21% non-RA controls (p < 0.001). The RA phenotype with abnormally high AoSI was a > 60 years old subject with systolic blood pressure > 129 mmHg, mitral annular calcification who was not receiving non-steroidal anti-inflammatory drug. By multivariate Cox regression analysis abnormally high AoSI independently predicted death or all-cause hospitalization (hazard ratio 2.85 (95% confidence interval 1.03-7.85)) at 12-month follow-up. CONCLUSIONS: Increased AoSI is common, can be predicted by an ordinary clinical assessment and is a strong predictor of adverse clinical outcome at mid-term follow-up in patients with RA.

Radial pseudoaneurysm after a puncture for blood gas analysis.

Radial pseudoaneurysm (PA) is a rare complication of the transradial approach for the arterial catheterization.

Insights from Cardiac Mechanics after Three Decades from Successfully Repaired Aortic Coarctation.

BACKGROUND AND AIMS: Patients who underwent a successful repair of the aortic coarctation show chronic hyperdynamic state and normal left ventricular (LV) geometry; however, there are few data regarding the LV systolic function in the long term. Accordingly, we assessed LV systolic mechanics and factors associated with LV systolic dysfunction (LVSD) in patients with repaired CoA. METHODS: Clinical and echocardiographic data from 19 repaired CoA were analyzed 28 ± 13 years after surgery. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (S') were analyzed as indexes of LV circumferential and longitudinal systolic function, respectively. Echocardiographic data of CoA patients were compared with 19 patients matched for age and hypertension and 38 healthy controls. Sc-MS was considered impaired if <89%, S' if <8.5 cm/s (10th percentiles of healthy controls, respectively). RESULTS: There were no statistical differences between study groups in LV volumes, mass and geometry. LV ejection fraction and Sc-MS were similar in all groups, however, CoA group had a significantly lower peak S' in comparison with matched and healthy controls (7.1 ± 1.3, 10.3 ± 1.9, and 11.1 ± 1.5, respectively; all P < 0.001). Prevalence of longitudinal LVSD defined as low S' was 84% in CoA, 13% in matched, and 5% in healthy control group (all P<0.05). Multivariate logistic regression analysis revealed that low peak S' was independently related to higher E/E' ratio and the presence of CoA. CONCLUSIONS: Patients who underwent a successful repair of CoA commonly show asymptomatic longitudinal LVSD associated with worse LV diastolic function in the long-term follow-up.

MMP-9 microsatellite polymorphism and susceptibility to carotid arteries atherosclerosis.

OBJECTIVE: The aims of this study were to compare a microsatellite polymorphism (PM) of matrix metalloproteinase (MMP)-9 in patients with carotid atherosclerosis and control population, and to assess the relationship between this PM and plaque structure. METHODS AND RESULTS: One hundred fifty patients referring to vascular diagnostic centers for suspected carotid atherosclerosis (at ultrasound examination: 110 positive, 40 negative) and controls (n=110) have been genotyped for MMP-9 PM. After controlling for risk factors, allelic and genotype frequencies were significantly different among the groups, with significant prevalence of long microsatellites in patients with carotid atherosclerosis. Long microsatellites (settled as 22 to 27 repeats) were associated with carotid atherosclerosis (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.9 to 9.2), compared with controls; an independent case control study on patients with coronary atherosclerosis confirmed such result. Binary logistic regression showed that hypertension, long microsatellites in MMP-9 PM and smoking habits were variables accounting for the difference between ultrasound-positive patients and controls. Long microsatellites were also associated to plaques with thin fibrous cap and echolucent core (OR, 13.1; 95% CI, 1.6 to 100). These alleles were slightly more represented in female patients (chi2 test=0.019; OR, 2.7; 95% CI, 1.2 to 6) but not associated with other risk factors. Plasma MMP-9 levels were related neither to MMP-9 PM nor to plaque type, and were related to gender and extension of atherosclerosis in carotid arteries. CONCLUSIONS: The number of repeats (> or =22 CA) in the microsatellite of MMP-9 promoter, but not MMP-9 plasma levels, is associated to carotid atherosclerosis and particularly to plaques with a thin fibrous cap.

MMP-9 microsatellite polymorphism: association with the progression of intima-media thickening and constrictive remodeling of carotid atherosclerotic plaques.

Intima-media thickening (IMT) of carotid arteries and constrictive remodeling (CR) of atherosclerotic plaques are vascular pathologic characteristics that precede the onset of vascular events. SMC migration and proliferation are linked both to IMT and CR and are matrix metalloproteinase 9 (MMP-9) dependent. A genetic polymorphism (PM) of MMP-9, a CA (13-27) microsatellite in the promoter region, which accounts for differential expression of MMP-9, could be linked to progression of IMT and CR. Progression of IMT and CR of plaques in carotid arteries were studied in 55 consecutive patients with a 12-18 months follow-up. All patients were genotyped for MMP-9 PM. A positive linear relationship between the number of repeats and the progression of IMT (P=0.028) as well as of CR (P=0.018) was found. The analogous relationship was obtained when only the allele with longer microsatellite was considered. Carriers of more than 20 repeats in one allele showed faster both IMT growth (P=0.045) and stenosis progressions of plaques (P=0.019). In multivariate analysis, age, dyslipidemia, and MMP-9 PM were determinants of IMT progression, while MMP-9 PM was the only one of CR. In conclusion, the high number of CA repeats in MMP-9 promoter is positively correlated with faster IMT and CR progression.

Percutaneous revascularization of femoropopliteal artery disease: PTA and PTA plus stent. Results after six years' follow-up.

PURPOSE: To compare the long-term patency after the treatment of mild-to-moderate femoropopliteal artery disease by percutaneous transluminal angioplasty (PTA) alone (PTA group) and PTA plus stenting (STENT group) in a non-randomised retrospective study. MATERIALS AND METHODS: Eighty-six limbs in 64 patients (mean age 67+/-8 years, 47 males and 17 females) with femoropopliteal artery disease and symptomatic for mild-to-moderate intermittent claudication (Rutherford's category 1-2) were treated by percutaneous revascularization. None of the patients had critical lower limb ischaemia. Of the 86 lesions, 63 (40 stenoses and 23 occlusions) were treated by PTA alone and 23 (12 stenoses and 11 occlusions) by PTA plus stent implantation. The success was defined as a maximal = or < 30% residual stenosis of vessel lumen diameter, as defined by biplane angiography. The angiography findings were confirmed by colour-Doppler sonography of the treated segment. A peak systolic velocity = or < 150 cm/sec in the treated segment and an improvement of the ankle/brachial index by gs; 0.15 were considered indications of haemodynamic success. Restenosis at follow-up (mean 21 months, range 1-72 months) was defined by colour-Doppler sonography as a peak systolic velocity gs; 230 cm/sec or a peak systolic velocity ratio gs; 2.5 in the treated area and a gs; 0.15 decrease in ankle/brachial index compared with post-procedure measurements. RESULTS: Treatment by PTA plus stenting enabled correction of residual stenosis in 15/23 limbs, relief of PTA complications in 7/23 limbs and correction of restenosis after a PTA in 1/23. In the PTA group the treatment was successful in 59/86 limbs (68%) versus 21/23 (91%) in the STENT group (chi squared value= 0,04). As a whole, major complications occurred in 5.8% of cases (n=5), 3 in the PTA group and 2 in the STENT group. The primary patency rates at 6, 12, and 24 months were 70%, 66% and 58% in the PTA group versus 74%, 67% and 46% in the STENT group (Gehan p value=0.96). The secondary patency rates at 6, 12, 24 months were 75%, 73%, 65% in the PTA group versus 84%, 76%, 64% in the STENT group (Gehan p value=0,59). DISCUSSION AND CONCLUSIONS: In this study, stenting and PTA for the treatment of mild-to-moderate femoropopliteal peripheral artery disease improved the primary technical success of PTA by correcting residual stenosis, elastic recoil and occlusive intimal flaps. Moreover, stenting can prevent delayed constrictive remodelling. However, stenting did not improve long-term outcomes in comparison with PTA alone given that stent implantation increases the risk of restenosis due to myointimal hyperplasia. Our findings regarding the complication rates and long-term outcome agree with those published by other authors. Colour-Doppler US monitoring enabled early detection of restenosis in the treated area and its differentiation from the development of new lesions in other areas.

[Why are cardiologists to be concerned about obliterating arterial disease of the lower leg?]. / Perché il cardiologo deve occuparsi dell'arteriopatia obliterante degli arti inferiori?

Peripheral arterial disease, which is caused by atherosclerotic stenosis or occlusion of the leg arteries, is an important manifestation of systemic atherosclerosis. The age-adjusted prevalence of symptomatic and asymptomatic peripheral arterial disease is approximately 12% in the general population. The overall prevalence and incidence of the disease is likely to increase with the aging of the population. Peripheral arterial disease is a relatively benign condition in terms of local disease. Five years after the diagnosis, 75% of the patients remain clinically stable. On the contrary, life expectancy, even in the absence of any history of myocardial infarction or ischemic stroke, has decreased by 10 years. These patients have approximately the same relative risk of death from cardiovascular causes as do patients with history of coronary or cerebrovascular disease. Moreover, the severity of peripheral arterial disease is closely associated with the risk of myocardial infarction and death from vascular disease. The lower the ankle-brachial index, the greater the risk of cardiovascular events. Furthermore, peripheral arterial disease is a significant independent predictor for cardiovascular mortality also in coronary patients. The risk factors associated with peripheral arterial disease are essentially the same as for coronary heart disease: older age, cigarette smoking, diabetes mellitus, hypertension, and hyperlipidemia. The excess morbidity and mortality for cardiovascular disease in these patients has not been fully explained. Patients with peripheral arterial disease show a systemic endothelial dysfunction and an increase in the serum concentration of activated white blood cells, endothelin, and C-reactive protein that may trigger acute coronary syndromes. In peripheral arterial disease the functional status is often severely impaired. Peak exercise performance has decreased to about 50% of that of age-matched controls, equivalent to moderate-severe heart failure. Epidemiological studies support the concept that patients affected by peripheral arterial disease, without established coronary heart disease, have a coronary heart disease high risk equivalent. In spite of this, peripheral arterial disease remains an underdiagnosed and undertreated disease. As the role of cardiologists is expanding, the purpose of this review was to awaken the clinician to the significance of lower limb atherosclerotic occlusive diseases.

[Control of anticoagulant therapy with portable prothrombin time device in patients with mechanical heart valve prostheses: two-year follow-up]. / Il trattamento anticoagulante con coagulometro portatile nei pazienti portatori di protesi valvolari meccaniche: un follow-up di due anni.

BACKGROUND: Monitoring patients on oral anticoagulation is essential to prevent haemorrhage and recurrent thrombosis, but it is still difficult. We studied a group of 348 patients with mechanical heart valve prostheses to verify whether the use of a new portable prothrombin time device might improve the management of oral anticoagulant therapy. METHODS AND MATERIAL: We used a new portable prothrombin time device to check the anticoagulation therapy in a group of 348 patients with mechanical heart valve prostheses to validate its results by comparing to routine I.N.R. determinations (28 pts) and verify its user-friendliness by a face-to-face interview. Furthermore, the incidence of haemorrhagic and thromboembolic events has been studied by a two-year follow-up. RESULTS: Pearson correlation indicated an R2 = 0.9 between I.N.R. values determined by routine or by a new portable prothrombin time device. All patients agreed to replace the routine I.N.R. determinations with those by the new procedure, particularly female, young and those with usually difficult blood collections. During the two-year follow-up period, 21 haemorrhagic (2.6/100/patients/year) and 5 thromboembolic events (0.6/100/patients/year) occurred; but neither replaced valves' thrombi nor fatal events were found out. CONCLUSIONS: I.N.R.s determined using a new portable prothrombin time device are convincing as routine determinations. Such new procedure improves the quality of life, and the therapeutical range of anticoagulation is maintained safer and longer than by routine determinations. These results suggest that the control of anticoagulation in patients to a set I.N.R. therapeutic range is improved by using portable prothrombin time device in expert anticoagulation clinics, such improvement may result in reducing mortality as well as morbidity in patients treated with oral anticoagulants.