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Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality

Author/s: 
Inoue, K., Ritz, B., Brent, G.A.

Importance  Subclinical hypothyroidism is a common clinical entity among US adults associated in some studies with an increase in the risk of cardiovascular disease (CVD) and mortality. However, the extent to which CVD mediates the association between elevated serum thyrotropin (TSH) and mortality has not yet been well established or sufficiently quantified.

Objective  To elucidate the extent to which subclinical hypothyroidism, elevated serum TSH and normal serum free thyroxine, or high-normal TSH concentrations (ie, upper normative–range TSH concentrations) are associated with mortality through CVD among US adults.

Design, Setting, and Participants  This cohort study relied on representative samples of US adults enrolled in the National Health and Nutrition Examination Survey in 2001 to 2002, 2007 to 2008, 2009 to 2010, and 2011 to 2012 and their mortality data through 2015. Data were analyzed from January to August 2019.

Main Outcomes and Measures  Cox proportional hazards regression models were used to investigate associations between the TSH concentration category (subclinical hypothyroidism or tertiles of serum TSH concentrations within the reference range; low-normal TSH, 0.34-1.19 mIU/L; middle-normal TSH, 1.20-1.95 mIU/L; and high-normal TSH, 1.96-5.60 mIU/L) and all-cause mortality. Mediation analysis was used within the counterfactual framework to estimate natural direct associations (not through CVD) and indirect associations (through CVD).

Results  Of 9020 participants, 4658 (51.6%) were men; the mean (SD) age was 49.4 (17.8) years. Throughout follow-up (median [interquartile range], 7.3 [5.4-8.3] years), serum thyroid function test results consistent with subclinical hypothyroidism and high-normal TSH concentrations were both associated with increased all-cause mortality (subclinical hypothyroidism: hazard ratio, 1.90; 95% CI, 1.14-3.19; high-normal TSH: hazard ratio, 1.36; 95% CI, 1.07-1.73) compared with the middle-normal TSH group. Cardiovascular disease mediated 14.3% and 5.9% of the associations of subclinical hypothyroidism and high-normal TSH with all-cause mortality, respectively, with the CVD mediation being most pronounced in women (7.5%-13.7% of the association) and participants aged 60 years and older (6.0%-14.8% of the association).

Conclusions and Relevance  In this study, CVD mediated the associations of subclinical hypothyroidism and high-normal TSH concentrations with all-cause mortality in the US general population. Further studies are needed to examine the clinical benefit of thyroid hormone replacement therapy targeted to a middle-normal TSH concentration or active CVD screening for people with elevated TSH concentrations.

Keywords 
subclinical hypothyroidism

Osteoporosis Screening in Younger Postmenopausal Women

Author/s: 
Crandall, C.J., Ensrud, Kristine E.

Osteoporotic fractures, especially hip fractures, are associated with mobility limitations, chronic disability, loss of independence, and reduced quality of life.

Several randomized trials have demonstrated the benefit of drug treatment in reducing clinical fractures among postmenopausal women with existing vertebral fractures or bone mineral density (BMD) T-scores of −2.5 or lower and among adults aged 50 years and older with recent hip fracture.

Thus, osteoporosis in the clinical setting should be diagnosed in patients with a history of hip or clinical vertebral fracture not due to excessive trauma, those with existing radiographic vertebral fractures, and those with a BMD T-score of −2.5 or lower at the hip (femoral neck or total hip) or lumbar spine. In the absence of a history of hip or vertebral fracture, osteoporosis screening is aimed at identifying individuals with a BMD T-score of −2.5 or lower because those individuals may be candidates for osteoporosis pharmacotherapy. The BMD T-score quantifies the difference (expressed in standard deviations) between a patient’s BMD and the average BMD of young adult white women (reference group).

Keywords 
osteoporosis screening

Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017

Author/s: 
Osei , A.D., Mirbolouk, M., Orimoloye, O.A., Dzaye, O.

Introduction: The association between e-cigarette use and chronic bronchitis, emphysema, and
chronic obstructive pulmonary disease has not been studied thoroughly, particularly in populations
defined by concomitant combustible smoking status.

Methods: Using pooled 2016 and 2017 data from the Behavioral Risk Factor Surveillance System,
investigators studied 705,159 participants with complete self-reported information on e-cigarette use,
combustible cigarette use, key covariates, and chronic bronchitis, emphysema, or chronic obstructive
pulmonary disease. Current e-cigarette use was the main exposure, with current use further classified
as daily or occasional use. The main outcome was defined as reported ever having a diagnosis of

chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. For all the analyses, multi-
variable adjusted logistic regression was used, with the study population stratified by combustible ciga-
rette use status (never, former, or current). All the analyses were conducted in 2019.

Results: Of 705,159 participants, 25,175 (3.6%) were current e-cigarette users, 64,792 (9.2%) current
combustible cigarette smokers, 207,905 (29.5%) former combustible cigarette smokers, 432,462

(61.3%) never combustible cigarette smokers, and 14,036 (2.0%) dual users of e-cigarettes and combus-
tible cigarettes. A total of 53,702 (7.6%) participants self-reported chronic bronchitis, emphysema, or

chronic obstructive pulmonary disease. Among never combustible cigarette smokers, current e-ciga-
rette use was associated with 75% higher odds of chronic bronchitis, emphysema, or chronic obstruc-
tive pulmonary disease compared with never e-cigarette users (OR=1.75, 95% CI=1.25, 2.45), with

daily users of e-cigarettes having the highest odds (OR=2.64, 95% CI=1.43, 4.89). Similar associations
between e-cigarette use and chronic bronchitis, emphysema, or chronic obstructive pulmonary disease
were noted among both former and current combustible cigarette smokers.
Conclusions: The results suggest possible e-cigarette−related pulmonary toxicity across all thecategories of combustible cigarette smoking status, including those who had never smoked combus-
tible cigarettes.

Keywords 
vaping e-cigarette

Effect of Catheter Ablation vs Medical Therapy on Quality of Life Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial

Author/s: 
Mark, Daniel B., Anstrom, Kevin J., Sheng, Shubin, Piccini, Jonathan P., Baloch, Khaula N., Monahan, Kristi H., Daniels, Melanie R., Bahnson, Tristram D., Poole, Jeanne E., Rosenberg, Yves, Lee, Kerry L., Packer, Douglas L.

IMPORTANCE:

Catheter ablation is more effective than drug therapy in restoring sinus rhythm in patients with atrial fibrillation (AF), but its incremental effect on long-term quality of life (QOL) is uncertain.

OBJECTIVE:

To determine whether catheter ablation is more beneficial than conventional drug therapy for improving QOL in patients with AF.

DESIGN, SETTING, AND PARTICIPANTS:

An open-label randomized clinical trial of catheter ablation vs drug therapy in 2204 symptomatic patients with AF older than 65 years or 65 years or younger with at least 1 risk factor for stroke. Patients were enrolled from November 2009 to April 2016 from 126 centers in 10 countries. Follow-up ended in December 2017.

INTERVENTIONS:

Pulmonary vein isolation, with additional ablation procedures at the discretion of the investigators, for the catheter ablation group (n = 1108) and standard rhythm and/or rate-control drugs selected and managed by investigators for the drug therapy group (n = 1096).

MAIN OUTCOMES AND MEASURES:

Prespecified co-primary QOL end points at 12 months, including the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary score (range, 0-100; 0 indicates complete disability and 100 indicates no disability; patient-level clinically important difference, ≥5 points) and the Mayo AF-Specific Symptom Inventory (MAFSI) frequency score (range, 0-40; 0 indicates no symptoms and 40 indicates the most severe symptoms; patient-level clinically important difference, ≤-1.6 points) and severity score (range, 0-30; 0 indicates no symptoms and 30 indicates the most severe symptoms; patient-level clinically important difference, ≤-1.3 points).

RESULTS:

Among 2204 randomized patients (median age, 68 years; 1385 patients [63%] were men, 946 [43%] had paroxysmal AF, and 1256 [57%] had persistent AF), the median follow-up was 48.5 months, and 1968 (89%) completed the trial. The mean AFEQT summary score was more favorable in the catheter ablation group than the drug therapy group at 12 months (86.4 points vs 80.9 points) (adjusted difference, 5.3 points [95% CI, 3.7-6.9]; P < .001). The mean MAFSI frequency score was more favorable for the catheter ablation group than the drug therapy group at 12 months (6.4 points vs 8.1 points) (adjusted difference, -1.7 points [95% CI, -2.3 to -1.2]; P < .001) and the mean MAFSI severity score was more favorable for the catheter ablation group than the drug therapy group at 12 months (5.0 points vs 6.5 points) (adjusted difference, -1.5 points [95% CI, -2.0 to -1.1]; P < .001).

CONCLUSIONS AND RELEVANCE:

Among patients with symptomatic atrial fibrillation, catheter ablation, compared with medical therapy, led to clinically important and significant improvements in quality of life at 12 months. These findings can help guide decisions regarding management of atrial fibrillation.

Keywords 
atrial fib catheter ablation medical therapy QOL
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