Increased Cardiovascular Disease Mortality Associated With Excessive Exercise in Heart Attack Survivors

ObjectiveTo test whether greater exercise is associated with progressively lower mortality after a cardiac event.Patients and MethodsWe used Cox proportional hazard analyses to examine mortality vs estimated energy expended by running or walking measured as metabolic equivalents (3.5 mL O₂/kg per min per day or metabolic equivalent of task-h/d [MET-h/d]) in 2377 self-identified heart attack survivors, where 1 MET-h/d is the energy equivalent of running 1 km/d. Mortality surveillance via the National Death Index included January 1991 through December 2008.ResultsA total of 526 deaths occurred during an average prospective follow-up of 10.4 years, 376 (71.5%) of which were related to cardiovascular disease (CVD) (International Statistical Classification of Diseases, 10th Revision codes I00-I99). CVD-related mortality compared with the lowest exercise group decreased by 21% for 1.07 to 1.8 MET-h/d of running or walking (P=.11), 24% for 1.8 to 3.6 MET-h/d (P=.04), 50% for 3.6 to 5.4 MET-h/d (P=.001), and 63% for 5.4 to 7.2 MET-h/d (P<.001) but decreased only 12% for ≥7.2 MET-h/d (P=.68). These data represent a 15% average risk reduction per MET-h/d for CVD-related mortality through 7.2 MET-h/d (P<.001) and a 2.6-fold risk increase above 7.2 MET-h/d (P=.009). Relative to the risk reduction at 7.2 MET-h/d, the risk for ≥7.2 MET-h/d increased 3.2-fold (P=.006) for all ischemic heart disease (IHD)–related mortalities but was not significantly increased for non–IHD-CVD, arrhythmia-related CVD, or non–CVD-related mortalities.ConclusionRunning or walking decreases CVD mortality risk progressively at most levels of exercise in patients after a cardiac event, but the benefit of exercise on CVD mortality and IHD deaths is attenuated at the highest levels of exercise (running: above 7.1 km/d or walking briskly: 10.7 km/d).     

Incidence of Leukocytoclastic Vasculitis, 1996 to 2010: A Population-Based Study in Olmsted County,Minnesota

ObjectiveTo determine the population-based incidence of leukocytoclastic vasculitis (LCV).Patients and MethodsThis is a retrospective population-based study of all Olmsted County, Minnesota, residents with a skin biopsy–proven diagnosis of LCV from January 1, 1996, through December 31, 2010.ResultsA total of 84 patients (mean age at diagnosis, 48.3 years) with newly diagnosed skin biopsy–proven LCV (43 women and 41 men) were identified. The incidence rate (age and sex adjusted to the 2000 US white population) was 4.5 per 100,000 person-years (95% CI, 3.5-5.4). The incidence of LCV increased significantly with age at diagnosis (P<.001) and did not differ between female and male patients. Subtypes of LCV were cutaneous small-vessel vasculitis (CSVV), 38 patients (45%); IgA vasculitis, 25 (30%); urticarial vasculitis, 10 (12%); cryoglobulinemic vasculitis, 3 (4%); and antineutrophil cytoplasmic antibody–associated vasculitis, 8 (10%). LCV was idiopathic in 29 of 38 patients with CSVV (76%) and 24 of 25 patients with IgA vasculitis (96%). Thirty-nine of 84 patients (46%) had systemic involvement, with the renal system most commonly involved (17 of 39 [44%]). Twenty-four of 80 patients (30%) with follow-up data available had recurrent disease. Compared with the Minnesota white population, observed survival in the incident LCV cohort was significantly poorer than expected (P<.001), including the subset of patients with idiopathic CSVV (P=.03).ConclusionThe incidence of LCV was higher than that reported in previously published studies. Idiopathic LCV was more common in our population-based cohort than that described previously. Overall survival was significantly poorer (P<.001) and should be explored further in future studies.     

Bone Mass in Individuals With Chronic Spinal Cord Injury: Associations With Activity-Based Therapy,Neurologic and Functional Status,a Retrospective Study

ObjectiveTo describe the prevalence of osteoporosis and its association with functional electrical stimulation (FES) use in individuals with spinal cord injury (SCI)-related paralysis.DesignRetrospective cross-sectional evaluation.SettingClinic.ParticipantsConsecutive persons with SCI (N=364; 115 women, 249 men) aged between 18 and 80 years who underwent dual-energy x-ray absorptiometry (DXA) examinations.InterventionsNot applicable.Main Outcome MeasurePrevalence of osteoporosis defined as DXA T score ≤−2.5.ResultsThe prevalence of osteoporosis was 34.9% (n=127). Use of FES was associated with 31.2% prevalence of osteoporosis compared with 39.5% among persons not using FES. In multivariate adjusted logistic regression analysis, FES use was associated with 42% decreased odds of osteoporosis after adjusting for sex, age, body mass index, type and duration of injury, Lower Extremity Motor Scores, ambulation, previous bone fractures, and use of calcium, vitamin D, and anticonvulsant; (adjusted odds ratio [OR]=.58; 95% confidence interval [CI], .35–.99; P=.039). Duration of injury >1 year was associated with a 3-fold increase in odds of osteoporosis compared with individuals with injury <1 year; (adjusted OR=3.02; 95% CI, 1.60–5.68; P=.001).ConclusionsFES cycling ergometry may be associated with a decreased loss of bone mass after paralysis. Further prospective examination of the role of FES in preserving bone mass will improve our understanding of this association.     

Body Composition and Mortality in a Large Cohort With Preserved Ejection Fraction: Untangling the Obesity Paradox

ObjectiveTo evaluate the effects of body composition as a function of lean mass index (LMI) and body fat (BF) on the correlation between increasing body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and decreasing mortality, which is known as the obesity paradox.Patients and MethodsWe retrospectively assessed 47,866 patients with preserved left ventricular ejection fraction (≥50%). We calculated BF by using the Jackson-Pollock equation and LMI using (1 − BF) × BMI. The population was divided according to the sex-adjusted BMI classification, sex-adjusted LMI classification, and sex-adjusted BF tertiles. The population was analyzed by using multivariate analysis for total mortality over a mean follow-up duration of 3.1 years by using the National Death Index, adjusting for left ventricular ejection fraction, left ventricular mass index, age, sex, and relative wall thickness.ResultsIn the entire population, higher BMI was narrowly associated (hazard ratio [HR], 0.99; P<.001) with lower mortality. The higher LMI group was clearly protective (HR, 0.71; P<.001), whereas BF tertile was associated with lower mortality only if no adjustment was made for LMI (HR, 0.87; P<.001 without LMI; HR, 0.97; P=.23 with LMI). In the lean patients, low BMI was clearly associated with higher mortality (HR, 0.92; P<.001) and lower BF tertile was associated with lower mortality only if no adjustment was made for LMI (HR, 0.80; P<.001 without LMI; HR, 1.01; P=.83 with LMI). The underweight patients stratified by BF seemed to have an increased mortality (HR, 1.91; 95% CI, 1.56-2.34) that was independent of LMI. However, in obese patients, both BMI (HR, 1.03; P<.001) and BF (HR, 1.18; P=.003) were associated with higher mortality, even after adjusting for LMI, which remained protective (HR, 0.57; P<.001) independently of BF.ConclusionBody composition could explain the inverse J shape of the mortality curve noted with increasing BMI. Body fat seems to be protective in this cohort only if no adjustment was made for LMI, although being underweight stratified by BF seems to be an independent risk factor. Lean mass index seems to remain protective in obese patients even when BMI is not.     

Moderate Cardiorespiratory Fitness Is Positively Associated With Resting Metabolic Rate in Young Adults

ObjectiveTo determine whether moderate cardiorespiratory fitness (CRF) or moderate to vigorous physical activity (MVPA) is associated with elevations in resting metabolic rate (RMR) similar to findings previously observed in endurance athletes.Participants and MethodsUsing a cross-sectional design, we measured CRF, RMR, body composition, energy expenditure, and time in MVPA via an arm-based activity monitor in 423 young adults (mean age, 27.6 years). Based on the results of a fitness test, participants were classified into CRF tertiles (low, moderate, or high) by sex.ResultsThere were significant differences among the low-, moderate-, and high-CRF groups for mean ± SD body mass index (calculated as the weight in kilograms divided by the height in meters squared) (28.1±4.1, 25.1±3.4, and 23.6±2.5, respectively; P<.001) and fat mass (28.8±9.7, 20.5±8.2, and 14.8±6.5 kg, respectively; P<.001) but not fat-free mass (53.1±11.5, 53.5±12.4, and 54.7±12.1 kg, respectively; P=.49). There were no differences in mean ± SD unadjusted RMR among the groups (1533.2±266.2, 1519.7±267.6, and 1521.9±253.9 kcal/d, respectively). However, after statistical adjustment for differences in body composition, the moderate- and high-CRF groups had a higher RMR compared with low-CRF individuals by 39.7 and 59.9 kcal/d, respectively (P<.05). After further adjustment for MVPA, RMR was higher in the high-CRF group compared with the low-CRF group by 51.2 kcal/d (P<.05).ConclusionIn this large sample of young adults representing a range of CRF, there was a positive stepwise gradient in RMR across tertiles of CRF independent of body composition. Also, MVPA was independently associated with RMR, although this relationship was modest. These findings underscore the multidimensional role of CRF and MVPA on health.Trial Registrationclinicaltrials.gov Identifier: NCT01746186     

Impaired Executive Function Can Predict Recurrent Falls in Parkinson's Disease

ObjectiveTo examine whether impairment in executive function independently predicts recurrent falls in people with Parkinson's disease (PD).DesignProspective cohort study.SettingUniversity motor control research laboratory.ParticipantsA convenience sample of community-dwelling people with PD (N=144) was recruited from a patient self-help group and movement disorders clinics.InterventionsNot applicable.Main Outcome MeasuresExecutive function was assessed with the Mattis Dementia Rating Scale Initiation/Perseveration (MDRS-IP) subtest, and fear of falling (FoF) with the Activities-specific Balance Confidence (ABC) Scale. All participants were followed up for 12 months to record the number of monthly fall events.ResultsForty-two people with PD had at least 2 falls during the follow-up period and were classified as recurrent fallers. After accounting for demographic variables and fall history (P=.001), multiple logistic regression analysis showed that the ABC scores (P=.014) and MDRS-IP scores (P=.006) were significantly associated with future recurrent falls among people with PD. The overall accuracy of the prediction was 85.9%. With the use of the significant predictors identified in multiple logistic regression analysis, a prediction model determined by the logistic function was generated: Z = 1.544 + .378 (fall history) − .045 (ABC) − .145 (MDRS-IP).ConclusionsImpaired executive function is a significant predictor of future recurrent falls in people with PD. Participants with executive dysfunction and greater FoF at baseline had a significantly greater risk of sustaining a recurrent fall within the subsequent 12 months.     

Long-term Outcome of Globus Pallidus Internus Deep Brain Stimulation in Patients With Tourette Syndrome

ObjectiveTo evaluate the effectiveness of deep brain stimulation (DBS) of the globus pallidus internus (GPi) on tic severity and common comorbidities in patients with severe Tourette syndrome that is refractory to pharmacological treatment and psychotherapy.Patients and MethodsWe retrospectively assessed the long-term clinical outcomes of 13 patients with treatment-refractory Tourette syndrome who underwent DBS targeting the GPi at the Beijing Tiantan Hospital from January 1, 2006, through May 31, 2013. The primary outcome was a change in tic severity as measured by the Yale Global Tic Severity Scale, and the secondary outcome was a change in associated behavioral disorders and mood as measured by the Gilles de la Tourette Syndrome–Quality of Life Scale assessment.ResultsCompared with baseline, the mean reduction in the total Yale Global Tic Severity Scale scores at last follow-up (mean, 41.9 months; range, 13-80 months) was 52.1% (range, 4.3%-83.6%), and the mean improvement rates at 1 month, 6 months, 12 months, 18 months, 24 months, 30 months, and 36 or more months were 11.8%, 20.0%, 26.8%, 36.7%, 44.7%, 49.0%, and 56.7%, respectively. A paired-sample t test revealed significant improvement of tic symptoms after 6 months of DBS programming (P<.05). The Gilles de la Tourette Syndrome–Quality of Life Scale score improved by a mean of 45.7% (range, 11.0%-77.2%).ConclusionThis study is currently the largest reported GPi DBS case series of patients with treatment-refractory TS with the longest follow-up. Our results support the potential beneficial effect of GPi DBS on disabling tic reduction and improvement of quality of life.     

Balance Exercise Program Reduced Falls in People With Multiple Sclerosis: A Single-Group,Pretest-Posttest Trial

ObjectiveTo evaluate the effects of a balance exercise program on falls in people with mild to moderate multiple sclerosis (MS).DesignMulticenter, single-blinded, single-group, pretest-posttest trial.SettingSeven rehabilitation units within 5 county councils.ParticipantsCommunity-dwelling adults with MS (N=32) able to walk 100m but unable to maintain 30-second tandem stance with arms alongside the body.InterventionSeven weeks of twice-weekly, physiotherapist-led 60-minute sessions of group-based balance exercise targeting core stability, dual tasking, and sensory strategies (CoDuSe).Main Outcome MeasuresPrimary outcomes: number of prospectively reported falls and proportion of participants classified as fallers during 7 preintervention weeks, intervention period, and 7 postintervention weeks. Secondary outcomes: balance performance on the Berg Balance Scale, Four Square Step Test, sit-to-stand test, timed Up and Go test (alone and with cognitive component), and Functional Gait Assessment Scale; perceived limitations in walking on the 12-item MS Walking Scale; and balance confidence on the Activities-specific Balance Confidence Scale rated 7 weeks before intervention, directly after intervention, and 7 weeks later.ResultsNumber of falls (166 to 43; P≤.001) and proportion of fallers (17/32 to 10/32; P≤.039) decreased significantly between the preintervention and postintervention periods. Balance performance improved significantly. No significant differences were detected for perceived limitations in walking, balance confidence, the timed Up and Go test, or sit-to-stand test.ConclusionsThe CoDuSe program reduced falls and proportion of fallers and improved balance performance in people with mild to moderate MS but did not significantly alter perceived limitations in walking and balance confidence.     

Association of Dysglycemia and All-Cause Mortality Across the Spectrum of Coronary Artery Disease

ObjectiveTo assess the association between fasting plasma glucose (FPG) and all-cause mortality across the spectrum of coronary artery disease (CAD).Patients and MethodsThe study included 18,999 patients during a study period of April 1, 2004, through October 31, 2010. The primary end points were in-hospital and follow-up all-cause mortality. According to the quartiles of FPG levels, patients were categorized into 4 groups: quartile 1, less than 5.1 mmol/L; quartile 2, 5.1 to less than 5.9 mmol/L; quartile 3, 5.9 to less than 7.5 mmol/L; and quartile 4, 7.5 mmol/L or greater. The conversion factor for units of plasma glucose is 1.00 mmol/L equals 18 mg/dL. Presented as mg/dL, the 4 quartile ranges of plasma glucose concentrations used in our data analysis are ≤90.0 mg/dL, 90.1-106.0 mg/dL, 106.1 mg/dL-135.0 mg/dL and ≥135.1 mg/dL. Quartile 1 was recognized as the lower glycemic group, quartiles 2 and 3 as the normoglycemic groups, and quartile 4 as the higher glycemic group.ResultsIn patients with acute myocardial infarction, all-cause mortality for the dysglycemic groups was higher than for the normoglycemic groups: in-hospital mortality for quartiles 1, 2, 3, and 4 was 1.0%, 0.9%, 0.2%, and 1.5%, respectively (P=.001); follow-up mortality for quartiles 1, 2, 3, and 4 was 1.7%, 0.9%, 0.3%, and 1.8%, respectively (P<.001). In patients with stable CAD, no significant differences in mortality were found among groups. However, in patients with unstable angina pectoris, the normoglycemic groups had lower follow-up mortality and roughly equal in-hospital mortality compared with the dysglycemic groups. After adjusting for confounding factors, this observation persisted.ConclusionThe association between lower FPG level and mortality differed across the spectrum of CAD. In patients with acute myocardial infarction, there was a U-shaped relationship. In patients with stable CAD or unstable angina pectoris, mildly to moderately decreasing FPG level was associated with neither higher nor lower all-cause mortality.     

Sex Differences in Patients With Different Stages of Knee Osteoarthritis

ObjectiveTo quantify the differences in physical impairments and in performance-based measures and patient-reported outcomes in men and women seeking nonoperative management of symptomatic moderate knee osteoarthritis (OA) and those with symptomatic end-stage knee OA scheduled for total knee arthroplasty compared with healthy controls.DesignCross-sectional analysis of individuals referred to physical therapy, community participants, and subjects from a 2-year longitudinal study.SettingUniversity research department.ParticipantsCross-sectional analysis of participants (N=289) consisting of a moderate OA group (n=83), a severe OA group (n=143), and a healthy control group (n=63).InterventionsNot applicable.Main Outcome MeasuresQuadriceps strength, timed Up and Go test, stair-climbing test, 6-minute walk test, Knee Outcome Survey–Activities of Daily Living Scale (KOS-ADLS), and Physical Component Summary (PCS) of the Medical Outcomes Study 36-Item Short-Form Health Survey.ResultsWomen had worse scores than men for physical impairment and performance-based measures (P<.001). In the moderate OA group, women had significantly lower KOS-ADLS (P=.007) and PCS (P=.026) scores than men, with no differences seen between sexes in the other 2 groups for patient-reported measures.ConclusionsDifferences between women and men with knee OA on physical impairments and performance-based measures are not echoed in the differences seen in patient-reported measures. These measures signal different domains of knee function in patients with knee OA and should be used as part of a comprehensive functional evaluation.     

Neutralizing the Adverse Prognosis of Coronary Artery Calcium

ObjectivesTo report and compare the outcomes and survival of patients with abnormal computed tomography–derived coronary artery calcium (CT-CAC) scores undergoing aggressive medical treatment at a cardiac prevention clinic.Patients and MethodsWe conducted a retrospective analysis of 849 patients with intermediate risk based on the Framingham risk score and an abnormal CT-CAC score who were aggressively treated in a preventive cardiology risk factor modification program from June 23, 2000, to September 1, 2012. The primary outcome was a composite end point of myocardial infarction, resuscitated cardiac arrest, revascularization, and cardiovascular death. The effect of the CT-CAC subgroup on major adverse coronary heart disease events (MACEs) was evaluated by calculating hazard ratios with Cox proportional hazards regression modeling. The Centers for Disease Control and Prevention Wonder database was used to identify age- and sex-matched controls from the general population of Kansas and Missouri.ResultsThe mean age of the study patients was 65.4 years (58.4% men [496]). The median follow-up was 58 months, and the mean CT-CAC score was 336 Agatston units. Thirty-four patients (4.0%) reached the primary end point, including 4 deaths. The adjusted 10-year mortality rates were similar in the study group and control group (9.3 vs 10.6; P=.80). After adjustment, a CT-CAC score greater than 400 Agatston units correlated with a higher risk of MACEs (hazard ratio, 3.55; P=.01).ConclusionThese results suggest that intermediate-risk patients with abnormal CT-CAC scores when treated with intensive risk factor reduction have lower rates of MACEs than predicted by the Framingham risk score and the presence of coronary artery calcium.     

Prognostic Factors and Outcomes of Adults With Hemophagocytic Lymphohistiocytosis

ObjectiveTo describe the prognostic factors and outcomes of adults with hemophagocytic lymphohistiocytosis (HLH), a rare disorder caused by pathologic activation of the immune system.Patients and MethodsThe study population consisted of a consecutive cohort of adult (age ≥18 years) patients treated at Mayo Clinic in Rochester, Minnesota, from January 1, 1996, through December 31, 2011, in whom a diagnosis of HLH was suspected and subsequently confirmed by retrospective review using the HLH-04 diagnostic criteria.ResultsOf 250 adult patients suspected of having HLH, 62 met the HLH-04 diagnostic criteria and were included in the final analysis. The median age was 49 years (range, 18-87 years), and 42 (68%) were male. The underlying cause of HLH was malignant tumor in 32 patients (52%), infection in 21 patients (34%), autoimmune disorder in 5 patients (8%), and idiopathic disease in 4 patients (6%). After a median follow-up of 42 months, 41 patients (66%) had died. The median overall survival of the entire cohort was 2.1 months. The median overall survival of patients with tumor–associated HLH was 1.4 months compared with 22.8 months for patients with non-tumor–associated HLH (P=.01). The presence of a malignant tumor and hypoalbuminemia were significant predictors of inferior survival on multivariate analysis.ConclusionIn this large series of adults with secondary HLH treated at a single tertiary care center, patients with low serum albumin levels and tumor–associated HLH had a markedly worse survival. Hemophagocytic lymphohistiocytosis remains elusive and challenging to clinicians who must maintain a high index of suspicion. The recent discovery of several novel diagnostic and therapeutic modalities may improve outcomes of adult patients with HLH.     

Influence of Early Surgical Treatment on the Prognosis of Left-Sided Infective Endocarditis: A Multicenter Cohort Study

ObjectiveTo analyze the influence of early valve operation on mortality in patients with left-sided infective endocarditis (IE).Patients and MethodsA multicenter cohort study was carried out between 1990 and 2010. Data from consecutive patients with definite IE and possible left-sided IE were collected. Propensity score matching and adjustment for survivor bias were used to control for confounders. The primary outcome was in-hospital mortality.ResultsA total of 1019 patients with a mean age of 61 years (interquartile range, 47-71 years) were included. Early surgical treatment was performed in 417 episodes (40.9%). By propensity score, we matched 316 episodes: 158 who underwent early surgical treatment and 158 who did not (medical treatment group). In-hospital mortality and late mortality were lower in the surgically treated group (26.6% vs 41.8%; absolute risk reduction [ARR], −15.2%; P=.004 and 29.7% vs 46.2%; ARR, −16.5%; P=.002, respectively). Operation was independently associated with a lower risk of in-hospital mortality (odds ratio, 0.42; 95% CI, 0.22-0.79; P=.007). Operation was associated with reduced mortality in patients with paravalvular complications (ARR, −40.5%), severe heart failure (ARR, −32%), and native valve endocarditis (ARR, −17.8%).ConclusionThis study supports the benefit of surgical treatment in patients with left-sided IE carried out during the initial phase of hospitalization, especially in patients with moderate or severe heart failure and paravalvular extension of infection.     

Cardiac Amyloidosis Without Increased Left Ventricular Wall Thickness

ObjectivesTo determine how often left ventricular wall thickness (LVWT) is normal and to assess the effect of LVWT on clinical outcomes of patients with immunoglobulin light chain (AL) cardiac amyloidosis.Patients and MethodsA total of 117 patients with systemic AL amyloidosis were retrospectively categorized from April 1, 1995, to September 15, 2012; group A included cardiac amyloidosis patients with an LVWT greater than 12 mm (45 patients); group B, cardiac amyloidosis patients with an LVWT of 12 mm or less (25 patients); and group C, no evidence of cardiac amyloidosis (47 patients). We compared echocardiographic parameters and survival rates among the 3 groups.ResultsNo differences were found between groups A and B in the following parameters: left ventricular ejection fraction (median, 56% [interquartile range (IQR), 46%-63%] vs 56% [IQR, 49%-63%], P=.76), left arterial volume index (median, 44.5 [IQR, 38.5-59.7] vs 43.9 [IQR, 33.8-57.1] mL/m², P=.79), eˈ (median, 0.04 [IQR, 0.03-0.05] vs 0.05 [IQR, 0.04-0.06] m/s, P=.10), and E/eˈ (early diastolic mitral inflow velocity (E)/eˈ) (median, 18.4 [IQR, 12.0-23.3] vs 18.0 [IQR, 13.6-25.0], P=.98). Patients in group C exhibited significantly different values for these parameters (median, 65% [IQR, 61%-69%], 23.4 [IQR, 18.0-29.0] mL/m², 0.08 [IQR, 0.06-0.09] m/s, and 8.8 [IQR, 7.2-10.5], respectively; all P<.001). The survival rates were statistically different, with median survival times of 422, 729, and 2080 days in groups A, B, and C, respectively (P=.002). Using multivariate Cox proportional hazards regression analysis, we found that age, an N-terminal pro–B-type natriuretic peptide level of 1800 pg/mL or greater, E/eˈ, and complete hematologic remission were significant predictors of survival.ConclusionsA third of patients with AL cardiac amyloidosis were diagnosed as having an LVWT of 12 mm or less. Because appropriate therapy can improve the survival of patients with AL cardiac amyloidosis, early detection by sensitive diagnostic methods should be pursued even when LVWT is not increased.     

Association of Exercise Heart Rate Response and Incidence of Hypertension in Men

ObjectiveTo examine the association of heart rate (HR) responses at rest, during exercise, and after exercise with incident hypertension (HTN) in men.Participants and MethodsA total of 10,418 healthy normotensive men without abnormalities on electrocardiography or a history of myocardial infarction, stroke, cancer, or diabetes underwent a maximal exercise test and were followed up for incidence of HTN. Heart rate reserve was defined as the maximal HR minus resting HR. Heart rate recovery was defined as HR 5 minutes after the exercise test.ResultsDuring a mean follow-up of 6 years, there were 2831 cases of HTN. Compared with men who had lower HR reserve, the risk of incident HTN was significantly lower for men with higher HR reserve (hazard ratio, 0.84; 95% CI, 0.74-0.95 for the highest quartile vs the lowest quartile of HR reserve; P=.002) when adjusted for age, baseline examination year, smoking, heavy drinking, body mass index, resting blood pressure, cholesterol and glucose levels, and cardiorespiratory fitness. Compared with men who had higher HR recovery, the risk of incident HTN was significantly lower for men with lower HR recovery (hazard ratio, 0.90; 95% CI, 0.80-0.99 for quartile 3 vs highest quartile; P=.04) after adjusting for the aforementioned confounders. However, the overall linear trend for HR recovery was not significant (P=.26).ConclusionThe risk of HTN decreased in men with higher HR reserve. Therefore, HR reserve may be considered as a useful exercise parameter for predicting the risk of HTN in men.     

Association of Multiple Adiposity Exposures and Cardiorespiratory Fitness With All-Cause Mortality in Men: The Cooper Center Longitudinal Study

ObjectiveTo examine the additive effects of an increased number of positive adiposity exposures on all-cause mortality in men before and after stratification by cardiorespiratory fitness (CRF) level.Patients and MethodsA total of 36,836 men underwent a physical examination at the Cooper Clinic from January 1, 1971, through December 31, 2006. Exposures included body mass index, waist circumference, percentage of body fat, and CRF as determined by duration of a maximal exercise test. Participants were identified as being either obese (positive) or nonobese (negative) for each adiposity exposure and then grouped into 4 categories: group 1, negative for all adiposity exposures; group 2, positive for any 1 exposure; group 3, positive for any 2 exposures; and group 4, positive for all exposures. Then CRF was grouped as fit or unfit on the basis of the upper 80% and lower 20% of the age-standardized CRF distribution as previously reported in the Cooper Center Longitudinal Study. Hazard ratios were computed with Cox regression analysis.ResultsA total of 2294 deaths occurred during a mean ± SD of 15.5±8.1 years of follow-up. Adjusted hazard ratios across adiposity groups were 1.0 (referent), 1.05, 1.37, and 1.87 for groups 1 through 4, respectively (P for trend <.001). Mortality rates were significantly lower within each of the first 3 adiposity groups in fit compared with unfit men (P<.009 for all comparisons).ConclusionAn increasing number of positive adiposity exposures were associated with increased mortality in men. Because moderate to high CRF attenuated mortality rates in all adiposity groups, measurement of CRF should be included for identifying men at increased risk for all-cause mortality.     

Treatment Discontinuations With New Oral Agents for Long-term Anticoagulation: Insights From a Meta-analysis of 18 Randomized Trials Including 101,801 Patients

ObjectiveTo systematically examine discontinuation rates with new US Food and Drug Administration–approved oral anticoagulants (NOACs) in patients with various indications for long-term anticoagulation.Patients and MethodsPoor adherence to medications is considered a potential and frequent cause of treatment failure. We searched the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, EBSCO, Web of Science, and CINAHL databases for articles published from January 1, 2001, through September 15, 2013. The following Medical Subject Heading terms and/or keywords were used for our database searches: rivaroxaban, dabigatran, apixaban, new oral anticoagulants, oral thrombin inhibitors, and oral factor Xa inhibitors. Articles in English that focused on randomized controlled trials (RCTs) comparing NOACs (apixaban, dabigatran, and rivaroxaban) with conventional therapy or placebo were abstracted. Independent extraction of relevant data was performed by 2 authors. The primary end point of interest was discontinuation due to all causes. Other end points of interest were discontinuation due to adverse events, consent withdrawal, and nonadherence.ResultsEighteen RCTs including a total of 101,801 patients were included for analysis. Total study drug discontinuation rates were not statistically different with NOACs in comparison to pharmacologically active comparators for treatment of venous thromboembolism/pulmonary embolism (risk ratio [RR], 0.91; 95% CI, 0.74-1.13; P=.40) and for NOACs in comparison to warfarin and aspirin for prevention of stroke in patients with atrial fibrillation (RR, 1.01; 95% CI, 0.87-1.17; P=.92). In contrast, in acute coronary syndromes, total study drug discontinuation with NOACs was significantly higher than with placebo (RR, 1.40; 95% CI, 1.07-1.83; P=.01). Overall discontinuations were comparable to those with active comparators.ConclusionStudy drug discontinuations with NOACs were not significantly different from those with conventional drugs in treatment of venous thromboembolism/pulmonary embolism and prevention of stroke in patients with atrial fibrillation but were worse in acute coronary syndromes as noted in evidence from contemporary RCTs.     

Safety and Efficacy of Extracorporeal Shock Wave Myocardial Revascularization Therapy for Refractory Angina Pectoris

ObjectiveTo assess the safety and efficacy of extracorporeal shockwave myocardial revascularization (ESMR) therapy in treating patients with refractory angina pectoris.Patients and MethodsA single-arm multicenter prospective trial to assess safety and efficacy of the ESMR therapy in patients with refractory angina (class III/IV angina) was performed. Screening exercise treadmill tests and pharmacological single-photon emission computed tomography (SPECT) were performed for all patients to assess exercise capacity and ischemic burden. Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy end points were exercise capacity by using treadmill test as well as ischemic burden on pharmacological SPECT at 4 months after the last ESMR treatment. Safety measures included electrocardiography, echocardiography, troponin, creatine kinase, and brain natriuretic peptide testing, and pain questionnaires.ResultsFifteen patients with medically refractory angina and no revascularization options were enrolled. There was a statistically significant mean increase of 122.3±156.9 seconds (38% increase compared with baseline; P=.01) in exercise treadmill time from baseline (319.8±157.2 seconds) to last follow-up after the ESMR treatment (422.1±183.3 seconds). There was no improvement in the summed stress perfusion scores after pharmacologically induced stress SPECT at 4 months after the last ESMR treatment in comparison to that at screening; however, SPECT summed stress score revealed that untreated areas had greater progression in ischemic burden vs treated areas (3.69±6.2 vs 0.31±4.5; P=.03). There was no significant change in the mean summed echo score from baseline to posttreatment (0.4±5.1; P=.70). The ESMR therapy was performed safely without any adverse events in electrocardiography, echocardiography, troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR treatment was minimal (a score of 0.5±1.2 to 1.1±1.2 out of 10).ConclusionIn this multicenter feasibility study, ESMR seems to be a safe and efficacious treatment for patients with refractory angina pectoris. However, larger sham-controlled trials will be required to confirm these findings.     

Systematic Review and Meta-Analysis of Noninvasive Cranial Nerve Neuromodulation for Nervous System Disorders

ObjectiveTo systematically review the medical literature and comprehensively summarize clinical research done on rehabilitation with a novel portable and noninvasive electrical stimulation device called the cranial nerve noninvasive neuromodulator in patients suffering from nervous system disorders.Data SourcesPubMed, MEDLINE, and Cochrane Database of Systematic Reviews from 1966 to March 2013.Study SelectionStudies were included if they recruited adult patients with peripheral and central nervous system disorders, were treated with the cranial nerve noninvasive neuromodulator device, and were assessed with objective measures of function.Data ExtractionAfter title and abstract screening of potential articles, full texts were independently reviewed to identify articles that met inclusion criteria.Data SynthesisThe search identified 12 publications: 5 were critically reviewed, and of these 5, 2 were combined in a meta-analysis. There were no randomized controlled studies identified, and the meta-analysis was based on pre-post studies. Most of the patients were individuals with a chronic balance dysfunction. The pooled results demonstrated significant improvements in the dynamic gait index postintervention with a mean difference of 3.45 (95% confidence interval, 1.75–5.15; P<.001), Activities-specific Balance Confidence scale with a mean difference of 16.65 (95% confidence interval, 7.65–25.47; P<.001), and Dizziness Handicap Inventory with improvements of −26.07 (95% confidence interval, −35.78 to −16.35; P<.001). Included studies suffered from small sample sizes, lack of randomization, absence of blinding, use of referral populations, and variability in treatment schedules and follow-up rates.ConclusionsGiven these limitations, the results of the meta-analysis must be interpreted cautiously. Further investigation using rigorous randomized controlled trials is needed to evaluate this promising rehabilitation tool for nervous system disorders.     

Frequency and Implication of Autoimmune Serologies in Idiopathic Pulmonary Fibrosis

ObjectiveTo assess the frequency and clinical implications of positive autoimmune serologies in patients with biopsy-confirmed idiopathic pulmonary fibrosis (IPF).Patients and MethodsWe reviewed the records of patients at our institution with biopsy-confirmed usual interstitial pneumonia (UIP) from January 1, 1995, through December 31, 2010, for frequency and distribution of autoimmune serologies. Patients with IPF with and without positive serologies were compared.ResultsThree hundred eighty-nine consecutive patients with biopsy-confirmed IPF underwent serologic testing, with positive serologic test results being found in 112 (29%). Of 2051 individual screening serologic tests performed, results of 163 tests were positive (8%), with antinuclear antibody being the most frequent (47%). There was no difference in age at biopsy (P=.21), gender (P=.21), or presenting radiologic features between those with or without positive serology. More frequent use of immunosuppressive treatment (P=.02) was noted in those with positive serology. No survival difference was observed (log-rank; P=.43). Median follow-up for the whole cohort was 43.5 months.ConclusionPositive autoimmune serology may occur in as much as one-third of the patients with biopsy-confirmed IPF with no associated clinical implication or survival advantage. Systematic use of autoimmune laboratory panels in patients without clinical features of connective tissue disease should be reconsidered in patients with suspected UIP on chest computed tomography scan or confirmed UIP on biopsy.