Background Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. Methods We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid stimulating hormone (TSH) 0.45–4.49mIU/l, and subclinical hypothyroidism as TSH 4.5–19.9mIU/l with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. Results Of 30,085 participants from 11 cohorts (278,955 person-years of follow-up), 1,958 (6.5%) had subclinical hypothyroidism, and 2,574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio=1.45; 95% confidence interval, 1.26–1.66, for the highest quartile vs the lowest quartile of fT4, p for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. Conclusion In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.
Subclinical thyroid dysfunction comprises subclinical hypothyroidism (SHypo), defined as elevated thyroid-stimulating hormone (TSH) by normal free thyroxine (FT4), and subclinical hyperthyroidism (SHyper) with decreased or undetectable TSH and normal FT4. Up to 10% of the elderly have SHypo, which is usually asymptomatic. Individual participant data (IPD) analyses of prospective cohort studies from the international Thyroid Studies Collaboration show that SHypo is associated with increased coronary heart disease (CHD) mortality [hazard ratio (HR) 1,58 for TSH ≥ 10 mIU/L, 95% CI 1.10-2.27), as well as increased risk of stroke, and heart failure (HF) for both higher and lower TSH. Small studies found that SHypo affects carotid intima media thickness (CIMT), diastolic function, peripheral vascular resistance, endothelial function, and lipid profile. SHyper is associated with increased risk of atrial fibrillation (AF) (HR 1.68, 95% CI 1.16-2.43) and CHD events (HR 1.21, 95% CI 0.99-1.46). The TSH threshold for initiating treatment is unclear. In the absence of large randomized controlled trials, the best evidence suggests SHypo therapy should be started at TSH ≥ 10 mIU/L, and SHyper therapy at TSH < 0.1 mIU/L. Recommendations on screening are discordant, but most guidelines advocate that thyroid function should be checked in those at risk for hypothyroidism, those over 60, and those with known CHD and HF. This review updates current evidence on the association between thyroid dysfunction and cardiovascular disease, as well as on screening and treatment of subclinical thyroid dysfunction.
The DRA adjudication guide is the first standardized chart review method to identify DRA in older persons. Content validity, feasibility of use and inter-rater reliability were found to be satisfactory. The method can be used as an outcome measure for interventions targeted at improving quality and safety of medication use in older people.
Introduction Multimorbidity and polypharmacy are current challenges when caring for the older population. Both have led to an increase of potentially inappropriate medication (PIM), illustrating the need to assess patients’ attitudes towards deprescribing. We aimed to assess the prevalence of PIM use and whether this was associated with patient factors and willingness to deprescribe. Method We analysed data from the LESS Study, a cross-sectional study on self-reported medication and on barriers and enablers towards the willingness to deprescribe (rPATD questionnaire). The survey was conducted among multimorbid (≥3 chronic conditions) participants ≥70 years with polypharmacy (≥5 long-term medications). A subset of the Beers 2019 criteria was applied for the assessment of medication appropriateness. Results Data from 300 patients were analysed. The mean age was 79.1 years (SD 5.7). 53% had at least one PIM (men: 47.8%%, women: 60.4%%; p = 0.007). A higher number of medications was associated with PIM use (p = 0.002). We found high willingness to deprescribe in both participants with and without PIM. Willingness to deprescribe was not associated with PIM use (p = 0.25), nor number of PIMs (p = 0.81). Conclusion The willingness of older adults with polypharmacy towards deprescribing was not associated with PIM use in this study. These results suggest that patients may not be aware if they are taking PIMs. This implies the need for raising patients’ awareness about PIMs through education, especially in females, in order to implement deprescribing in daily practice.
Main Outcome MeasuresPrimary outcome was incident hip fracture. Secondary outcomes were any, non-vertebral, and vertebral fractures. Results were presented as hazard ratios (HR) with 95% confidence interval (CI) adjusted for age and sex. For clinical relevance, we studied TSH according to five categories: 0.45-0.99mIU/L; 1.00-1.49mIU/L; 1.50-2.49mIU/L; 2.50-3.49mIU/L; 3.50-4.49mIU/L (reference). FT4 was assessed as study-specific standard deviation increase, because assays varied between cohorts. Results During 659,059 person-years, 2,565/56,835 participants had hip fracture (4.5%; 12 studies with data on hip fracture). The pooled adjusted HR (95% CI) for hip fracture was 1.25 (1.05-1.49) for TSH 0.45-0.99mIU/L, 1.19 (1.01-1.41) for TSH 1.00-1.49mIU/L, 1.09 (0.93-1.28) for TSH 1.50-2.49mIU/L, and 1.12 (0.94-1.33) for TSH 2.50-3.49mIU/L (P for trend = 0.004). Hip fracture was also associated with FT4 (HR [95%CI] 1.22 [1.11-1.35] per one standard deviation increase in FT4). FT4 only was associated with any and non-vertebral fracture. Results remained similar in sensitivity analyses. Conclusions Among euthyroid adults, lower TSH and higher FT4 are associated with an increased risk of hip fracture. These findings may help refine the definition of optimal ranges of thyroid function tests.In an individual participant data analysis of 13 prospective cohorts, lower thyroid-stimulating hormone within reference range and higher FT4 were associated with an increased hip fractures risk. INTRODUCTIONOvert hyperthyroidism is a well-known risk factor for fracture and is associated with decreased bone mineral density (BMD) (1). We recently showed that subclinical hyperthyroidism was also associated with increased fracture incidence (2). Thyroid hormones stimulate bone turnover acting directly and indirectly on osteoclasts and osteoblasts (3). Anabolic action is net during growth, but in adults, catabolic action leads to greater bone loss and higher fracture risk (3). Thyroid hormones might also decrease muscular strength and coordination, and increase the risk of fall (4, 5). Administering TSH reduces bone resorption and increases bone formation in postmenopausal women monitored for thyroid cancer (6). Conversely, high TSH levels can degrade bone quality by increasing cortical, rather than trabecular bone.The reference range for thyroid function tests -"euthyroidism" -is defined by the 2.5 to 97.5 percentiles in an apparently healthy population. However, the studies from which TSH reference range was derived did not exclude participants with occult or underlying disease, e.g. those with positive anti-thyroid antibodies, which might bias the reference range towards higher TSH values (7, 8). In medicine, reference ranges can be derived from normative data, as for thyroid function tests, or preferably determining levels associated with important risks or outcomes, as for lipids, or blood pressure.TSH within the lower reference range has been associated with osteoporosis and fracture mostly in cross-sectional studies of healthy po...
Higher odds of having anemia were observed in participants with both hypothyroid function and hyperthyroid function. In addition, reduced thyroid function at baseline showed a trend of increased risk of developing anemia during follow-up. It remains to be assessed in a randomized controlled trial whether treatment is effective in reducing anemia.
OBJECTIVES: As a person's age increases and his/her health status declines, new challenges arise that may lead physicians to consider deprescribing statins. We aimed to provide insight into recommendations available in international cardiovascular disease prevention guidelines regarding discontinuation of statin treatment applicable to older adults. DESIGN: We systematically searched PubMed, EMBASE, EMCARE, and the websites of guideline development organizations and online guideline repositories for cardiovascular disease prevention guidelines aimed at the general population. We selected all guidelines with recommendations (instructions and suggestions) on discontinuation of statin treatment applicable to older adults, published between January 2009 and April 2019. In addition, we performed a synthesis of information from all other recommendations for older adults regarding statin treatment. Methodological quality of the included guidelines was appraised using the appraisal of guidelines for research & evaluation II (AGREE II) instrument. RESULTS: Eighteen international guidelines for cardiovascular disease prevention in the general adult population provided recommendations for statin discontinuation that were applicable to older adults. We identified three groups of instructions for statin discontinuation related to statin intolerance, and none was specifically aimed at older adults. Three guidelines also included suggestions to consider statin discontinuation in patients with poor health status. Of the 18 guidelines included, 16 made recommendations regarding statin treatment in older adults, although details on how to implement these recommendations in practice were not provided. CONCLUSION: Current international cardiovascular disease prevention guidelines provide little specific guidance for physicians who are considering statin discontinuation in older adults in the context of declining health status and short life expectancy. J Am Geriatr Soc 68:417-425, 2020.
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