Search

Aims: This study aims to determine the familial incidence of dilated (DCM) and hypertrophic cardiomyopathy (HCM) in first‐degree, second‐degree, and third‐degree relatives of affected individuals. Methods and results: In this population‐based multigenerational cohort study, full‐siblings, half‐siblings, and cousin pairs born to Swedish parents between 1932 and 2015 were included, and register‐based DCM and HCM diagnoses among relatives were ascertained. Adjusted odds ratios (ORs) for DCM and HCM were calculated for relatives of individuals with DCM and HCM compared with relatives of individuals without DCM and HCM for reference. Total study population included 6 334 979 subjects and consisted of 5 577 449 full‐siblings, 1 321 414 half‐siblings, and 3 952 137 cousins. Overall, 10 272 (0.16%) unique individuals were diagnosed with DCM and 3769 (0.06%) with HCM. Of these, 7716 (75.12%) and 2375 (63.01%) were males, respectively. Familial risk ORs for DCM were 5.35 [95% confidence intervals (CI): 4.85–5.90] for full‐siblings, 2.68 (95% CI:1.86–3.87) for half‐siblings, and 1.72 (95% CI:1.12–2.64) for cousins of affected individuals. The ORs for HCM were 42.44 (95% CI:37.66–47.82) for full‐siblings, 32.70 (95% CI:21.32–50.15) for half‐siblings, and 36.96 (95% CI:29.50–46.31) for cousins of affected individuals. In sex‐stratified analysis, relatives of affected females were found more likely to be affected than were relatives of affected males, with stronger aggregation observed for HCM. Conclusions: Familial risk of HCM and DCM is high and associated with genetic resemblance, with strongest aggregations observed in relatives of affected females with HCM, whereas this association was distinctly attenuated for DCM. The finding of a Carter effect, more pronounced in HCM, suggests a multifactorial threshold model of inheritance. [ABSTRACT FROM AUTHOR]

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.)

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.)

Background: Risk factors included in the cardiovascular (CHA 2 DS 2 -VASc) score, currently used for atrial fibrillation (AF), may predispose to cardiovascular events whether or not AF is present. The aim was to explore the predictive role of CHA 2 DS 2 -VASc score on cardiovascular outcomes in diabetic patients without AF., Methods: We accessed individual data from 610 diabetic patients without AF at baseline included in the prospective cohort of the Malmö Diet and Cancer study. Main outcome measure was the occurrence of cardiovascular events (stroke, coronary events) and death. Mean follow-up was 14.5 ± 5 years (8845 person/years)., Results: The CHA 2 DS 2 -VASc score significantly predicted the risk of all outcome measures. There was a significant increase in stroke, coronary events, and death risk by each point of CHA 2 DS 2 -VASc score elevation [stroke: adjusted hazard ratio (aHR) 1.43, 95% CI 1.14-1.79, P = 0.001; coronary events: aHR 1.55, 95% CI 1.34-1.80, P < 0.0001; death: aHR 1.94, 95% CI 1.71-2.21, P < 0.0001]. A CHA 2 DS 2 -VASc score ≥4 was associated with higher incidence of ischemic stroke (aHR 1.47, 95% CI 1.18-1.82; P = 0.001), coronary events (aHR 1.32; 95% CI 1.11-1.58; P = 0.002), and death (aHR 1.36; 95% CI 1.20-1.54; P < 0.001)., Conclusions: In this population-based study on diabetic patients without AF, the CHA 2 DS 2 -VASc score was an independent predictor of ischemic stroke, coronary events, and overall mortality. Regardless of the AF status, the CHA 2 DS 2 -VASc score might represent a rapid and user-friendly tool for clinical assessment of diabetic patients at higher cardiovascular risk., (© 2019 John Wiley & Sons, Ltd.)

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.)

Background: Increased somatostatin plasma concentration has been found in patients with vascular dementia. However, it is unknown whether or not somatostatin levels may predict dementia development in the general population. To this end, we sought to assess the association of circulating N-terminal prosomatostatin (NT-proSST) with incident dementia among community-dwelling older adults., Methods: In the prospective population-based Malmö Preventive Project, 5,347 study participants (mean age: 69 ± 6years; 70% men) provided plasma for the determination of NT-proSST concentration. Of these, 373 participants (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) during a follow-up period of 4.6 ± 1.3 years. The association of NT-proSST with the risk of dementia and its subtypes was studied using multivariable-adjusted Cox regression models controlling for age, gender, body mass index, systolic blood pressure, antihypertensive treatment, smoking, diabetes, lipid levels and prevalent stroke., Results: Higher levels of NT-proSST were significantly associated with an increased risk of vascular dementia (hazard ratio [HR] per 1 SD: 1.29; 95% CI 1.05-1.59; p = 0.016), whereas no association was observed with Alzheimer's disease (HR per 1 SD: 0.99; 95% CI 0.81-1.20; p = 0.91), all-cause dementia (HR per 1 SD: 1.04; 95% CI 0.94-1.16; p = 0.44), and mixed dementia (HR per 1 SD: 0.98; 95% CI 0.79-1.21; p = 0.84). Levels of NT-proSST above 563 pmol/L (highest quartile) conferred distinctly increased risk of vascular dementia (HR 1.66; 95% CI 1.05-2.63; p = 0.029) compared with lower values., Conclusions: Higher levels of circulating N-terminal-prosomatostatin are associated with increased incidence of vascular dementia. Our findings might be of importance for the understanding of dementia development in older adults., (© 2017 S. Karger AG, Basel.)