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  1. Poorthuis MHF, Sherliker P, de Borst GJ, Carter JL, Lam KBH, Jones NR, et al.
    J Am Heart Assoc, 2021 04 20;10(8):e019025.
    PMID: 33853362 DOI: 10.1161/JAHA.120.019025
    Background Associations between adiposity and atrial fibrillation (AF) might differ between sexes. We aimed to determine precise estimates of the risk of AF by body mass index (BMI) and waist circumference (WC) in men and women. Methods and Results Between 2008 and 2013, over 3.2 million adults attended commercial screening clinics. Participants completed health questionnaires and underwent physical examination along with cardiovascular investigations, including an ECG. We excluded those with cardiovascular and cardiac disease. We used multivariable logistic regression and determined joint associations of BMI and WC and the risk of AF in men and women by comparing likelihood ratio χ2 statistics. Among 2.1 million included participants 12 067 (0.6%) had AF. A positive association between BMI per 5 kg/m2 increment and AF was observed, with an odds ratio of 1.65 (95% CI, 1.57-1.73) for men and 1.36 (95% CI, 1.30-1.42) for women among those with a BMI above 20 kg/m2. We found a positive association between AF and WC per 10 cm increment, with an odds ratio of 1.47 (95% CI, 1.36-1.60) for men and 1.37 (95% CI, 1.26-1.49) for women. Improvement of likelihood ratio χ2 was equal after adding BMI and WC to models with all participants. In men, WC showed stronger improvement of likelihood ratio χ2 than BMI (30% versus 23%). In women, BMI showed stronger improvement of likelihood ratio χ2 than WC (23% versus 12%). Conclusions We found a positive association between BMI (above 20 kg/m2) and AF and between WC and AF in both men and women. BMI seems a more informative measure about risk of AF in women and WC seems more informative in men.
  2. Poorthuis MHF, Morris DR, de Borst GJ, Bots ML, Greving JP, Visseren FLJ, et al.
    Br J Surg, 2021 Aug 19;108(8):960-967.
    PMID: 33876207 DOI: 10.1093/bjs/znab040
    BACKGROUND: Recommendations for screening patients with lower-extremity arterial disease (LEAD) to detect asymptomatic carotid stenosis (ACS) are conflicting. Prediction models might identify patients at high risk of ACS, possibly allowing targeted screening to improve preventive therapy and compliance.

    METHODS: A systematic search for prediction models for at least 50 per cent ACS in patients with LEAD was conducted. A prediction model in screened patients from the USA with an ankle : brachial pressure index of 0.9 or less was subsequently developed, and assessed for discrimination and calibration. External validation was performed in two independent cohorts, from the UK and the Netherlands.

    RESULTS: After screening 4907 studies, no previously published prediction models were found. For development of a new model, data for 112 117 patients were used, of whom 6354 (5.7 per cent) had at least 50 per cent ACS and 2801 (2.5 per cent) had at least 70 per cent ACS. Age, sex, smoking status, history of hypercholesterolaemia, stroke/transient ischaemic attack, coronary heart disease and measured systolic BP were predictors of ACS. The model discrimination had an area under the receiver operating characteristic (AUROC) curve of 0.71 (95 per cent c.i. 0.71 to 0.72) for at least 50 per cent ACS and 0.73 (0.72 to 0.73) for at least 70 per cent ACS. Screening the 20 per cent of patients at greatest risk detected 12.4 per cent with at least 50 per cent ACS (number needed to screen (NNS) 8] and 5.8 per cent with at least 70 per cent ACS (NNS 17). This yielded 44.2 and 46.9 per cent of patients with at least 50 and 70 per cent ACS respectively. External validation showed reliable discrimination and adequate calibration.

    CONCLUSION: The present risk score can predict significant ACS in patients with LEAD. This approach may inform targeted screening of high-risk individuals to enhance the detection of ACS.

  3. Mhatre S, Lacey B, Sherliker P, Chatterjee N, Rajaraman P, Goel M, et al.
    Int J Epidemiol, 2021 Sep 22.
    PMID: 34550362 DOI: 10.1093/ije/dyab197
    BACKGROUND: In India, as elsewhere, the incidence of gall-bladder cancer (GBC) is substantially higher in women than in men. Yet, the relevance of reproductive factors to GBC remains poorly understood.

    METHODS: We used logistic regression adjusted for age, education and area to examine associations between reproductive factors and GBC risk, using 790 cases of histologically confirmed GBC and group-matched 1726 visitor controls. We tested the interaction of these associations by genetic variants known to increase the risk of GBC.

    RESULTS: Parity was strongly positively associated with GBC risk: each additional pregnancy was associated with an ∼25% higher risk {odds ratio [OR] 1.26 [95% confidence interval (95% CI) 1.17-1.37]}. After controlling for parity, GBC risk was weakly positively associated with later age of menarche [postmenopausal women, OR 1.11 (95% CI 1.00-1.22) per year], earlier menopause [OR 1.03 (95% CI 1.00-1.06) per year] and shorter reproductive lifespan [OR 1.04 (95% CI 1.01-1.07) per year], but there was little evidence of an association with breastfeeding duration or years since last pregnancy. Risk alleles of single-nucleotide polymorphisms in the ABCB4 and ABCB1 genetic regions had a multiplicative effect on the association with parity, but did not interact with other reproductive factors.

    CONCLUSIONS: We observed higher GBC risk with higher parity and shorter reproductive lifespan, suggesting an important role for reproductive and hormonal factors.

  4. Carter JL, Abdullah N, Bragg F, Murad NAA, Taylor H, Fong CS, et al.
    Int J Obes (Lond), 2023 Sep;47(9):855-864.
    PMID: 37460680 DOI: 10.1038/s41366-023-01339-9
    BACKGROUND: No large-scale studies have compared associations between body composition and cardiovascular risk factors across multi-ethnic populations.

    METHODS: Population-based surveys included 30,721 Malay, 10,865 Indian and 25,296 Chinese adults from The Malaysian Cohort, and 413,737 White adults from UK Biobank. Sex-specific linear regression models estimated associations of anthropometry and body composition (body mass index [BMI], waist circumference [WC], fat mass, appendicular lean mass) with systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), triglycerides and HbA1c.

    RESULTS: Compared to Malay and Indian participants, Chinese adults had lower BMI and fat mass while White participants were taller with more appendicular lean mass. For BMI and fat mass, positive associations with SBP and HbA1c were strongest among the Chinese and Malay and weaker in White participants. Associations with triglycerides were considerably weaker in those of Indian ethnicity (eg 0.09 [0.02] mmol/L per 5 kg/m2 BMI in men, vs 0.38 [0.02] in Chinese). For appendicular lean mass, there were weak associations among men; but stronger positive associations with SBP, triglycerides, and HbA1c, and inverse associations with LDL-C, among Malay and Indian women. Associations between WC and risk factors were generally strongest in Chinese and weakest in Indian ethnicities, although this pattern was reversed for HbA1c.

    CONCLUSION: There were distinct patterns of adiposity and body composition and cardiovascular risk factors across ethnic groups. We need to better understand the mechanisms relating body composition with cardiovascular risk to attenuate the increasing global burden of obesity-related disease.

  5. Armas Rojas NB, Lacey B, Soni M, Charles S, Carter J, Varona-Pérez P, et al.
    BMC Public Health, 2021 05 27;21(1):963.
    PMID: 34039286 DOI: 10.1186/s12889-021-10911-9
    BACKGROUND: Cardiovascular disease accounts for about one-third of all premature deaths (ie, age =120 mmHg), diabetes, and BMI (>=22.5 kg/m2): 20 mmHg higher usual SBP about doubled cardiovascular mortality (RR 2.02, 95%CI 1.88-2.18]), as did diabetes (2.15, 1.95-2.37), and 10 kg/m2 higher usual BMI (1.92, 1.64-2.25). RR were similar in men and in women. The association with BMI and cardiovascular mortality was almost completely attenuated following adjustment for the mediating effect of SBP. Elevated SBP (>=120 mmHg), diabetes and raised BMI (>=22.5 kg/m2) accounted for 27%, 14%, and 16% of cardiovascular deaths, respectively.

    CONCLUSIONS: This large prospective study provides direct evidence for the effects of these major risk factors on cardiovascular mortality in Cuba. Despite comparatively low levels of these risk factors by international standards, the strength of their association with cardiovascular death means they nevertheless exert a substantial impact on premature mortality in Cuba.

  6. Armas Rojas NB, Lacey B, Simadibrata DM, Ross S, Varona-Pérez P, Burrett JA, et al.
    EClinicalMedicine, 2021 Mar;33:100692.
    PMID: 33768200 DOI: 10.1016/j.eclinm.2020.100692
    Background: The associations of cause-specific mortality with alcohol consumption have been studied mainly in higher-income countries. We relate alcohol consumption to mortality in Cuba.

    Methods: In 1996-2002, 146 556 adults were recruited into a prospective study from the general population in five areas of Cuba. Participants were interviewed, measured and followed up by electronic linkage to national death registries until January 1, 2017. After excluding all with missing data or chronic disease at recruitment, Cox regression (adjusted for age, sex, province, education, and smoking) was used to relate mortality rate ratios (RRs) at ages 35-79 years to alcohol consumption. RRs were corrected for long-term variability in alcohol consumption using repeat measures among 20 593 participants resurveyed in 2006-08.

    Findings: After exclusions, there were 120 623 participants aged 35-79 years (mean age 52 [SD 12]; 67 694 [56%] women). At recruitment, 22 670 (43%) men and 9490 (14%) women were current alcohol drinkers, with 15 433 (29%) men and 3054 (5%) women drinking at least weekly; most alcohol consumption was from rum. All-cause mortality was positively and continuously associated with weekly alcohol consumption: each additional 35cl bottle of rum per week (110g of pure alcohol) was associated with ∼10% higher risk of all-cause mortality (RR 1.08 [95%CI 1.05-1.11]). The major causes of excess mortality in weekly drinkers were cancer, vascular disease, and external causes. Non-drinkers had ∼10% higher risk (RR 1.11 [1.09-1.14]) of all-cause mortality than those in the lowest category of weekly alcohol consumption (<1 bottle/week), but this association was almost completely attenuated on exclusion of early follow-up.

    Interpretation: In this large prospective study in Cuba, weekly alcohol consumption was continuously related to premature mortality. Reverse causality is likely to account for much of the apparent excess risk among non-drinkers. The findings support limits to alcohol consumption that are lower than present recommendations in Cuba.

    Funding: Medical Research Council, British Heart Foundation, Cancer Research UK, CDC Foundation (with support from Amgen).

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