Cardiovascular disease (CVD) is traditionally treated through medications and lifestyle modifications, yet adherence to these treatments is often poor. The use of complementary therapies is increasing, and it is vital for physicians to be aware of the risks and benefits of these options. This article summarizes the current evidence base on integrative therapies for the prevention and treatment of CVD, including hypertension, hyperlipidemia, coronary artery disease, heart failure, and arrhythmias. Where applicable, recommendations are included for therapies that may be used as an adjunct to traditional medical care to improve cardiovascular health and quality of life.
BACKGROUND: Although HIV is associated with increased atherosclerotic cardiovascular disease (CVD) risk, it is unknown whether guidelines can identify HIV-infected adults who may benefit from statins. We compared the 2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III recommendations in HIV-infected adults and evaluated associations with carotid artery intima-media thickness and plaque.
METHODS AND RESULTS: Carotid artery intima-media thickness was measured at baseline and 3 years later in 352 HIV-infected adults without clinical atherosclerotic CVD and not on statins. Plaque was defined as IMT >1.5 mm in any segment. At baseline, the median age was 43 (interquartile range, 39-49), 85% were men, 74% were on antiretroviral medication, and 50% had plaque. The American College of Cardiology/American Heart Association guidelines were more likely to recommend statins compared with the Adult Treatment Panel III guidelines, both overall (26% versus 14%; P<0.001), in those with plaque (32% versus 17%; P=0.0002), and in those without plaque (16% versus 7%; P=0.025). In multivariable analysis, older age, higher low-density lipoprotein cholesterol, pack per year of smoking, and history of opportunistic infection were associated with baseline plaque. Baseline IMT (hazard ratio, 1.18 per 10% increment; 95% confidence interval, 1.05-1.33; P=0.005) and plaque (hazard ratio, 2.06; 95% confidence interval, 1.02-4.08; P=0.037) were each associated with all-cause mortality, independent of traditional CVD risk factors.
CONCLUSIONS: Although the American College of Cardiology/American Heart Association guidelines recommended statins to a greater number of HIV-infected adults compared with the Adult Treatment Panel III guidelines, both failed to recommend therapy in the majority of HIV-affected adults with carotid plaque. Baseline carotid atherosclerosis but not atherosclerotic CVD risk scores was an independent predictor of mortality. HIV-specific guidelines that include detection of subclinical atherosclerosis may help to identify HIV-infected adults who are at increased atherosclerotic CVD risk and may be considered for statins.
Lipodystrophy is a heterogeneous group of disorders characterized by loss of adipose tissue. Here, we report on clinical spectra of neuromuscular manifestations of Turkish patients with lipodystrophy. Seventy-four patients with lipodystrophy and 20 healthy controls were included. Peripheral sensorimotor neuropathy was a common finding (67.4%) in lipodystrophic patients with diabetes. Neuropathic foot ulcers were observed in 4 patients. Drop foot developed in 1 patient with congenital generalized lipodystrophy type 1. Muscle symptoms and hypertrophy were consistent findings in congenital generalized lipodystrophy (21/21) and familial partial lipodystrophy (25/34); on the other hand, overt myopathy with elevated creatine kinase activity was a distinctive characteristic of congenital generalized lipodystrophy type 4. Muscle biopsies revealed myopathic changes at different levels. Accumulation of triglycerides was observed which contributes to insulin resistance. All patients with congenital generalized lipodystrophy suffered from tight Achilles tendons at various levels. Scoliosis was observed in congenital generalized lipodystrophy type 4 (2/2) and familial partial lipodystrophy type 2 (2/17). Atlantoaxial instability was unique to congenital generalized lipodystrophy type 4 (2/2). Bone cysts were detected in congenital generalized lipodystrophy type 1 (7/10) and congenital generalized lipodystrophy type 2 (2/8). Our study suggests that lipodystrophies are associated with a wide spectrum of neuromuscular abnormalities.
Synovial lipoma arborescens is a rare and benign fatty proliferative lesion of the synovium that is most commonly seen within the suprapatellar pouch of the knee, but increasingly reported to involve tendon sheaths, including those of the ankle. We present the third known case of tenosynovial lipoma arborescens isolated to the peroneal tendon sheath without ankle joint involvement. To our knowledge, this is the first to report this entity utilizing a unique combination of radiographic, sonographic, and MR imaging, along with intraoperative and histologic correlation. Knowledge of this case is important when interpreting radiographic or sonographic images of this condition to raise the possibility of the rare entity of lipoma arborescens involving the peroneal tendon sheath.
BACKGROUND: Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles?
DISCUSSION: Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments. Statins are the cornerstone for the treatment of hypercholesterolemia. They have been shown to slow the progression or promote regression of coronary plaque, and could also exert an anti-inflammatory and immunomodulatory effect. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. The debate between American and European guidelines is still open and, also considering the independent risk factor represented by HIV, specific guidelines are warranted. Ezetimibe reduces the intestinal absorption of cholesterol. It is effective alone or in combination with rosuvastatin. It does not modify plasmatic concentrations of antiretrovirals. A number of experimental new classes of drugs for the treatment of hypercholesterolemia are being studied. Fibrates represent the first choice for treatment of hypertriglyceridemia, however, the renal toxicity of fibrates and statins should be considered. Omega 3 fatty acids have a good safety profile, but their efficacy is limited. Another concern is the high dose needed. Other drugs are acipimox and tesamorelin. Current antiretroviral therapies are less toxic and more effective than regimens used in the early years. Lipodistrophy and dyslipidemia are the main causes of long-term toxicities. Not all antiretrovirals have similar toxicities. Protease Inhibitors may cause dyslipidemia and lipodystrophy, while integrase inhibitors have a minimal impact on lipids profile, and no evidence of lipodystrophy. There is still much to be written with the introduction of new drugs in clinical practice.
CONCLUSIONS: Cardiovascular risk among HIV infected patients, interventions on behavior and lifestyles, use of drugs to reduce the risk, and switch in antiretroviral therapy, remain nowadays major issues in the management of HIV-infected patients.
Cardiovascular Diseases (5), Blood Disorders and Hematology (4), Anti-Obesity and Weight Loss (1) Dyslipidemias (4), Lipodystrophy (3), Hypercholesterolemia (2), more mentions
BACKGROUND: Interpretation of missense variants can be especially difficult when the variant is also found in control populations. This is what we encountered for the LMNA c.992G>A (p.(Arg331Gln)) variant. Therefore, to evaluate the effect of this variant, we combined an evaluation of clinical data with functional experiments and morphological studies.
METHODS AND RESULTS: Clinical data of 23 probands and 35 family members carrying this variant were retrospectively collected. A time-to-event analysis was performed to compare the course of the disease with carriers of other LMNA mutations. Myocardial biopsies were studied with electron microscopy and by measuring force development of the sarcomeres. Morphology of the nuclear envelope was assessed with immunofluorescence on cultured fibroblasts. The phenotype in probands and family members was characterized by atrioventricular conduction disturbances (61% and 44%, respectively), supraventricular arrhythmias (69% and 52%, respectively), and dilated cardiomyopathy (74% and 14%, respectively). LMNA p.(Arg331Gln) carriers had a significantly better outcome regarding the composite end point (malignant ventricular arrhythmias, end-stage heart failure, or death) compared with carriers of other pathogenic LMNA mutations. A shared haplotype of 1 Mb around LMNA suggested a common founder. The combined logarithm of the odds score was 3.46. Force development in membrane-permeabilized cardiomyocytes was reduced because of decreased myofibril density. Structural nuclear LMNA-associated envelope abnormalities, that is, blebs, were confirmed by electron microscopy and immunofluorescence microscopy.
CONCLUSIONS: Clinical, morphological, functional, haplotype, and segregation data all indicate that LMNA p.(Arg331Gln) is a pathogenic founder mutation with a phenotype reminiscent of other LMNA mutations but with a more benign course.
AIMS: To explore urodynamic characteristics and their clinical value in pelvic lipomatosis (PL) patients.
METHODS: We reviewed the clinical information of 84 PL patients. A voiding pressure-flow study was used to classify patients into nonoutlet obstruction (NOO), latter-half-section obstruction (LHSO), or whole-section bladder outlet obstruction (BOO) groups. Urinary morphologic features were measured by imaging examination and cystoscopy.
RESULTS: A unique LHSO that presented as sudden increasing detrusor pressure (Pdet) and decreasing flow rate in the latter half of voiding was observed for 52.4% (44 of 84) patients. Overall, 27.4% (23 of 84 patients) were diagnosed with BOO with whole-section increasing Pdet and decreasing flow rate. According to the morphologic feature analyses, the NOO patients had the largest angle of anteroposterior vesical walls (P < 0.001) and the least severe thickened bladder trigone (P = 0.015). The external compression at the bladder neck and thickened bladder trigone caused a prolonged and strictured bladder outlet tract (see the Supplementary video). There were 0, 5, and 4 urinary diversions performed in the NOO, LHSO, and BOO groups at diagnosis (P = 0.055). No patients in the NOO group, seven in the LHSO group, and two patients in the BOO group had disease progression at follow-up. Two LHSO patients and one BOO patients without hydronephrosis at diagnosis developed to hydronephrosis during follow-up.
CONCLUSIONS: Morphologic alterations of the urinary system of PL patients lead to unique LHSO or BOO on UDS. The presences of LHSO and BOO are associated with disease severity and progression.
BACKGROUND CONTEXT: Although lumbar disc herniations are common, only a small portion of these herniations lead to cauda equina syndrome (CES) which is an uncommon but debilitating disorder. Why some patients with herniation develop CES, when most do not, remains unknown. Pre-existing subclinical epidural lipomatosis may limit canal space such that an otherwise benign herniation causes CES.
PURPOSE: This study determines whether patients with an acute disc herniation and CES have a greater body mass index (BMI) and greater quantity of epidural fat compared to control subjects with non-CES symptomatic lumbar herniated discs.
STUDY DESIGN/SETTING: Retrospective case-control series at a university-based level-1 trauma centre.
PATIENT SAMPLE: 33 CES and 66 control subjects were identified from a prospectively maintained database of patients who underwent surgical management for a lumbar disc herniation between 2007 and 2012. Each CES case had two non-CES control patients matched by gender and age within 5 years except 5 CES cases that matched only one non-CES control.
OUTCOME MEASURES: The outcome measures included weight, height, age, gender, and BMI. Radiographic outcome measures included the proportion of lumbar spinal canal occupied by fat and herniated disc on preoperative MRI.
METHODS: Patient charts and preoperative radiographs were retrospectively reviewed. For each patient a blinded reviewer determined the proportion of lumbar spinal canal occupied by fat, and the maximal proportion of the canal occupied by herniated material at the involved level. Patient demographics and radiographic measures were compared between CES and control groups using Chi Square or Student's t tests. A second blinded reviewer re-assessed a series of radiographs and the intra-observer variability was determined by Spearman's correlation. Logistic regression was used to model the preoperative factors associated with having an acute disc herniation and CES. The authors have no financial or personal relationships that could inappropriately influence this work.
RESULTS: CES cases had higher BMI (31.8 kg/m2 [95% CI 29.5-34.0] versus 28.1 kg/m2 [95% CI 26.7-29.5] in controls; p = 0.007), focally narrower canals (14.6mm [95%CI 13.8-15.3mm] versus 16.4mm [95%CI 15.4-17.3mm] in controls; p=0.003), and a greater percentage of spinal canal occupied by epidural fat (31.3% [95% CI 26.1-36.6%) versus 21.9% [95% CI 18.7-25.1%] in controls; p = 0.003) and herniated disc material (54.5% [95%CI 46.9-62.0%] versus 34.4% [95%CI 30.3-38.5%] in controls; p<0.0001). Logistic regression confirmed canal width at the involved level, BMI, amount of canal occupied disc, and proportion of canal occupied by fat as independent predictors of having an acute disc herniation and CES.
CONCLUSIONS: Obesity is a risk factor for CES from disc herniation. CES cases also had a greater amount of herniated material, focally narrower canal, and larger epidural fat deposits. The latter may be the mechanism linking obesity with CES.
Anti-Obesity and Weight Loss (5) Obesity (4), Herniated Disc (3), Lipomatosis (3), more mentions
Nonalcoholic fatty liver disease (NAFLD) is becoming the major chronic liver disease in many countries. Its pathogenesis is multifactorial but twin and familial studies indicate significant heritability, which is not fully explained by currently-known genetic susceptibility loci. Notably, mutations in genes encoding nuclear lamina proteins, including lamins, cause lipodystrophy syndromes that include NAFLD. We hypothesized that variants in lamina-associated proteins predispose to NAFLD and used a candidate gene-sequencing approach to test for variants in 10 nuclear lamina-related genes in a cohort of 37 twin and sibling pairs: 21 individuals with, and 53 without, NAFLD. Twelve heterozygous sequence variants were identified in four lamina-related genes (ZMPSTE24/TMPO/SREBF1/SREBF2). The majority of NAFLD patients (>90%) had at least one variant, compared to <40% of controls (P<0.0001). When only insertions/deletions and changes in conserved residues were considered, the difference between the groups was similarly striking (>80% versus <25%; P<0.0001). Presence of a lamina variant segregated with NAFLD independent of the PNPLA3 I148M polymorphism. Several variants were found in TMPO, which encodes the lamina-associated polypeptide-2 (LAP2) that has not previously been associated with liver disease. One of these, a frameshift insertion that generates truncated LAP2, abrogated lamin-LAP2 binding, caused LAP2 mislocalization, altered endogenous lamin distribution, increased lipid droplet accumulation after oleic acid treatment in transfected cells, and led to cytoplasmic association with the ubiquitin-binding protein p62/SQSTM1.
CONCLUSION: Novel variants in nuclear lamina-related genes were identified in a cohort of twins and siblings with NAFLD. One novel variant, which results in a truncated LAP2 protein and a dramatic phenotype in cell culture, represents the first association of TMPO/LAP2 variants with NAFLD and underscores the potential importance of the nuclear lamina in NAFLD. This article is protected by copyright. All rights reserved.
Liver Diseases (2), Fatty Liver (2), Lipodystrophy (1), more mentions