Search

Background: The identification of novel predictors of poor outcome may help stratify cardiovascular risk. Aim was to evaluate the individual contribution of blood cell count parameters, as well as their clustering, on the risk of death and cardiovascular events over the long term in the population-based Malmö Diet and Cancer Study cohort., Methods: In 30,447 individuals (age 57 ± 8 years), we assessed the incidence of all-cause death (primary endpoint) and major adverse cardiovascular events (MACE, secondary outcome measure) according to absence or presence of one, two and three factors at baseline out of the following: anaemia, leukocytosis and thrombocytosis. Median follow-up was 16 years., Results: The percentages of all-cause death were 19.5% in individuals without factors, 21.3% in those with one factor, 27.4% with two and 46.4% with three (log-rank test P < .001). The crude incidence of MACE was 28.0%, 29.2%, 35.5% and 57.1%, respectively (log-rank test P < .001). At multivariate analysis, we found a stepwise increase in overall mortality with increasing number of prevalent factors (one factor: HR 1.23, 95% CI 1.14-1.31, P < .001; two factors: 1.61, 1.37-1.89, P < .001; three factors: 2.69, 1.44-5.01, P = .002, vs no factor). Similar findings were observed for the incidence of MACE (one factor: adjusted HR 1.18, 95% CI 1.11-1.24, P < .001; two factors: 1.52, 1.33-1.76, P < .001; three factors: 2.03, 1.21-3.67, P < .001, vs no factor)., Conclusions: The easily assessable clustering of anaemia, leukocytosis and thrombocytosis heralds higher incidence of death and adverse cardiovascular events., (© 2021 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

There are a few studies that report cognitive impairment as a complication of treatment with beta- blockers. We aimed to evaluate the longitudinal association between use of beta-blockers, as a class, and incident risk of all-cause dementia, vascular dementia, Alzheimer's and mixed dementia in the prospective population-based Malmö Preventive Project. We included 18,063 individuals (mean age 68.2, males 63.4%) followed up for 84,506 person-years. Dementia cases were retrieved from the Swedish National Patient Register and validated by review of medical records and neuroimaging data. We performed propensity score matching analysis, resulting in 3720 matched pairs of beta-blocker users and non-users at baseline, and multivariable Cox proportional-hazards regression. Overall, 122 study participants (1.6%) were diagnosed with dementia during the follow-up. Beta-blocker therapy was independently associated with increased risk of developing vascular dementia, regardless of confounding factors (HR: 1.72, 95%CI 1.01-3.78; p = .048). Conversely, treatment with beta-blockers was not associated with increased risk of all-cause, Alzheimer's and mixed dementia (HR:1.15; 95%CI 0.80-1.66; p = .44; HR:0.85; 95%CI 0.48-1.54; P = .59 and HR:1.35; 95%CI 0.56-3.27; p = .50, respectively). We observed that use of beta-blockers, as a class, is associated with increased longitudinal risk of vascular dementia in the general elderly population, regardless of cardiovascular risk factors, prevalent or incident history of atrial fibrillation, stroke, coronary events and heart failure. Further studies are needed to confirm our findings in the general population and to explore the mechanisms underlying the relationship between use of beta- blockers and increased risk of vascular dementia., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Studies evaluating the relationship between platelet indices and cardiovascular (CV) outcomes yielded conflicting results. We assessed the incidence of adverse events according to baseline quintiles of platelet indices in the prospective cohort of the Malmö Diet and Cancer Study. A total of 30,314 individuals (age 57 ± 8 years) were followed for a median of 16 years (468,490 person-years). Outcome measures included all-cause death, CV death, myocardial infarction (MI), and ischemic stroke. The fifth quintile of platelet count (> 274.6 × 10 9 /L) was associated with higher incidence of all-cause death (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.32, p  < 0.001), CV death (HR 1.19, 95% CI 1.00-1.42; p  = 0.044), MI (HR 1.32, 95% CI 1.12-1.54; p  = 0.001), and ischemic stroke (HR 1.27, 95% CI 1.08-1.50, p  = 0.004) compared with the first quintile (≤ 185 × 10 9 /L), and also associated with a lower survival, regardless of previous history of MI ( p for interaction = 0.58) or stroke ( p for interaction = 0.42). In the highest quintile, history of stroke had a higher risk of CV death (HR 3.18, 95% CI 1.54-6.54) compared with no previous stroke (HR 1.12, 95% CI 0.96-1.31). The risk of MI and stroke was greatest in the fifth quintile, regardless of previous MI or previous stroke, respectively. The risk of all adverse events was similar across different quintiles of mean platelet volume. In conclusion, elevated platelet count is associated with higher mortality and risk of CV events, regardless of previous MI and stroke. Platelet count may thus be a useful marker for further stratification of CV risk, and especially of death., Competing Interests: G.P.: Speaker/consultant/advisory board for Amgen, Sanofi, Bayer, Boehringer-Ingelheim, BMS-Pfizer, Daiichi Sankyo, Astra Zeneca, Sigma-Tau, Malesci, PIAM, and MSD, outside the submitted work. G.R.: Speaker/consultant/advisory board for Boehringer-Ingelheim, Daiichi-Sankyo, and Bayer. V.H.: Educational funding from Boston Scientific and shareholder in AstraZeneca and Swedish Orphan Biovitrum, outside the submitted work. R.S.: Consultant to Medtronic Inc., member of speakers' bureau of Abbott Labs and stock holder in Edwards Lifescience, Boston Scientific Inc., and AstraZeneca PLC. R.D.C.: Fees, honoraria, and research funding from Sanofi-Aventis, Boehringer-Ingelheim, Bayer, BMS/Pfizer, Daiichi-Sankyo, Novartis, MSD, and Portola, outside the submitted work. G.R.: Personal fees from Bayer, Boehringer-Ingelheim, Daiichi Sankyo, outside the submitted work. A.F.: Speaker/consultant/advisory board for Medtronic and honoraria and royalties from Cardiome and Thermofisher, outside the submitted work. R.S.: Other from Boston Scientific, Astra Zeneca PLC, Edwards Lifescience, personal fees from Medtronic, Abbott laboratories, outside the submitted work. All other authors report no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To assess the role of four biomarkers of neuroendocrine activation and endothelial dysfunction in the longitudinal prediction of fragility fractures., Methods: We analysed a population-based prospective cohort of 5415 community-dwelling individuals (mean age, 68.9±6.2 years) enrolled in the Malmö Preventive Project followed during 8.1±2.9 years, and investigated the longitudinal association between C-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1 precursor fragment (CT-proET-1), the mid-regional fragments of pro-adrenomedullin (MR-proADM) and pro-atrial natriuretic peptide (MR-proANP), and incident vertebral, pelvic and extremity fractures., Results: Overall, 1030 (19.0%) individuals suffered vertebral, pelvic or extremity fracture. They were older (70.7±5.8 vs 68.4±6.3 years), more likely women (46.9% vs 26.3%), had lower body mass index and diastolic blood pressure, were more often on antihypertensive treatment (44.1% vs 38.4%) and had more frequently history of fracture (16.3% vs 8.1%). Higher levels of MR-proADM (adjusted HR (aHR) per 1 SD: 1.51, 95% CI 1.01 to 2.28, p<0.001) and MR-proANP (aHR: 1.23, 95% CI 1.05 to 1.45, p<0.001) were independently associated with increased risk of any fracture. The fracture risk increased linearly across MR-proANP quartiles. Individuals who were in the top quartile of all four biomarkers had a significant higher risk of fracture at any site (aHR: 2.32, 95% CI 1.86 to 2.91), vertebral fracture (aHR: 3.16, 95% CI 1.97 to 5.07) and femoral fracture (aHR: 2.35, 95% CI 1.64 to 3.36)., Conclusions: Elevated levels of MR-proADM and MR-proANP independently predict fragility fractures in older adults. In subjects with top quartile levels of all four biomarkers there is a twofold to threefold increase in risk of vertebral and femoral fractures., Competing Interests: Competing interests: AF reports personal fees from Cardiome and a patent Thermo Fisher pending outside the submitted work. RS reports personal fees and other from Medtronic, Abbott Laboratories outside the submitted work; performs consultancy for Medtronic; is a member of the speakers' bureau of Abbott Laboratories; and is a shareholder in Boston Scientific, Edwards Lifesciences and AstraZeneca., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)