Cholesterol as a Risk Factor for Subarachnoid Hemorrhage: A Systematic Review

BackgroundThe role played by total cholesterol (TC) in risk for subarachnoid hemorrhage (SAH) is unclear because studies report both high and low TC each as a risk factor. We performed a systematic review to clarify associations between lipid profile and SAH.MethodsOur literature search comprised Pubmed, Scopus, and Cochrane Library databases with no language, publication year, or study type limitations. The Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) checklist guided our reporting. Data forms adapted from the Critical Appraisal Skills Program (CASP), and Cochrane Collaboration guidelines provided a platform for risk-of-bias evaluation. We used a random effects model to calculate pooled estimates and assessed heterogeneity with I²-statistics.ResultsOf the final 21 studies reviewed, 12 were prospective and 9 retrospective. All studies assessed TC, four assessed HDL, and none LDL in risk for SAH. Heterogeneity among all, retrospective, and Asian studies was high (I² = 79.5%, I² = 89.0%, and I² = 84.3%) and considerable in prospective (I² = 46.0%). We therefore focused on qualitative analysis and found that only two studies had a low risk of bias. According to these studies high TC increases risk for SAH in men, whereas the role of HDL remained unclear.ConclusionThe low-risk-of-bias studies suggest that elevated TC levels elevate risk for SAH in men. Due to the high prevalence of hypercholesterolemia, population attributable risk (PAR) of hypercholesterolemia may exceed the PARs of smoking and hypertension in men. Apart from diabetes and obesity, the risk-factor profile of SAH seems to resemble that of other cerebrovascular diseases, at least in men.     

Diabetes Mellitus as a Risk Factor for Open-Angle Glaucoma: A Systematic Review and Meta-Analysis

Objective

To determine the association between diabetes mellitus (DM) and primary open-angle glaucoma (POAG).

Methods

This is a systematic review and meta-analysis of case-control and cohort studies. The literature search included two databases (PubMed and Embase) and the reference lists of the retrieved studies. Separate meta-analyses for case-control studies and cohort studies were conducted using random-effects models, with results reported as adjusted odds ratios (ORs) and relative risks (RRs), respectively.

Results

Thirteen studies—seven case-control studies and six population-based cohort studies—were included in this meta-analysis. The pooled RR of the association between DM and POAG based on the risk estimates of the six cohort studies was 1.40 (95% CI, 1.25–1.57). The pooled OR of the association between DM and POAG based on the risk estimates of the seven case-control studies was 1.49 (95% CI, 1.17–1.88). There was considerable heterogeneity among the case-control studies that reported an association between DM mellitus and POAG (P<0.001) and no significant heterogeneity among the cohort studies (P = 0.377). After omitting the case-control study that contributed significantly to the heterogeneity, the pooled OR for the association between DM and POAG was 1.35 (95% CI, 1.06–1.74).

Conclusions

Individuals with DM have an increased risk of developing POAG.     

Organic Solvents as Risk Factor for Autoimmune Diseases: A Systematic Review and Meta-Analysis

Background

Genetic and epigenetic factors interacting with the environment over time are the main causes of complex diseases such as autoimmune diseases (ADs). Among the environmental factors are organic solvents (OSs), which are chemical compounds used routinely in commercial industries. Since controversy exists over whether ADs are caused by OSs, a systematic review and meta-analysis were performed to assess the association between OSs and ADs.

Methods and Findings

The systematic search was done in the PubMed, SCOPUS, SciELO and LILACS databases up to February 2012. Any type of study that used accepted classification criteria for ADs and had information about exposure to OSs was selected. Out of a total of 103 articles retrieved, 33 were finally included in the meta-analysis. The final odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by the random effect model. A sensitivity analysis confirmed results were not sensitive to restrictions on the data included. Publication bias was trivial. Exposure to OSs was associated to systemic sclerosis, primary systemic vasculitis and multiple sclerosis individually and also to all the ADs evaluated and taken together as a single trait (OR: 1.54; 95% CI: 1.25–1.92; p-value<0.001).

Conclusion

Exposure to OSs is a risk factor for developing ADs. As a corollary, individuals with non-modifiable risk factors (i.e., familial autoimmunity or carrying genetic factors) should avoid any exposure to OSs in order to avoid increasing their risk of ADs.     

Homocysteine as a Risk Factor for Hypertension: A 2-Year Follow-Up Study

Homocysteine (Hcy) is regarded as a risk factor for hypertension, but research on the causal relationship between Hcy and hypertension is limited. In the present study, we prospectively tracked the blood pressure progression of a normotensive population with different Hcy levels over a 2-year period. The incidence of hypertension with increasing Hcy quartiles produced an approximately U-shaped curve, with significance in males. Compared with the third quartile, the risk of hypertension in the first and second quartiles was increased by 1.55 (95% confidence interval [CI] 1.154–2.081) fold and 1.501 (95% CI 1.119–2.013) fold, respectively, with the increase being more significant in males. In conclusion, Hcy is related to hypertension incidence with the results approximating an U-shaped curve. Low Hcy levels might also increase the risk of hypertension.     

Hypercoagulability Is a Stronger Risk Factor for Ischaemic Stroke than for Myocardial Infarction: A Systematic Review

Background and Purpose

Hypercoagulability increases the risk of arterial thrombosis; however, this effect may differ between various manifestations of arterial disease.

Methods

In this study, we compared the effect of coagulation factors as measures of hypercoagulability on the risk of ischaemic stroke (IS) and myocardial infarction (MI) by performing a systematic review of the literature. The effect of a risk factor on IS (relative risk for IS, RR_IS) was compared with the effect on MI (RR_MI) by calculating their ratio (RRR = RR_IS/RR_MI). A relevant differential effect was considered when RRR was >1+ its own standard error (SE) or <1−SE.

Results

We identified 70 publications, describing results from 31 study populations, accounting for 351 markers of hypercoagulability. The majority (203/351, 58%) had an RRR greater than 1. A larger effect on IS risk than MI risk (RRE>1+1SE) was found in 49/343 (14%) markers. Of these, 18/49 (37%) had an RRR greater than 1+2SE. On the opposite side, a larger effect on MI risk (RRR<1-1SE) was found in only 17/343 (5%) markers.

Conclusions

These results suggest that hypercoagulability has a more pronounced effect on the risk of IS than that of MI.     

Association between Alcohol Consumption and Pancreatic Cancer Risk: A Case-Control Study

Purpose

Evidence is inconsistent regarding alcohol and pancreatic cancer risk, although heavy drinking may increase risk.

Methods

A population-based case-control study was conducted using 345 pancreas cancer cases diagnosed 2011–2012 and 1,285 frequency-matched controls from Ontario, Canada. Logistic regression was used to evaluate alcohol consumption and pancreatic cancer risk; data was also stratified by sex and smoking status to assess interaction.

Results

Alcohol consumption was not associated with pancreatic cancer risk (age-adjusted odds ratio=0.78, 95% CI: 0.58, 1.05 for 1 - 3 drinks/week; age-adjusted odds ratio=0.86, 95% CI: 0.63, 1.17 for 4 - 20 drinks/week), however there was a non-significant increased risk for heavy drinkers consuming ≥21 drinks/week (age-adjusted odds ratio=1.35, 95% CI: 0.81, 2.27). Cigarette smoking modified the alcohol-cancer relationship; among current smokers, heavy alcohol consumption was associated with a significantly increased pancreatic cancer risk (age-adjusted odds ratio=4.04, 95% CI: 1.58, 10.37), whereas this significant association with heavy drinking was not observed among non-smokers (age-adjusted odds ratio=2.01, 95% CI: 0.50, 8.18). Furthermore, light – moderate alcohol intake was associated with increased pancreas cancer risk among current smokers.

Conclusions

While alcohol was not significantly associated with pancreatic cancer risk, smoking status modified this relationship such that among current smokers, alcohol intake was associated with a greater than two-fold increased risk of pancreatic cancer. The results should be interpreted with caution due to small sample sizes within subgroups and correction for multiple comparisons should be considered. These findings should be replicated in larger studies where more precise estimates of risk can be obtained.     

Uncovering Treatment Burden as a Key Concept for Stroke Care: A Systematic Review of Qualitative Research

Background

Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.

Methods and Findings

The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.

Conclusions

Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems.

Systematic Review Registration

International Prospective Register of Systematic Reviews CRD42011001123 Please see later in the article for the Editors'' Summary     

Systemic Hypertension as a Risk Factor for Open-Angle Glaucoma: A Meta-Analysis of Population-Based Studies

Background/Aims

Systemic hypertension is thought to increase the risk for developing open-angle glaucoma (OAG) through several mechanisms. However, previous epidemiological studies have shown conflicting results regarding this potential association. We systematically evaluated this issue by conducting a meta-analysis of population-based studies.

Methods

A comprehensive search for articles published before 31 March 2014 was performed using PubMed, Embase, and reference lists. The pooled odds ratio (OR) was calculated using the fixed- and random-effects models, and meta-regression was performed according to age. Subgroup analyses were also conducted, and publication bias was assessed using a funnel plot and Egger’s regression test.

Results

This meta-analysis included 16 studies involving 60,084 individuals, with substantial homogeneity among the studies. The pooled OR for OAG was 1.22 (95% confidence interval, CI: 1.09–1.36) using the fixed-effects model and 1.22 (95% CI: 1.08–1.37) using the random-effects model in all included studies. For subgroup analyses, the pooled OR for high-tension glaucoma (HTG) was higher than that for normal-tension glaucoma (NTG) (OR = 1.92 and 0.94, respectively). No significant difference was detected between Asian and Western populations, and no publication bias was detected in either analysis.

Conclusions

Systemic hypertension increases the risk for developing OAG, especially in those with HTG.     

Inadequate Exercise as a Risk Factor for Sepsis Mortality

Objective

Test whether inadequate exercise is related to sepsis mortality.

Research Design and Methods

Mortality surveillance of an epidemiological cohort of 155,484 National Walkers'' and Runners'' Health Study participants residing in the United States. Deaths were monitored for an average of 11.6-years using the National Death index through December 31, 2008. Cox proportional hazard analyses were used to compare sepsis mortality (ICD-10 A40-41) to inadequate exercise (<1.07 METh/d run or walked) as measured on their baseline questionnaires. Deaths occurring within one year of the baseline survey were excluded.

Results

Sepsis was the underlying cause in 54 deaths (sepsis_underlying) and a contributing cause in 184 deaths (sepsis_contributing), or 238 total sepsis-related deaths (sepsis_total). Inadequate exercise was associated with 2.24-fold increased risk for sepsis_underlying (95%CI: 1.21 to 4.07-fold, P = 0.01), 2.11-fold increased risk for sepsis_contributing (95%CI: 1.51- to 2.92-fold, P<10⁻⁴), and 2.13-fold increased risk for sepsis_total (95%CI: 1.59- to 2.84-fold, P<10⁻⁶) when adjusted for age, sex, race, and cohort. The risk increase did not differ significantly between runners and walkers, by sex, or by age. Sepsis_total risk was greater in diabetics (P = 10⁻⁵), cancer survivors (P = 0.0001), and heart attack survivors (P = 0.003) and increased with waist circumference (P = 0.0004). The sepsis_total risk associated with inadequate exercise persisted when further adjusted for diabetes, prior cancer, prior heart attack and waist circumference, and when excluding deaths with cancer, or cardiovascular, respiratory, or genitourinary disease as the underlying cause. Inadequate exercise also increased sepsis_total risk in 2163 baseline diabetics (4.78-fold, 95%CI: 2.1- to 13.8-fold, P = 0.0001) when adjusted, which was significantly greater (P = 0.03) than the adjusted risk increase in non-diabetics (1.80-fold, 95%CI: 1.30- to 2.46-fold, P = 0.0006).

Conclusion

Inadequate exercise is a risk factor for sepsis mortality, particular in diabetics.     

C-Reactive Protein as a Prognostic Factor for Human Osteosarcoma: A Meta-Analysis and Literature Review

Background

Osteosarcoma is the most common primary bone cancer in growing adolescents and young adults. The prognostic role of C-reactive protein (CRP) in patients with osteosarcoma is not fully investigated. The purpose of this study is to perform a meta-analysis and literature review on the role of CRP in osteosarcoma and to assess the potential role of serum CRP as a prognostic factor for patients with osteosarcoma.

Methods

A detailed literature search was made in Medline for related research publications written in English. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, risk ratio (RR) and corresponding confidence intervals (CIs) were calculated and summarized respectively.

Results

Final analysis of 397 patients from 2 eligible studies was performed. Combined RR of CRP expression suggested that the raised serum CRP level had an adverse prognostic effect on overall survival of patients with osteosarcoma (n = 397 in 2 studies; RR = 0.35; 95% CI: 0.18–0.68; p = 0.002). In the uni- and multivariate survival analysis, response rate and CRP levels were the only independent prognostic variables.

Conclusions

The results of this meta-analysis suggest that CRP expression confers a worse prognosis in patients with osteosarcoma. Large prospective studies are necessary to provide solid data to confirm the prognostic significance of CRP.     

Nursing Workload as a Risk Factor for Healthcare Associated Infections in ICU: A Prospective Study

Introduction

Nurse understaffing is frequently hypothesized as a potential risk factor for healthcare-associated infections (HAI). This study aimed to evaluate the role of nursing workload in the occurrence of HAI, using Nursing Activities Score (NAS).

Methods

This prospective cohort study enrolled all patients admitted to 3 Medical ICUs and one step-down unit during 3 months (2009). Patients were followed-up until HAI, discharge or death. Information was obtained from direct daily observation of medical and nursing rounds, chart review and monitoring of laboratory system. Nursing workload was determined using NAS. Non-compliance to the nurses’ patient care plans (NPC) was identified. Demographic data, clinical severity, invasive procedures, hospital interventions, and the occurrence of other adverse events were also recorded. Patients who developed HAI were compared with those who did not.

Results

195 patients were included and 43 (22%) developed HAI: 16 pneumonia, 12 urinary-tract, 8 bloodstream, 2 surgical site, 2 other respiratory infections and 3 other. Average NAS and average proportion of non compliance with NPC were significantly higher in HAI patients. They were also more likely to suffer other adverse events. Only excessive nursing workload (OR: 11.41; p: 0.019) and severity of patient’s clinical condition (OR: 1.13; p: 0.015) remained as risk factors to HAI.

Conclusions

Excessive nursing workload was the main risk factor for HAI, when evaluated together with other invasive devices except mechanical ventilation. To our knowledge, this study is the first to evaluate prospectively the nursing workload as a potential risk factor for HAI, using NAS.     

Insufficient Milk Supply and Breast Cancer Risk: A Systematic Review

Background

An association between insufficient milk supply, the inability of a mother''s breast milk to provide sufficiently for her infant, and breast cancer has been suggested by observations in animal models. To determine if an association has been reported in epidemiological studies of human breast cancer, a systematic review of the literature has been conducted. We also sought to identify the methodological limitations of existing studies to guide the design of any future prospective studies in this field.

Methodology/Principal Findings

PubMed, EMBASE, Web of Science, BIOSIS, and CAB abstracts were searched. We selected any study that (1) assessed breast cancer in association with breastfeeding history and (2) examined the relationship between insufficient milk supply with breast cancer. Seven relevant studies were identified that met both criteria. There was statistically significant heterogeneity among the results which likely reflects clinically significant differences in definitions of insufficient milk supply and reference groups that were used. Among premenopausal women who had experienced insufficient milk supply, odds ratios (ORs) for breast cancer risk ranged from 0.9 to 16.3. Among postmenopausal women, ORs ranged from 0.6 to 6.7. Based on the range of odds ratios obtained in the studies reported in this review, it remains unclear if there is a true association between insufficient milk supply and breast cancer.

Conclusions/Significance

Although some studies have shown a strong positive association, there is no consistent evidence for an effect of insufficient milk supply on breast cancer risk. Exposure definitions are in need of improvement in order to focus on primary insufficient milk supply. Reference groups consisting of women who have successfully breastfed may also introduce positive bias (inflation of the odds ratio) into study results because of the protective effect of prolonged breastfeeding in the control group.     

Environmental Contamination as a Risk Factor for Intra-Household Staphylococcus aureus Transmission

Background

The household is a recognized community reservoir for Staphylococcus aureus. This study investigated potential risk factors for intra-household S. aureus transmission, including the contribution of environmental contamination.

Methods

We investigated intra-household S. aureus transmission using a sample of multiple member households from a community-based case-control study examining risk factors for CA-MRSA infection conducted in Northern Manhattan. During a home visit, index subjects completed a questionnaire. All consenting household members were swabbed, as were standardized environmental household items. Swabs were cultured for S. aureus. Positive isolates underwent further molecular characterization. Intra-household transmission was defined as having identical strains among two or more household members. Multiple logistic regression was used to identify independent risk factors for transmission.

Results

We enrolled 291 households: 146 index cases, 145 index controls and 687 of their household contacts. The majority of indexes were Hispanic (85%), low income (74%), and female (67%), with a mean age of 31 (range 1–79). The average size of case and control households was 4 people. S. aureus colonized individuals in 62% of households and contaminated the environment in 54% of households. USA300 was the predominant clinical infection, colonizing and environmental strain. Eighty-one households had evidence of intra-household transmission: 55 (38%) case and 26 (18%) control households (P<.01). Environmental contamination with a colonizing or clinical infection strain (aOR: 5.4 [2.9–10.3] P<.01) and the presence of a child under 5 (aOR: 2.3 [1.2–4.5] P = .02) were independently associated with transmission. In separate multivariable models, environmental contamination was associated with transmission among case (aOR 3.3, p<.01) and control households (aOR 27.2, p<.01).

Conclusions

Environmental contamination with a colonizing or clinical infection strain was significantly and independently associated with transmission in a large community-based sample. Environmental contamination should be considered when treating S. aureus infections, particularly among households with multiple infected members.     

Peridontitis as a Risk Factor for Attention Deficit Hyperactivity Disorder: Possible Neuro-inflammatory Mechanisms

Periodontitis is a condition caused mostly by the creation of a biofilm by the bacterium P. gingivalis, which releases toxins and damages the tooth structure. Recent research studies have reported association between dental health and neuropsychiatric illnesses. Neuroinflammation triggered by the first systemic inflammation caused by the bacterium present in the oral cavities is a plausible explanation for such a relationship. Substantial amount of evidence supports the role of neuroinflammation and dysfunction of the dopaminergic system in the pathology of ADHD (Attention deficit hyperactivity disorders). Recent epidemiological, microbiological and inflammatory findings strengthen that, periodontal bacteria, which cause systemic inflammation can contribute to neuroinflammation and finally ADHD. Although both diseases are characterized by inflammation, the specific pathways and crosslink’s between periodontitis and ADHD remain unknown. Here, the authors describe the inflammatory elements of periodontitis, how this dental illness causes systemic inflammation, and how this systemic inflammation contributes to deteriorating neuroinflammation in the evolution of ADHD. Therefore, the aim of this review is to present possible links and mechanisms that could confirm the evidence of this association.

     

A Low Serum Bicarbonate Concentration as a Risk Factor for Mortality in Peritoneal Dialysis Patients

Background and Aim

Metabolic acidosis is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, this relationship has not yet been determined in peritoneal dialysis (PD) patients.

Methods

This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum bicarbonate (TA-Bic) levels, we aimed to investigate whether a low serum bicarbonate concentration can predict mortality in these patients.

Results

Among the baseline parameters, serum bicarbonate level was positively associated with hemoglobin level and residual glomerular filtration rate (GFR), while it was negatively associated with albumin, C-reactive protein (CRP) levels, peritoneal Kt/V urea, and normalized protein catabolic rate (nPCR) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. After adjustment for age, diabetes, coronary artery disease, serum albumin, ferritin, CRP, residual GFR, peritoneal Kt/V urea, nPCR, and percentage of lean body mass, TA-Bic level was associated with a significantly decreased risk of mortality (HR per 1 mEq/L increase, 0.83; 95% CI, 0.76-0.91; p < 0.001). In addition, compared to patients with a TA-Bic level of 24-26 mEq/L, those with a TA-Bic level < 22 and between 22-24 mEq/L conferred a 13.10- and 2.13-fold increased risk of death, respectively.

Conclusions

This study showed that a low serum bicarbonate concentration is an independent risk factor for mortality in PD patients. This relationship between low bicarbonate levels and adverse outcome could be related to enhanced inflammation and a more rapid loss of RRF associated with metabolic acidosis. Large randomized clinical trials to correct acidosis are warranted to confirm our findings.     

LINE-1 Hypomethylation in Blood and Tissue Samples as an Epigenetic Marker for Cancer Risk: A Systematic Review and Meta-Analysis

Objective

A systematic review and a meta-analysis were carried out in order to summarize the current published studies and to evaluate LINE-1 hypomethylation in blood and other tissues as an epigenetic marker for cancer risk.

Methods

A systematic literature search in the Medline database, using PubMed, was conducted for epidemiological studies, published before March 2014. The random-effects model was used to estimate weighted mean differences (MDs) with 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by sample type (tissue or blood samples), cancer types, and by assays used to measure global DNA methylation levels. The Cochrane software package Review Manager 5.2 was used.

Results

A total of 19 unique articles on 6107 samples (2554 from cancer patients and 3553 control samples) were included in the meta-analysis. LINE-1 methylation levels were significantly lower in cancer patients than in controls (MD: −6.40, 95% CI: −7.71, −5.09; p<0.001). The significant difference in methylation levels was confirmed in tissue samples (MD −7.55; 95% CI: −9.14, −65.95; p<0.001), but not in blood samples (MD: −0.26, 95% CI: −0.69, 0.17; p = 0.23). LINE-1 methylation levels were significantly lower in colorectal and gastric cancer patients than in controls (MD: −8.33; 95% CI: −10.56, −6.10; p<0.001 and MD: −5.75; 95% CI: −7.75, −3.74; p<0.001) whereas, no significant difference was observed for hepatocellular cancer.

Conclusions

The present meta-analysis adds new evidence to the growing literature on the role of LINE-1 hypomethylation in human cancer and demonstrates that LINE-1 methylation levels were significantly lower in cancer patients than in control samples, especially in certain cancer types. This result was confirmed in tissue samples, both fresh/frozen or FFPE specimens, but not in blood. Further studies are needed to better clarify the role of LINE-1 methylation in specific subgroups, considering both cancer and sample type, and the methods of measurement.     

LDL Cholesterolemia as a Novel Risk Factor for Radiographic Progression of Rheumatoid Arthritis: A Single-Center Prospective Study

Dyslipidemia has been implicated in various musculoskeletal diseases, including rheumatoid arthritis (RA). Evidence is emerging that there might be a pathogenic interaction among inflammation, dyslipidemia, and adipokines. We prospectively investigated the association of cumulative lipid levels with radiographic progression of RA. RA patients (n = 242) underwent plasma cholesterol assessment at four visits. Disease activity parameters and X-rays of the hands and feet were also serially monitored in these patients. The cumulative inflammatory burden and lipid levels were estimated by time-integrated values. Serum leptin and adiponectin concentrations were determined by ELISA. When patients were divided into three groups according to time-integrated lipid levels, as expected, patients with LDL cholesterol and/or triglyceride levels in the third tertile had persistently higher ESR and CRP levels. In parallel, a more rapid radiographic progression over two years was observed in patients with higher LDL cholesterol and/or triglyceride levels. In multivariate analysis, time-integrated LDL cholesterol was independently associated with radiographic progression. Particularly, the risk of radiographic progression was 5.6-fold in a subgroup with both LDL cholesterol and triglyceride levels in the third tertile. Moreover, LDL cholesterol synergistically increased the adjusted probability of radiographic progression in patients with high serum leptin levels but not in those without. These results demonstrate that LDL cholesterolemia is a novel serum marker that can be used to predict radiographic progression of RA, which seems to be related to circulatory leptin levels. We suggest that personalized and more aggressive anti-rheumatic therapy is required for dyslipidemic subgroups in RA patients.     

The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Myocardial Infarction: A Meta-Analysis

Background

The PlA2 polymorphism of glycoprotein IIIa (GPIIIa) has been previously identified as being associated with myocardial infarction (MI), but whether this represents a true association is entirely unclear due to differences in findings from different studies. We performed a meta-analysis to evaluate whether this polymorphism is a risk factor for MI.

Methods

Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where acute coronary events were recorded in association with genetic analysis, pooled odds ratios (ORs) were calculated using fixed-effects and random-effects models. The primary outcome measure was MI, and a secondary analysis was also performed for acute coronary syndromes (ACS) more generally.

Findings

57 studies were eligible for statistical analysis and included 17,911 cases and 24,584 controls. Carriage of the PlA2 allele was significantly associated with MI (n = 40,692; OR 1.077, 95% CI 1.024–1.132; p = 0.004) but with significant publication bias (p = 0.040). The degree of association with MI increased with decreasing age of subjects (≤45 years old: n = 9,547; OR 1.205, 95% CI 1.067–1.360; p = 0.003) and with adjustment of data for conventional cardiovascular risk factors (n = 12,001; OR 1.240, 95% CI 1.117–1.376; p<0.001). There was a low probability of publication bias for these subgroup analyses (all p<0.05).

Conclusions

The presence of significant publication bias makes it unclear whether the association between carriage of the PlA2 allele and MI is true for the total population studied. However for younger subjects, the relative absence of conventional cardiovascular risk factors results in a significant association between carriage of the PlA2 allele and MI.     

Obesity and Risk of Colorectal Cancer: A Systematic Review of Prospective Studies

Background

Mounting evidence indicates that obesity may be associated with the risk of colorectal cancer (CRC). To conduct a systematic review of prospective studies assessing the association of obesity with the risk of CRC using meta-analysis.

Methodology/Principal Findings

Relevant studies were identified by a search of MEDLINE and EMBASE databases before January 2012, with no restrictions. We also reviewed reference lists from retrieved articles. We included prospective studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between general obesity [measured using body mass index (BMI)] or central obesity [measured using waist circumference (WC)] and the risk of colorectal, colon, or rectal cancer. Approximately 9, 000, 000 participants from several countries were included in this analysis. 41 studies on general obesity and 13 studies on central obesity were included in the meta-analysis. The pooled RRs of CRC for the obese vs. normal category of BMI were 1.334 (95% CI, 1.253–1.420), and the highest vs. lowest category of WC were 1.455 (95% CI, 1.327–1.596). There was heterogeneity among studies of BMI (P<0.001) but not among studies of WC (P = 0.323).

Conclusions

Both of general and central obesity were positively associated with the risk of CRC in this meta-analysis.