Cardiovascular and autoimmune diseases in females: The role of microvasculature and dysfunctional endothelium.

Cardiovascular (CV) diseases are becoming increasingly frequent and associated with a high incidence of CV events, disability and death. It is known that there is a relationship between CV burden and systemic autoimmune diseases (SADs) that is mainly due to inflammation and autoimmunity, but the other mechanisms underlying the high CV risk of SAD patients have not yet been fully clarified. The aim of this review article is to discuss some of the specific factors associated with the accelerated atherosclerosis (ATS) characterising SADs (female sex, the microcirculation and the endothelium) in order to highlight the importance of an early diagnosis and the prompt implementation of preventive measures, as well as the possible role of new therapeutic strategies such as vaccine immunomodulation. Finally, as the natural history of ATS begins with endothelial injury (a potentially reversible process that is influenced by various factors) and microvascular damage plays a central role in the etiopathogenesis of SADs, it underlines the crucial need for the development of reliable means of detecting sub-clinical abnormalities in the microcirculation, particularly coronary microcirculation dysfunction.

New parameters for identifying subclinical atherosclerosis in patients with primary Sjögren's syndrome: a pilot study.

OBJECTIVES: We investigated sub-clinical cardiovascular involvement in primary Sjögren's syndrome (pSS) patients by means of ADMA, coronary flow reserve (CFR), intima media thickness (cIMT), pulse wave velocity (PWV) and myocardial deformation. METHODS: The study involved 22 outpatients with pSS (6 males, 16 females; mean age 60.14±7.81 years) and no documentable cardiovascular disease, and 22 age- and gender-matched controls. Dipyridamole transthoracic stress echocardiography was used to evaluate wall motion and CFR. A CFR value of <2.5 was considered a sign of impaired coronary function. We also evaluated cIMT arterial stiffness PWV and plasma ADMA levels, and made a speckle tracking echocardiography (STE) analysis. RESULTS: All of the patients were affected by pSS. Although within the normal range, the patients' CFR was lower than that of the controls (median 2.70; IQR 2.40-2.90 vs. 3.20; IQR 3.06-3.33; p<0.0001), whereas their ADMA levels were significantly higher (median 0.81 µM; IQR 0.79-0.85 µM vs. 0.54 µM; IQR 0.52-0.58 µM; p<0.0001). Both left and right PWV values were significantly higher in the patients than in the controls (median 8.8 m/s right and 8.9 m/s left vs. 6.86 and 6.89 m/s), whereas QIMT was substantially similar in the two groups. CONCLUSIONS: Higher ADMA levels suggest the presence of endothelial dysfunction and sub-clinical atherosclerosis in pSS patients, even in the case of a normal CFR. This finding is supported by the PWV values, which were higher in the pSS patients. ADMA levels and PWV values may be useful markers for identifying early endothelial dysfunction in pSS patients.

Effects of long-term disease-modifying antirheumatic drugs on endothelial function in patients with early rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease and cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality. It is well known that disease modifying antirheumatic drugs (DMARDs) are able to improve the course of the disease and the quality of life of these patients, but little is known about the effects of DMARDs on CV risk and endothelial dysfunction. Our goal was to examine the effects of long-term therapy with DMARDs on endothelial function and disease activity in early RA (ERA). Twenty-five ERA patients (mean age 52 ± 14.6 years, disease duration 6.24 ± 4.10 months) without evidence of CV involvement were evaluated for disease activity score (DAS-28), 2D-echo derived coronary flow reserve (CFR), common carotid intima-media thickness (IMT) and plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 18 months of treatment with DMARDs (10 patients with methotrexate and 10 with adalimumab). DMARDs significantly reduced DAS-28 (6.0 ± 0.8 vs. 2.0 ± 0.7; P < 0.0001) and improved CFR (2.4 ± 0.2 vs. 2.7 ± 0.5; P < 0.01). Common carotid IMT and plasma ADMA levels did not show significant changes. The present study shows that DMARDs, beyond the well known antiphlogistic effects, are able to improve coronary microcirculation without a direct effect on IMT and ADMA, clinical markers of atherosclerosis. Treatment strategies in ERA patients with high inflammatory activity must be monitored to identify beneficial effects on preclinical markers of vascular function.

[Cardiac involvement in rheumatoid arthritis]. / Il coinvolgimento cardiaco nell'artrite reumatoide.

Rheumatoid arthritis (RA) is a systemic disease of unknown etiology characterized by a chronic inflammatory process mainly leading to destruction of synovial membrane of small and major diarthrodial joints. The prevalence of RA within the general adult population is about 1% and female subjects in fertile age result mostly involved. It's an invalidating disease, associated with changes in life quality and a reduced life expectancy. Moreover, we can observe an increased mortality rate in this population early after the onset of the disease. The mortality excess can be partially due to infective, gastrointestinal, renal or pulmonary complications and malignancy (mainly lung cancer and non-Hodgkin lymphoma). Among extra-articular complications, cardiovascular (CV) involvement represents one of the leading causes of morbidity and mortality. Every cardiac structure can be affected by different pathogenic pathways: heart valves, conduction system, myocardium, endocardium, pericardium and coronary arteries. Consequently, different clinical manifestations can be detected, including: pericarditis, myocarditis, myocardial fibrosis, arrhythmias, alterations of conduction system, coronaropathies and ischemic cardiopathy, valvular disease, pulmonary hypertension and heart failure. Considering that early cardiac involvement negatively affects the prognosis, it is mandatory to identify high CV risk RA patients to better define long-term management of this population.

Cigarette smoking and ambulatory blood pressure: a case-control study in normotensives.

The aim of our study was the evaluation of the effects of cigarette smoking on ambulatory blood pressure (ABP) in normotensive subjects participating to a cardiovascular prevention program. All subjects were followed up for an average time of 97+/-42 months to assess the event of hypertension development. Prevalence of hypertension development was higher in smokers even if regression logistic analysis was not able to predict hypertension development.

Evaluation of systolic blood pressure control in elderly patients with isolated systolic hypertension.

The aim of this retrospective study was the evaluation of systolic blood pressure (SBP) control in elderly patients (pts) with isolated systolic hypertension (ISH). We assessed SBP control (i.e. average of 2 clinic BP measurements < 140 mmHg) in 152 pts (44 M, 108 F, 75 +/- 6 years) with ISH (149/84 +/- 17/6 mmHg), treated for at least 3 months by general practitioners or specialists with treatments of their choice. Most antihypertensive drugs were used at starting doses in monotherapy or combination treatment, as usual in clinical practice. ECG was abnormal in 82/152 pts (54.0%). All pts were divided in 2 groups according to SBP control. The 2 groups were compared by chi-square test for categorical variables and by Mann-Whitney test for quantitative variables. A p value < 0.05 was considered statistically significant. The global SBP control rate was 41.4% (63/152 pts). BP was higher in pts with poor SBP control, as expected, but the 2 groups were similar for sex distribution, age, prevalence of other cardiovascular risk factors and type of care (general practitioner or specialist). Pts with poor SBP control had a higher prevalence of abnormal ECG tracings (p = 0.003), a lower prevalence of combination regimes (p = 0.007) and prescriptions of dihydropyridine calcium antagonists or thiazide diuretics (p = 0.006). Global SBP control rate in our retrospective study in pts with ISH was unsatisfactory. Use of dihydropyridines or thiazides, drugs of choice in the management of ISH according to ESH/ESC and JNCVII guidelines, as single drugs or in combination regimes, can improve BP control and prevent cardiac damage.

Atherectomy of the subclavian artery for patients with symptomatic coronary-subclavian steal syndrome.

OBJECTIVES: This study addresses the efficacy of directional atherectomy in the subclavian artery for the relief of angina in patients with the coronary-subclavian steal syndrome. In addition, we review the histologic findings from the atherectomy specimens. BACKGROUND: The coronary-subclavian steal syndrome may occur after internal mammary-coronary artery bypass grafting. It is due to a stenosis in the subclavian artery proximal to the origin of the internal mammary artery and causes frank ischemia to the area supplied by the graft. Currently, surgery is the corrective procedure of choice. METHODS: In three patients with severe subclavian artery stenoses and unstable angina, directional atherectomy was performed using a peripheral atherectomy catheter through a percutaneous femoral approach. The patients ranged from 43 to 71 years of age and had undergone internal mammary-coronary artery bypass grafting 3 to 10 years previously. Each patient had severe peripheral vascular and cerebrovascular disease. RESULTS: All three patients had immediate symptomatic relief after the atherectomy, and postprocedure exercise testing demonstrated improved cardiac function. Two patients remain asymptomatic at 7 and 8 months, respectively; the third patient developed unstable angina 9 months later because of severe restenosis that was again successfully treated with atherectomy. Histologic examination of the specimens revealed atherosclerotic plaque, occasionally with adventitia. The specimen from the repeat atherectomy showed severe intimal hyperplasia. CONCLUSIONS: Directional atherectomy appears to be a safe and effective treatment for coronary-subclavian steal syndrome. This procedure may be the treatment of choice for patients in whom a vascular bypass operation is not feasible.

The Simon nitinol filter: evaluation by MR and ultrasound.

In this prospective blinded study of inferior vena caval (IVC) patency, 18 patients underwent 25 duplex ultrasound (US) and magnetic resonance (MR) angiography examinations over an eight-month period following Simon nitinol filter placement. Clinical examination for lower extremity venous stasis and plain abdominal radiography were also performed. Twenty-three of 24 MR examinations and 11 of 24 US examinations were judged technically adequate by the blinded observers. One technically adequate US exam was false positive for intraluminal caval thrombus. Thirteen technically inadequate US examinations missed 3 complete caval occlusions and 2 partial occlusions. MR identified all patients with complete or partial caval occlusion. The authors conclude that duplex US reliably confirms IVC patency only when strict criteria for technical adequacy and interpretation are met (good visualization of filter and IVC above and below filter). MR, although expensive, more reliably identifies nonoccluding intraluminal thrombus and caval occlusion. It should be the noninvasive study of choice in symptomatic patients with venous stasis and patients with recurrent pulmonary emboli.

Peripheral directional atherectomy: 4-year experience.

Directional atherectomy alone or with supplemental percutaneous transluminal angioplasty was used to treat peripheral vascular lesions in 77 patients (85 procedures). Lesions involved 17 iliac arteries, 45 infrainguinal arteries, and 23 laser extremity vein bypass grafts. Technical success, defined as reduction of stenosis diameter to 30% or less of the normal vessel diameter, was achieved in 78 of 85 (92%) cases. The complication rate was 21% (18 of 85 procedures). Most complications were minor and were related to puncture sites. Patients underwent noninvasive follow-up studies, including measurement of ankle-brachial index and segmental pressures, plethysmography, and clinical examination. The mean follow-up period was 13.5 months. The probability of 1-, 2-, and 3-year patency for lesions treated with atherectomy alone was 92%, 84%, and 84%, respectively. Kaplan-Meier survival analysis revealed no difference in 2- to 3-year patency rate on the basis of lesion location or presence of calcification, eccentricity, or ulceration. Diabetic patients, however, had a higher restenosis rate than did patients who were not diabetic (P less than .03).

Sciatic neuropathies in childhood: a report of ten cases and review of the literature.

Primary lesions affecting the sciatic nerve are uncommon, especially in children. Isolated sciatic nerve involvement was found in ten patients during an 8 1/2-year period at a metropolitan children's hospital. Etiologic mechanisms included three with compression and one each with stretch injury after operation using the lithotomy position, stretch injury after closed reduction of hip dislocation, puncture wound, lymphoma, hypersensitivity vasculitis associated with hypereosinophilia, indeterminate lesion associated with transverse myelitis, and idiopathic progressive lesion with negative findings on exploration. Neonatal injuries associated with breech delivery or intragluteal injections were not causative factors in this series. Children with sciatic neuropathies have a variable prognosis depending on the etiology. Compression was the only potentially preventable pathophysiologic mechanism.