Background: The benefit of levothyroxine treatment of subclinical hypothyroidism (SCH) is subject to debate. This study compared treatment satisfaction between older adults with SCH using... Show moreBackground: The benefit of levothyroxine treatment of subclinical hypothyroidism (SCH) is subject to debate. This study compared treatment satisfaction between older adults with SCH using levothyroxine or placebo. Methods: We analyzed pooled individual participant data from two randomized, double-blind, placebocontrolled trials investigating the effects of levothyroxine treatment in older adults with SCH. Communitydwelling participants aged ‡65 years, with SCH (persistent thyrotropin levels 4.60–19.99 mIU/L for >3 months and normal free T4 level), were included. Intervention dose titration until thyrotropin levels normalized, with a mock dose adjustment of placebo. Treatment satisfaction was determined during the final study visit using the Treatment Satisfaction Questionnaire for Medication (TSQM), encompassing perceived effectiveness, side effects, convenience, and global satisfaction, along with the participants’ desire to continue study medication after the trial. Results: We included 536 participants. At baseline, the median (interquartile range [IQR]) age was 74.9 (69.7– 81.4) years, and 292 (55%) were women. The median (IQR) thyrotropin levels were 5.80 (5.10–7.00) mIU/L at baseline in both groups; at final visit, 4.97 (3.90–6.35) mIU/L in the placebo and 3.24 (2.49–4.41) mIU/L in the levothyroxine group. After treatment, the groups did not differ significantly in global satisfaction (mean difference [CI] -1.1 [-4.5 to 2.1], p = 0.48), nor in any other domain of treatment satisfaction. These results held true regardless of baseline thyrotropin levels or symptom burden. No major differences were found in the numbers of participants who wished to continue medication after the trial (levothyroxine 35% vs. placebo 27%), did not wish to continue (levothyroxine 27% vs. placebo 30%), or did not know (levothyroxine 37% vs. placebo 42%) (p = 0.14). In a subpopulation with high symptom burden from hypothyroid symptoms at baseline, those using levothyroxine more often desired to continue the medication after the trial than those using placebo (mean difference [CI]: -21.1% [-35.6% to -6.5%]). Show less
Aims The aim of this study was to derive and validate the SCORE2-Older Persons (SCORE2-OP) risk model to estimate 5- and 10-year risk of cardiovascular disease (CVD) in individuals aged over 70... Show moreAims The aim of this study was to derive and validate the SCORE2-Older Persons (SCORE2-OP) risk model to estimate 5- and 10-year risk of cardiovascular disease (CVD) in individuals aged over 70 years in four geographical risk regions.Methods and results Sex-specific competing risk-adjusted models for estimating CVD risk (CVD mortality, myocardial infarction, or stroke) were derived in individuals aged over 65 without pre-existing atherosclerotic CVD from the Cohort of Norway (28 503 individuals, 10 089 CVD events). Models included age, smoking status, diabetes, systolic blood pressure, and total- and high-density lipoprotein cholesterol. Four geographical risk regions were defined based on country-specific CVD mortality rates. Models were recalibrated to each region using region-specific estimated CVD incidence rates and risk factor distributions. For external validation, we analysed data from 6 additional study populations {338 615 individuals, 33 219 CVD validation cohorts, C-indices ranged between 0.63 [95% confidence interval (CI) 0.61-0.65] and 0.67 (0.64-0.69)}. Regional calibration of expected-vs.-observed risks was satisfactory. For given risk factor profiles, there was substantial variation across the four risk regions in the estimated 10-year CVD event risk.Conclusions The competing risk-adjusted SCORE2-OP model was derived, recalibrated, and externally validated to estimate 5- and 10-year CVD risk in older adults (aged 70 years or older) in four geographical risk regions. These models can be used for communicating the risk of CVD and potential benefit from risk factor treatment and may facilitate shared decision-making between clinicians and patients in CVD risk management in older persons. Show less
Gimbel, M.E.; Tavenier, A.H.; Bor, W.; Hermanides, R.S.; Vrey, E. de; Heestermans, T.; ... ; Berg, J.M. ten 2020
There are no randomised data on which antiplatelet agent to use in elderly patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and an indication for oral anticoagulation (OAC). The... Show moreThere are no randomised data on which antiplatelet agent to use in elderly patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and an indication for oral anticoagulation (OAC). The randomised POPular Age trial, in patients of 70 years or older with NSTE-ACS, showed a reduction in bleeding without increasing thrombotic events in patients using clopidogrel as compared to ticagrelor. In this sub-analysis of the POPular AGE trial, we compare clopidogrel with ticagrelor in patients with a need for oral anticoagulation. The follow-up duration was one year. The primary bleeding outcome was Platelet Inhibition and Patient Outcomes (PLATO) major and minor bleeding. The primary thrombotic outcome consisted of cardiovascular death, myocardial infarction and stroke. The primary net clinical benefit outcome was a composite of all-cause death, myocardial infarction, stroke, and PLATO major and minor bleeding. A total of 184/1011 (18.2%) patients on OAC were included in this subanalysis; 83 were randomized to clopidogrel and 101 to ticagrelor. The primary bleeding outcome was lower in the clopidogrel group (17/83, 20.9%) compared to the ticagrelor group (33/101, 33.5%; p = 0.051), as was the thrombotic outcome (7/83, 8.4% vs. 19/101, 19.2%; p = 0.035) and the primary net clinical benefit outcome (23/83, 27.7% vs. 49/101, 48.5%; p = 0.003). In this subgroup of patients using OAC, clopidogrel reduced PLATO major and minor bleeding compared to ticagrelor without increasing thrombotic risk. This analysis therefore suggests that, in line with the POPular Age trial, clopidogrel is a better option than ticagrelor in NSTE-ACS patients >= 70 years using OAC. Show less
Gimbel, M.; Qaderdan, K.; Willemsen, L.; Hermanides, R.; Bergmeijer, T.; Vrey, E. de; ... ; Berg, J. ten 2020
Background Current guidelines recommend potent platelet inhibition with ticagrelor or prasugrel in patients after an acute coronary syndrome. However, data about optimal platelet inhibition in... Show moreBackground Current guidelines recommend potent platelet inhibition with ticagrelor or prasugrel in patients after an acute coronary syndrome. However, data about optimal platelet inhibition in older patients are scarce. We aimed to investigate the safety and efficacy of clopidogrel compared with ticagrelor or prasugrel in older patients with non-STelevation acute coronary syndrome (NSTE-ACS).Methods We did the open-label, randomised controlled POPular AGE trial in 12 sites (ten hospitals and two university hospitals) in the Netherlands. Patients aged 70 years or older with NSTE-ACS were enrolled and randomly assigned in a 1:1 ratio using an internet-based randomisation procedure with block sizes of six to receive a loading dose of clopidogrel 300 mg or 600 mg, or ticagrelor 180 mg or prasugrel 60 mg, and then a maintenance dose for the duration of 12 months (clopidogrel 75 mg once daily, ticagrelor 90 mg twice daily, or prasugrel 10 mg once daily) on top of standard care. Patient and treating physicians were aware of the allocated treatment strategy, but the outcome assessors were masked to treatment allocation. Primary bleeding outcome consisted of PLATelet inhibition and patient Outcomes (PLATO; major or minor bleeding [superiority hypothesis]). Co-primary net clinical benefit outcome consisted of allcause death, myocardial infarction, stroke, PLATO major and minor bleeding (non-inferiority hypothesis, margin of 2%). Follow-up duration was 12 months. Analyses were done on intention-to-treat basis. This trial is registered with the Netherlands Trial Register (NL3804), ClinicalTrials.gov (NCT02317198), and EudraCT (2013-001403-37).Findings Between June 10, 2013, and Oct 17, 2018, 1002 patients were randomly assigned to clopidogrel (n=500) or ticagrelor or prasugrel (n=502). Because 475 (95%) patients received ticagrelor in the ticagrelor or prasugrel group, we will refer to this group as the ticagrelor group. Premature discontinuation of the study drug occurred in 238 (47%) of 502 ticagrelor group patients randomly assigned to ticagrelor, and in 112 (22%) of 500 patients randomly assigned to clopidogrel. Primary bleeding outcome was significantly lower in the clopidogrel group (88 [18%] of 500 patients) than in the ticagrelor group (118 [24%] of 502; hazard ratio 0.71, 95% CI 0.54 to 0.94; p=0.02 for superiority). Co-primary net clinical benefit outcome was non-inferior for the use of clopidogrel (139 [28%]) versus ticagrelor (161 [32%]; absolute risk difference -4%, 95% CI -10.0 to 1.4; p=0.03 for non-inferiority). The most important reasons for discontinuation were occurrence of bleeding (n=38), dyspnoea (n=40), and the need for treatment with oral anticoagulation (n=35).Interpretation In patients aged 70 years or older presenting with NSTE-ACS, clopidogrel is a favourable alternative to ticagrelor, because it leads to fewer bleeding events without an increase in the combined endpoint of all-cause death, myocardial infarction, stroke, and bleeding. Clopidogrel could be an alternative P2Y12 inhibitor especially for elderly patients with a higher bleeding risk. Show less
Ferreira, J.P.; Verdonschot, J.; Collier, T.; Wang, P.; Pizard, A.; Bar, C.; ... ; Zannad, F. 2019
BACKGROUND: Identifying the mechanistic pathways potentially associated with incident heart failure (HF) may provide a basis for novel preventive strategies.METHODS AND RESULTS: To identify... Show moreBACKGROUND: Identifying the mechanistic pathways potentially associated with incident heart failure (HF) may provide a basis for novel preventive strategies.METHODS AND RESULTS: To identify proteomic biomarkers and the potential underlying mechanistic pathways that may be associated with incident HF defined as the first hospitalization for HF, a nested-matched case-control design was used with cases (incident HF) and controls (without HF) selected from 3 cohorts (> 20 000 individuals). Controls were matched on cohort, follow-up time, age, and sex. Two independent sample sets (a discovery set with 286 cases and 591 controls and a replication set with 276 cases and 280 controls) were used to discover and replicate the findings. Two hundred fifty-two circulating proteins in the plasma were studied. Adjusting for the matching variables age, sex, and follow-up time (and correcting for multiplicity of tests), 89 proteins were found to be associated with incident HF in the discovery phase, of which 38 were also associated with incident HF in the replication phase. These 38 proteins pointed to 4 main network clusters underlying incident HF: (1) inflammation and apoptosis, indicated by the expression of the TNF (tumor necrosis factor)-family members; (2) extracellular matrix remodeling, angiogenesis and growth, indicated by the expression of proteins associated with collagen metabolism, endothelial function, and vascular homeostasis; (3) blood pressure regulation, indicated by the expression of natriuretic peptides and proteins related to the reninangiotensin- aldosterone system; and (4) metabolism, associated with cholesterol and atherosclerosis.CONCLUSIONS: Clusters of biomarkers associated with mechanistic pathways leading to HF were identified linking inflammation, apoptosis, vascular function, matrix remodeling, blood pressure control, and metabolism. These findings provide important insight on the pathophysiological mechanisms leading to HF. Show less
Inflammation plays an important role in the development of cognitive decline and dementia in old age. Galectin-3 is known for its role in acute and chronic inflammation. We assessed whether genetic... Show moreInflammation plays an important role in the development of cognitive decline and dementia in old age. Galectin-3 is known for its role in acute and chronic inflammation. We assessed whether genetic variation in the LGALS3 gene, encoding for galectin-3, associates with cognitive function in the 5804 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). The rs4644, rs4652, and rs1009977 polymorphisms were genotyped to cover the genomic region of the LGALS3 gene. Subjects carrying the variant alleles of each LGALS3 single nucleotide polymorphism (SNP) had significantly higher baseline C-reactive protein concentrations (p < 0.01). Carriers of the variant alleles had significantly worse performance at baseline compared with carriers of the wild-type allele (all p < 0.05). In the longitudinal analysis, we found that carriers of the variant alleles had worse performance at the attention tasks compared with carriers of the wild-type allele. Although observed differences were small, these data suggest that genetic variation in the LGALS3 gene might be associated with cognitive function in an elderly population. Further research is warranted to confirm these results. Show less
