Clustering of Major Cardiovascular Risk Factors and the Association with Unhealthy Lifestyles in the Chinese Adult Population

Background

Previous studies indicated that lifestyle-related cardiovascular risk factors tend to be clustered in certain individuals. However, population-based studies, especially from developing countries with substantial economic heterogeneity, are extremely limited. Our study provides updated data on the clustering of cardiovascular risk factors, as well as the impact of lifestyle on those factors in China.

Methods

A representative sample of adult population in China was obtained using a multistage, stratified sampling method. We investigated the clustering of four cardiovascular disease (CVD) risk factors (defined as two or more of the following: hypertension, diabetes, dyslipidemia and overweight) and their association with unhealthy lifestyles (habitual drinking, physical inactivity, chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and a low modified Dietary Approaches to Stop Hypertension (DASH) score).

Results

Among the 46,683 participants enrolled in this study, only 31.1% were free of any pre-defined CVD risk factor. A total of 20,292 subjects had clustering of CVD risk factors, and 83.5% of them were younger than 65 years old. The adjusted prevalence of CVD risk factor clustering was 36.2%, and the prevalence was higher among males than among females (37.9% vs. 34.5%). Habitual drinking, physical inactivity, and chronic use of NSAIDs were positively associated with the clustering of CVD risk factors, with ORs of 1.60 (95% confidence interval [CI] 1.40 to1.85), 1.20 (95%CI 1.11 to 1.30) and 2.17 (95%CI 1.84 to 2.55), respectively. The modified DASH score was inversely associated with the clustering of CVD risk factors, with an OR of 0.73 (95%CI 0.67 to 0.78) for those with modified DASH scores in the top tertile. The lifestyle risk factors were more prominent among participants with low socioeconomic status.

Conclusion

Clustering of CVD risk factors was common in China. Lifestyle modification might be an effective strategy to control CVD risk factors.     

Genetically proxied therapeutic inhibition of antihypertensive drug targets and risk of common cancers: A mendelian randomization analysis

BackgroundEpidemiological studies have reported conflicting findings on the potential adverse effects of long-term antihypertensive medication use on cancer risk. Naturally occurring variation in genes encoding antihypertensive drug targets can be used as proxies for these targets to examine the effect of their long-term therapeutic inhibition on disease outcomes.Methods and findingsWe performed a mendelian randomization analysis to examine the association between genetically proxied inhibition of 3 antihypertensive drug targets and risk of 4 common cancers (breast, colorectal, lung, and prostate). Single-nucleotide polymorphisms (SNPs) in ACE, ADRB1, and SLC12A3 associated (P < 5.0 × 10⁻⁸) with systolic blood pressure (SBP) in genome-wide association studies (GWAS) were used to proxy inhibition of angiotensin-converting enzyme (ACE), β-1 adrenergic receptor (ADRB1), and sodium-chloride symporter (NCC), respectively. Summary genetic association estimates for these SNPs were obtained from GWAS consortia for the following cancers: breast (122,977 cases, 105,974 controls), colorectal (58,221 cases, 67,694 controls), lung (29,266 cases, 56,450 controls), and prostate (79,148 cases, 61,106 controls). Replication analyses were performed in the FinnGen consortium (1,573 colorectal cancer cases, 120,006 controls). Cancer GWAS and FinnGen consortia data were restricted to individuals of European ancestry. Inverse-variance weighted random-effects models were used to examine associations between genetically proxied inhibition of these drug targets and risk of cancer. Multivariable mendelian randomization and colocalization analyses were employed to examine robustness of findings to violations of mendelian randomization assumptions. Genetically proxied ACE inhibition equivalent to a 1-mm Hg reduction in SBP was associated with increased odds of colorectal cancer (odds ratio (OR) 1.13, 95% CI 1.06 to 1.22; P = 3.6 × 10⁻⁴). This finding was replicated in the FinnGen consortium (OR 1.40, 95% CI 1.02 to 1.92; P = 0.035). There was little evidence of association of genetically proxied ACE inhibition with risk of breast cancer (OR 0.98, 95% CI 0.94 to 1.02, P = 0.35), lung cancer (OR 1.01, 95% CI 0.92 to 1.10; P = 0.93), or prostate cancer (OR 1.06, 95% CI 0.99 to 1.13; P = 0.08). Genetically proxied inhibition of ADRB1 and NCC were not associated with risk of these cancers. The primary limitations of this analysis include the modest statistical power for analyses of drug targets in relation to some less common histological subtypes of cancers examined and the restriction of the majority of analyses to participants of European ancestry.ConclusionsIn this study, we observed that genetically proxied long-term ACE inhibition was associated with an increased risk of colorectal cancer, warranting comprehensive evaluation of the safety profiles of ACE inhibitors in clinical trials with adequate follow-up. There was little evidence to support associations across other drug target–cancer risk analyses, consistent with findings from short-term randomized controlled trials for these medications.

In a Mendelian randomization analysis, James Yarmolinsky and colleagues investigate associations between genetically-proxied inhibition of antihypertensive drug targets and breast, colorectal, lung, and prostate cancer risk.     

用杆状病毒为载体在昆虫细胞中表达马立克病病毒pp38基因

鸡马立克病病毒(MDV)38kd磷蛋白(pp38)基因中包括起始密码子和终止密码子的完整编码序列被整合进杆状病毒AcNPV的转移载体质粒pVL1392,用所得的含pp38基因的重组转移载体质粒pVLpp38I与野生型杆状病毒AcNPV的DNA共转染昆虫传代细胞系Sf9细胞后,用荧光抗体法以抗MDV单克隆抗体H_(19)筛选到能表达MDVpp38的重组杆状病毒克隆BP38 I。免疫印迹试验表明,在重组病毒BP38 I感染的Sf9细胞溶解物中,可表现一条分子量约为35—36kd的为单克隆抗体H_(19)识别的MDV特异性蛋白带。     

Framingham risk score and alternatives for prediction of coronary heart disease in older adults

Background

Guidelines for the prevention of coronary heart disease (CHD) recommend use of Framingham-based risk scores that were developed in white middle-aged populations. It remains unclear whether and how CHD risk prediction might be improved among older adults. We aimed to compare the prognostic performance of the Framingham risk score (FRS), directly and after recalibration, with refit functions derived from the present cohort, as well as to assess the utility of adding other routinely available risk parameters to FRS.

Methods

Among 2193 black and white older adults (mean age, 73.5 years) without pre-existing cardiovascular disease from the Health ABC cohort, we examined adjudicated CHD events, defined as incident myocardial infarction, CHD death, and hospitalization for angina or coronary revascularization.

Results

During 8-year follow-up, 351 participants experienced CHD events. The FRS poorly discriminated between persons who experienced CHD events vs. not (C-index: 0.577 in women; 0.583 in men) and underestimated absolute risk prediction by 51% in women and 8% in men. Recalibration of the FRS improved absolute risk prediction, particulary for women. For both genders, refitting these functions substantially improved absolute risk prediction, with similar discrimination to the FRS. Results did not differ between whites and blacks. The addition of lifestyle variables, waist circumference and creatinine did not improve risk prediction beyond risk factors of the FRS.

Conclusions

The FRS underestimates CHD risk in older adults, particularly in women, although traditional risk factors remain the best predictors of CHD. Re-estimated risk functions using these factors improve accurate estimation of absolute risk.     

PCR improves diagnostic yield from lung aspiration in Malawian children with radiologically confirmed pneumonia

Background

Accurate data on childhood pneumonia aetiology are essential especially from regions where mortality is high, in order to inform case-management guidelines and the potential of prevention strategies such as bacterial conjugate vaccines. Yield from blood culture is low, but lung aspirate culture provides a higher diagnostic yield. We aimed to determine if diagnostic yield could be increased further by polymerase chain reaction (PCR) detection of bacteria (Streptococcus pneumoniae and Haemophilus influenzae b) and viruses in lung aspirate fluid.

Methods

A total of 95 children with radiological focal, lobar or segmental consolidation had lung aspirate performed and sent for bacterial culture and for PCR for detection of bacteria, viruses and Pneumocystis jirovecii. In children with a pneumococcal aetiology, pneumococcal bacterial loads were calculated in blood and lung aspirate fluid.

Results

Blood culture identified a bacterial pathogen in only 8 patients (8%). With the addition of PCR on lung aspirate samples, causative pathogens (bacterial, viral, pneumocystis) were identified singly or as co-infections in 59 children (62%). The commonest bacterial organism was S.pneumoniae (41%), followed by H. influenzae b (6%), and the commonest virus identified was adenovirus (16%), followed by human bocavirus (HBoV) (4%), either as single or co-infection.

Conclusions

In a select group of African children, lung aspirate PCR significantly improves diagnostic yield. Our study confirms a major role of S.pneumoniae and viruses in the aetiology of childhood pneumonia in Africa.     

Small birth weight and later body composition and fat distribution in adolescents: the Avena study

Objective: To assess the association between birth weight and body composition and fat distribution in adolescents, and to test the possible sex‐specific effect in these relationships. Methods and Procedures: A total of 1,223 adolescents 13–18.5 years old (553 male adolescents and 670 female adolescents) born at >35 weeks, were selected from a cross‐sectional multicenter study conducted in five Spanish cities in 2000–2002. BMI was calculated from weight and height. Triceps and subscapular skinfold thickness (ST) were measured on the left side, and fat mass (FM) and fat‐free mass (FFM) were estimated according to the equations of Slaughter et al. Subscapular skinfold adjusted by tricipital (ST) and waist circumference were used as markers of central adiposity. Results: Birth weight Z‐score was positively associated with FFM in female adolescents (P < 0.001), but not in male adolescents, after controlling for age, pubertal stage, gestational age, socioeconomic status, physical activity, and current height (P < 0.001 for interaction between adjusted birth weight Z‐score and sex). Adjusted birth weight Z‐score was inversely associated with central adiposity in male and female adolescents as measured by ST (P = 0.026). Discussion: These results provide further evidence that gender has an important influence on the programming effect of birth weight on later FFM in adolescents because the effect was only observed in female adolescents. Our results suggest that small size for gestational age at birth could program more central subcutaneous fat deposition in adolescents of both sexes, but further research is needed on this issue.     

The Impact of the Thai Motorcycle Transition on Road Traffic Injury: Thai Cohort Study Results

Objectives

The aim of this study was to investigate the impact of motorcycle to car transitioning and urbanisation on traffic injury rates in Thailand.

Design

Analysis of two consecutive surveys of a large national cohort study.

Setting

Thailand.

Participants

The data derived from 57,154 Thai Cohort Study (TCS) participants who provided relevant data on both the 2005 and 2009 surveys.

Primary and secondary outcome measures

Motorcycle and car traffic crash injury self-reported in 2009, with twelve months’ recall.

Results

In 2009, 5608(10%) participants reported a traffic crash injury. Most crashes involved a motorcycle (74%). Car access increased and motorcycle use decreased between 2005 and 2009. Among those who used a motorcycle at both time points, traffic injury incidence was 2.8 times greater compared to those who did not use a motorcycle at either time point. Multivariable logistic regression models were used to test longitudinal and cross sectional factors associated with traffic crash injury: in the adjusted model, cars were negatively and motorcycles positively associated with injury. Living in an urban area was not injury protective in the adjusted model of traffic crash injury.

Conclusions

Ongoing urbanisation in Thailand can be expected to lead to further reductions in road traffic injuries based on transition from motorcycles to cars in urban areas. Cities, however, do not provide an intrinsically safer traffic environment. To accommodate a safe transition to car use in Thailand, traffic infrastructural changes anticipating the growing car density in urban areas is warranted.     

The Costs of Scaling Up HIV Prevention for High Risk Groups: Lessons Learned from the Avahan Programme in India

Objective

The study objective is to measure, analyse costs of scaling up HIV prevention for high-risk groups in India, in order to assist the design of future HIV prevention programmes in South Asia and beyond.

Design

Prospective costing study.

Methods

This study is one of the most comprehensive studies of the costs of HIV prevention for high-risk groups to date in both its scope and size. HIV prevention included outreach, sexually transmitted infections (STI) services, condom provision, expertise enhancement, community mobilisation and enabling environment activities. Economic costs were collected from 138 non-government organisations (NGOs) in 64 districts, four state level lead implementing partners (SLPs), and the national programme level (Bill and Melinda Gates Foundation (BMGF)) office over four years using a top down costing approach, presented in US$ 2011.

Results

Mean total unit costs (2004–08) per person reached at least once a year and per monthly contact were US$ 235(56–1864) and US$ 82(12–969) respectively. 35% of the cost was incurred by NGOs, 30% at the state level SLP and 35% at the national programme level. The proportion of total costs by activity were 34% for expertise enhancement, 37% for programme management (including support and supervision), 22% for core HIV prevention activities (outreach and STI services) and 7% for community mobilisation and enabling environment activities. Total unit cost per person reached fell sharply as the programme expanded due to declining unit costs above the service level (from US$ 477 per person reached in 2004 to US$ 145 per person reached in 2008). At the service level also unit costs decreased slightly over time from US$ 68 to US$ 64 per person reached.

Conclusions

Scaling up HIV prevention for high risk groups requires significant investment in expertise enhancement and programme administration. However, unit costs decreased with programme expansion in spite of an increase in the scope of activities.     

Special care and school difficulties in 8-year-old very preterm children: the Epipage cohort study

Objectives

To investigate school difficulties, special care and behavioral problems in 8 year-old very preterm (VPT) children.

Patient and Methods

Longitudinal population-based cohort in nine regions of France of VPT children and a reference group born at 39–40 weeks of gestation (WG). The main outcome measures were information about school, special care and behavioral problems using Strengths and Difficulties Questionnaire from a questionnaire to parents.

Results

Among the 1439 VPT children, 5% (75/1439) were in a specialised school or class, 18% (259/1439) had repeated a grade in a mainstream class and 77% (1105/1439) were in the appropriate grade-level in mainstream class; these figures were 1% (3/327) , 5% (16/327) and 94% (308/327) , respectively, for the reference group. Also, 15% (221/1435) of VPT children in a mainstream class received support at school versus 5% (16/326) of reference group. More VPT children between the ages of five and eight years received special care (55% (794/1436)) than children born at term (38% (124/325)); more VPT children (21% (292/1387)) had behavioral difficulties than the reference group (11% (35/319)). School difficulties, support at school, special care and behavioral difficulties in VPT children without neuromotor or sensory deficits varied with gestational age, socioeconomic status, and cognitive score at the age of five.

Conclusions

Most 8-year-old VPT children are in mainstream schools. However, they have a high risk of difficulty in school, with more than half requiring additional support at school and/or special care. Referral to special services has increased between the ages of 5 and 8 years, but remained insufficient for those with borderline cognitive scores.