Low- and high-density lipoprotein cholesterol goal attainment in dyslipidemic women: The Lipid Treatment Assessment Project (L-TAP) 2

Background Differences between women and men have been documented for both diagnostic testing and treatment in cardiology. This analysis evaluates whether low-density lipoprotein cholesterol (LDL-C) success rates according to current guidelines and high-density lipoprotein cholesterol (HDL-C) levels differ by gender in the L-TAP 2 population. Methods Patients aged >= 20 years with dyslipidemia on stable lipid-lowering therapy were assessed in 9 countries between September 2006 and April 2007. Low-density lipoprotein cholesterol goal attainment by cardiovascular risk level and region and determinants of low HDL-C were compared between genders. Results Of 9,955 patients (45.3% women) evaluated, women had a significantly lower overall LDL-C success rate than men (71.5% vs 73.7%, P = .014), due entirely to the difference in the high-risk/coronary heart disease (CHD) group (LDL-C goal <100 mg/dL, 62.6% vs 70.6%, P < .0001) Among CHD patients with >= 2 additional risk factors, only 26.7% of women and 31.5% of men (P = .021) attained the optional LDL-C goal of <70 mg/dL. High-density lipoprotein cholesterol was <50 mg/dL in 32.2% of women and <40 mg/dL in 26.8% of men (P < .0001), including 38.2% of women and 29.8% of men in the high risk/CHD group (P < .0001). Predictors of low HDL-C in women included diabetes, smoking, waist circumference, and hypertension. Conclusions Cholesterol treatment has, improved substantially since the original L-TAP a decade ago, when only 39% of women attained their LDL-C goal. However, high-risk women are undertreated compared to men, and a substantial opportunity remains to reduce their cardiovascular risk. (Am Heart J 2009; 158:860-6.)

Massage for Low Back Pain An Updated Systematic Review Within the Framework of the Cochrane Back Review Group

Study Design. Systematic Review. Objectives. To assess the effects of massage therapy for nonspecific low back pain. Summary of Background Data. Low back pain is one of the most common and costly musculoskeletal problems in modern society. Proponents of massage therapy claim it can minimize pain and disability, and speed return to normal function. Methods. We searched MEDLINE, EMBASE, CINAHL from their beginning to May 2008. We also searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, issue 3), HealthSTAR and Dissertation abstracts up to 2006. There were no language restrictions. References in the included studies and in reviews of the literature were screened. The studies had to be randomized or quasi-randomized trials investigating the use of any type of massage (using the hands or a mechanical device) as a treatment for nonspecific low back pain. Two review authors selected the studies, assessed the risk of bias using the criteria recommended by the Cochrane Back Review Group, and extracted the data using standardized forms. Both qualitative and meta-analyses were performed. Results. Thirteen randomized trials were included. Eight had a high risk and 5 had a low risk of bias. One study was published in German and the rest in English. Massage was compared to an inert therapy (sham treatment) in 2 studies that showed that massage was superior for pain and function on both short- and long-term follow-ups. In 8 studies, massage was compared to other active treatments. They showed that massage was similar to exercises, and massage was superior to joint mobilization, relaxation therapy, physical therapy, acupuncture, and self-care education. One study showed that reflexology on the feet had no effect on pain and functioning. The beneficial effects of massage in patients with chronic low back pain lasted at least 1 year after the end of the treatment. Two studies compared 2 different techniques of massage. One concluded that acupuncture massage produces better results than classic (Swedish) massage and another concluded that Thai massage produces similar results to classic (Swedish) massage. Conclusion. Massage might be beneficial for patients with subacute and chronic nonspecific low back pain, especially when combined with exercises and education. The evidence suggests that acupuncture massage is more effective than classic massage, but this need confirmation. More studies are needed to confirm these conclusions, to assess the impact of massage on return-to-work, and to determine cost-effectiveness of massage as an intervention for low back pain.

Lipid Treatment Assessment Project 2 A Multinational Survey to Evaluate the Proportion of Patients Achieving Low-Density Lipoprotein Cholesterol Goals

Background-Information about physicians` adherence to cholesterol management guidelines remains scant. The present survey updates our knowledge of lipid management worldwide. Methods and Results-Lipid levels were determined at enrollment in dyslipidemic adult patients on stable lipid-lowering therapy in 9 countries. The primary end point was the success rate, defined as the proportion of patients achieving appropriate low-density lipoprotein cholesterol (LDL-C) goals for their given risk. The mean age of the 9955 evaluable patients was 62 +/- 12 years; 54% were male. Coronary disease and diabetes mellitus had been diagnosed in 30% and 31%, respectively, and 14% were current smokers. Current treatment consisted of a statin in 75%. The proportion of patients achieving LDL-C goals according to relevant national guidelines ranged from 47% to 84% across countries. In low-, moderate-, and high-risk groups, mean LDL-C was 119, 109, and 91 mg/dL and mean high-density lipoprotein cholesterol was 62, 49, and 50 mg/dL, respectively. The success rate for LDL-C goal achievement was 86% in low-, 74% in moderate-, and 67% in high-risk patients (73% overall). However, among coronary heart disease patients with >= 2 risk factors, only 30% attained the optional LDL-C goal of < 70 mg/dL. In the entire cohort, high-density lipoprotein cholesterol was < 40 mg/dL in 19%, 40 to 60 mg/dL in 55%, and > 60 mg/dL in 26% of patients. Conclusions-Although there is room for improvement, particularly in very-high-risk patients, these results indicate that lipid-lowering therapy is being applied much more successfully than it was a decade ago. (Circulation. 2009; 120: 28-34.)

Rosuvastatin and Cardiovascular Events in Patients Undergoing Hemodialysis

Background Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. Methods We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. Results After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P = 0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P = 0.51). Conclusions In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.)

Reaching C-Reactive Protein and Low-Density Lipoprotein Cholesterol Goals in Dyslipidemic Patients (from the Lipid Treatment Assessment Project [L-TAP] 2)

The purpose of the present substudy of the Lipid Treatment Assessment Project 2 was to assess dual C-reactive protein (CRP) and low-density lipoprotein (LDL) cholesterol goal attainment across a spectrum of low-, moderate-, and high-risk patients with dyslipidemia in 8 countries in North America, Latin America, Europe, and Asia. Of the 9,518 patients studied overall, 45% were women, 64% had hypertension, 31% had diabetes, 14% were current smokers, 60% were high risk, and 79% were taking a statin. The median CRP level was 1.5 mg/L (interquartile range 0.2 to 2.8). On multivariate analysis, higher CRP levels were associated with older age, female gender, hypertension, current smoking, greater body mass index, larger waist circumference, LDL cholesterol level, and triglyceride/high-density lipoprotein cholesterol ratio. In contrast, being from Asia or taking a statin was associated with lower levels. Across all risk groups, 59% of patients attained the CRP target of <2 mg/L, and 33% had <1 mg/L. Overall, 44% of patients attained both their National Cholesterol Education Program Adult Treatment Panel III LDL cholesterol target and a CRP level of <2 mg/L, but only 26% attained their LDL cholesterol target and a CRP level of <1 mg/L. In the very high-risk group with coronary heart disease and >= 2 risk factors, only 19% attained both their LDL cholesterol goal and a CRP level of <2 mg/L and 12% their LDL cholesterol goal and a CRP level of <1 mg/L. In conclusion, with current treatment, most dyslipidemic patients do not reach the dual CRP and LDL cholesterol goals. Smoking cessation, weight reduction, and the greater use of more potent statins at higher doses might be able to improve these outcomes. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1639-1643)

A synergistic relationship of elevated low-density lipoprotein cholesterol levels and systolic blood pressure with coronary artery calcification

We sought to evaluate this ""response-to-injury"" hypothesis of atherosclerosis by studying the interaction between systolic blood pressure (SBP) and LDL-cholesterol (LDL-C) in predicting the presence of coronary artery calcification (CAC) in asymptomatic men. We Studied 526 men (46 +/- 7 years of age) referred for electron-beam tomography (EBT) exam. The prevalence of CAC was determined across LDL-C tertiles (low: <115 mg/dl; middle: 115-139 mg/dl high: >= 140 mg/dl) within tertiles of SBP (low: <121 mmHg; middle: 121-130 mmHg; high: >= 131 mmHg). CAC was found in 220 (42%) men. There was no linear trend in the presence of CAC across LDL-C tertiles in the low (p = 0.6 for trend) and middle (p = 0.3 for trend) SBP tertile groups, respectively. In contrast, there was a significant trend for increasing CAC with increasing LDL-C (1st: 44%; 2nd: 49%; 3rd: 83%; p < 0.0001 for trend) in the high SBP tertile group. In multivariate logistic analyses (adjusting for age, smoking, triglyceride levels, HDL-cholesterol levels, body mass index, and fasting glucose levels), the odds ratio for any CAC associated with increasing LDL-C was significantly higher in those with highest SBP levels, whereas no such relationship was observed among men with SBP in the lower two tertiles. An interaction term (LDL-C x SBP) incorporated in the multivariate analyses was statistically significant (p = 0.038). The finding of an interaction between SBP and LDL-C relation to CAC in asymptomatic men support the response-to-injury model of atherogenesis. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Accentuated osteoclastic response to parathyroid hormone undermines bone mass acquisition in osteonectin-null mice

Matricellular proteins play a unique role in the skeleton as regulators of bone remodeling, and the matricellular protein osteonectin (SPARC, BM-40) is the most abundant non-collagenous protein in bone In. the absence of osteonectin, mice develop progressive low turnover osteopenia, particularly affecting trabecular bone. Polymorphisms in a regulatory region of the osteonectin gene are associated with bone mass in a subset of idiopathic osteoporosis patients, and these polymorphisms likely regulate osteonectin expression. Thus it is important to determine how osteonectin gene dosage affects skeletal function. Moreover, intermittent administration of parathyroid hormone (PTH) (1-34) is the only anabolic therapy approved for the treatment of osteoporosis, and it is critical to understand how modulators of bone remodeling, such as osteonectin, affect skeletal response to anabolic agents. In this study, 10 week old female wild type, osteonectin-haploinsufficient, and osteonectin-null mice (C57Bl/6 genetic background) were given 80 mu g/kg body weight/day PTH(1-34) for 4 weeks. Osteonectin gene dosage had a profound effect on bone microarchitecture. The connectivity density of trabecular bone in osteonectin-haploinsufficient mice was substantially decreased compared with that of wild type mice, suggesting compromised mechanical properties. Whereas mice of each genotype had a similar osteoblastic response to PTH treatment, the osteoclastic response was accentuated in osteonectin-haploinsufficient and osteonectin-null mice. Eroded surface and osteoclast number were significantly higher in PTH-treated osteonectin-null mice, as was endosteal area. In vitro studies confirmed that PTH induced the formation of more osteoclast-like cells in marrow from osteonectin-null mice compared with wild type. PTH treated osteonectin-null bone marrow cells expressed more RANKL mRNA compared with wild type. However, the ratio of RANKL:OPG mRNA was somewhat lower in PTH treated osteonectin-null cultures. Increased expression of RANKL in response to PTH could contribute to the accentuated osteoclastic response in osteonectin(-/-) mice, but other mechanisms are also likely to be involved. The molecular mechanisms by which PTH elicits bone anabolic vs. bone catabolic effects remain poorly understood. Our results imply that osteonectin levels may play a role in modulating the balance of bone formation and resorption in response to PTH. (c) 2008 Elsevier Inc. All rights reserved.

K/DOQI-recommended intact PTH levels do not prevent low-turnover bone disease in hemodialysis patients

The guidelines proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that intact parathyroid hormone (iPTH) should be maintained in a target range between 150 and 300 pg ml(-1) for patients with stage 5 chronic kidney disease. Our study sought to verify the effectiveness of that range in preventing bone remodeling problems in hemodialysis patients. We measured serum ionized calcium and phosphorus while iPTH was measured by a second-generation assay. Transiliac bone biopsies were performed at the onset of the study and after completing 1 year follow-up. The PTH levels decreased within the target range in about one-fourth of the patients at baseline and at the end of the study. The bone biopsies of two-thirds of the patients were classified as showing low turnover and a one-fourth showed high turnover, the remainder having normal turnover. In the group achieving the target levels of iPTH 88% had low turnover. Intact PTH levels less than 150 pg ml(-1) for identifying low turnover and greater than 300 pg ml(-1) for high turnover presented a positive predictive value of 83 and 62%, respectively. Our study suggests that the iPTH target recommended by the K/DOQI guidelines was associated with a high incidence of low-turnover bone disease, suggesting that other biochemical markers may be required to accurately measure bone-remodeling status in hemodialysis patients.

Lipid goals among patients with diabetes or metabolic syndrome: Lipid Treatment Assessment Project (L-TAP) 2

Objective: This analysis of the Lipid Treatment Assessment Project 2 population compared lipid goal attainment by diabetes and metabolic syndrome status. Research design and methods: Dyslipidaemic patients aged >= 20 years on stable lipid lowering therapy had their lipid levels determined once during enrolment at investigation sites in nine countries between September 2006 and April 2007. Achievement of low-density lipoprotein (LDL) cholesterol success, triglycerides < 150 mg/dl (1.7 mmol/l), and high-density lipoprotein (HDL) cholesterol success (> 40 mg/dl [1.0 mmol/l] in men or > 50 mg/dl [1.3 mmol/l] in women) was compared using logistic regression. Results: A total of 9955 patients were evaluated. Patients with diabetes, compared with those without diabetes, had lower achievement of LDL cholesterol goals (according to National Cholesterol Education Program Adult Treatment Panel [NCEP ATP] III guidelines; 67% vs. 75%), triglycerides < 150 mg/dl (55% vs. 64%), and HDL cholesterol success (61% vs. 74%; p < 0.0001 for all comparisons). The significantly lower lipid goal attainment in patients with diabetes was consistent across participating world regions. Patients with metabolic syndrome, compared with those without metabolic syndrome, had lower achievement of NCEP ATP III LDL cholesterol goals (69% vs. 76%), triglycerides < 150 mg/dl (36% vs. 83%), and HDL cholesterol success (49% vs. 89%; p < 0.0001 for all comparisons). As the number of metabolic syndrome components increased, lipid success rates progressively decreased (p < 0.0001 for LDL cholesterol success, triglycerides < 150 mg/dl, and HDL cholesterol success). Conclusions: This analysis indicates that despite their increased cardiovascular risk, patients with diabetes or metabolic syndrome remain undertreated.

Prostate cryoablation: Prospective analysis comparing high- and low-risk prostate cancer outcomes

Aim: To evaluate percutaneous cryotherapy as a primary treatment option for prostate cancer, comparing different risk groups. Patients and Methods: Forty-seven prostate cryoablation procedures were performed on 44 patients. Patients median age was 70.9, and average pretreatment PSA of 13.8 ng/dl. Patients were divided into low-risk (13 patients), high-risk (24 patients) and radiation failure patients (7 patients). The follow-up period ranged from 18 to 60 months (median 41 months). Results: In the low-risk group, we found after 12 and 24 months of follow-up, 92 and 86% of patients free of PSA relapse (PSA < 1 ng/ml), respectively. In the high-risk group, the PSA failure was 39 and 52.9%. For the radiation failure group, 86 and 71.4% of patients had PSA below 1 ng/dl. At 48 months of follow-up, 80% of the low-risk patients, 42.8% of the high-risk group and 71.4% of the radiation failure group were free of PSA relapse. The complication rates were low, with 13% of urinary incontinence and no cases of rectal injury. Conclusion: Prostate cryoablation is a viable and promising minimally invasive alternative for localized or locally advanced prostate cancer patients. Copyright (c) 2008 S. Karger AG, Basel.

Low Hematocrit Levels Increase Intracranial Pressure in an Animal Model of Cryogenic Brain Injury

Background: Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over optimal fluid management for these patients. This study aimed to investigate the effects of acute hemodilution with hydroxyethyl starch (HES) or lactated Ringer`s solution (LR) in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in dogs submitted to a cryogenic brain injury model. Methods: Design-Prospective laboratory animal study. Setting-Research laboratory in a teaching hospital. Subjects-Thirty-five male mongrel dogs. Interventions-Animals were enrolled to five groups: control, hemodilution with LR or HES 6% to an hematocrit target of 27% or 35%. Results: ICP and CPP levels were measured after cryogenic brain injury. Hemodilution promotes an increment of ICP levels, which decreases CPP when hematocrit target was estimated in 27.% after hemodilution. However, no differences were observed regarding crystalloid or colloid solution used for hemodilution in ICP and CPP levels. Conclusions: Hemodilution to a low hematocrit level increases ICP and decreases CPP scores in dogs submitted to a cryogenic brain injury. These results suggest that excessive hemodilution to a hematocrit below 30% should be avoided in traumatic brain injury patients.

The prevalence of headache among elderly in a low-income area of Sao Paulo, Brazil

There are scarce data about headache prevalence and its characteristics among elderly people. The aim was to carry out a cross-sectional study to determine the 1-year prevalence of tension-type and migraine headaches in people > 65 years old in the city of Sao Paulo, Brazil. All 1615 people living in the study catchment area who agreed to participate in the study answered a questionnaire based in the International Headache Society criteria. Prevalence (mean and 95% confidence interval) of any type of headache in the last year was 45.6% (43.2, 48.0). Prevalence of tension-type headache in the last year was 33.1% (30.8, 35.4): 28.1% (24.6, 31.6) for men and 36.4% (33.4, 39.4) for women; for migraine headaches, prevalence in the last year was 10.6% (9.1, 12.1): 5.1% (3.4, 6.8) for men and 14.1% (11.9, 16.3) for women. One-year prevalence rates of headaches, and especially of migraine headaches, are very high among the elderly in Brazil.

Cardiovascular risk factors associated with migraine among the elderly with a low income: The Sao Paulo Ageing & Health Study (SPAH)

Background: To investigate the association between cardiovascular risk-factor profile and migraine in the elderly, we evaluated a population sample of ageing men and women (65 years or more) living in a low-income area in the city of Sao Paulo, Brazil. Patients and Methods: We investigated migraine status and cardiovascular profile from a baseline of 1450 participants (65-102 years of age) of the Sao Paulo Ageing & Health Study (SPAH), a longitudinal population-based study with low-income elderly in Brazil. The following age and sex-adjusted cardiovascular risk factors were analyzed: blood pressure, pulse pressure, serum total and high-density lipoprotein cholesterol, body mass index, smoking, history of hypertension, diabetes and the 10-year risk of myocardial infarction or coronary heart disease death based on the Framingham Risk Score. Results: The overall prevalence of migraine was 11.4%, and it was 3 times more frequent among women than men (15.3% vs 5.4%; P < 0.0001). Migraineurs were younger than non-migraineurs (mean age 70.6 years vs 72.1 years; P = 0.001, respectively). There was no statistically significant difference regarding the cardiovascular risk-factor profile after adjustment for age and sex among migraineurs and non-migraineurs. Only a decrease in the risk of hypertension among women (OR 0.58; 95% CI 0.38-0.90; P = 0.01) was also observed even after adjustment for age. Conclusions: Overall, we did not find a worse cardiovascular risk profile among elderly migraineurs. An inverse association between hypertension and migraine in women warrants further investigation.

HDL-C concentration is related to markers of absorption and of cholesterol synthesis: Study in subjects with low vs. high HDL-C

Background: The antiatherogenic functions of high density lipoprotein (HDL-C) include its role in reverse cholesterol transport, but to what extent the concentration of HDL-C interferes with the whole-body cholesterol metabolism is unknown. Therefore, we measured markers of body cholesterol synthesis (desmosterol and lathosterol) and of intestinal cholesterol absorption (campesterol and beta-sitosterol) in healthy subjects that differ according to their plasma HDL-C concentrations. Methods: Healthy participants presented either low HDL-C (<40 mg/dl, n = 33,17 male and 16 female) or high HDL-C (>60 mg/dl, n = 33, 17 male and 16 female), BMI <30 kg/m(2), were paired according to age and gender, without secondary factors that might interfere with their plasma lipid concentrations. Plasma concentrations of non-cholesterol sterols were measured by the combined GC-MS analysis. Results: Plasma desmosterol did not differ between the two groups; however, as compared with the high HDL-C participants, the low HDL-C participants presented higher concentration of lathosterol and lower concentration of the intestinal cholesterol absorption markers campesterol and beta-sitosterol. Conclusion: Plasma concentrations of HDL, and not the activities of LCAT and CETP that regulate the reverse cholesterol transport system, correlate with plasma sterol markers of intestinal cholesterol absorption directly, and of cholesterol synthesis reciprocally. (C) 2010 Elsevier B.V. All rights reserved.

Low bone mass in juvenile onset sclerosis systemic: the possible role for 25-hydroxyvitamin D insufficiency

Juvenile onset systemic sclerosis (JoSSc) is a rare disease, and there are no studies focusing in bone mineral density and biochemical bone parameters. Ten consecutive patients with JoSSc and 10 controls gender, age, menarche age, and physical activity matched were selected. Clinical data were obtained at the medical visit and chart review. Laboratorial analysis included autoantibodies, 25-hydroxyvitamin D (25OHD), intact parathyroid hormone, calcium, phosphorus, alkaline phosphatase and albumin sera levels. Bone mineral density was analyzed by dual-energy X-ray absorptiometry, and bone mineral apparent density (BMAD) was calculated. A lower BMAD in femoral neck (0.294 +/- A 0.060 vs. 0.395 +/- A 0.048 g/cm(3), P = 0.001) and total femur (0.134 +/- A 0.021 vs. 0.171 +/- A 0.022 g/cm(3), P = 0.002) was observed in JoSSc compared to controls. Likewise, a trend to lower BMAD in lumbar spine (0.117 +/- A 0.013 vs. 0.119 +/- A 0.012 g/cm(3), P = 0.06) was also found in these patients. Serum levels of 25OHD were significantly lower in JoSSc compared to controls (18.1 +/- A 6.4 vs. 25.1 +/- A 6.6 ng/mL, P = 0.04), and all patients had vitamin D insufficiency (< 20 ng/mL) compared to 40% of controls (P = 0.01). All other biochemical parameters were within normal range and alike in both groups. BMAD in femoral neck and total femur was correlated with 25OHD levels in JoSSc (r = 0.82, P = 0.004; r = 0.707, P = 0.02; respectively). We have identified a remarkable high prevalence of 25OHD insufficiency in JoSSc. Its correlation with hip BMAD suggests a causal effect and reinforces the need to incorporate this hormone evaluation in this disease management.