Association of Coronary Artery Calcification With Hepatic Steatosis in Asymptomatic Individuals

ObjectiveTo determine the association of coronary artery calcification with hepatic steatosis in asymptomatic volunteers.Patients and MethodsThe study group comprised 400 asymptomatic volunteers, enrolled from April 1, 2011, to September 30, 2012, without known coronary artery disease who were self-referred for screening noncontrast computed tomography to determine coronary calcium score (CCS). Computed tomographic images were used to determine the presence of hepatic steatosis. An a priori model was created to predict a CCS of 100 Agatston units (AU) or higher on the basis of Framingham risk factors, diabetes mellitus, and metabolic syndrome. Hepatic steatosis was then added to this model. Computation of the odds ratio (OR) for hepatic steatosis predicting a CCS of 100 AU or higher was performed. Finally, the OR for a CCS of 100 AU or higher being associated with hepatic steatosis was calculated.ResultsWhen hepatic steatosis was added to traditional coronary risk factors, it was independently associated with a CCS of 100 AU or higher (OR, 2.85). This was greater than the OR of Framingham factors, diabetes mellitus, or metabolic syndrome. A CCS of 100 AU or higher was independently associated with an increased risk for hepatic steatosis (OR, 2.4). This OR was higher than traditional hepatic steatosis risk factors or metabolic syndrome.ConclusionHepatic steatosis is a strong independent predictor of a CCS of 100 AU or higher in asymptomatic patients. It is associated with an increased risk of coronary artery disease beyond that expected from traditional coronary risk factors and/or metabolic syndrome. Additional studies are needed to clarify the role of hepatic steatosis as a possible independent risk factor for the development of coronary artery disease.     

Protective Role of Resting Heart Rate on All-Cause and Cardiovascular Disease Mortality

ObjectiveTo study the protective role of lower resting heart rate (RHR) in cardiovascular disease (CVD) and all-cause mortality.Patients and MethodsPatients (n=53,322) who received a baseline medical examination between January 1, 1974, and December 31, 2002, were recruited from the Cooper Clinic, Dallas, Texas. They completed a medical questionnaire and underwent clinical evaluation. Patients with CVD or cancer or who had less than 1 year of mortality follow-up were excluded from the study. Relative risks and 95% CIs for all-cause and CVD mortality across RHR categories were estimated using Cox proportional hazards models.ResultsHighest cardiorespiratory fitness with lower mortality was found in individuals with an RHR of less than 60 beats/min. Similarly, patients with a higher RHR (≥80 beats/min) were at greater risk for CVD and all-cause mortality compared with an RHR of less than 60 beats/min. This analysis was followed by stratification of the data by hypertension, where hypertensive individuals with high RHRs (≥80 beats/min) were found to be at greater risk for CVD and all-cause mortality compared with those with hypertension and lower RHRs (<60 beats/min). In addition, unfit individuals with high RHRs had the greatest risk of CVD and all-cause mortality. The unfit with low RHR group had a similar risk for CVD and all-cause mortality as the fit with high RHR group.ConclusionLower cardiorespiratory fitness levels and higher RHRs are linked to greater CVD and all-cause mortality.     

Clinical Predictors of Risk for Atrial Fibrillation: Implications for Diagnosis and Monitoring

ObjectiveTo create a risk score using clinical factors to determine whom to screen and monitor for atrial fibrillation (AF).Patients and MethodsThe AF risk score was developed based on the summed odds ratios (ORs) for AF development of 7 accepted clinical risk factors. The AF risk score is intended to assess the risk of AF similar to how the CHA₂DS₂-VASc score assesses stroke risk. Seven validated risk factors for AF were used to develop the AF risk score: age, coronary artery disease, diabetes mellitus, sex, heart failure, hypertension, and valvular disease. The AF risk score was tested within a random population sample of the Intermountain Healthcare outpatient database. Outcomes were stratified by AF risk score for OR and Kaplan-Meier analysis.ResultsA total of 100,000 patient records with an index follow-up from January 1, 2002, through December 31, 2007, were selected and followed up for the development of AF through the time of this analysis, May 13, 2013, through September 6, 2013. Mean ± SD follow-up time was 3106±819 days. The ORs of subsequent AF diagnosis of patients with AF risk scores of 1, 2, 3, 4, and 5 or higher were 3.05, 12.9, 22.8, 34.0, and 48.0, respectively. The area under the curve statistic for the AF risk score was 0.812 (95% CI, 0.805-0.820).ConclusionWe developed a simple AF risk score made up of common clinical factors that may be useful to possibly select patients for long-term monitoring for AF detection.     

Alcohol and Cardiovascular Health: The Dose Makes the Poison…or the Remedy

Habitual light to moderate alcohol intake (up to 1 drink per day for women and 1 or 2 drinks per day for men) is associated with decreased risks for total mortality, coronary artery disease, diabetes mellitus, congestive heart failure, and stroke. However, higher levels of alcohol consumption are associated with increased cardiovascular risk. Indeed, behind only smoking and obesity, excessive alcohol consumption is the third leading cause of premature death in the United States. Heavy alcohol use (1) is one of the most common causes of reversible hypertension, (2) accounts for about one-third of all cases of nonischemic dilated cardiomyopathy, (3) is a frequent cause of atrial fibrillation, and (4) markedly increases risks of stroke—both ischemic and hemorrhagic. The risk-to-benefit ratio of drinking appears higher in younger individuals, who also have higher rates of excessive or binge drinking and more frequently have adverse consequences of acute intoxication (for example, accidents, violence, and social strife). In fact, among males aged 15 to 59 years, alcohol abuse is the leading risk factor for premature death. Of the various drinking patterns, daily low- to moderate-dose alcohol intake, ideally red wine before or during the evening meal, is associated with the strongest reduction in adverse cardiovascular outcomes. Health care professionals should not recommend alcohol to nondrinkers because of the paucity of randomized outcome data and the potential for problem drinking even among individuals at apparently low risk. The findings in this review were based on a literature search of PubMed for the 15-year period 1997 through 2012 using the search terms alcohol, ethanol, cardiovascular disease, coronary artery disease, heart failure, hypertension, stroke, and mortality. Studies were considered if they were deemed to be of high quality, objective, and methodologically sound.     

Hemoglobin A1c in Nondiabetic Patients: An Independent Predictor of Coronary Artery Disease and Its Severity

ObjectiveTo examine the association between hemoglobin A_1c (HbA_1c) and the presence, severity, and complexity of angiographically proven coronary artery disease (CAD) in nondiabetic patients.Patients and MethodsWe performed a single-center, observational, cross-sectional study of 1141 consecutive nondiabetic patients who underwent coronary angiography from January 1, 2011, through December 31, 2011. The study population was divided into 4 interquartiles according to HbA_1c levels (<5.5%, 5.5%-5.7%, 5.8%-6.1%, and >6.1%).ResultsPatients with higher HbA_1c levels tended to be older, overweight, and hypertensive, had higher blood glucose levels, and had lower glomerular filtration rates. Higher HbA_1c levels were associated in a graded fashion with the presence of CAD, disease severity (higher number of diseased vessels and presence of left main and/or triple vessel disease), and disease complexity (higher SYNTAX score, higher number of patients in intermediate or high SYNTAX tertiles, coronary calcium, and chronic total occlusions). After adjustment for major conventional cardiovascular risk factors, compared with patients with HbA_1c levels less than 5.5%, the odds ratios of occurrence of CAD in the HbA_1c quartiles of 5.5% to 5.7%, 5.8% to 6.1%, and greater than 6.1% were 1.8 (95% CI, 1.2-2.7), 3.5 (95% CI, 2.3-5.3), and 4.9 (95% CI, 3.0-8.1), respectively.ConclusionThe HbA_1c level has a linear incremental association with CAD in nondiabetic individuals. The HbA_1c level is also independently correlated with disease severity and higher SYNTAX scores. Thus, HbA_1c measurement could be used to improve cardiovascular risk assessment in nondiabetic individuals.     

Resting Heart Rate in First Year Survivors of Myocardial Infarction and Long-term Mortality: A Community Study

ObjectiveTo evaluate the long-term prognostic effect of resting heart rate (HR) at index myocardial infarction (MI) and during the first year after MI among 1-year survivors.Patients and MethodsThe community-based cohort consisted of 1571 patients hospitalized with an incident MI from January 1, 1983, through December 31, 2007, in Olmsted County, Minnesota, who were in sinus rhythm at index MI and had HR measurements on electrocardiography at index and during the first year after MI. Outcomes were all-cause and cardiovascular deaths.ResultsDuring a median follow-up of 7.0 years, 627 deaths and 311 cardiovascular deaths occurred. Using patients with HRs of 60/min or less as the referent, this study found that long-term all-cause mortality risk increased progressively with increasing HR at index (hazard ratio, 1.62; 95% CI, 1.25-2.09) and even more with increasing HR during the first year after MI (hazard ratio, 2.16; 95% CI, 1.64-2.84) for patients with HRs greater than 90/min, adjusting for clinical characteristics and β-blocker use. Similar results were observed for cardiovascular mortality (adjusted hazard ratio, 1.66; 95% CI, 1.14-2.42; and adjusted hazard ratio, 1.93; 95% CI, 1.27-2.94; for HR at index and within 1 year after MI, respectively).ConclusionThese data from a large MI community cohort indicate that HR is a strong predictor of long-term all-cause and cardiovascular mortality not only at initial presentation of MI but also during the first year of follow-up.     

Myocardial Infarction Risk Among Patients With Fractures Receiving Bisphosphonates

ObjectiveTo determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI).Patients and MethodsA cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed.ResultsAfter controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation.ConclusionOur observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required.     

Serum Polyclonal Immunoglobulin Free Light Chain Levels Predict Mortality in People With Chronic Kidney Disease

ObjectiveTo determine whether elevated serum polyclonal free light chain (FLC) levels predict mortality in a population of individuals with chronic kidney disease (CKD).Patients and MethodsFrom January 2, 2006, through July 31, 2007, we recruited a cohort of 848 people with CKD who were not receiving renal replacement therapy and did not have monoclonal gammopathy. We measured serum kappa FLC and lambda FLC isotype levels to determine combined FLC (cFLC) levels. The cohort was prospectively followed up for a median of 63 months (interquartile range, 0-93 months). Cox regression analysis was performed to determine variables predictive of mortality.ResultsHigh cFLC levels were an independent risk factor for death (hazard ratio [HR], 2.71; 95% CI, 1.98-3.70; P<.001). Other independent risk factors were age (HR, 1.79; 95% CI, 1.52-2.10; P<.001), South Asian ethnicity (HR, 0.33; 95% CI, 0.14-0.64; P=.02), preexisting cardiovascular disease (HR, 1.59; 95% CI, 1.09-2.31; P=.02), and high-sensitivity C-reactive protein (HR, 1.13; 95% CI, 1.00-1.28; P=.04). Neither estimated glomerular filtration rate nor albuminuria was an independent risk factor for death.ConclusionHigh cFLC levels independently predict mortality in people with CKD.     

Effect of β-Blockers and Other Antihypertensive Drugs On the Risk of Melanoma Recurrence and Death

ObjectiveTo verify preliminary studies on patients with melanoma exposed to β-blockers that suggested a reduced risk of disease recurrence and death.Patients and MethodsData were obtained from all consecutive patients diagnosed as having melanoma between January 1, 1993, and December 31, 2009, at the Department of Dermatology of the University of Florence, Azienda Sanitaria di Firenze. Participants were excluded if at baseline they reported a previous diagnosis of cutaneous malignant melanoma or another malignant disease. We also excluded participants with evidence of visceral, lymph nodal, and in-transit metastasis at the time of the diagnosis.ResultsOf 741 consecutive patients with melanoma, 79 (11%) were prescribed β-blockers (for hypertension in most cases) for 1 or more years (treated) and 662 (89%) were not (untreated). The multivariate Cox model indicated that the treated group had improved overall survival after a median follow-up of 4 years (P=.005). For each year of β-blocker use, the risk of death was reduced by 38%. The presence of hypertension, the use of antihypertensive agents for 1 or more years, or the use of other commonly used medicines were not associated with a better outcome for patients with melanoma.ConclusionThe results confirm and strengthen previous findings that β-blocker use is associated with a reduced risk of melanoma recurrence and death. The results also indicate the strong need for a randomized clinical trial to conclusively assess whether β-blockers afford protection against melanoma recurrence and death.     

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).     

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.     

Characteristics and Outcomes of Patients Who Achieve High Workload (≥10 Metabolic Equivalents) During Treadmill Exercise Echocardiography

ObjectiveTo determine the frequency and prognostic significance of abnormal exercise echocardiographic results for patients achieving a workload of 10 or more metabolic equivalents during treadmill exercise echocardiography.Patients and MethodsPatients who underwent treadmill exercise echocardiography from November 1, 2003, through December 31, 2008, and exercised for 9 or more minutes using the Bruce protocol (N=7236) were included. Clinical and exercise echocardiographic characteristics and outcomes were evaluated. Variables associated with abnormal exercise echocardiographic results and mortality were identified.ResultsExercise echocardiographic results were positive for ischemia in 862 patients (12%). Extensive ischemia developed in 265 patients (4%). For patients with normal exercise echocardiographic results, all-cause and cardiovascular mortality rates were 0.30% and 0.05% per person-year of follow-up, respectively. For patients who had extensive ischemia, all-cause and cardiovascular mortality rates were 0.84% and 0.25% per person-year of follow-up, respectively. Patients at highest risk were those who had extensive and severe regional wall motion abnormalities at rest (n=58), and their all-cause and cardiovascular mortality rates were 2.65% and 0.76% per person-year of follow-up. Exercise echocardiographic variables did not identify sizable patient subgroups at risk for death and did not provide incremental prognostic information (C statistic was 0.74 compared with 0.73 for the clinical plus exercise electrocardiography model).ConclusionPatients achieving a workload of 10 or more metabolic equivalents during treadmill exercise testing do not often have extensive ischemic abnormalities on exercise echocardiography. Although exercise echocardiographic results provide some prognostic information, it is not of incremental value for these patients, whose short-term and medium-term prognosis is excellent.     

Prognostic Value of Exercise Capacity in Patients With Coronary Artery Disease: The FIT (Henry Ford ExercIse Testing) Project

ObjectiveTo examine the prognostic value of exercise capacity in patients with nonrevascularized and revascularized coronary artery disease (CAD) seen in routine clinical practice.Patients and MethodsWe analyzed 9852 adults with known CAD (mean ± SD age, 61±12 years; 69% men [n=6836], 31% black race [n=3005]) from The Henry Ford ExercIse Testing (FIT) Project, a retrospective cohort study of patients who underwent physician-referred stress testing at a single health care system between January 1, 1991, and May 31, 2009. Patients were categorized by revascularization status (nonrevascularized, percutaneous coronary intervention [PCI], or coronary artery bypass graft [CABG] surgery) and by metabolic equivalents (METs) achieved on stress testing. Using Cox regression models, hazard ratios for mortality, myocardial infarction (MI), and downstream revascularizations were calculated after adjusting for potential confounders, including cardiac risk factors, pertinent medications, and stress testing indication.ResultsThere were 3824 all-cause deaths during median follow-up of 11.5 years. In addition, 1880 MIs, and 1930 revascularizations were ascertained. Each 1-MET increment in exercise capacity was associated with a hazard ratio (95% CI) of 0.87 (0.85-0.89), 0.87 (0.85-0.90), and 0.86 (0.84-0.89) for mortality; 0.98 (0.96-1.01), 0.88 (0.84-0.92), and 0.93 (0.90-0.97) for MI; and 0.94 (0.92-0.96), 0.91 (0.88-0.95), and 0.96 (0.92-0.99) for downstream revascularizations in the nonrevascularized, PCI, and CABG groups, respectively. In each MET category, the nonrevascularized group had similar mortality risk as and higher MI and downstream revascularization risk than the PCI and CABG surgery groups (P<.05).ConclusionExercise capacity was a strong predictor of mortality, MI, and downstream revascularizations in this cohort. Furthermore, patients with similar exercise capacities had an equivalent mortality risk, irrespective of baseline revascularization status.     

Association Between Alcohol Consumption and Risk of Cardiovascular Disease and All-Cause Mortality in Patients With Hypertension: A Meta-Analysis of Prospective Cohort Studies

ObjectiveTo conduct a meta-analysis summarizing the risk of cardiovascular disease (CVD) and all-cause mortality (ACM) in relation to alcohol consumption in patients with hypertension, focusing on clarifying dose-response associations.Patients and MethodsPubMed and EMBASE were searched for eligible prospective cohort studies from December 3, 1949, through January 18, 2014. The semi-parameter method and dose-response analysis were used.ResultsNine studies (11 cohorts) were included in the meta-analysis. Compared with the lowest alcohol level (abstainers/occasional drinkers), the pooled relative risk (RR) was 0.72 (95% CI, 0.68-0.77) for the third highest category (median, 10 g/d), 0.81 (95% CI, 0.71-0.93) for the second highest category (median, 20 g/d), and 0.60 (95% CI, 0.54-0.67) for the highest category (median, 30 g/d). A J-shaped relationship between alcohol use and ACM was observed, and the nadir (RR, 0.82; 95% CI, 0.76-0.88) was found to be at a dose of 8 to 10 g of alcohol consumption per day.ConclusionFindings of this meta-analysis suggest that low-to-moderate alcohol consumption was inversely significantly associated with the risk of CVD and ACM in patients with hypertension.     

Characteristics of Resistant Hypertension in a Large,Ethnically Diverse Hypertension Population of an Integrated Health System

ObjectiveTo evaluate the prevalence of and characterize resistant hypertension in a large representative population with successful hypertension management and reliable health information.Patient and MethodsWe performed a cross-sectional study using clinical encounter, laboratory, and administrative information from the Kaiser Permanente Southern California health system between January 1, 2006, and December 31, 2007. From individuals older than 17 years with hypertension, resistant hypertension was identified and prevalence was determined. Multivariable logistic regression was used to calculate odds ratios (ORs), with adjustments for demographic characteristics, clinical variables, and medication use.ResultsOf 470,386 hypertensive individuals, 60,327 (12.8%) were identified as having resistant disease, representing 15.3% of those taking medications. Overall, 37,061 patients (7.9%) had uncontrolled hypertension while taking 3 or more medicines. The ORs (95% CIs) for resistant hypertension were greater for black race (1.68 [1.62-1.75]), older age (1.11 [1.10-1.11] for every 5-year increase), male sex (1.06 [1.03-1.10]), and obesity (1.46 [1.42-1.51]). Medication adherence rates were higher in those with resistant hypertension (93% vs 89.8%; P<.001). Chronic kidney disease (OR, 1.84; 95% CI, 1.78-1.90), diabetes mellitus (OR, 1.58; 95% CI, 1.53-1.63), and cardiovascular disease (OR, 1.34; 95% CI, 1.30-1.39) were also associated with higher risk of resistant hypertension.ConclusionIn a more standardized hypertension treatment environment, we observed a rate of resistant hypertension comparable with that of previous studies using more fragmented data sources. Past observations have been limited due to nonrepresentative populations, reliability of the data, heterogeneity of the treatment environments, and less than ideal control rates. This cohort, which was established using an electronic medical record–based approach, has the potential to provide a better understanding of resistant hypertension and outcomes.     

The Effect of Resistance Exercise on All-Cause Mortality in Cancer Survivors

ObjectiveTo examine the independent associations of leisure-time aerobic physical activity (PA) and resistance exercise (RE) on all-cause mortality in cancer survivors.Patients and MethodsPatients included 2863 male and female cancer survivors, aged 18 to 81 years, who received a preventive medical examination between April 8, 1987, and December 27, 2002, while enrolled in the Aerobics Center Longitudinal Study in Dallas, Texas. Physical activity and RE were assessed by self-report at the baseline medical examination. Cox proportional hazards regression analysis was performed to determine the independent associations of PA and RE with all-cause mortality in participants who had a history of cancer.ResultsPhysical activity in cancer survivors was not associated with a lower risk of all-cause mortality. In contrast, RE was associated with a 33% lower risk of all-cause mortality (95% CI, 0.45-0.99) after adjusting for potential confounders, including PA.ConclusionIndividuals who participated in RE during cancer survival had a lower risk for all-cause mortality. The present findings provide preliminary evidence for benefits of RE during cancer survival. Future randomized controlled trials examining RE and its effect on lean body mass, muscular strength, and all-cause mortality in cancer survivors are warranted.     

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.     

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.     

Proton Pump Inhibitors and the Risk for Hospital-Acquired Clostridium difficile Infection

ObjectiveTo examine the relationship between proton pump inhibitor (PPI) usage and nosocomial Clostridium difficile infection (CDI) and determine the duration of therapy at which CDI risk increases.Patients and MethodsThis retrospective case-control study included consecutive adult patients in whom nosocomial CDI developed after hospitalization for 3 or more days at one of 2 affiliated hospitals between June 1, 2010, and October 31, 2011. These patients were matched to patients hospitalized within 6 months who did not have CDI development in a 1:2 ratio using age, sex, and antibiotic usage. Potential risk factors for CDI, including PPI use and duration, were evaluated. Multivariate analysis was performed to control for confounding variables and identify risk factors.ResultsA total of 201 patients were evaluated, 67 with CDI and 134 matched controls. Patients in whom CDI developed were more likely to have received a PPI (76% vs 39%; P<.001) and had a longer duration of PPI therapy (median [range], 5 [0-20] days vs 0 [0-11] days; P<.001) than those who did not have CDI development. After controlling for prior hospital admission, intensive care unit admission, admission from a skilled nursing facility, immunosuppression, number of antibiotics received, PPI duration, and time to event via multivariate analysis, PPI duration was found to be a risk factor for CDI (odds ratio, 1.14; 95% CI, 1.02-1.27; P=.018). The probability for CDI was higher when PPI use exceeded 2 days in patients without a prior hospital admission and 1 day in patients with a prior admission.ConclusionThe duration of PPI therapy is significantly associated with CDI. Clinicians should strongly consider restricting PPI use given the short exposure time associated with this increased risk.     

Biobank Participants' Preferences for Disclosure of Genetic Research Results: Perspectives From the OurGenes,OurHealth, OurCommunity Project

ObjectiveTo assess biobank participants' preferences for disclosure of genetic research results.Patients and MethodsWe conducted a cross-sectional survey of participants in the OurGenes, OurHealth, OurCommunity biobank. Respondents were surveyed about preferences for disclosure, importance of disclosure, communication of results with practitioners, and sharing of results after respondents' death. Multivariate regression analysis was used to assess independent sociodemographic and clinical predictors of disclosure preferences. Data collection occurred from June 6, 2011, to June 25, 2012.ResultsAmong 1154 biobank participants, 555 (48%) responded. Most thought that research result disclosure was important (90%). Preference for disclosure varied, depending on availability of disease treatment (90% vs 64%, P<.001), high vs low disease risk (79% vs 66%, P<.001), and serious vs mild disease (83% vs 68%, P<.001). More than half of respondents (57%) preferred disclosure even when there is uncertainty about the results' meaning, and 87% preferred disclosure if the disease is highly heritable. Older age was positively associated with interest in disclosure, whereas female sex, nonwhite race, diabetes mellitus, and depression and/or anxiety were negatively associated with disclosure. More than half of respondents (52%) would want their results returned to their nearest biological relative after death.ConclusionsOurGenes biobank participants report strong preferences for disclosure of research results, and most would designate a relative to receive results after death. Participant preferences for serious vs mild disease, high vs low disease risk, and availability of disease treatment differed significantly. Future research should consider family members' preferences for receiving research results from enrolled research participants.