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In the general population, low body weight and body mass index (BMI) are significant risk factors for any fracture, but the specific association between body weight, BMI, and prevalence of vertebral fractures in osteoporotic women is not fully recognized. Hence, the association between body weight, BMI, and prevalent vertebral fractures was investigated in 362 women with never-treated postmenopausal osteoporosis. All participants underwent measurement of BMI, bone mineral density (BMD), and semiquantitative assessment of vertebral fractures. Thirty percent of participants had ≥1 vertebral fracture. Body weight and BMI were associated with L1-L4 BMD (R = 0.29, P < 0.001 and R = 0.17, P = 0.009, respectively). In logistic regression analysis, BMI was positively associated with the presence of vertebral fractures independent of age and other traditional risk factors for fractures. Including weight and height instead of BMI in the multivariate model, showed weight as a positive and significant covariate of the presence of vertebral fractures (OR = 1.045; P = 0.016; 95% CI 1.008-1.084). BMI was associated with the number of vertebral fractures (rho = 0.18; P = 0.001), this association being confirmed also in the multivariate analysis (β = 0.14; P = 0.03) after correction for smoking, early menopause, family history of fragility fractures and BMD. In conclusion, among postmenopausal women with osteoporosis, body weight and BMI are associated with a higher likelihood of having a vertebral fracture, irrespective of the positive association between weight and BMD.

Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.

Cholesterol elevations are associated with systemic inflammation and endothelial fragmentation into microparticles. The cholesterol-lowering efficacy of nutraceutical combinations (NC) has not been investigated in patients with low-grade systemic inflammation and normal-borderline cholesterol levels. This is a 3-month prospective randomized open-label interventional study in patients with elevated plasma high sensitivity C-reactive protein (hsCRP) levels (>2 mg/L) and low-density lipoprotein (LDL) cholesterol of 100–160 mg/dL. The effect of either an oral cholesterol-lowering nutraceutical combination (NC) or no active treatment (noNC) was tested on LDL cholesterol, hsCRP and endothelial microparticle (EMPs) levels. Patients taking the NC had a significant reduction of total (−12%) and LDL cholesterol (−23%) compared to those who received noNC (p < 0.001 for both). Also, hsCRP and EMPs were significantly reduced by the NC (−41% and −16%, respectively). LDL cholesterol change was positively associated with hsCRP (rho = 0.21, p = 0.04) and EMP changes (rho = 0.56, p < 0.001), hsCRP and EMP changes being associated with each other (rho = 0.28, p = 0.005). Patients experiencing both LDL cholesterol and hsCRP reduction were those having the greatest EMP decrease. In conclusion, among patients with low-grade systemic inflammation, an oral NC significantly improved cholesterol profile and attenuated the degree of systemic inflammation and endothelial injury.

Abstract Background Experimental CCR5 antagonism with maraviroc in atherosclerosis-prone mice and preliminary data in humans suggest an anti-atherosclerotic effect of the drug. We assessed the impact of maraviroc treatment in persons living with HIV on subclinical indicators of atherosclerosis. Methods Persons living with HIV on effective antiretroviral therapy (ART) including only protease inhibitors were recruited if they had a Framingham risk score >20% and brachial flow-mediated dilation (bFMD) <4%, as indices of high cardiovascular risk. Maraviroc (300 mg per os for 24 weeks) was administered, in addition to ongoing ART, to all patients using a crossover design. Brachial FMD, carotid-femoral pulse wave velocity (cfPWV), and carotid intima-media thickness (cIMT) were measured as markers of atherosclerosis. Vascular competence—as expressed by the ratio of circulating endothelial microparticles (EMPs) to endothelial progenitor cells (EPCs)—and markers of systemic inflammation and monocyte and platelet activation were assessed. Results Maraviroc treatment significantly improved bFMD, cfPWV, and cIMT by 66%, 11%, and 13%, respectively (P = .002, P = .022, P = .038, respectively). We also found a beneficial effect of maraviroc on the EMP/EPC ratio (P < .001) and platelet/leucocyte aggregates (P = .013). No significant changes in markers of systemic inflammation, monocyte activation, and microbial translocation were observed. Conclusions Maraviroc led to significant improvements in several markers for cardiovascular risk, endothelial dysfunction, arterial stiffness, and early carotid atherosclerosis, which was accompanied by an increase of vascular competence, without seeming to affect systemic inflammation. Our data support the need for larger studies to test for any effects of maraviroc on preventing atherosclerosis-driven pathologies.

Endothelial dysfunction, a marker of cardiovascular (CV) risk, is common in human immunodeficiency virus (HIV)-infected patients. Microalbuminuria is frequent in HIV-infected patients and is a predictor of renal impairment and CV risk. We investigated the association between microalbuminuria and endothelial dysfunction among HIV-infected patients receiving highly-active antiretroviral therapy (HAART). Endothelial function, measured by brachial artery flow-mediated dilatation (bFMD) and urine albumin-to-creatinine ratio (UACR), were measured in 170 HAART-treated HIV-infected adults. The relationship between UACR and bFMD was evaluated. The prevalence of increased UACR, defined by two cut-off levels (20 mg/g and 30 mg/g), was 29% and 17%. UACR was significantly higher while bFMD was lower among patients with metabolic syndrome (MS). UACR was associated with bFMD (r = −0.31; p < 0.001). This association was stronger in MS-patients (r = −0.44; p = 0.003). UACR above 20 mg/g was associated with an increased risk (OR 2.37, 95% CI 1.15–4.89, p = 0.020) of severely impaired bFMD (bFMD ≤ 2.1%). Patients with MS and increased UACR had the lowest bFMD compared with those with none or one of the two conditions. Microalbuminuria and endothelial dysfunction are positively associated in HIV-infected patients regardless of known confounders. The coexistence of microalbuminuria and MS amplifies their deleterious influence on endothelial function.

Background Inflammatory rheumatic diseases have been associated with increased cardiovascular risk and arterial stiffness. Polymyalgia rheumatica (PMR), a disease which affects primarily older people, is characterised by a systemic inflammatory response but little is known about aortic involvement in PMR. A study was undertaken to investigate whether aortic stiffness is increased in PMR and whether it improves after steroid treatment. Methods Thirty-nine patients with PMR (age 72±8 years, 44% men, blood pressure (BP) 134/75±16/9 mm Hg) and 39 age-, sex- and BP-matched control subjects underwent aortic pulse wave velocity (PWV) determination. Aortic augmentation as a measure of the impact of the reflection wave on central haemodynamics was also measured and corrected for heart rate. Twenty-nine of the patients were re-examined after 4 weeks of treatment with prednisone at a dose of 15 mg/day. Results Aortic PWV was higher in patients with PMR than in control subjects (12.4±4 vs 10.2±2 m/s, p<0.01). Treatment was followed by a reduction in heart rate (from 78±12 to 70±10 beats/min, p<0.001) and no significant change in BP. Aortic PWV decreased after prednisone treatment (from 11.8±3 to 10.5±3 m/s, p=0.015), and the difference was independent of BP and heart rate changes. The change in aortic PWV had a direct correlation with percentage change in plasma C reactive protein (r=0.40, p=0.037). Treatment was also associated with a significant reduction in aortic augmentation index (from 34±7% to 29±8%, p=0.012). Conclusions Polymyalgia rheumatica is associated with increased aortic stiffness which may improve upon reduction of systemic inflammation induced by treatment with glucocorticoids.

Background Atrial fibrillation (AF) is associated with a substantial risk of thromboembolism and mortality, significantly reduced by oral anticoagulation. Adherence to guidelines may lower the risks for both all cause and cardiovascular (CV) deaths. Methods Our objective was to evaluate if antithrombotic prophylaxis according to the 2012 European Society of Cardiology (ESC) guidelines is associated to a lower rate of adverse outcomes. Data were obtained from REPOSI; a prospective observational study enrolling inpatients aged ≥65 years. Patients enrolled in 2012 and 2014 discharged with an AF diagnosis were analysed. Results Among 2535 patients, 558 (22.0 %) were discharged with a diagnosis of AF. Based on ESC guidelines, 40.9 % of patients were on guideline-adherent thromboprophylaxis, 6.8 % were overtreated, and 52.3 % were undertreated. Logistic analysis showed that increasing age ( p  = 0.01), heart failure ( p  = 0.04), coronary artery disease ( p  = 0.013), peripheral arterial disease ( p  = 0.03) and concomitant cancer ( p  = 0.003) were associated with non-adherence to guidelines. Specifically, undertreatment was significantly associated with increasing age ( p  = 0.001) and cancer ( p  < 0.001), and inversely associated with HF ( p  = 0.023). AF patients who were guideline adherent had a lower rate of both all-cause death ( p  = 0.007) and CV death ( p  = 0.024) compared to those non-adherent. Kaplan–Meier analysis showed that guideline-adherent patients had a lower cumulative risk for both all-cause ( p  = 0.002) and CV deaths ( p  = 0.011). On Cox regression analysis, guideline adherence was independently associated with a lower risk of all-cause and CV deaths ( p  = 0.019 and p  = 0.006). Conclusions Non-adherence to guidelines is highly prevalent among elderly AF patients, despite guideline-adherent treatment being independently associated with lower risk of all-cause and CV deaths. Efforts to improve guideline adherence would lead to better outcomes for elderly AF patients.

The dramatic demographic changes that are occurring in the third millennium are modifying the mission of generalist professionals such as primary care physicians and internists. Multiple chronic diseases and the related prescription of multiple medications are becoming typical problems and present many challenges. Unfortunately, the available evidence regarding the efficacy of medications has been generated by clinical trials involving patients completely different from those currently admitted to internal medicine: much younger, affected by a single disease and managed in a highly controlled research environment. Because only registries can provide information on drug effectiveness in real-life conditions, REPOSI started in 2008 with the goal of acquiring data on elderly people acutely admitted to medical or geriatric hospital wards in Italy. The main goals of the registry were to evaluate drug prescription appropriateness, the relationship between multimorbidity/polypharmacy and such cogent outcomes as hospital mortality and re-hospitalization, and the identification of disease clusters that most often concomitantly occur in the elderly. The findings of 3-yearly REPOSI runs (2008, 2010, 2012) suggest the following pertinent tasks for the internist in order to optimally handle their elderly patients: the management of multiple medications, the need to become acquainted with geriatric multidimensional tools, the promotion and implementation of a multidisciplinary team approach to patient health and care and the corresponding involvement of patients and their relatives and caregivers. There is also a need for more research, tailored to the peculiar features of the multimorbid elderly patient.

Kümmell’s disease is the current eponym of avascular osteonecrosis (AVN) of a vertebral body leading to a delayed non-healing vertebral compression fracture (VCF) and thus pseudo-arthrosis. AVN is characterized by production of gas that outlines a radiolucent zone in the vertebral body, called vacuum cleft sign (VCS) or “Kümmell’s sign”. This sign has been observed in up to one-third of VCFs and is often associated with osteoporosis and never with malignant or inflammatory diseases. Generally, treatment strategies are conservative management and percutaneous vertebroplasty. Teriparatide (rhPTH [1-34]) is an osteoanabolic agent approved for treatment of osteoporosis and helpful in fracture’s healing too. Here, we describe the case of an 81-year-old osteoporotic woman presented with a 1-year history of persistent low back pain onset after a trauma. A lumbar spine Computer Tomography (CT) scan performed 2 months after the injury (November 2006) showed the VCS within a VCF of the first lumbar vertebra; a control CT scan 1 year later showed persistence of the finding. After 12 months of treatment with teriparatide 20 mcg/day, symptoms disappeared and vacuum was significantly reduced. In conclusion, Kümmell’s disease may be hypothesized in patients with chronic spinal symptoms, especially in the presence of osteoporosis. Moreover in this condition, osteoanabolic treatment may be used in patients with Kümmell’s disease to enhance vertebral fracture’s healing and contribute to back pain relief.