A Perspective on the New American College of Cardiology/American Heart Association Guidelines for Cardiovascular Risk Assessment

The recently published American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for cardiovascular risk assessment provide equations to estimate the 10-year and lifetime atherosclerotic cardiovascular disease (ASCVD) risk in African Americans and non-Hispanic whites, include stroke as an adverse cardiovascular outcome, and emphasize shared decision making. The guidelines provide a valuable framework that can be adapted on the basis of clinical judgment and individual/institutional expertise. In this review, we provide a perspective on the new guidelines, highlighting what is new, what is controversial, and potential adaptations. We recommend obtaining family history of ASCVD at the time of estimating ASCVD risk and consideration of imaging to assess subclinical disease burden in patients at intermediate risk. In addition to the adjuncts for ASCVD risk estimation recommended in the guidelines, measures that may be useful in refining risk estimates include carotid ultrasonography, aortic pulse wave velocity, and serum lipoprotein(a) levels. Finally, we stress the need for research efforts to improve assessment of ASCVD risk given the suboptimal performance of available risk algorithms and suggest potential future directions in this regard.     

Lipoprotein(a), Cardiovascular Disease,and Contemporary Management

Elevated lipoprotein(a) (Lp[a]) is a causal genetic risk factor for cardiovascular disease. To determine if current evidence supports both screening and treatment for elevated Lp(a) in high-risk patients, an English-language search of PubMed and MEDLINE was conducted. In population studies, there is a continuous association between Lp(a) concentrations and cardiovascular risk, with synergistic effects when low-density lipoprotein (LDL) is also elevated. Candidates for Lp(a) screening include patients with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, recurrent cardiovascular events, or inadequate LDL cholesterol (LDL-C) responses to statins. Given the comparative strength of clinical evidence, reducing LDL-C to the lowest attainable value with a high-potency statin should be the primary focus of lipid-modifying therapies. If the Lp(a) level is 30 mg/dL or higher in a patient who has the aforementioned characteristics plus residual LDL-C elevations (≥70-100 mg/dL) despite maximum-potency statins or combination statin therapy, the clinician may consider adding niacin (up to 2 g/d). If, after these interventions, the patient has progressive coronary heart disease (CHD) or LDL-C levels of 160-200 mg/dL or higher, LDL apheresis should be contemplated. Although Lp(a) is a major causal risk factor for CHD, no currently available controlled studies have suggested that lowering it through either pharmacotherapy or LDL apheresis specifically and significantly reduces coronary risk. Further research is needed to (1) optimize management in order to reduce CHD risk associated with elevated Lp(a) and (2) determine what other intermediate- or high-risk groups might benefit from Lp(a) screening.     

Evaluation and Management of Patients With Heart Disease and Cancer: Cardio-Oncology

The care for patients with cancer has advanced greatly over the past decades. A combination of earlier cancer diagnosis and greater use of traditional and new systemic treatments has decreased cancer-related mortality. Effective cancer therapies, however, can result in short- and long-term comorbidities that can decrease the net clinical gain by affecting quality of life and survival. In particular, cardiovascular complications of cancer treatments can have a profound effect on the health of patients with cancer and are more common among those with recognized or unrecognized underlying cardiovascular diseases. A new discipline termed cardio-oncology has thus evolved to address the cardiovascular needs of patients with cancer and optimize their care in a multidisciplinary approach. This review provides a brief introduction and background on this emerging field and then focuses on its practical aspects including cardiovascular risk assessment and prevention before cancer treatment, cardiovascular surveillance and therapy during cancer treatment, and cardiovascular monitoring and management after cancer therapy. The content of this review is based on a literature search of PubMed between January 1, 1960, and February 1, 2014, using the search terms cancer, cardiomyopathy, cardiotoxicity, cardio-oncology, chemotherapy, heart failure, and radiation.     

Cardiovascular Health Metrics and Accelerometer-Measured Physical Activity Levels: National Health and Nutrition Examination Survey, 2003-2006

ObjectiveTo determine whether relationships exist between accelerometer-measured moderate-to-vigorous physical activity (MVPA) and other cardiovascular (CV) health metrics in a large sample.Patients and MethodsData from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) collected from January 1, 2003, through December 31, 2006, were used. Overall, 3454 nonpregnant adults 20 years or older who fasted for 6 hours or longer, with valid accelerometer data and with CV health metrics, were included in the study. Blood pressure (BP), body mass index (BMI), smoking status, diet, fasting plasma glucose level, and total cholesterol level were defined as ideal, intermediate, and poor on the basis of American Heart Association criteria. Results were weighted to account for sampling design, oversampling, and nonresponse.ResultsSignificant increasing linear trends in mean daily MVPA were observed across CV health levels for BMI, BP, and fasting plasma glucose (P<.001). Those with a poor BMI and BP had significantly lower mean daily MVPA than those with intermediate and ideal BMIs and BPs (all P<.001). In addition, individuals with an intermediate fasting plasma glucose level had significantly lower mean daily MVPA than individuals at the ideal levels (P<.001). No significant linear trends were observed for cholesterol, smoking, and diet. A significant linear trend was observed for mean daily MVPA and the overall number of other CV health metrics (P<.001).ConclusionObjectively measured MVPA was related to other CV health metrics in this large sample. These results support the inclusion of physical activity in the overall definition of ideal CV health.     

Sudden Cardiac Death From the Perspective of Coronary Artery Disease

Sudden cardiac death accounts for approximately 50% of all deaths attributed to cardiovascular disease in the United States. It is most commonly associated with coronary artery disease and can be its initial manifestation or may occur in the period after an acute myocardial infarction. Decreasing the rate of sudden cardiac death requires the identification and treatment of at-risk patients through evidence-based pharmacotherapy and interventional strategies aimed at primary and secondary prevention. For this review, we searched PubMed for potentially relevant articles published from January 1, 1970, through March 1, 2014, using the following key search terms: sudden cardiac death, ischemic heart disease, coronary artery disease, myocardial infarction, and cardiac arrest. Searches were enhanced by scanning bibliographies of identified articles, and those deemed relevant were selected for full-text review. This review outlines various mechanisms for sudden cardiac death in the setting of coronary artery disease, describes risk factors for sudden cardiac death, explores the management of cardiac arrest, and outlines optimal practice for the monitoring and treatment of patients after an acute ST-segment elevation myocardial infarction to decrease the risk of sudden death.     

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.     

Role of Dietary Salt and Potassium Intake in Cardiovascular Health and Disease: A Review of the Evidence

The objective of this review was to provide a synthesis of the evidence on the effect of dietary salt and potassium intake on population blood pressure, cardiovascular disease, and mortality. Dietary guidelines and recommendations are outlined, current controversies regarding the evidence are discussed, and recommendations are made on the basis of the evidence. Designed search strategies were used to search various databases for available studies. Randomized trials of the effect of dietary salt intake reduction or increased potassium intake on blood pressure, target organ damage, cardiovascular disease, and mortality were included. Fifty-two publications from January 1, 1990, to January 31, 2013, were identified for inclusion. Consideration was given to variations in the search terms used and the spelling of terms so that studies were not overlooked, and search terms took the following general form: (dietary salt or dietary sodium or [synonyms]) and (dietary potassium or [synonyms]) and (blood pressure or hypertension or vascular disease or heart disease or chronic kidney disease or stroke or mortality or [synonyms]). Evidence from these studies demonstrates that high salt intake not only increases blood pressure but also plays a role in endothelial dysfunction, cardiovascular structure and function, albuminuria and kidney disease progression, and cardiovascular morbidity and mortality in the general population. Conversely, dietary potassium intake attenuates these effects, showing a linkage to reduction in stroke rates and cardiovascular disease risk. Various subpopulations, such as overweight and obese individuals and aging adults, exhibit greater sensitivity to the effects of reduced salt intake and may gain the most benefits. A diet that includes modest salt restriction while increasing potassium intake serves as a strategy to prevent or control hypertension and decrease cardiovascular morbidity and mortality. Thus, the body of evidence supports population-wide sodium intake reduction and recommended increases in dietary potassium intake as outlined by current guidelines as an essential public health effort to prevent kidney disease, stroke, and cardiovascular disease.     

Systematic Analysis Underlying the Quality of the Scientific Evidence and Conflicts of Interest in Interventional Medicine Subspecialty Guidelines

ObjectiveTo determine the validity of guidelines published by interventional medical societies.MethodsWe reviewed the interventional medicine subspecialty society websites of the American Association for Bronchology and Interventional Pulmonology (AABIP), American Society of Diagnostic and Interventional Nephrology (ASDIN), American Society for Gastrointestinal Endoscopy (ASGE), and Society for Cardiovascular Angiography and Interventions (SCAI) as of November 15, 2012, for published interventional guidelines. The study was performed between November 15, 2012, and January 1, 2013. The AABIP did not publish guidelines, so American Thoracic Society and American College of Chest Physicians guidelines were reviewed. All the guidelines were reviewed for graded levels of evidence, methods used to grade the evidence, and disclosures of conflicts of interest (COIs).ResultsOf 153 interventional guidelines evaluated, 4 were duplicates. Forty-six percent of guidelines (69 of 149) graded the quality of evidence using 7 different methods. The ASGE graded 71% of guidelines (46 of 65) compared with 29% (23 of 78) by the SCAI and 0 by the ASDIN (n=4) and the pulmonary societies (n=2). Of the 3425 recommendations reviewed, 11% (n=364) were supported by level A, 42% (n=1432) by level B, and 48% (n=1629) by level C. The mean age of the guidelines was 5.2 years. Additionally, 62% of the guidelines (92 of 149) failed to comment on COIs; when disclosed, 91% of guidelines (52 of 57) reported COIs. In total, 1827 COIs were reported by 45% of the authors (317 of 697), averaging 5.8 COIs per author.ConclusionMost of the interventional guidelines failed to grade the evidence. When present, most guidelines used lower-quality evidence. Furthermore, most guidelines failed to disclose COIs. When commented on, numerous COIs were present. Future guidelines should clearly state the quality of evidence, use a standard grading system, be transparent regarding potential biases, and provide frequent updates.     

Youth-Onset Type 2 Diabetes Mellitus: Lessons Learned From the TODAY Study

Type 2 diabetes mellitus is increasingly diagnosed in obese children and adolescents. Evidence suggests that this disease commonly progresses more rapidly in youth compared with adults and is associated with high rates of early microalbuminuria, hypertension, and dyslipidemia. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study was the first multiethnic, multicenter randomized trial in the United States to compare 3 treatment approaches in obese youth with new-onset type 2 diabetes (n=699; ages 10-17 years): monotherapy with metformin, metformin with rosiglitazone, and metformin with an intensive lifestyle intervention. The primary outcome was glycemic control. Diabetes-related complications and cardiovascular risk factors were also examined. Approximately half of the participants could not maintain glycemic control by using metformin alone. Combination therapy with metformin and rosiglitazone resulted in better durability of glycemic control, and metformin plus intensive lifestyle intervention was intermediate but not superior to metformin alone. Deterioration in glycemic control was associated with rapid loss of beta cell function, not worsened insulin sensitivity, and could not be explained by differences in adherence or body mass index. After 3.9 years, 236 (33.8%) of participants had hypertension and 116 participants (16.6%) had microalbuminuria. Only 55.9% of participants had a low-density lipoprotein cholesterol level less than 100 mg/dL (to convert to mmol/L, multiply by 0.0259) after 3 years, and 71 of 517 participants (13.7%) had retinopathy. The significance of the findings from this important trial for the management of youth and young adults with youth-onset type 2 diabetes and its complications is discussed. An aggressive multifaceted approach is needed to prevent or forestall premature microvascular and macrovascular complications in youth-onset type 2 diabetes.     

Succinct Review of the New VTE Prevention and Management Guidelines

Venous thromboembolism is a major source of morbidity and mortality in the United States. The American College of Chest Physicians Antithrombotic Guidelines, 9th edition, includes a large number of clinical practice recommendations regarding the diagnosis, treatment, and prevention of venous thromboembolism. This succinct clinical review of these guidelines specifically focuses on the evaluation, treatment, and prevention of venous thromboembolic disease.     

Assessing the Risk of Aortic Valve Replacement for Severe Aortic Stenosis in the Transcatheter Valve Era

Surgical aortic valve replacement had been the only definitive treatment of severe aortic stenosis before the availability of transcatheter valve technology. Historically, many patients with severe aortic stenosis had not been offered surgery, largely related to professional and patient perception regarding the risks of operation relative to anticipated benefits. Such patients have been labeled as “high risk” or “inoperable” with respect to their suitability for surgery. The availability of transcatheter aortic valve replacement affords a new treatment option for patients previously not felt to be optimal candidates for surgical valve replacement and allows for the opportunity to reexamine the methods for assessing operative risk in the context of more than 1 available treatment. Standardized risk assessment can be challenging because of both the imprecision of current risk scoring methods and the variability in ascertaining risk related to operator experience as well as local factors and practice patterns at treating facilities. Operative risk in actuality is not an absolute but represents a spectrum from very low to extreme, and the conventional labels of high risk and inoperable are incomplete with respect to their utility in clinical decision making. Moving forward, the emphasis should be on developing an individual assessment that takes into account procedure risk as well as long-term outcomes evaluated in a multidisciplinary fashion, and incorporating patient preferences and goals in a model of shared decision making.     

Risk Factors for Recurrent Spontaneous Epistaxis

ObjectiveTo identify risk factors associated with spontaneous recurrent epistaxis.Patients and MethodsThis was a retrospective cohort study assessing patients in the Marshfield Clinic system diagnosed as having epistaxis between January 1, 1991, and January 1, 2011. There were 461 cases with at least 2 episodes of spontaneous epistaxis within 3 years and 912 controls with only 1 episode in the same time frame. More than 50 potential risk factors were investigated, including demographic features, substance use, nasal anatomical abnormalities, nasal infectious and inflammatory processes, medical comorbidities, medications, and laboratory values. A Cox proportional hazards regression modeling approach was used to calculate hazard ratios of epistaxis recurrence.ResultsTraditional risk factors for epistaxis, including nasal perforation, nasal septum deviation, rhinitis, sinusitis, and upper respiratory tract infection, did not increase the risk of recurrence. Significant risk factors for recurrent epistaxis included congestive heart failure, diabetes mellitus, hypertension, and a history of anemia. Warfarin use increased the risk of recurrence, independent of international normalized ratio. Aspirin and clopidogrel were not found to increase the risk of recurrence. Few major adverse cardiovascular events were observed within 30 days of the first epistaxis event.ConclusionCongestive heart failure is an underappreciated risk factor for recurrent epistaxis. Hypertension and diabetes mellitus may induce atherosclerotic changes in the nasal vessels, making them friable and more at risk for bleeding. Patients with recurrent epistaxis may also be more susceptible to developing anemia. Physicians should promote antiplatelet and antithrombotic medication adherence despite an increased propensity for recurrent epistaxis to prevent major adverse cardiovascular events.     

The Necessity for Clinical Reasoning in the Era of Evidence-Based Medicine

Clinical decisions are increasingly driven by evidence-based recommendations of guideline groups, which aim to be based on the highest quality knowledge—randomized clinical trials (RCTs) and meta-analyses. Although RCTs provide the best assessment of the overall value of a therapy, high-quality evidence from RCTs is often incomplete, contradictory, or absent even in areas that have been most exhaustively studied. Moreover, the likelihood of the success or failure of a therapy is not identical in all the individuals treated in any trial because therapy is not the only determinant of outcome. Therefore, the overall results of a trial cannot be assumed to apply to any particular individual, not even someone who corresponds to all the entry criteria for the trial. In addition, the potential for bias due to financial conflicts remains in many guideline groups. Guidelines are key sources of knowledge. Nevertheless, limitations in the extent, quality, generalizability, and transferability of evidence mean that we clinicians must still reason through the best choices for an individual because even in the absence of full and secure knowledge, clinical decisions must still be made. Clinical reasoning is the pragmatic, tried-and-true process of expert clinical problem solving that does value mechanistic reasoning and clinical experience as well as RCTs and observational studies. Clinicians must continue to value clinical reasoning if our aim is the best clinical care for all the individuals we treat.     

Development and Validation of a Risk Calculator for Predicting Postoperative Pneumonia

ObjectiveTo identify preoperative factors associated with an increased risk of postoperative pneumonia and subsequently develop and validate a risk calculator.Patients and MethodsThe American College of Surgeons’ National Surgical Quality Improvement Program, a multicenter, prospective data set (2007-2008) was used. Univariate and multivariate logistic regression analyses were performed. The 2007 data set (N=211,410) served as the training set, and the 2008 data set (N=257,385) served as the validation set.ResultsIn the training set, 3825 patients (1.8%) experienced postoperative pneumonia. Patients who experienced postoperative pneumonia had a significantly higher 30-day mortality (17.0% vs 1.5%; P<.001). On multivariate logistic regression analysis, 7 preoperative predictors of postoperative pneumonia were identified: age, American Society of Anesthesiologists class, chronic obstructive pulmonary disease, dependent functional status, preoperative sepsis, smoking before operation, and type of operation. The risk model based on the training data set was subsequently validated on the validation data set, with model performance being very similar (C statistic: 0.860 and 0.855, respectively). The high C statistic indicates excellent predictive performance. The risk model was used to develop an interactive risk calculator.ConclusionPreoperative variables associated with an increased risk of postoperative pneumonia include age, American Society of Anesthesiologists class, chronic obstructive pulmonary disease, dependent functional status, preoperative sepsis, smoking before operation, and type of operation. The validated risk calculator provides a risk estimate for postoperative pneumonia and is anticipated to aid in surgical decision making and informed patient consent.     

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.     

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.     

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.     

Ulcerative Colitis: Epidemiology,Diagnosis, and Management

Ulcerative colitis is a chronic idiopathic inflammatory bowel disease characterized by continuous mucosal inflammation that starts in the rectum and extends proximally. Typical presenting symptoms include bloody diarrhea, abdominal pain, urgency, and tenesmus. In some cases, extraintestinal manifestations may be present as well. In the right clinical setting, the diagnosis of ulcerative colitis is based primarily on endoscopy, which typically reveals evidence of continuous colonic inflammation, with confirmatory biopsy specimens having signs of chronic colitis. The goals of therapy are to induce and maintain remission, decrease the risk of complications, and improve quality of life. Treatment is determined on the basis of the severity of symptoms and is classically a step-up approach. 5-Aminosalycilates are the mainstay of treatment for mild to moderate disease. Patients with failed 5-aminosalycilate therapy or who present with more moderate to severe disease are typically treated with corticosteroids followed by transition to a steroid-sparing agent with a thiopurine, anti–tumor necrosis factor agent, or adhesion molecule inhibitor. Despite medical therapies, approximately 15% of patients still require proctocolectomy. In addition, given the potential risks of complications from the disease itself and the medications used to treat the disease, primary care physicians play a key role in optimizing the preventive care to reduce the risk of complications.     

Drug-Induced Liver Injury

Drug hepatoxicity can be nonidiosyncratic (predictable), as in the case of acetaminophen, or idiosyncratic (unpredictable). This review article focuses primarily on idiosyncratic drug-induced liver injury (DILI). New epidemiologic data suggest that approximately 20 new cases of DILI per 100,000 persons occur each year. Idiosyncratic DILI accounts for 11% of the cases of acute liver failure in the United States. Risk factors for DILI include medication dose, drug lipophilicity, and extent of hepatic metabolism. There is mixed evidence to support the role of host factors such as age, sex, and chronic liver disease in the development of DILI. For specific drugs, a genetic predisposition appears to be a risk factor for DILI. Suspected cases of idiosyncratic DILI should be categorized as hepatitic, cholestatic, or mixed on the basis of the degree/ratio of abnormalities in the alanine aminotransferase and alkaline phosphatase. A careful evaluation for other causes of liver disease should be performed, though a liver biopsy is rarely needed. There is evidence that some patients with DILI may actually have hepatitis E and this diagnosis should be considered. Amoxicillin/clavulanate isoniazid, and nonsteroidal anti-inflammatory drugs are among the most common causes of DILI. Drug discontinuation or dechallenge should lead to an improvement in liver biochemistries in most patients, though a bilirubin value of more than 3 g/dL is associated with mortality of at least 10%. New biomarkers for DILI using proteomics and micro RNA appear promising but require further study. New studies on drugs with potential for causing DILI are reviewed herein, including tumor necrosis factor-alpha antagonists, fluoroquinolones, tyrosine kinase inhibitors, statins, and supplements. PubMed was used with search terms of drug induced liver injury OR DILI with filter settings of “English language” and “humans” and custom date range of “January 1, 2000.” The authors also manually searched bibliographies from key references and included seminal references before the year 2000.