Alexandra Bremner

Age-Related Changes in Thyroid Function: A Longitudinal Study of a Community-Based Cohort

CONTEXT In cross-sectional studies, serum TSH concentrations increase with age. This has not been examined longitudinally, and it is uncertain whether the TSH increase reflects healthy aging or occult thyroid failure. METHODS We measured serum TSH, free T(4), thyroid peroxidase, and thyroglobulin antibodies in 1100 participants in the 1981 and 1994 Busselton Health Surveys and derived a reference group of 908 individuals without thyroid disease or thyroid antibodies. We examined changes in thyroid function longitudinally and, in 781 participants, explored associations with the CAPZB polymorphism rs10917469. RESULTS At 13 yr follow-up, mean serum TSH increased from 1.49 to 1.81 mU/liter, a change in mean TSH (ΔTSH) of 0.32 mU/liter [95% confidence interval (CI) 0.27, 0.38, P < 0.001], whereas mean free T(4) concentration was unchanged (16.6 vs. 16.6 pmol/liter, P = 0.7). The TSH increase was most marked in the elderly, such that gender-adjusted ΔTSH increased by 0.08 mU/liter (95% CI 0.04, 0.11) for each decade of baseline age. People with higher baseline TSH values had proportionally smaller increases in TSH, with each additional 1.0 mU/liter of baseline TSH associated with a 0.13 mU/liter decrease (age and gender adjusted) in ΔTSH (95% CI 0.09, 0.16). The ΔTSH did not differ significantly by CAPZB genotype. CONCLUSIONS Aging is associated with increased serum TSH concentrations, with no change in free T(4) concentrations. The largest TSH increase is in people with the lowest TSH at baseline. This suggests that the TSH increase arises from age-related alteration in the TSH set point or reduced TSH bioactivity rather than occult thyroid disease.

Erectile dysfunction as a predictor for subsequent atherosclerotic cardiovascular events: Findings from a linked-data study

INTRODUCTION In spite of the mounting interest in the nexus between erectile dysfunction (ED) and cardiovascular (CV) diseases, there is little published information on the role of ED as a predictor for subsequent CV events. AIM This study aimed to investigate the role of ED as a predictor for atherosclerotic CV events subsequent to the manifestation of ED. Method. The investigation involved the retrospective study of data on a cohort of men with ED linked to hospital morbidity data and death registrations. By using the linked data, the incidence rates of atherosclerotic CV events subsequent to the manifestation of ED were estimated in men with ED and no atherosclerotic CV disease reported prior to the manifestation of ED. The risk of subsequent atherosclerotic CV events in men with ED was assessed by comparing these incidence rates with those in the general male population. MAIN OUTCOME MEASURE Standardized incidence rate ratio (SIRR), comparing the incidence of atherosclerotic CV events subsequent to the manifestation of ED in a cohort of 1,660 men with ED to the incidence in the general male population. RESULTS On the basis of hospital admissions and death registrations, men with ED had a statistically significantly higher incidence of atherosclerotic CV events (SIRR 2.2; 95% confidence interval 1.9, 2.4). There were significantly increased incidence rate ratios in all age groups younger than 70 years, with a statistically highly significant downward trend with increase of age (P < 0.0001) across these age groups. Younger age at first manifestation of ED, cigarette smoking, presence of comorbidities and socioeconomic disadvantage were all associated with higher hazard ratios for subsequent atherosclerotic CV events. CONCLUSIONS The findings show that ED is not only significantly associated with but is also strongly predictive of subsequent atherosclerotic CV events. This is even more striking when ED presents at a younger age.

Thyrotropin and thyroid antibodies as predictors of hypothyroidism: a 13-year, longitudinal study of a community-based cohort using current immunoassay techniques.

CONTEXT Longitudinal studies of risk factors for hypothyroidism are required to inform debate regarding the TSH reference range. There are limited longitudinal data on the predictive value of thyroid antibodies measured by automated immunoassay (as opposed to semiquantitative methods). METHODS We measured TSH, free T(4), thyroid peroxidase antibodies (TPOAbs), and thyroglobulin antibodies (TgAbs) using the Immulite platform on sera from 1184 participants in the 1981 and 1994 Busselton Health Surveys. Outcome measures at follow-up were hypothyroidism, defined as TSH greater than 4.0 mU/liter or on thyroxine treatment; and overt hypothyroidism, defined as TSH above 10.0 mU/liter or on thyroxine treatment. Receiver-operator characteristic analysis was used to determine optimal cutoffs for baseline TSH, TPOAbs, and TgAbs as predictors of hypothyroidism. RESULTS At 13 yr follow-up, 110 subjects (84 women) had hypothyroidism, of whom 42 (38 women) had overt hypothyroidism. Optimal cutoffs for predicting hypothyroidism were baseline TSH above 2.5 mU/liter, TPOAbs above 29 kIU/liter, and TgAbs above 22 kIU/liter, compared with reference range upper limits of 4.0 mU/liter, 35 kIU/liter, and 55 kIU/liter, respectively. In women with positive thyroid antibodies (TPOAbs or TgAbs), the prevalence of hypothyroidism at follow-up (with 95% confidence intervals) was 12.0% (3.0-21.0%) when baseline TSH was 2.5 mU/liter or less, 55.2% (37.1-73.3%) for TSH between 2.5 and 4.0 mU/liter, and 85.7% (74.1-97.3%) for TSH above 4.0 mU/liter. CONCLUSIONS The use of TSH cutoffs of 2.5 and 4.0 mU/liter, combined with thyroid antibodies, provides a clinically useful estimate of the long-term risk of hypothyroidism.

Thyroid dysfunction and serum lipids: a community‐based study

Objective  It is uncertain whether subclinical hypothyroidism (SCH) is associated with hypercholesterolaemia, particularly in subjects with SCH and serum TSH ≤ 10 mU/l.

Subclinical thyroid dysfunction and blood pressure : a community-based study

Objective  Overt hypothyroidism and hyperthyroidism are associated with hypertension, but it is uncertain whether the same is true of subclinical hypothyroidism and hyperthyroidism.

A randomized controlled equivalence trial of short‐term complications and efficacy of tension‐free vaginal tape and suprapubic urethral support sling for treating stress incontinence

To establish the equivalence between the tension‐free vaginal tape (TVT) and the suprapubic urethral support sling (SPARC). Approximately 35% of women have stress urinary incontinence (SUI), and although TVT is now perceived as the standard treatment, the SPARC is a very similar procedure and is thought to have fewer peri‐operative complications.

Subclinical Thyroid Dysfunction and Fracture Risk: A Meta-analysis

IMPORTANCE Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. CONCLUSIONS AND RELEVANCE Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.

Male Erectile Dysfunction and Cardiovascular Disease: Is There an Intimate Nexus?

INTRODUCTION Various studies report increased risk of erectile dysfunction (ED) in men with cardiovascular (CV) disease and postulate an intimate nexus between the two conditions. AIM To examine the association of ED with CV risk factors and disease in a population-based cross-sectional observational study conducted in Western Australia (WA). Method. Postal questionnaires were sent to randomly selected age-stratified male population samples obtained from the WA Electoral Roll. MAIN OUTCOME MEASURES In addition to items covering sociodemographic and self-reported clinical information, the 5-item International Index of Erectile Function (IIEF-5) was used. RESULTS Of the 1,580 participants, the ages of 1,514 were known and ranged from 20 to 99 years (mean 57.9, median 59.1, standard deviation 18.5). CV risk factors and disease were more prevalent with increasing age and among participants with ED and severe ED. The age-adjusted odds of ED were significantly higher among participants with hypertension (odds ratio [OR] 1.47; 95% confidence intervals [CI] 1.05, 2.07), ischemic heart disease (OR 1.80; 95% CI 1.10, 2.94), and stroke (OR 3.30; 95% CI 1.22, 8.88), and with these conditions and peripheral arterial disease grouped together as CV disease (OR 1.85; 95% CI 1.34, 2.56). Many participants with hyperlipidemia were receiving treatment, and the age-adjusted odds for ED were not significantly higher. The age-adjusted odds of ED among participants with diabetes mellitus were 2.76 (95% CI 1.52, 5.00), and were 3.21 (95% CI 1.03, 10.05) when hypertension and hyperlipidemia were also present. CONCLUSIONS The findings support the postulated intimate nexus between ED and CV disease. The adverse effects of age and CV risk factors and disease on erectile function compound each other. The socioeconomic, epidemiologic, and clinical implications are immense.

Audiovisual feedback device use by health care professionals during CPR: A systematic review and meta-analysis of randomised and non-randomised trials

OBJECTIVES A systematic appraisal of the literature to determine if audiovisual feedback devices can improve CPR quality delivered by health care practitioners (HCPs) and/or survival outcomes following cardiac arrest. METHODS We searched the Cochrane Central Register of Controlled Studies (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE, CIHAHL and AUSTHEALTH in May 2013 for experimental and observational (human or manikin) studies examining the effect of the use of audiovisual feedback devices by HCPs in simulated and actual cardiac arrest. The primary outcome for human studies was survival to hospital discharge with good neurologic outcome. Secondary outcomes were other survival data and quality of CPR performance; the latter was also reported for manikin studies. RESULTS Three human interventional studies (n=2100) and 17 manikin studies met the inclusion criteria. Overall quality of included studies was poor, with significant clinical heterogeneity. All three human studies reported no significant change to any survival outcomes despite improvement in chest compression (CC) depth by 2.5 mm (95% CI 0.9-4.3), CC rate 6 min(-1) closer to 100 (95% CI 2.4-10.7) and a reduction in no-flow fraction by 1.9% on meta-analysis. Manikin studies showed similar improvements in CC parameters. CONCLUSION In both manikin and human studies, feedback during resuscitation can result in rescuers providing CC parameters closer to recommendations. There is no evidence that this translates into improved patient outcomes. The reason for this is not yet evident and further patient centered research is warranted.

Significant inverse relationship between serum free T4 concentration and body mass index in euthyroid subjects: differences between smokers and nonsmokers.

Objective  There are conflicting data regarding the relationship between thyroid function and body mass index (BMI) in euthyroid subjects, and it is uncertain whether tobacco smoking modifies this relationship. The objective of this study was to examine the relationships between thyroid function, BMI and smoking in euthyroid subjects.