Measurement of somatostatin receptor subtype 2 mRNA in breast cancer and corresponding normal tissue

Somatostatin analogs are effective in inhibiting growth of human breast cancer cell lines. These antiproliferative effects are mediated by specific receptors located on cell membranes. The somatostatin receptor subtype 2 (sst2) is the principal mediator of somatostatin effects in normal and cancer cells, and its presence has already been demonstrated in breast cancer. The purpose of our study was to evaluate the clinical relevance of the expression of sst2 by quantifying its mRNA in a large group of infiltrating breast cancers and their corresponding normal tissues. The expression of sst2 mRNA was measured with quantitative real time RT-PCR in 169 breast cancers and in their corresponding unaffected tissues. We evaluated the association of sst2 expression with the commonest clinical-pathologic features of breast cancer. The correlation with a marker of cell proliferation (Ki-67) and with receptor concentration was also evaluated. In cancer tissues, we found that the absolute concentrations of sst2 mRNA were significantly higher in estrogen receptor (ER)-positive samples (P=0.002) as well as in lymph-node-negative cancers (P=0.04) (Student's t-test or one-way ANOVA). In addition, sst2 mRNA was significantly higher in breast cancers than in corresponding unaffected tissues (P=0.0002). However, when the clinical-pathologic parameters were considered, this gradient maintained its statistical significance only in tumors expressing positive prognostic markers, such as the presence of ER (P=0.0005) and progesterone receptors (PgR) (P=0005), and the lack of lymph-node involvement (P=0.0003). The same difference was also significant in postmenopausal women (P=0.001) and in T1 patients (P=0.001). In addition, sst2 mRNA expression was significantly higher (P=0.008) in low-proliferating breast cancers. Finally, we found that the quantitative expression of sst2 mRNA was directly related to the PgR concentration in breast cancer tissues (P<0.001). Our data seem to indicate that an upregulation of sst2 gene expression is a common feature of breast cancers which, on the basis of conventional predictive parameters, are expected to have a better prognosis. Featuring a possible role of somatostatin analogs in combined endocrine therapies for breast cancer, our results seem to confirm that the sst2 status of the tumor should be previously investigated.     

Epicardial adipose tissue is increased in patients with systemic lupus erythematosus

ObjectiveMorbidity and mortality secondary to premature cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) remain significant issues. The pathogenesis of CVD in SLE patients has not been fully explored. Epicardial adipose tissue (EAT) is believed to contribute to atherosclerosis development, through a paracrine and systemic inflammatory effect. We measured EAT volume in 162 SLE patients and 86 matched controls to assess the association of EAT with markers of atherosclerosis, cardiovascular risk and immunoactivation.MethodsClinical and laboratory characteristics collected included anthropomorphic measures, disease activity and damage indices, blood pressure measurement, lipid profile, inflammatory indices, adipokine levels and measures of adiposity. Coronary artery calcium (CAC) and EAT volume were measured using non-contrast cardiac computed tomography.ResultsEAT volume was greater in patients with SLE [(mean ± SD) 96.8 ± 45.9 cm³] than controls (78.2 ± 40.7 cm³; P = 0.001). The EAT volume was 31% larger (95% CI, 16.5%–47.4%) in SLE patients than controls (P < 0.001 adjusted for age, sex, and race; after additional adjustment for waist circumference P = 0.007). Within SLE patients, after adjusting for age, race, sex, and waist circumference, EAT volume was associated with cumulative corticosteroid dose (P = 0.007), current corticosteroid use (P < 0.001), HDL cholesterol (P = 0.033), and triglycerides (P = 0.005). EAT was significantly correlated with CAC score (P < 0.001), but the association was attenuated after adjustment for Framingham risk score (P = 0.051).ConclusionThe increased EAT volume seen in SLE patients is associated with corticosteroid use. Corticosteroids could have adverse cardiovascular effects in SLE via an increase in EAT volume, a marker of risk in the general population.     

Inverse Correlation Between Vascular Calcification and Bone Mineral Density in Human Immunodeficiency Virus-Infected Patients

HIV-infected individuals suffer from accelerated aging, which manifests as premature cardiovascular and bone disease. However, little is known of the association of these two disorders in the HIV population. Our objective was to investigate the association between a marker of atherosclerosis (coronary artery calcium [CAC]) and low bone mineral density (BMD) in a cross-sectional cohort of HIV-infected patients. The study was conducted at the University of Modena and Reggio Emilia, Italy. A total of 636 consecutive middle-aged, HIV-infected subjects were recruited between January 2006 and December 2010. All patients underwent CAC and BMD assessment. Patients were categorized according to a CAC score <100 or >100 units based on previous literature that identified this cut-point as a marker of increased risk. Low femoral and lumbar spine BMD was defined as <25th percentile value for the study cohort. Logistic regression and bootstrap analysis were used to assess the independent association between CAC and BMD. The main outcome measure was a CAC score >100. Patients with CAC > 100 were older and more likely to be men, diabetic, and overweight. Patients with CAC < 100 had better renal function and a lower cardiovascular risk profile. After adjusting for age, sex, traditional and HIV-specific risk factors, vitamin D level, and PTH level, there was a significant association between CAC > 100 and low BMD for the femur (OR = 2.33, 95 % CI 1.09–4.99; p = 0.02) but not for the spine. Bootstrap analyses confirmed these findings. In summary, CAC was independently associated with low femoral BMD in HIV-infected patients. Future studies should test whether therapies that attenuate cardiovascular risk in HIV favorably impact bone health.     

Approach to Cardiovascular Disease Prevention in Patients With Chronic Kidney Disease

OPINION STATEMENT: Chronic kidney disease (CKD) is associated with a large burden of cardiovascular risk factors ultimately leading to increased cardiovascular events and mortality. Prevention of cardiovascular disease (CVD) in CKD involves early identification of individuals at high-risk of renal disease. In fact, substantial evidence points to a complex bidirectional relationship between CKD and CVD. Therefore, most interventions directed at CKD prevention should include multiple risk factor interventions with the goal of preventing CVD events while slowing progression of CKD. Clearly, prevention of CVD in CKD is a complex task and requires a multidisciplinary team approach, with a well-defined program, rational targets for each risk factor, and implementation of the most effective intervention strategies. Although several interventions to prevent CVD have proven effective in the general population and in individuals at high risk for CVD, a true benefit in patients with CKD remains to be demonstrated for several of them. A few rational targets of intervention should be optimal blood pressure control, reduction of proteinuria, treatment of dyslipidemia, good control of diabetes, smoking cessation, dietary salt restriction, achievement of normal body mass index, partial correction of anemia, and management of mineral metabolism abnormalities. Lifestyle modification and pharmacological therapy with renin-angiotensin blockers, β-blockers, diuretics, statins, and aspirin should be encouraged in the early stages of CKD.     

Cinacalcet: will it play a role in reducing cardiovascular events?

Secondary hyperparathyroidism is a common complication of chronic kidney disease and it is associated with high morbidity and mortality. It is characterized by high parathyroid hormone levels and bone turnover leading to bone pain, deformity and fragility. Furthermore, secondary hyperparathyroidism adversely affects the cardiovascular system and has been associated with cardiovascular calcification and cardiomyopathy. Cinacalcet, a type II calcimimetic, is an effective and well-tolerated oral therapy for the management of secondary hyperparathyroidism. It is an allosteric activator of the calcium-sensing receptor enhancing sensitivity of parathyroid cells to extracellular calcium, which leads to inhibition of parathyroid hormone secretion. The calcium-sensing receptor expression in cardiomyocytes, endothelial cells and vascular smooth muscle cells raises the possibility that this receptor may be implicated in the pathophysiology of cardiovascular disease and constitute a potential therapeutic target. This article reviews the role of the calcimimetic agent cinacalcet in the prevention and progression of cardiovascular calcification and uremic cardiomyopathy in the chronic kidney disease setting.     

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.     

Canadian Cardiovascular Society Guidelines for the Diagnosis and Management of Stable Ischemic Heart Disease

This overview provides a guideline for the management of stable ischemic heart disease. It represents the work of a primary and secondary panel of participants from across Canada who achieved consensus on behalf of the Canadian Cardiovascular Society. The suggestions and recommendations are intended to be of relevance to primary care and specialist physicians with an emphasis on rational deployment of diagnostic tests, expedited implementation of long- and short-term medical therapy, timely consideration of revascularization, and practical follow-up measures.     

Anatomical features of tibia and femur: Influence on laxity in the anterior cruciate ligament deficient knee

Background

Until now, there has been a lack of in vivo analysis of the correlation between bony morphological features and laxity values after an anterior cruciate ligament (ACL) injury.