Genetic Determinants of On-Aspirin Platelet Reactivity: Focus on the Influence of PEAR1

Background

Platelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms determine platelet aggregation in aspirin-treated individuals.

Aim

To identify platelet-related single nucleotide polymorphisms (SNPs) influencing platelet aggregation during aspirin treatment. Furthermore, we explored to what extent changes in cyclooxygenase-1 activity and platelet activation may explain such influence.

Methods

We included 985 Danish patients with stable coronary artery disease treated with aspirin 75 mg/day mono antiplatelet therapy. Patients were genotyped for 16 common SNPs in platelet-related genes using standard PCR-based methods (TaqMan). Platelet aggregation was evaluated by whole blood platelet aggregometry employing Multiplate Analyzer (agonists: arachidonic acid and collagen) and VerifyNow Aspirin. Serum thromboxane B₂ was measured to confirm aspirin adherence and was used as a marker of cyclooxygenase-1 activity. Soluble P-selectin was used as marker of platelet activation. Platelet aggregation, cyclooxygenase-1 activity, and platelet activation were compared across genotypes in adjusted analyses.

Results

The A-allele of the rs12041331 SNP in the platelet endothelial aggregation receptor-1 (PEAR1) gene was associated with reduced platelet aggregation and increased platelet activation, but not with cyclooxygenase-1 activity. Platelet aggregation was unaffected by the other SNPs analyzed.

Conclusion

A common genetic variant in PEAR1 (rs12041331) reproducibly influenced platelet aggregation in aspirin-treated patients with coronary artery disease. The exact biological mechanism remains elusive, but the effect of this polymorphism may be related to changes in platelet activation. Furthermore, 14 SNPs previously suggested to influence aspirin efficacy were not associated with on-aspirin platelet aggregation.

Clinical Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01383304","term_id":"NCT01383304"}}NCT01383304     

Different Influences of Hematocrit on the Results of Two Point-Of-Care Platelet Function Tests,the VerifyNow Assay and Multiple Electrode Platelet Aggregometry

Objective

Previous studies have reported a considerable association between the VerifyNow (Accumetrics, San Diego, CA, USA) P2Y12 assay results and hematocrit. No reports, however, have described an association between the multiple electrode platelet aggregometry (MEA; Dynabyte, Munich, Germany) adenosine diphosphate (ADP) assay results and hematocrit. This study was conducted to evaluate the influence of hematocrit on the results of 2 different point-of-care platelet function tests.

Methods

A total of 462 consecutive patients who were undergoing percutaneous coronary intervention were enrolled. Platelet function was evaluated with both the VerifyNow P2Y12 and MEA ADP assays.

Results

Anemic patients (n = 152, 32.9%) demonstrated a significantly higher rate of cardiac death, myocardial infarction, and stroke (5.3% vs. 2.3%, p = 0.046) during the follow-up (median: 18.8 months). Although the VerifyNow P2Y12 assay results demonstrated a significant inverse correlation with hematocrit (r = −0.409, p<0.001), there was no such correlation between the MEA ADP assay results and hematocrit (r = 0.039, p = 0.401). In the multivariate analysis, anemia was an independent predictor of high on-treatment platelet reactivity, defined as a VerifyNow P2Y12 reaction unit level of ≥252.5 (odds ratio = 2.21, 95% confidence interval = 1.39–3.52; p = 0.001). Importantly, this association was independent of an intrinsic change in platelet reactivity as measured by the MEA ADP assay. Adjusting for the influence of hematocrit improved the strength of the correlation between the VerifyNow P2Y12 and MEA ADP assay results.

Conclusions

Hematocrit significantly influenced the VerifyNow P2Y12 assay results, a phenomenon that was presumably in-vitro. Hematocrit level should therefore be considered when interpreting results of the VerifyNow P2Y12 assay.     

Comparison of a New P2Y12 Receptor Specific Platelet Aggregation Test with Other Laboratory Methods in Stroke Patients on Clopidogrel Monotherapy

Background

Clinical studies suggest that 10-50% of patients are resistant to clopidogrel therapy. ADP induced platelet aggregation, a widely used test to monitor clopidogrel therapy, is affected by aspirin and is not specific for the P2Y12 receptor inhibited by clopidogrel.

Objectives

To develop a P2Y12-specific platelet aggregation test and to compare it with other methods used for monitoring clopidogrel therapy.

Patients/Methods

Study population included 111 patients with the history of ischemic stroke being on clopidogrel monotherapy and 140 controls. The effect of clopidogrel was tested by a newly developed ADP(PGE1) aggregation test in which prostaglandin E1 treated platelets are used. Results of conventional ADP induced platelet aggregation, VerifyNow P2Y12 assay and ADP(PGE1) aggregation were compared to those obtained by flow cytometric analysis of vasodilator stimulated phosphoprotein (VASP) phosphorylation. Reference intervals for all assays were determined according to the guidelines of Clinical Laboratory Standards Institute.

Results

The P2Y12-specificity of ADP(PGE1) test was proven by comparing it with ADP aggregation in the presence of P2Y1 antagonist, adenosine 3’, 5’-diphosphate. The method was not influenced by aspirin treatment. Approximately 50% of patients were clopidogrel resistant by conventional ADP aggregation and VerifyNow tests. The ADP(PGE1) method and the VASP phosphorylation assay identified 25.9% and 11.7% of patients as non-responders, respectively. ADP(PGE1) aggregation showed good correlation with VASP phosphorylation and had high diagnostic efficiency.

Conclusion

The new ADP(PGE1) method is a reliable test for monitoring P2Y12 receptor inhibition by platelet aggregation. As a subset of patients are non-responders, monitoring clopidogrel therapy by adequate methods is essential.     

Gender Differences in Survival and the Use of Primary Care Prior to Diagnosis of Three Cancers: An Analysis of Routinely Collected UK General Practice Data

Objective

To explore whether there are gender differences in the number of GP recorded cases, the probability of survival and consulting pattern prior to diagnosis amongst patients with three non-sex-specific cancers.

Design

Cross sectional study.

Setting

UK primary care.

Subjects

12,189 patients aged 16 years or over diagnosed with colorectal cancer (CRC), 11,081 patients with lung cancer and 4,352 patients with malignant melanoma, with first record of cancer diagnosis during 1997–2006.

Main outcome measures

Cancer cases recorded in primary care; probability of survival following diagnosis; and number of GP contacts within the 24 months preceding diagnosis.

Results

From 1997–2006, overall rates of GP recorded CRC and lung cancer cases recorded were higher in men than in women, but rates of malignant melanoma were higher in women than in men. Gender differences in survival were small; 49% of men and 53% of women survived at least 5 years following CRC diagnosis; 9% of men and 12% of women with lung cancer, and 77% of men and 86% of women with malignant melanoma. The adjusted male to female relative hazard ratio of death in all patients was 1.20 (95%CI 1.13–1.30), 1.24 (95%CI 1.16–1.33) and 1.73 (95%CI 1.51–2.00) for CRC, lung cancer and malignant melanoma respectively. However, gender differences in the relative risk were much smaller amongst those who died during follow-up. For each cancer, there was little evidence of gender difference in the percentage who consulted and the number of GP contacts made within 24 months prior to diagnosis.

Conclusions

This study found that patterns of consulting prior to cancer diagnosis differed little between two genders, providing no support for the hypothesis that gender differences in survival are explained by gender differences in consultation for more serious illness, and suggests the need for a more critical view of gender and consultation.     

Impact of Aspirin and Clopidogrel Interruption on Platelet Function in Patients Undergoing Major Vascular Surgery

Aims

To investigate functional platelet recovery after preoperative withdrawal of aspirin and clopidogrel and platelet function 5 days after treatment resumption.

Methods/Results

We conducted an observational study, which prospectively included consecutive patients taking aspirin, taking clopidogrel, and untreated controls (15 patients in each group). The antiplatelet drugs were withdrawn five days before surgery (baseline) and were reintroduced two days after surgery. Platelet function was evaluated by optical aggregation in the presence of collagen, arachidonic acid (aspirin) and ADP (clopidogrel) and by VASP assay (clopidogrel). Platelet-leukocyte complex (PLC) level was quantified at each time-point. At baseline, platelet function was efficiently inhibited by aspirin and had recovered fully in most patients 5 days after drug withdrawal. PLC levels five days after aspirin reintroduction were similar to baseline (+4±10%; p = 0.16), in line with an effective platelet inhibition. Chronic clopidogrel treatment was associated with variable platelet inhibition and its withdrawal led to variable functional recovery. PLC levels were significantly increased five days after clopidogrel reintroduction (+10±15%; p = 0.02), compared to baseline.

Conclusions

Aspirin withdrawal 5 days before high-bleeding-risk procedures was associated with functional platelet recovery, and its reintroduction two days after surgery restored antiplaletet efficacy five days later. This was not the case of clopidogrel, and further work is therefore needed to define its optimal perioperative management.     

Vitamin D and physical performance in elderly subjects: the Pro.V.A study

Background

The role of Vitamin D in musculoskeletal functionality among elderly people is still controversial. We investigated the association between serum 25-hydroxyvitamin D (25OHD) levels and physical performance in older adults.

Methods

2694 community-dwelling elderly women and men from the Progetto Veneto Anziani (Pro.V.A.) were included. Physical performances were assessed by: tandem test, 5 timed chair stands (TCS), gait speed, 6-minute walking (6 mW) distance, handgrip strength, and quadriceps strength. For each test, separate general linear models and loess plots were obtained in both genders, in relation to serum 25OHD concentrations, controlling for several potential confounders.

Results

Linear associations with 25OHD levels were observed for TCS, gait speed, 6 mW test and handgrip strength, but not for tandem test and quadriceps strength. After adjusting for potential confounders, linear associations with 25OHD levels were still evident for the 6 mW distance in both genders (p = .0002 in women; <.0001 in men), for TCS in women (p = .004) and for gait speed (p = .0006) and handgrip strength (p = .03) in men. In loess analyses, performance in TCS in women, in gait speed and handgrip strength in men and in 6 mW in both genders, improved with increasing levels of 25OHD, with most of the improvements occurring for 25OHD levels from 20 to 100 nmol/L.

Conclusion

lower 25OHD levels are associated with a worse coordination and weaker strength (TCS) in women, a slower walking time and a lower upper limb strength in men, and a weaker aerobic capacity (6 mW) in both genders. For optimal physical performances, 25OHD concentrations of 100 nmol/L appear to be more advantageous in elderly men and women, and Vitamin D supplementation should be encouraged to maintain their 25OHD levels as high as this threshold.     

Socioeconomic inequality in smoking in low-income and middle-income countries: results from the world health survey

Objectives

To assess the magnitude and pattern of socioeconomic inequality in current smoking in low and middle income countries.

Methods

We used data from the World Health Survey [WHS] in 48 low-income and middle-income countries to estimate the crude prevalence of current smoking according to household wealth quintile. A Poisson regression model with a robust variance was used to generate the Relative Index of Inequality [RII] according to wealth within each of the countries studied.

Results

In males, smoking was disproportionately prevalent in the poor in the majority of countries. In numerous countries the poorest men were over 2.5 times more likely to smoke than the richest men. Socioeconomic inequality in women was more varied showing patterns of both pro-rich and pro-poor inequality. In 20 countries pro-rich relative socioeconomic inequality was statistically significant: the poorest women had a higher prevalence of smoking compared to the richest women. Conversely, in 9 countries women in the richest population groups had a statistically significant greater risk of smoking compared to the poorest groups.

Conclusion

Both the pattern and magnitude of relative inequality may vary greatly between countries. Prevention measures should address the specific pattern of smoking inequality observed within a population.     

Dietary glycemic load and glycemic index and risk of coronary heart disease and stroke in Dutch men and women: the EPIC-MORGEN study

Background

The associations of glycemic load (GL) and glycemic index (GI) with the risk of cardiovascular diseases (CVD) are not well-established, particularly in men, and may be modified by gender.

Objective

To assess whether high dietary GL and GI increase the risk of CVD in men and women.

Methods

A large prospective cohort study (EPIC-MORGEN) was conducted within the general Dutch population among 8,855 men and 10,753 women, aged 21–64 years at baseline (1993–1997) and free of diabetes and CVD. Dietary intake was assessed with a validated food-frequency questionnaire and GI and GL were calculated using Foster-Powell''s international table of GI. Information on morbidity and mortality was obtained through linkage with national registries. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for incident coronary heart disease (CHD) and stroke, while adjusting for age, CVD risk factors, and dietary factors.

Results

During a mean follow-up of 11.9 years, 581 CHD cases and 120 stroke cases occurred among men, and 300 CHD cases and 109 stroke cases occurred among women. In men, GL was associated with an increased CHD risk (adjusted HR per SD increase, 1.17 [95% CI, 1.02–1.35]), while no significant association was found in women (1.09 [0.89–1.33]). GI was not associated with CHD risk in both genders, while it was associated with increased stroke risk in men (1.27 [1.02–1.58]) but not in women (0.96 [0.75–1.22]). Similarly, total carbohydrate intake and starch intake were associated with a higher CHD risk in men (1.23 [1.04–1.46]; and 1.24 [1.07–1.45]), but not in women.

Conclusion

Among men, high GL and GI, and high carbohydrate and starch intake, were associated with increased risk of CVD.     

Effects of Treatment with Zofenopril in Men and Women with Acute Myocardial Infarction: Gender Analysis of the SMILE Program

Background

the SMILE studies proved the prognostic benefit of zofenopril vs. placebo or other ACE-inhibitors (ACEIs) in post-acute myocardial infarction (AMI). In this retrospective pooled analysis of these studies we assessed whether the zofenopril effect is influenced by gender.

Methods

the four double-blind, randomized, parallel-group SMILE studies, compared the efficacy and safety of 6–48 week treatment with zofenopril 60 mg/day with that of placebo, lisinopril 10 mg/day or ramipril 10 mg/day in 3630 AMI patients. This pooled analysis compared treatment efficacy (1-year combined occurrence of death or hospitalization for CV causes) in 2733 men and 897 women.

Results

women were older than men, had a higher prevalence of diabetes and of other major CV risk factors. The risk of a major CV event was significantly larger for women (23% vs. 17% men, p<0.001). Between-gender risk difference was more marked for people living in Southern (+54%) than in Northern Europe (+12%). In both genders zofenopril similarly reduced the 1-year risk of CV morbidity and mortality vs. placebo (−39% men, p = 0.0001; −40% women, p = 0.005). The risk reduction was more marked with zofenopril than with the other ACEIs, particularly in men (−27%, p = 0.012; women: −14%, p = 0.479). The drug safety profile was similar between genders in zofenopril-treated patients, while it was worse in women treated with other ACEIs.

Conclusions

post-AMI women are at higher risk of CV complications than men, particularly when living in Mediterranean countries. Their response to ACE-inhibition varies according to the type of drug and is usually better in men.     

Gender-Specific Effects of Depression and Suicidal Ideation in Prosocial Behaviors

Background

Prosocial behaviors are essential to the ability to relate to others. Women typically display greater prosocial behavior than men. The impact of depression on prosocial behaviors and how gender interacts with those effects are not fully understood. We explored the role of gender in the potential effects of depression on prosocial behavior.

Methods

We examined prosocial behaviors using a modified version of the Trust Game in a clinical population and community controls. Study participants were characterized on the severity of depression and anxiety, presence of suicidal ideation, history of childhood trauma, recent stressful life events, and impulsivity. We correlated behavioral outcomes with gender and clinical variables using analysis of variance and multiple regression analysis.

Results

The 89 participants comprised four study groups: depressed women, depressed men, healthy women and healthy men (n = 16–36). Depressed men exhibited reciprocity more frequently than healthy men. Depression induced an inversion of the gender-specific pattern of self-centered behavior. Suicidal ideation was associated with increased reciprocity behavior in both genders, and enhancement of the effect of depression on gender-specific self-centered behavior.

Conclusions

Depression, particularly suicidal ideation, is associated with reversal of gender-specific patterns of prosocial behavior, suggesting abnormalities in sexual hormones regulation. This explanation is supported by known abnormalities in the hypothalamus-pituitary-adrenal and hypothalamus-pituitary-gonadal axes found in depression.     

Male Out-Migration: A Factor for the Spread of HIV Infection among Married Men and Women in Rural India

Introduction

Thus far, the reasons for increasing HIV prevalence in northern and eastern Indian states are unknown. We investigated the role of male out-migration in the spread of human immunodeficiency virus (HIV) infection through a case-control study in rural India.

Methods

Currently married men and women were recruited from HIV testing and treatment centers across seven selected districts with high rates of male out-migration in eastern and northern India in 2010 using a case-control study design. Case subjects (men: 595, women: 609) were people who tested HIV seropositive and control subjects (men: 611, women: 600) were those tested HIV seronegative. For each gender, we obtained adjusted odds ratios (AORs) and population attributable risks (PARs) for migration, and behavioral factors.

Results

For men, the prevalence of HIV was significantly higher among those with a migration history (AOR, 4·4); for women, the prevalence of HIV was higher among those with migrant husbands (AOR, 2·3). For both genders, the returned male migration (men: AOR, 3·7; women: AOR, 2·8) was significantly associated with higher prevalence of HIV infection. The PAR associated with male migration was higher for men (54·5%–68·6%) than for women (32·7%–56·9%) across the study areas.

Discussion

Male out-migration is the most important risk factor influencing the spread of HIV infection in rural areas with high out-migration rates, thereby emphasizing the need for interventions, particularly, for returned migrants and spouses of those migrants.     

Association of Simple Anthropometric Indices and Body Fat with Early Atherosclerosis and Lipid Profiles in Chinese Adults

Objective

The discriminatory capability of different adiposity indices for atherosclerosis and lipid abnormalities remains uncertain. This study aimed to identify the best adiposity index for predicting early atherosclerosis and abnormal lipid profiles among anthropometric parameters and body fat measures in middle-aged and elderly Chinese.

Method

A total of 2,063 women and 814 men (57.6±5.2 y) were recruited for this community-based cross-sectional study. Body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were assessed. Body fat mass and its percentage values for the whole body and trunk were measured by bioelectrical impedance analysis (BIA). The intima-media thicknesses (IMTs) of the common carotid arteries (CCA), internal carotid arteries (ICA) and bifurcation (BIF) were determined via B-mode ultrasound. The fasting lipid profiles were assessed.

Results

With per SD increase of adiposity indices, the magnitude of the changes of IMT values and lipid profiles was more substantial for WC, WHR and WHtR in both genders. A multivariate logistic regression analysis indicated that WC, WHR and WHtR were more sensitive in predicting the presence of intima-media thickening at the three segments as well as the lipids disturbances in women and men. In general, BIA-derived measures have no added predictive value for IMT-thickening as opposed to those three traditional abdominal measures.

Conclusion

Our findings suggest that abdominal anthropometric measures including WC, WHR and WHtR are sensitive for discriminating carotid atherosclerosis and lipids abnormalities. WC is the best index because of its simplicity in routine use.     

Increased Platelet Reactivity Is Associated with Circulating Platelet-Monocyte Complexes and Macrophages in Human Atherosclerotic Plaques

Objective

Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs) and macrophages in human atherosclerotic carotid plaques.

Methods

Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP), in two independent cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n = 91). Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort). Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort).

Results

We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range): 4153 (1585–11267) area under the curve (AUC) vs. 9633 (3580–21565) AUC, P<0.001). Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean±SD; 8969±3485 AUC vs. 7020±3442 AUC, P = 0.02). All associations remained significant after adjustment for age, sex and use of drugs against platelet activation.

Conclusion

Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.     

Clinical Presentations,Antiplatelet Strategies and Prognosis of Patients with Stent Thrombosis: An Observational Study of 140 Patients

Background

Until now there has been scarce evidence regarding an optimal antiplatelet strategy and clinical outcomes for patients who had suffered from stent thrombosis (ST).

Methods and Results

140 patients who suffered from stent thrombosis were prospectively registered. Patients received dual (aspirin and 150 mg clopidogrel, N = 66) or triple (additional cilostazol, N = 74) antiplatelet therapy at the physician’s discretion. Thereafter platelet reactivity and one year clinical outcomes were analyzed. The primary outcome included the composite of cardiac death, non-fatal myocardial infarction (MI) or stroke at one year,which developed in 41 (29.3%) patients, consisting of 31 (22.1%) cardiac death, 9 (6.4%) non-fatal MI and 1 (1.4%) stroke. Recurrent definite and probable ST according to ARC definition was observed in 8 (5.7%) and 14 (10.0%) patients, respectively. Triple therapy was associated with significantly lower platelet reactivities (50.2±17.8, % vs. 59.6±17.2, %, P = 0.002) compared to high dose dual antiplatelet therapy. However, the incidence of primary events (24.3% vs. 34.8%, P = 0.172) did not differ between triple and dual antiplatelet therapies. High on-treatment platelet reactivity (HR: 8.35, 95% CI: 2.234∼30.867, P = 0.002) and diabetes (HR: 3.732, 95% CI: 1.353∼10.298, P = 0.011) were independent predictors of primary events.

Conclusions

Patients who suffered from stent thrombosis have a poor prognosis even after revascularization with intensive antiplatelet therapy. Triple antiplatelet therapy was more effective in reducing on-treatment platelet reactivity, compared to high dose dual antiplatelet therapy.     

Likelihood of Treatment in a Coronary Care Unit for a First-Time Myocardial Infarction in Relation to Sex,Country of Birth and Socioeconomic Position in Sweden

Objective

To examine the relationship between sex, country of birth, level of education as an indicator of socioeconomic position, and the likelihood of treatment in a coronary care unit (CCU) for a first-time myocardial infarction.

Design

Nationwide register based study.

Setting

Sweden.

Patients

199 906 patients (114 387 men and 85,519 women) of all ages who were admitted to hospital for first-time myocardial infarction between 2001 and 2009.

Main outcome measures

Admission to a coronary care unit due to myocardial infarction.

Results

Despite the observed increasing access to coronary care units over time, the proportion of women treated in a coronary care unit was 13% less than for men. As compared with men, the multivariable adjusted odds ratio among women was 0.80 (95% confidence interval 0.77 to 0.82). This lower proportion of women treated in a CCU varied by age and year of diagnosis and country of birth. Overall, there was no evidence of a difference in likelihood of treatment in a coronary care unit between Sweden-born and foreign-born patients. As compared with patients with high education, the adjusted odds ratio among patients with a low level of education was 0.93 (95% confidence interval 0.89 to 0.96).

Conclusions

Foreign-born and Sweden-born first-time myocardial infarction patients had equal opportunity of being treated in a coronary care unit in Sweden; this is in contrast to the situation in many other countries with large immigrant populations. However, the apparent lower rate of coronary care unit admission after first-time myocardial infarction among women and patients with low socioeconomic position warrants further investigation.     

Different anthropometric adiposity measures and their association with cardiovascular disease risk factors: a meta-analysis

Objectives

To investigate which anthropometric adiposity measure has the strongest association with cardiovascular disease (CVD) risk factors in Caucasian men and women without a history of CVD.

Design

Systematic review and meta-analysis.

Methods

We searched databases for studies reporting correlations between anthropometric adiposity measures and CVD risk factors in Caucasian subjects without a history of CVD. Body mass index (BMI), waist circumference, waist-to-hip ratio, waist-to-height ratio and body fat percentage were considered the anthropometric adiposity measures. Primary CVD risk factors were: systolic blood pressure, diastolic blood pressure, high density lipoprotein (HDL) cholesterol, triglycerides and fasting glucose. Two independent reviewers performed abstract, full text and data selection.

Results

Twenty articles were included describing 21,618 males and 24,139 females. Waist circumference had the strongest correlation with all CVD risk factors for both men and women, except for HDL and LDL in men. When comparing BMI with waist circumference, the latter showed significantly better correlations to CVD risk factors, except for diastolic blood pressure in women and HDL and total cholesterol in men.

Conclusions

We recommend the use of waist circumference in clinical and research studies above other anthropometric adiposity measures, especially compared with BMI, when evaluating CVD risk factors.     

Age at menarche, the leg length to sitting height ratio, and risk of diabetes in middle-aged and elderly Chinese men and women

Aims

To evaluate the associations of age at menarche and the leg length-to-sitting-height ratio, markers of adolescent growth, with risk of diabetes in later life.

Materials and Methods

Information from 69,385 women and 55,311 men, aged 40–74 years from the Shanghai Women''s Health Study and Shanghai Men''s Health Study, were included in the current analyses. Diabetes status was ascertained through biennial in person follow-up. Cox models, with age as the time scale, were used.

Results

There were 2369 cases of diabetes (1831 women; 538 men) during an average of 7.3 and 3.6 years of follow-up of the women and men, respectively. In females, menarche age was inversely associated with diabetes risk after adjustment for birth cohort, education, and income (HR = 0.95, 0.92–0.98). In both genders, leg length-to-sitting-height ratio was inversely related to diabetes (HR = 0.88, 0.80–0.97 for men; HR = 0.91, 0.86–0.96 for women) after adjustment for birth cohort, education, and income. Further adjustment for adult BMI at study enrollment completely eliminated the associations of age at menarche (HR = 0.99, 0.96–1.02) and the leg length-to-sitting-height ratio (HR = 1.00, 0.91–1.10 for men; HR = 1.01, 0.96–1.07 for women) with diabetes risk.

Conclusions

Our study suggests that markers of an early age at peak height velocity, i.e. early menarche age and low leg-length-to-sitting height ratio, may be associated with diabetes risk later in life and this association is likely to be mediated through obesity.     

Representation of Women and Pregnant Women in HIV Research: A Limited Systematic Review

Background

HIV-related outcomes may be affected by biological sex and by pregnancy. Including women in general and pregnant women in particular in HIV-related research is important for generalizability of findings.

Objective

To characterize representation of pregnant and non-pregnant women in HIV-related research conducted in general populations.

Data Sources

All HIV-related articles published in fifteen journals from January to March of 2011. We selected the top five journals by 2010 impact factor, in internal medicine, infectious diseases, and HIV/AIDS.

Study Eligibility Criteria

HIV-related studies reporting original research on questions applicable to both men and women of reproductive age were considered; studies were excluded if they did not include individual-level patient data.

Study appraisal and synthesis methods.

Articles were doubly reviewed and abstracted; discrepancies were resolved through consensus. We recorded proportion of female study participants, whether pregnant women were included or excluded, and other key factors.

Results

In total, 2014 articles were published during this period. After screening, 259 articles were included as original HIV-related research reporting individual-level data; of these, 226 were determined to be articles relevant to both men and women of reproductive age. In these articles, women were adequately represented within geographic region. The vast majority of published articles, 183/226 (81%), did not mention pregnancy (or related issues); still fewer included pregnant women (n=33), reported numbers of pregnant women (n=19), or analyzed using pregnancy status (n=9).

Limitations

Data were missing for some key variables, including pregnancy. The time period over which published works were evaluated was relatively short.

Conclusions and implications of key findings.

The under-reporting and inattention to pregnancy in the HIV literature may reduce policy-makers’ ability to set evidence-based policy around HIV/AIDS care for pregnant women and women of child-bearing age.     

EBV seroepidemiology in married and unmarried women and men in Iran

Background:

Among the eight known human herpes viruses, Epstein- Barr virus (EBV) is considered to be sexually transmissible. This study was conducted to evaluate the seroepidemiology of this infection in married and unmarried Iranian couples.

Methods:

In this comparative observational and cross-sectional study, 160 men and women were divided into married and unmarried groups. Serum IgG and IgM antibodies to the EBV viral capsid antigen were analyzed by Enzyme-linked Immunosorbent Assays (ELISAs).

Results:

In this study 78 men and 82 women were enrolled. Ninety percent of the married and 76.2% of the unmarried women were anti-EBV IgG positive (P = 0.08), while 80% of the married and 94% of the unmarried men were antiEBV IgG positive (P = 0.052).

Conclusion:

Seroepidemiology of EBV is not significantly different in married vs. unmarried women and men in Iran; therefore, sexual contact may not be the primary mechanism of EBV transmission in Iran and other developing countries. Attention to other possible routes of transmission is recommended. Key Words: Epstein Barr Virus, Sexual contact, Anti-VCA     

The Relationship between Fractional Flow Reserve,Platelet Reactivity and Platelet Leukocyte Complexes in Stable Coronary Artery Disease

Background

The presence of stenoses that significantly impair blood flow and cause myocardial ischemia negatively affects prognosis of patients with stable coronary artery disease. Altered platelet reactivity has been associated with impaired prognosis of stable coronary artery disease. Platelets are activated and form complexes with leukocytes in response to microshear gradients caused by friction forces on the arterial wall or flow separation. We hypothesized that the presence of significantly flow-limiting stenoses is associated with altered platelet reactivity and formation of platelet-leukocyte complexes.

Methods

One hundred patients with stable angina were studied. Hemodynamic significance of all coronary stenoses was assessed with Fractional Flow Reserve (FFR). Patients were classified FFR-positive (at least one lesion with FFR≤0.75) or FFR-negative (all lesions FFR>0.80). Whole blood samples were stimulated with increasing concentrations of ADP, TRAP, CRP and Iloprost with substimulatory ADP. Expression of P-selectin as platelet activation marker and platelet–leukocyte complexes were measured by flowcytometry. Patients were stratified on clopidogrel use. FFR positive and negative patient groups were compared on platelet reactivity and platelet-leukocyte complexes.

Results

Platelet reactivity between FFR-positive patients and FFR-negative patients did not differ. A significantly lower percentage of circulating platelet-neutrophil complexes in FFR-positive patients and a similar non-significant decrease in percentage of circulating platelet-monocyte complexes in FFR-positive patients was observed.

Conclusion

The presence of hemodynamically significant coronary stenoses does not alter platelet reactivity but is associated with reduced platelet-neutrophil complexes in peripheral blood of patients with stable coronary artery disease.