Subclinical hyperthyroidism and the risk of coronary heart disease and mortality.

BACKGROUND: Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting.We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts. METHODS: Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications. RESULTS: Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio[HR], 1.24, 95% CI, 1.06-1.46), CHD mortality (HR,1.29; 95% CI, 1.02-1.62), CHD events (HR, 1.21; 95%CI, 0.99-1.46), and AF (HR, 1.68; 95% CI, 1.16-2.43).Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% forAF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L(for both, P value for trend, .03). CONCLUSION: Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.

Thyroid function and prevalent and incident metabolic syndrome in older adults: the Health, Ageing and Body Composition Study.

OBJECTIVE: Both subclinical hypothyroidism and the metabolic syndrome have been associated with increased risk of coronary heart disease events. It is unknown whether the prevalence and incidence of metabolic syndrome is higher as TSH levels increase, or in individuals with subclinical hypothyroidism. We sought to determine the association between thyroid function and the prevalence and incidence of the metabolic syndrome in a cohort of older adults. DESIGN: Data were analysed from the Health, Ageing and Body Composition Study, a prospective cohort of 3075 community-dwelling US adults. PARTICIPANTS: Two thousand one hundred and nineteen participants with measured TSH and data on metabolic syndrome components were included in the analysis. MEASUREMENTS: TSH was measured by immunoassay. Metabolic syndrome was defined per revised ATP III criteria. RESULTS: At baseline, 684 participants met criteria for metabolic syndrome. At 6-year follow-up, incident metabolic syndrome developed in 239 individuals. In fully adjusted models, each unit increase in TSH was associated with a 3% increase in the odds of prevalent metabolic syndrome (OR, 1.03; 95% CI, 1.01-1.06; P = 0.02), and the association was stronger for TSH within the normal range (OR, 1.16; 95% CI, 1.03-1.30; P = 0.02). Subclinical hypothyroidism with a TSH > 10 mIU/l was significantly associated with increased odds of prevalent metabolic syndrome (OR, 2.3; 95% CI, 1.0-5.0; P = 0.04); the odds of incident MetS was similar (OR 2.2), but the confidence interval was wide (0.6-7.5). CONCLUSIONS: Higher TSH levels and subclinical hypothyroidism with a TSH > 10 mIU/l are associated with increased odds of prevalent but not incident metabolic syndrome.

Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women.

The magnitude of coffee-induced thermogenesis and the influence of coffee ingestion on substrate oxidation were investigated in 10 lean and 10 obese women, over two 24-h periods in a respiratory chamber. On one occasion the subjects consumed caffeinated coffee and on the other occasion, decaffeinated coffee. The magnitude of thermogenesis was smaller in obese (4.9 +/- 2.0%) than in lean subjects (7.6 +/- 1.3%). The thermogeneic response to caffeine was prolonged during the night in lean women only. The coffee-induced stimulation of energy expenditure was mediated by a concomitant increase in lipid and carbohydrate oxidation. During the next day, in postabsorptive basal conditions, the thermogenic effect of coffee had vanished, but a significant increase in lipid oxidation was observed in both groups. The magnitude of this effect was, however, blunted in obese women (lipid oxidation increased by 29 and 10% in lean and obese women, respectively). Caffeine increased urinary epinephrine excretion. Whereas urinary caffeine excretion was similar in both groups, obese women excreted more theobromine, theophylline, and paraxanthine than lean women. Despite the high levels of urinary methylxanthine excretion, thermogenesis and lipid oxidation were less stimulated in obese than in lean subjects.

Decreased PM10 exposure attenuates age-related lung function decline: genetic variants in p53, p21, and CCND1 modify this effect.

BACKGROUND: Decreasing exposure to airborne particulates was previously associated with reduced age-related decline in lung function. However, whether the benefit from improved air quality depends on genetic background is not known. Recent evidence points to the involvement of the genes p53 and p21 and of the cell cycle control gene cyclin D1 (CCND1) in the response of bronchial cells to air pollution. OBJECTIVE: We determined in 4,326 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether four single-nucleotide polymorphisms in three genes [CCND1 (rs9344 [P242P], rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the previously observed attenuation of the decline in the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF(25-75)) associated with improved air quality. METHODS: Subjects of the prospective population-based SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and biological sample collection for genotyping. We assigned spatially resolved concentrations of particulate matter with aerodynamic diameter < or = 10 microm (PM(10)) to each participant's residential history 12 months before the baseline and follow-up assessments. RESULTS: The effect of diminishing PM(10) exposure on FEF(25-75) decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-microg/m(3) decline in average PM(10) exposure over an 11-year period attenuated the average annual decline in FEF(25-75) by 21.33 mL/year (95% confidence interval, 10.57-32.08) among participants homozygous for the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38-22.06) among GA genotypes, and by 6.00 mL/year (-4.54 to 16.54) among AA genotypes. CONCLUSIONS: Our results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults.

Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts.

BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L.

Right Hepatectomy in Patients over 70 Years of Age: An Analysis of Liver Function and Outcome.

BACKGROUND: As a consequence of the increase in life expectancy, hepatobiliary surgeons have to deal with an emerging aged population. We aimed to analyze the liver function and outcome after right hepatectomy (RH) in patients over 70 years of age. METHODS: From January 2006 to December 2009, we prospectively collected data of 207 consecutive elective hepatectomies. In patients who had RH, cardiac risk was assessed by a dedicated preoperative workup. Liver failure (LF) was defined by the "fifty-fifty" criteria at postoperative day 5 (POD) and morbidity by the Clavien-Dindo classification. Liver function tests (LFTs) and short-term outcome were retrospectively analyzed in patients over (elderly group, EG) and younger (young group, YG) than 70 years of age. RESULTS: Eighty-seven consecutive RH were performed during the study period. Indication for surgery included 90 % malignancy in 47 % of patients requiring preoperative chemotherapy. ASA grade > 2 (44 vs. 16 %, p = 0.027), ischemic heart disease (17 vs. 5 %, p = 0.076), and preoperative cardiac failure (26 vs. 2 %, p < 0.001) were more frequent in the EG (n = 23) than in the YG (n = 64). Both groups were similar regarding rates of normal liver parenchyma, chemotherapy and intraoperative parameters. The overall morbidity rates were comparable, but the serious complication (grades III-V) rate was relatively higher in the EG (39 vs. 25 %, p = 0.199), particularly in patients with diabetes mellitus (100 vs. 29 %, p = 0.04) and those who had additional nonhepatic surgery (67 vs. 35 %, p = 0.110) and transfusions (44 vs. 30 %, p = 0.523). The 90-day mortality rate was similar (9 % in the EG vs. 3 % in the YG, p = 0.28) and was related to heart failure in the EG. LFTs showed a similar trend from POD 1 to 8, and patients ≥70 years of age had no liver failure. CONCLUSIONS: Age ≥70 years alone is not a contraindication to RH. However, major morbidity is particularly higher in the elderly with diabetes. This high-risk group should be closely monitored in the postoperative course. Liver function is not altered in the elderly patient after RH.

How to interprete subclinical thyroid dysfunction in the prevention and management of heart failure events? Individual participant data analysis from six prospective cohorts

Background: Guidelines of the Diagnosis and Management of Heart Failure (HF) recommend investigating exacerbating conditions, such as thyroid dysfunction, but without specifying impact of different TSH levels. Limited prospective data exist regarding the association between subclinical thyroid dysfunction and HF events. Methods: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of HF events. Individual data on 25,390 participants with 216,247 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH 0.45-4.49 mIU/L, subclinical hypothyroidism as TSH 4.5-19.9 mIU/L and subclinical hyperthyroidism as TSH <0.45 mIU/L, both with normal free thyroxine levels. HF events were defined as acute HF events, hospitalization or death related to HF events. Results: Among 25,390 participants, 2068 had subclinical hypothyroidism (8.1%) and 648 subclinical hyperthyroidism (2.6%). In age- and gender-adjusted analyses, risks of HF events were increased with both higher and lower TSH levels (P for quadratic pattern<0.01): hazard ratio (HR) was 1.01 (95% confidence interval [CI] 0.81-1.26) for TSH 4.5-6.9 mIU/L, 1.65 (CI 0.84-3.23) for TSH 7.0-9.9 mIU/L, 1.86 (CI 1.27-2.72) for TSH 10.0-19.9 mIUL/L (P for trend <0.01), and was 1.31 (CI 0.88-1.95) for TSH 0.10-0.44 mIU/L and 1.94 (CI 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. Conclusion: Risks of HF events were increased with both higher and lower TSH levels, particularly for TSH ≥10 mIU/L and for TSH <0.10 mIU/L. Our findings might help to interpret TSH levels in the prevention and investigation of HF.

Cardiologie. Tests de réactivité plaquettaire: mise à jour pour le praticien [Cardiology. Platelet function testing for clinicians].

Platelet P2YI2 receptor inhibition with clopidogrel, prasugrel or ticagrelor plays a key role to prevent recurrent ischaemic events after percutaneous coronary intervention in acute coronary syndromes or elective settings. The degree of platelet inhibition depends on the antiplatelet medication used and is influenced by clinical and genetic factors. A concept of therapeutic window exists. On one side, efficient anti-aggregation is required in order to reduce cardio-vascular events. On the other side, an excessive platelet inhibition represents a risk of bleeding complications. This article describes the current knowledge about some platelet function tests and genetic tests and summarises their role in the clinical practice.

Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality

BACKGROUND: Data on the association between subclinical thyroid dysfunction and coronary heart disease (CHD) and mortality are conflicting. PURPOSE: To summarize prospective evidence about the relationship between subclinical thyroid dysfunction and CHD and mortality. DATA SOURCES: MEDLINE (1950 to January 2008) without language restrictions and reference lists of retrieved articles were searched. STUDY SELECTION: Two reviewers screened and selected cohort studies that measured thyroid function and then followed persons prospectively to assess CHD or mortality. DATA EXTRACTION: By using a standardized protocol and forms, 2 reviewers independently abstracted and assessed studies. DATA SYNTHESIS: Ten of 12 identified studies involved population-based cohorts that included 14 449 participants. All 10 population-based cohort studies examined risks associated with subclinical hypothyroidism (2134 CHD events and 2822 deaths), whereas only 5 examined risks associated with subclinical hyperthyroidism (1392 CHD events and 1993 deaths). In a random-effects model, the relative risk (RR) for subclinical hypothyroidism for CHD was 1.20 (95% CI, 0.97 to 1.49; P for heterogeneity = 0.14; I(2 )= 33.4%). Risk estimates were lower when higher-quality studies were pooled (RR, 1.02 to 1.08) and were higher among participants younger than 65 years (RR, 1.51 [CI, 1.09 to 2.09] for studies with mean participant age <65 years and 1.05 [CI, 0.90 to 1.22] for studies with mean participant age > or =65 years). The RR was 1.18 (CI, 0.98 to 1.42) for cardiovascular mortality and 1.12 (CI, 0.99 to 1.26) for total mortality. For subclinical hyperthyroidism, the RR was 1.21 (CI, 0.88 to 1.68) for CHD, 1.19 (CI, 0.81 to 1.76) for cardiovascular mortality, and 1.12 (CI, 0.89 to 1.42) for total mortality (P for heterogeneity >0.50; I(2 )= 0% for all studies). LIMITATIONS: Individual studies adjusted for different potential confounders, and 1 study provided only unadjusted data. Publication bias or selective reporting of outcomes could not be excluded. CONCLUSION: Subclinical hypothyroidism and hyperthyroidism may be associated with a modest increased risk for CHD and mortality, with lower risk estimates when pooling higher-quality studies and larger CIs for subclinical hyperthyroidism

Pulmonary function, cholinergic bronchomotor tone, and cardiac autonomic abnormalities in type 2 diabetic patients

This prospective study analyzed the involvement of the autonomic nervous system in pulmonary and cardiac function by evaluating cardiovascular reflex and its correlation with pulmonary function abnormalities of type 2 diabetic patients. Diabetic patients (N = 17) and healthy subjects (N = 17) were evaluated by 1) pulmonary function tests including spirometry, He-dilution method, N2 washout test, and specific airway conductance (SGaw) determined by plethysmography before and after aerosol administration of atropine sulfate, and 2) autonomic cardiovascular activity by the passive tilting test and the magnitude of respiratory sinus arrhythmia (RSA). Basal heart rate was higher in the diabetic group (87.8 ± 11.2 bpm; mean ± SD) than in the control group (72.9 ± 7.8 bpm, P<0.05). The increase of heart rate at 5 s of tilting was 11.8 ± 6.5 bpm in diabetic patients and 17.6 ± 6.2 bpm in the control group (P<0.05). Systemic arterial pressure and RSA analysis did not reveal significant differences between groups. Diabetes intragroup analysis revealed two behaviors: 10 patients with close to normal findings and 7 with significant abnormalities in terms of RSA, with the latter subgroup presenting one or more abnormalities in other tests and clear evidence of cardiovascular autonomic dysfunction. End-expiratory flows were significantly lower in diabetic patients than in the control group (P<0.05). Pulmonary function tests before and after atropine administration demonstrated comparable responses by both groups. Type 2 diabetic patients have cardiac autonomic dysfunction that is not associated with bronchomotor tone alterations, probably reflecting a less severe impairment than that of type 1 diabetes mellitus. Yet, a reduction of end-expiratory flow was detected.

Cardiorespiratory fitness, pulmonary function and C-reactive protein levels in nonsmoking individuals with diabetes

The objective of this study was to evaluate cardiorespiratory fitness and pulmonary function and the relationship with metabolic variables and C-reactive protein (CRP) plasma levels in individuals with diabetes mellitus (DM). Nineteen men with diabetes and 19 age- and gender-matched control subjects were studied. All individuals were given incremental cardiopulmonary exercise and pulmonary function tests. In the exercise test, maximal workload (158.3±22.3vs 135.1±25.2, P=0.005), peak heart rate (HRpeak: 149±12 vs 139±10, P=0.009), peak oxygen uptake (VO2peak: 24.2±3.2 vs18.9±2.8, P<0.001), and anaerobic threshold (VO2VT: 14.1±3.4 vs 12.2±2.2, P=0.04) were significantly lower in individuals with diabetes than in control subjects. Pulmonary function test parameters, blood pressure, lipid profile (triglycerides, HDL, LDL, and total cholesterol), and CRP plasma levels were not different in control subjects and individuals with DM. No correlations were observed between hemoglobin A1C (HbA1c), CRP and pulmonary function test and cardiopulmonary exercise test performance. In conclusion, the results demonstrate that nonsmoking individuals with DM have decreased cardiorespiratory fitness that is not correlated with resting pulmonary function parameters, HbA1c, and CRP plasma levels.

The correlation between tests of visual function and perceived visual ability in central field loss patients

Purpose: To investigate the correlation between tests of visual function and perceived visual ability recorded with a 'quality-of-life' questionnaire for patients with central field loss. Method: 12 females and 7 males (mean age = 53.1 years; Range = 23 - 80 years) with subfoveal neovascular membranes underwent a comprehensive assessment of visual function. Tests included unaided distance vision, high and low contrast distance logMAR visual acuity (VA), Pelli-Robson contrast senstivity (at 1m), near logMAR word VA and text reading speed. All tests were done both monocularly and binocularly. The patients also completed a 28 point questionnaire separated into a 'core' section consisting of general questions about perceived visual function and a 'module' section with specific questions on reading function. Results: Step-wise multiple regression analysis was used to determine which visual function tests were correlated with the patients's perceived visual function and to rank them in order of importance. The visual function test that explains most of the variance in both 'core' score (66%0 and the 'module' score (68%) of the questionnaire is low contrast VA in the better eye (P<0.001 in both cases). Further, the module score also accounts for a significant proportion of the variance (P<0.01) of the distance logMAR VA in both the better and worse eye, and the near logMAR in both the better eye and binocularly. Conclusions: The best predictor of both perceived reading ability and of general perceived visual ability in this study is low contrast logMAR VA. The results highlight that distance VA is not the only relevant measure of visual fucntion in relation to a patients's perceived visual performance and should not be considered a determinant of surgical or management success.

Reliability and validity of physical fitness field tests for adults aged 55 to 70 years

The aim of this study was to examine the reliability and validity of field tests for assessing physical function in mid-aged and young-old people (55–70 y). Tests were selected that required minimal space and equipment and could be implemented in multiple field settings such as a general practitioner's office. Nineteen participants completed 2 field and 1 laboratory testing sessions. Intra-class correlations showed good reliability for the tests of upper body strength (lift and reach, R= .66), lower body strength (sit to stand, R= .80) and functional capacity (Canadian Step Test, R= .92), but not for leg power (single timed chair rise, R= .28). There was also good reliability for the balance test during 3 stances: parallel (94.7% agreement), semi-tandem (73.7%), and tandem (52.6%). Comparison of field test results with objective laboratory measures found good validity for the sit to stand (cf 1RM leg press, Pearson r= .68, p< .05), and for the step test (cf PWC140, r= −.60, p< .001), but not for the lift and reach (cf 1RM bench press, r= .43, p> .05), balance (r= −.13, −.18, .23) and rate of force development tests (r= −.28). It was concluded that the lower body strength and cardiovascular function tests were appropriate for use in field settings with mid-aged and young-old adults.

Spirometric Function Improves in the Morbidly Obese After 1-Year Post-surgery

Obesity can negatively affect pulmonary function tests, with or without clinical symptoms, but the impact of bariatric weight loss is still debated. Aiming to document such profile in a consecutive homogeneous population, a prospective cohort study was undertaken. Sixty-one patients (100% females, age 40 +/- 8 years, BMI 49 +/- 5 kg/m(2) and without respiratory disease) were enrolled. Spirometric analysis was carried out to compare preoperative respiratory pattern with outcome after 6 and 12 months. Variables included vital capacity (VC), expiratory reserve volume (ERV), forced expiratory volume (1 s) (FEV1), FEV1/FVC ratio and maximum voluntary ventilation (MVV). Correlation of results with weight loss was examined. The following initial variables exhibited significant difference when compared to the 12-month postoperative control: FVC (P = 0.0308), FEV1/FVC (P = 0.1998), MVV (P = 0.0004) and ERV (P = 0.2124). Recovery of FVC and FEV1/FVC occurred earlier by 6 months. The most seriously depressed preoperative finding was ERV, which even after 1 year still remained inadequate. (1) Pulmonary limitations were diagnosed in approximately one third of the population. (2) Changes were demonstrated for FVC, FEV1/FVC, ERV and MVV. (3) FEV1 and FEV1/FVC were acceptable due to the absence of an obstructive pattern. (4) Two variables increased by 6 months (FEV1/FVC and ERV), whereas recovery for others was confirmed after 1 year. (5) The only exception was ERV which continued below the acceptable range.