De Luca G; Dirksen MT, Spaulding C, et al. Drug-eluting vs bare-metal stents in primary

angioplasty: a pooled patient-level meta-analysis of randomized trials. Arch Intern Med.

In patients undergoing elective percutaneous coronary intervention (PCI), drug-eluting stents (DES), compared with bare metal stents (BMS), have consistently been 

shown to reduce the risk of target vessel revascularization (TVR) without a significant risk of myocardial infarction or death.1 This benefit is even more pronounced among the third-generation DES.2,3 While stent thrombosis (ST) continues to be a concern with DES, recent large-scale studies suggest even lower ST with some thirdgeneration DES compared with BMS in elective PCI.2 Despite the reassuring data regarding safety and efficacy of DES for elective coronary interventions, concerns remain about ST in higher-risk patients, such as those presenting with non-ST elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI).4 The risk of stent thrombosis per year is about 4.4% for STEMI patients, compared with NSTEMI (~1.5%) or elective PCI (0.1-0.6%).4

A number of mechanisms may explain why individuals with STEMI experience higher rates of ST, including noncompliance, technical errors such as undersizing, and issues related to plaque morphology, inflammation, and lateacquired stent malapposition (LASM).5 Because of this concern, many randomized clinical trials have evaluated the safety and efficacy of DES compared with BMS in patients undergoing PCI for STEMI.6 However, many of these studies have small sample size and relatively short duration of follow-up to address concerns regarding late ST and reinfarction.

To address some of these limitations, De Luca et al6 conducted a pooled patient- level meta-analysis of randomized clinical trials for DES in primary angioplasty.

A patient-level meta-analysis of 11 of the 16 available trials resulted in an analysis of 3980 patients randomized to receive DES and 2318 who underwent BMS. Study design varied substantially between trials, with variable follow-up and some studies requiring routine follow-up angiography. The majority of patients received a paclitaxel-eluting stent (PES; 72.3%), followed by sirolimus-eluting stent (SES; 26.7%) and zotarolimus-eluting stent (1.0%). Of note, a significantly higher number of patients received long-term dual antiplatelet therapy in the DES group compared with BMS patients. Otherwise, the 2 groups were similar with regard to other important baseline characteristics.

Using a fixed-effects model, DES use was associated with a 43% (number needed to treat [NNT], 12) relative risk (RR) reduction in TVR and a 46% (NNT, 12) RR reduction in target lesion revascularization (TLR). No statistically significantly differences in all-cause (P = 0.11) or cardiac (P = 0.19) mortality were identified; however, the trends appear to favor DES use. On the other hand, DES was associated with a significant increase in the risk of reinfarction (hazard ratio [HR], 2.06; 95% confidence

interval [CI], 1.22-3.49; P = 0.03). Similarly, the risk of long-term definite or probable ST was 3 times higher with DES compared with BMS (HR, 2.81; 95% CI, 1.28-6.19; P = 0.04). More alarming was the high rate of ST in both populations, 5.8% in the DES and 4.3% in the BMS group. The authors concluded that “among patients with STEMI

undergoing primary PCI, compared to BMS, SES and PES are associated with significant and sustained reductions in TVR, without significant differences in stent thrombosis, reinfarction, or death.”

1. Stettler C, Wandel S, Allemann S, et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. Lancet.  007;370:937-948.

2. Palmerini T, Biondi-Zoccai G, Della Riva D, et al. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. Lancet. 2012;379:1393-1402.

3. Kedhi E, Joesoef KS, McFadden E, et al. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet

4. Dangas GD, Caixeta A, Mehran R, et al Frequency and predictors of stent thrombo-sis after percutaneous coronary intervention in acute myocardial infarction. Circulation. 2011;123:1745-1756.

5. Guagliumi G, Costa MA, Sirbu V, et al. Strut coverage and late malapposition with paclitaxel-eluting stents compared with bare metal stents in acute myocardial infarction: optical coherence tomography substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) Trial. Circulation. 2011;123:274-281.

6. De Luca G, Dirksen MT, Spaulding C, et al. Drug-eluting vs bare-metal stents in primary angioplasty: a pooled patient-level meta-analysis of randomized trials. Arch

Intern Med. 2012;172:611-621; discussion 621-622.

7. Singh IM, Filby SJ, Sakr FE, et al. Clinical outcomes of drug-eluting versus bare-metal in-stent restenosis. Catheter Cardiovasc Interv. 2010;75:338-342.

8. Chen MS, John JM, Chew DP, Lee DS, Ellis SG, Bhatt DL. Bare metal stent restenosis is not a benign clinical entity. Am Heart J. 2006;151:1260-1264.

9. Räber L, Windecker S. Primary percutaneous coronary intervention and risk of stent thrombosis: a look beyond the HORIZON. Circulation. 2011;123:1709-1712.

The current patient-level meta-analysis by De Luca and colleagues confirms that DES substantially decreases the risk of TVR and TLR in patients undergoing primary PCI for STEMI. However, despite the authors’ assurance, concerns about late ST and reinfarction remain. Indeed, the rate of ST in the DES group was 5.8%, significantly higher than the 0.5% risk reported in patients undergoing elective PCI using third-generation DES.2 The study is helpful, but many limitations and questions remain unanswered. Over 5% of patients were lost to follow-up. Furthermore, many of the trials did not have mandated long-term follow-up to address important concerns about late ST and cardiac death. Given the mandatory requirement for routine angiographic follow-up, the need for TVR and TLR may have been overinflated (4 trials had 100% routine angiographic follow-up). Obviously, lower TVR and TLR could impact the cost-effectiveness of DES over BMS for primary PCI. Other important factors such as generalizability, patient compliance, lack of data on third-generation DES, and more potent antiplatelet agents such as prasugrel and ticagrelor limit the impact of this analysis on current daily practice.

The decision regarding the use of DES or BMS in the setting of STEMI is always challenging. Patients are frequently under distress, therefore, accurate assessment of bleeding, ST risk, and compliance to dual antiplaletet therapy is difficult. Because of these issues, and the belief that BMS restenosis is a more “benign” condition than ST, many interventionalists may lean toward using BMS over DES in this setting. However, there have been reports of increased reinfarction with in-stent restenosis, and the complications and cost associated with reintervention is also not trivial.7,8 Therefore, rather than recommending one device for all patients, a more personalized approach according to risk may be more appropriate when deciding to use DES or BMS in this setting.

Another important issue is the lack of data on thirdgeneration DES for primary PCI. Clearly, the newer stents have significantly lowered the rate of stent thrombosis and restenosis in the setting of elective PCI compared with first-generation DES.2 There is little reason to believe that this added advantage is not present for STEMI; however, this assumption must be confirmed by randomized clinical trials.

A major limitation of the randomized trials of DES versus BMS in the setting of STEMI is lack of technical data. Autopsy specimens have shown more inflammation, fibrin deposition, and uncovered stent struts among patients with STEMI receiving DES.9 Furthermore, intravascular ultrasound (IVUS) and optical coherence tomography (OCT) data from HORIZONS-AMI have also confirmed the presence of LASM and higher rates of uncovered struts with DES compared with BMS at 13 months.5  Collectively, given the inflammatory nature of STEMI and the known risk of stent undersizing in this setting, supplemental imaging with IVUS or OCT are even more important and should be frequently utilized. At the present time, data do not support the routine use of DES for all patients undergoing primary PCI for STEMI. A personalized approach that accounts for patients’ age and morbidity, compliance, and the risk of bleeding and ST is most ideal. This approach, coupled with the use of third-generation DES supplemented by IVUS or OCT guidance and newer antiplatelet agents, should help reduce the risk of ST in the setting of STEMI.

Mehdi H Shishehbor, DO , MPH, is the Director of Endovascular Services in the Robert and Suzanne Tomsich Department of Cardiovascular Medicine at the Cleveland Clinic. He is a specialist in vascular medicine, interventional cardiology, and endovascular intervention. He received his DO from Nova Southeastern University in Florida and a master’s degree in public health at Cleveland State University. He is presently working on a doctorate in epidemiology at Case Western Reserve University. He is widely published on cardiovascular epidemiology, interventional cardiology outcomes, and techniques, and is coauthor of 2 books on coronary intensive care and

Articles

CME Reviews

Drug-Eluting Versus Bare-Metal Stents in Primary Angioplasty

CTT Collaborators. The effects of lowering LDL cholesterol with statin therapy in people

at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.

Lancet. 2012;doi.10.1016/SO140-6736(12)60367-5.

Intensive lowering of LDL cholesterol has previously been found to reduce major vascular events by 20%.1 However, questions still remain about the use of statins for primary prevention and in low-risk individuals. This recent meta-analysis by the Cholesterol Treatment Trialists’ (CTT) Collaborators sought to answer these questions by comparing 134,537 patients (median follow-up of 4.8 years) in trials of statins versus controls, and 39,612 patients (median follow-up of 5.1 years) in trials of low-dose versus high-dose statin therapy.2 The baseline 5-year risk of a major vascular event (MVE) was determined for each participant and stratified into categories (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, >30%), with MVE, defined as nonfatal myocardial infarction, coronary death, coronary revascularization, or stroke. The analysis calculated the rate ratio (RR) per 1 mmol/L of low-density lipoprotein (LDL) cholesterol lowering.

Overall, the investigators found that lowering LDL cholesterol by 1 mmol/L (39 mg/dL) decreased the risk of MVE by 21%, irrespective of age, sex, baseline LDL  cholesterol values, or previous vascular disease. All risk groups benefited from statin therapy (Table). Remarkably, the risk reduction was lowest in the lowest-risk categories, with a 38% reduction of MVE in the <5% group. This reduction corresponds to an absolute risk reduction of MVE of 11 events per 1000 patients for every 1 mmol/L (39 mg/dL) LDL reduction for individuals with a baseline risk of <10%. The study also stratified the analysis by individuals with or without a history of cardiovascular disease, and found that statins had comparable results in the 2 groups, reducing MVE (RR 0.75; 95% CI, 0.70-0.80), vascular mortality (RR 0.85; 95% CI, 0.77-0.95), and all-cause mortality (RR 0.91; 95% CI, 0.85-0.97) in individuals without a history of cardiovascular disease. Overall, a reduction in stroke risk was seen (RR 0.85; 95% CI, 0.80-0.89) and the reduction in risk among subjects with <10% baseline risk was similar to that in higher-risk categories (P for trend = 0.3). Finally, the study also evaluated cancer incidence and cancer deaths with statin use and found no increased risk.

1. Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trails. Lancet. 2010;376:1670-1681.

2. Cholesterol Treatment Trialists’ Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomized trials. Lancet. 2012;doi.10.1016/SO140-6736(12)60367-5.

3. Gutierrez J, Ramirez G, Rundek T, Sacco RL. Statin therapy in the prevention of recurrent cardiovascular events. Arch Intern Med. 2012;172:909-919.

4. Sattar N, Preiss D, et al. (2010). Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 375:735-742.

5. Kerr AJ, Broad J, Wells S, Riddell T, Jackson R. Should the first priority in cardiovascular risk management be those with prior cardiovascular disease? Heart. 2009;95:125-129.

Heterogeneity between participants without and with vascular disease: χ2

MVE, major vascular event; RR, rate ratio; CI, confidence interval.

Reprinted from The Lancet, doi:10.1016/S0140-6736(12)60367-5, Cholesterol Treatment Trialists’ (CTT) Collaborators, “The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.” Published online May 17, 2012. Copyright 2012, with permission from Elsevier.

Impact of Statins on Reduction of Vascular Events

This study adds to the growing body of evidence that statin therapy has a significant impact on the reduction of vascular events that is attributable to LDL lowering. The authors suggest that given this substantial risk reduction in low-risk individuals, LDLlowering guidelines in this population may need to be reconsidered. The cornerstone of primary prevention is to first recommend lipid lowering for the at-risk population through lifestyle changes such as diet, weight loss, and exercise. Medication guidelines are considered when such changes are not adequately effective and include statin therapy, with additional pharmacotherapy as needed. Current guidelines

are based on the goal of reducing LDL levels, no matter what the means.

It was disappointing that the authors did not present an analysis stratified by sex to address whether results were comparable in men and women. A recent meta- analysis by Gutierrez and colleagues3 in the Archives of Internal Medicine provided a sex-based analysis of secondary prevention trials, concluding that the reduced risk of CVD with statins was comparable in women (RR = 0.81; 95% CI, 0.74-0.89) and men (RR = 0.82; 95% CI, 0.78-0.85). Whether these results also apply to the primary prevention setting and low-risk populations remains uncertain. Moreover, Gutierrez et al found that statins significantly reduced stroke and all-cause mortality in men but not in women.3 In the low-risk populations in the present meta-analysis, it would have been helpful to have had a comparison arm with LDL lowering through lifestyle modifications without statin therapy. This would have further differentiated whether statin therapy has benefits beyond LDL lowering. One may hypothesize that the reduction in MVE and all-cause mortality seen in the low-risk population may not be wholly attributable to LDL reduction, but also may be due to the decrease in inflammation related to statins. It is well-known that statin therapy lowers inflammatory markers, and inflammation is implicated in both cardiovascular and nonvascular disease processes.

In order to achieve a reduction in MVE as shown in this meta-analysis, individuals have to lower LDL by 1 mmol/L (39 mg/dL). Although most statins achieve significant LDL lowering, statin therapy is not a one-sizefits- all medication, and individual responses to statins vary. Lack of response may be due to differences in metabolism, polypharmacy, or medication noncompliance. Statin therapy also has known side effects such as myalgias and liver enzyme abnormalities. More recently, in another meta-study published in The Lancet, a slight increase in type 2 diabetes was found with statin use.4 The authors noted the incidence of diabetes in primary prevention trials was 5% per 5-years, or about 0.1% per 1000, much lower than the cardiovascular benefit seen from statins. Certainly there are risks and benefits involved with taking any medication.

Today, over half of cardiovascular events occur in lowrisk individuals with no previous history of vascular disease. 5 It is difficult to argue with the dramatic reduction in vascular events with statin therapy in both primary and secondary prevention populations and the relatively small numbers needed to treat. With anticipated updates in the National Cholesterol Education Program Adult Treatment Panel IV guidelines due to be released later this year, the prediction is that the LDL goal may in fact be lowered

for primary prevention. While this current meta-analysis supports the need to reassess lipid-lowering guidelines, future studies should focus on (1) whether MVE lowering in a low-risk population applies to all LDL-lowering methods or is reserved for statin therapy; (2) whether results apply equally to men and women; and (3) whether allcause mortality is also reduced.

Chrisandra Shufelt, MD, MS, NCMP, is the Associate Director of the Women’s Heart Center and Preventive and Rehabilitative Cardiac Center at the Heart Institute at Cedars-Sinai Medical Center, Los Angeles, CA, and Assistant Professor, Cedars-Sinai Medical Center. She was assisted in the writing of this article by JoAnn E. Manson, MD, DrPH, NCMP, FAHA , Chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health at Harvard Medical School, Boston MA. Dr Manson has been Principal Investigator (PI) of the Boston center for the Women’s Health Initiative (WHI) since study inception in 1993, PI of the CVD component of the Harvard Nurses’ Health Study for 12 years, and PI of the recently launched VITamin D and OmegA-3 TriaL (VITAL).

Lowering LDL Cholesterol With Statin Therapy in Low-Risk Populations

Subscription to ACCEL audio provides clinicians access to up to date reports on diagnosis, treatment, research, literature

reviews, editorials, and coverage of meetings and conferences throughout the world. Created by the American College of Cardiology and the Audio-Digest Foundation, the service allows clinicians to search for and retrieve information from an online audio journal, and download the materials to a computer or MP3 player. The service also provides continuing education opportunities were users can submit tests online or via mail. Users will need to sign up for an Audio-Digest account in order to use the service.

http://www.audio-digest.org/cgi-bin/htmlos/current/ACCEL_landing.html

This beta site for Healio.com covers news and education and allows users to select and tailor news to fit the needs of their cardiology practice. It features industry news, including research on treatments, medication, specific cardiology fields, multimedia and video resources, and subject-oriented blogs. It also includes video resources and meeting and conference coverage focused on research developments. In addition, the website includes links to CME opportunities, meeting resources, and a careers section.

This American Heart Association resource includes tools to help cardiologists implement the association’s protocol in their hospitals. The library covers topics such as management management and evaluation summaries, discharge orders and instructions, patient education tools, mortality risk models, and pertinent algorithms. It offers links to other resources that provide implementation tips, diagnosis codes, and solutions to common implementation barriers. A feedback session allows users to submit their opinions and contribute to developing new tools.

http://www.heart.org/HEARTORG/HealthcareProfessional/GetWithTheGuidelinesHFStroke/GetWithTheGuidelines-HeartFailureHomePage/Heart-Failure-Clinical-Tools-Library_UCM_305817_Article.jsp

HCP Live offers health resources for a variety of cardiac conditions, including atrial fibrillation, atherosclerosis, heart failure, and hypertension. Resourced include articles August 2012 | Cardiology Review 39 on the latest cardiac resource, news from industry leaders, and information on relevant clinical trials. Website visitors can find videos on new devices and treatments, counseling, and other topics. For those who are unable to watch videos at work, the site also offers a selection of podcasts

for breaks or trips to and from the office. An events section helps clinicians keep track of upcoming conferences and meetings. Online issues of Cardiology Review are available with references here as well.

http://www.hcplive.com/specialty/cardiology

iHeart Touch, by Nucleus Medical Media, assists clinicians in explaining the progression and diagnosis of coronary artery disease through medical animations, patient handouts, and interactive simulations. It includes and explains various treatment options and includes frequently used items such as atherosclerosis, coronary artery angiography, coronary artery bypass graft, and corononary artery bypass grafts. The app, used with the iPad, covers the normal anatomy of the heart, making it useful for variety of clinical consults.

http://itunes.apple.com/us/app/iheart-touch/id534675711?mt=8

This resource from Baylor College of Medicine’s Lipids Online website offers a collection of educational talks on lipid management from Lipids Online’s Editorial Board. The talks focus on managing atherosclerosis and other lipid-related disorders, such as dyslipidemia, cardiovascular disease, or inflammation. Topics include clinical case studies, metabolic

risk, lipid management studies, risk assessment and management guidelines, and other areas. Presentations include

slides, talking points, and references that are linked to PubMed, as well as keywords that are linked to additional slides. Talks can be viewed individually or in conjunction with other presentations. Resources are in PowerPoint format, allowing viewers to download the information to a computer. In addition, several presentations are offered as CME activties.

My Studies brings the latest data from research studies to the iPad, while also accommodating clinicians’ busy schedules. The application condenses medical studies to the most relevant information, including important baseline characteristics, statistically significant results, absolute and relative numbers, confidence intervals, and other pertinent information. Studies are searchable by acronym, condition, therapy, year, journal, or a full-text abstract search. My Studies offers a free trial with sample studies, however, access to more studies requires a yearly or monthly subscription. It is compatible with iPad but not other Apple devices.

http://itunes.apple.com/us/app/mystudies/id486085066?mt=8

The National Cardiovascular Data Registry’s (NCDR’s) PINNACLE registry is cardiology’s largest database of  outpatient records and aims to improve quality of care. The centralized system is meant to promote practice innovations by allowing users to submit data on their experience while also being able to view results. It is a portion of the NCDR suite of registry and allows clinicians to determine whether a treatment course improves quality of life. Registry membership includes quarterly benchmark reports; access to data on coronary artery disease, hypertension, heart failure, and atrial fibrillation; and a data submission system designed to integrate with practice workflow.

https://www.pinnacleregistry.org/Pinnacle/PINNACLERegistry/Default.aspx

Overview

Web Resources

The term “cardiology” derives from the Greek word “καρδιÎ¬,” transliterated as “kardia,” and meaning “heart” or “inner self.” Since 1628, when Dr William Harvey first  described blood circulation to Shumway and colleagues at Stanford, cardiology as a medical specialty has dealt with more than simply disorders of the heart; it also includes diseases or conditions that affect blood vessels. Therefore, the specialty has expanded to cover the study of cardiovascular health, better reflecting the true scope of the field.

Cardiology is a specialty that has seen some of the most revolutionary medical advances to have occurred in the last century. Dr Christiaan Barnard’s performance of the first human heart allograft operation in Cape Town, South Africa, in 1967, easily comes to mind, and we can also cite 1982 and 1986 as hallmark years that gave us the first artificial heart and the first coronary stent, respectively. These are only a few of the advances that we have seen in this specialty; there are many innovations in

medications and other treatments, such as the human embryonic stem cell that was first used to successfully repair and, essentially, “regrow” human heart tissue in a laboratory.

From the early days until the present time, and even as I am writing this article, cardiology is dynamically changing. It is a field that embodies a unique mix of hands-on practical application associated with physiological principles, supported by rich and continually evolving evidence-based practice. As cardiologists we have to pursue all of this new knowledge. It is a never-ending learning experience, but the reward is also very gratifying: to be able to change the prognosis and life expectancy related to our patients’ cardiovascular diseases. It’s worth the effort. As Sir William Osler once said, “Medicine is a science of uncertainty and an art of probability.” We can learn all the latest and available technology, but many of the chronic diseases that affect humanity remain incurable, so uncertainty is a word that we always have in our minds when we start treating our patients.

The time has come for me to finish my residency in Internal Medicine. After 3 brief and stimulating years, it is time to start a new phase in my professional life. It seems like yesterday that I had my first interview with a patient or performed my first procedure. I can say now that after 3 years of continuous training, I have gained a great deal of knowledge and experience. Finally, during my third year as a Resident, I began to feel confident providing inpatient and outpatient care.

Thankfully, I was lucky to have the support of my faculty, who were always by my side to guide me along this journey. Now is the time to start walking by myself, and to take full responsibility for my medical decisions—something that is exciting but that also represents a big challenge. My peers and I, as recently graduated doctors of Internal Medicine, are ready to take different pathways in our careers. I consider myself lucky to have taken the one path that has excited me the most since I first began to study medicine: cardiology. Murmurs, hemodynamics, cardiovascular pathophysiology, and electrocardiograms have always been very appealing topics to me. Cardiology has become an important part of my family’s personal experience because, unfortunately, my father had a myocardial infarction many years ago and is now faced with heart failure and waiting for a heart transplant. I have personally witnessed how, thanks to all the advances in cardiovascular medicine, my father is now stable. He has become the greatest inspiration for me to continue in this career.

The internist phase of my training has finished; now I will open the door to a whole new and different world of cardiovascular health. The time has arrived to start the training to perform procedures, treat arrhythmias, repair “broken” hearts, and treat valvular diseases, just to name some of the skills to be acquired as a training fellow.

The lifestyle of a cardiologist is hence an interesting topic. Do cardiologists have more fun? According to the Pew report in 2006, 34% of Americans say that they are “very happy,” 50% “pretty happy,” and 15% “not too happy.”1 Medscape’s Physician Lifestyle Report 2012 asked US physicians how happy they were with their lives outside of medicine and to rate their level of happiness on a scale of 1 to 5.2 The average happiness score for physicians who responded was 3.96, which is on the cheerful side. However, cardiologists were less happy than the average physician, with a score of 3.92, tenth from the bottom of the specialty list. Their closest neighbors in misery/happiness were nephrologists, diabetologists, and critical care physicians, who—perhaps coincidentally&mdash;treat many of the same chronic illnesses.

What about physical health? Cardiologists are considered among the healthiest specialists, along with plastic surgeons, endocrinologists, orthopedists, and hematologists. So, as contradictory as it sounds, cardiologists are more depressed but physically healthier compared with other specialties. Depression levels are likely related to the level of stress and long hours of working that this specialty demands.

I aspire to have a career in cardiovascular medicine in spite of all of the stress and continuous training that it implies. I am looking forward to a wonderfully expansive specialty with ample opportunity to do meaningful research, in both academia and clinical practice. The rewards will definitely be invaluable. To have the opportunity to help people, to be challenged, and to learn throughout my life—what else could I ask for?

I close with a quotation of Voltaire’s, which reflects my admiration and respect for this noble profession of medicine: “Men, who are occupied in the restoration of health to other men, by the joint exertion of skill and humanity, are above all the great of the earth. They even partake of divinity, since to preserve and renew is almost as noble as

1. Pew Research Center. Are We Happy Yet? Washington, DC, 2006. pewresearch.org/pubs/301/are-we-happy-yet. Accessed July 12,2012.

2. Medscape. Medscape Physician Lifestyle Report 2012. http://www.medscape.com/features/slideshow/lifestyle/2012/public. Accessed July 12, 2012.

Resident's Corner

Cardiology Fellowship: Fun and Games, or Life in a Pressure Cooker?

Conference Calendar

Ticagrelor Now Recommended for NSTEMI by AHA and ACCF

The American Heart Association (AHA) and the American College of Cardiology Foundation (ACCF) have updated their joint guideline for management of non-ST-segment myocardial infarction (NSTEMI) and unstable angina to officially recommend ticagrelor (Brilinta) for patients with either condition, along with clopidogrel (Plavix) and prasugrel (Effient).

The recommendation for all the agents includes the use of aspirin (81 mg) in all patients presenting with unstable angina and NSTEMI as soon as they’re hospitalized, for as long as it is tolerated.

The guideline now lists ticagrelor along with clopidogrel and prasugrel as an option for use with aspirin in dual antiplatelet therapy for patients undergoing percutaneous

coronary intervention (PCI) (level B evidence for ticagrelor and prasugrel compared with level A for clopidogrel).

The guideline writing committee noted that the new document does not recommend one agent over another because there have not been head-to-head trials of the 3 agents in the same clinical setting. Dr Hani Jneid, of Baylor College of Medicine and lead author of the update, said, “Doctors now have a choice for second-line therapy after

aspirin, depending on the patient’s clinical scenario, physician preference, and cost.”

The update also recommends ticagrelor as an alternative to clopidogrel for conservatively managed (non-PCI) patients, to be added to aspirin as soon as possible after admission and administered for up to 1 year.

The writing committee noted the potential bleeding risk with the newer antiplatelet agents over clopidogrel

Jneid H, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction. Circulation. 2012;DOI:10.1161/CIR.0b013e318256f1e0. 

http://circ.ahajournals.org/content/early/2012/07/16/CIR.0b013e318256f1e0.full.pdf+html.

Task Force Recommends Obesity Screening for All Patients

The US Preventive Services Task Force (USPSTF) has recommended that doctors screen all patients for obesity. The USPSTF recommended universal screening in 2003, but the new statement goes one step further by recommending that doctors refer obese patients to intensive counseling for weight loss. The task force also advised doctors to counsel certain nonobese patients who are at risk about better lifestyle choices. Most doctors do not now screen for obesity, noted task force

member David Grossman, MD, MPH, senior investigator and medical director for preventive care.

Obesity screening is done by calculating body mass index (BMI), with BMIs of 30 or above considered obese, BMI of 25 to 29.9 overweight, and BMI of 18.5 to 24.9 normal.

If referral to a weight loss program is needed, it should be an intensive one, offering 12 to 26 sessions over a year. The programs should also help patients become accountable for weight loss and management, teaching calorie counting or monitoring fat intake. Maintaining weight loss after the program ends is critical, said Dr Grossman.

The task force’s recommendations have been published online in the Annals of Internal Medicine (http://annals.org/article. aspx?articleid=1200996), as well as on the Task Force website at 

http://www.uspreventiveservicestaskforce.org/uspstf/uspsobes.htm

The FDA approved the weight-loss drug Qsymia, a controlled-release combination of phentermine and topiramate, for adults with body mass index (BMI) >30 kg/m2 or adults with BMI of >27 and at least 1 weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia. The drug is indicated in addition to a reduced-calorie

diet and exercise for chronic weight management.

Qsymia is available in 2 doses: 7.5 mg phentermine/46 mg topiramate extended-release and 15 mg phentermine/92 mg topiramate extended-release. Results from 2 clinical trials show that after 1 year of treatment with the recommended and highest daily dose of Qsymia, patients had an average weight loss of 6.7% and 8.9%, respectively, over placebo.

Qsymia was approved with a Risk Evaluation and Mitigation Strategy (REMS). The drug must not be used during pregnancy because of the increased risk of birth defects associated with first-trimester exposure to topiramate. Females of reproductive potential should have a negative pregnancy test before starting Qsymia and every month while using it, and should use effective contraception consistently while taking Qsymia. Qsymia will be dispensed only through specially certified pharmacies.

Consult Qsymia’s product labeling for detailed prescribing information. For more information, visit 

www.fda.gov/newsevents/ newsroom/pressannouncements/ucm312468.htm.

News & Trends

American Diabetes Association 72nd Scientific Sessions

More than 14,000 researchers, physicians, and health care professionals gathered in Philadelphia, PA, to attend the American Diabetes Association’s 72nd Scientific

Sessions on June 8 through 12, 2012. With nearly 26 million children and adults in the United States affected by diabetes, the research-related news on diabetes that is released at the meeting is highly anticipated and discussed.

In this edition of Meeting Highlights, news is presented from 6 studies discussed at the ADA meeting: new data on Lantus, early use of insulin (ORIGIN trial), treating children with type 2 diabetes, the rise of childhood diabetes, and the TODAY study.

Early Use of Insulin Shows No Cardiovascular Benefit—But Neither Does It Show Harm

To investigate the possible benefit of early insulin use with respect to cardiovascular outcomes, researchers with the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) study randomized more than 12,500 people at high risk for, or in the early stages of, type 2 diabetes to receive either 1 daily injection of glargine (Lantus) insulin or standard care (no insulin), over a median of 6.2 years. Researchers found no difference among the 2 groups of patients in rates of heart attack, stroke, or cardiovascular-related mortality. The data also showed that there was no association between glargine and cancer.

The results were called “neutral” in terms of primary end point, according to Dr Hertzel Gerstein of McMaster University in Hamilton, Ontario, Canada, who presented the ORIGIN results. He noted that there had been concerns going back some years that giving diabetic patients insulin could lead to an acceleration of cardiovascular disease. The researchers had hypothesized, however, that regulating blood glucose levels with insulin glargine might prevent future cardiovascular events.

Another researcher, Dr Lars Ryden of Karolinska Institutet in Stockholm, said because many people with coronary artery disease have disturbed glucose metabolism, it was reassuring that glargine is safe to use, does not cause a lot of hypoglycemia, and does not carry any risk of cancer.

The ORIGIN Trial Investigators, “n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia.” N Engl J Med. 2012;DOI:10.1056/NEJMoa1203859.

http://www.nejm.org/doi/full/10.1056/NEJMoa1203858?query=featured_home#t=article

. ORIGIN was funded by Sanofi. Dr Gerstein received consulting and lecture fees from Sanofi; consulting and/or lecture fees from Bayer, Merck, Novo Nordisk, GlaxoSmith-Kline, Roche, Novartis, Janssen, Abbott, and AstraZeneca; and grant support from Eli Lilly and Boehringer Ingelheim. Dr Ryden reports consulting fees from Bristol-Myers Squibb and AstraZeneca and lecture fees and grant support from Roche and Sanofi.

More Data From the TODAY Trial: New Treatments Needed for Youth

The initial results of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, published in the New England Journal of Medicine in April 2012, showed that combining rosiglitazone with metformin was superior to metformin alone or with lifestyle intervention in 699 children aged 10 to 17 years with type 2 diabetes who had been diagnosed within 2 years and initially treated with metformin. The trial showed that nearly 50% of youth with type 2 diabetes needed insulin therapy within

Even though the initial results of TODAY had not indicated any safety issues and despite the positive findings that combining metformin with rosiglitazone helped more of the children to maintain glycemic control, rosiglitazone cannot be recommended for use in children because the drug’s use has been limited by the FDA due to safety concerns.

Additional results from the TODAY trial were presented at the ADA meeting by Phil Zeitler, MD, PhD, of the University of Colorado in Denver. The study also measured comorbidities that developed in children with type 2 diabetes: hypertension occurred in almost one-third of the subjects in less than 4 years, as well as a more than doubling of albuminuria; 13% had signs of retinopathy.

Key results of the study were as follows:

• Metformin monotherapy was not adequate for sustained diabetes control in half of the adolescents studied;

• Addition of a second agent provided 23% more adolescents with glycemic control;

• Intensive lifestyle intervention was not successful in prolonging glycemic control;

• Gender, race, and ethnicity played a role in glycemic control; and

• Half the adolescents were able to get durable glycemic control.

http://www.nejm.org/doi/full/10.1056/NEJMoa1109333

. The TODAY Trial was funded by the National Institute of Diabetes and Digestive

and Kidney Diseases of the National Institutes of Health.

In one of the most anticipated studies at the ADA meeting, researchers presented US and European data suggesting there is no difference between analogue insulins—glargine (Lantus) and human insulin (NPH)&mdash;in terms of cancer risk. The issue of a possible cancer risk associated with glargine first arose in 2009, when 4 large studies were published together and presented conflicting results. Three of these studies found a doseresponse relationship between glargine and cancer, while the fourth found no relationship. These mixed results led US and UK researchers to analyze more data.

Data were presented from 3 large, new independent analyses from 5 European countries, the University of North Carolina, and Kaiser Permanente of California. The studies, which compared glargine with NPH insulin, found no increased risk of a variety of cancers studied both individually (breast cancer, colorectal cancer, prostate cancer) and collectively (all cancers).

The largest of the 3 analyses was the European study, which evaluated 447,821 patients with diabetes who used insulin, with over 1.5 million person-years of observation and 17,500 new cases of cancer in the cohorts. The average follow-up of this analysis was 3.1 years, longer than the 2009 studies— which had been faulted for their short follow-up periods.

The Kaiser Permanente researchers, who studied 115,000 patients for over a year, did note a “suggestion” of cancer between glargine and breast cancer, but only in users who were new to insulin therapy. The UNC study compared 43,000 patients on glargine to 9000 patients on NPH, both for over a year.

Taken with the results of the ORIGIN trial (presented earlier), which found no increased risk of cancer in more than 12,000 patients with pre-diabetes or early diabetes who were randomized to insulin or no insulin for over 6 years, the new studies provide reassurance that there does not appear to be an association between insulin glargine and cancer.

Boyle P, Northern European database study of insulin and cancer risk. ADA 2012 Scientific Sessions; June 11, 2012. Abstract CT-SY13. Habel LA, Results from Kaiser-Permanente collaboration. ADA 2012 Scientific Sessions; June 11, 2012. Abstract CT-SY13. Buse JB, What we know about insulin and cancer. ADA 2012 Scientific Sessions; June 11, 2012. Abstract CT-SY13.

Childhood Diabetes—Both Type 1 and Type 2&mdash;On the Rise

The incidence of both type 1 and type 2 diabetes has increased in the United States during the past decade, according to results of the SEARCH for Diabetes in Youth study, sponsored by the US Centers for Disease Control and Prevention and National Institutes of Health. From 2001 to 2009 the prevalence of type 1 and type 2 diabetes increased 23% and 21%, respectively.

The study looked at the prevalence of diabetes in children and those younger than 20 years of age across all ethnicities and in boys and girls, although the largest increase in type 2 diabetes occurred in non-Hispanic white and Hispanic children.

Study co-chair Dr Elizabeth Mayer-Davis of the University of North Carolina, Chapel Hill, said that based on the study registry, there are approximately 188,000 children and adolescents with diabetes in the United States, including 168,000 with type 1 diabetes and 19,000 with type 2 diabetes. The data also show that these patients have signs of early chronic complications of diabetes, even those who had it for a relatively short time.

Although the proportion of youth with type 2 diabetes was highest in American Indians and African Americans, the increase was particularly observed among non-Hispanic white youth and Hispanic youth. Nearly 1 in 5 diabetic adolescents smoke, and 90% of children with type 2 diabetes are obese.

The increase in type 1 diabetes in children younger than 20 years of age increased from 1.7 cases per 1000 to 2.1 cases per 1000; the increase occurred in male and female children of all ages, except those 4 years and younger, and in all ethnicities except American Indians. Non-Hispanic white children are the group at highest risk for type 1 diabetes. The reason for the increase in type 1 diabetes remains unknown.

Hamman RF, Pettitt DJ, Dabelea D, et al. Estimates of the burden of diabetes in United States Youth in 2009. ADA 2012 Scientific Sessions; June 9, 2012. Abstract 1369-P.

Meeting Report

Meeting Report: American Diabetes Association 72nd Scientific Sessions

Ragavendra Baliga, MD, MBA, FACP, FRCP (Edin), FACC

Marin JM, Agusti A, Villar I, et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012;307:2197-2198.

Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre, et al; for the Spanish Sleep and Breathing Network. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA. 2012;307:2161-2168.

In the same issue of the Journal of the American Medical Association, 2 Spanish studies investigated obstructive sleep apnea (OSA) and the effect of treatment with 

continuous positive airway pressure (CPAP). The potential role of CPAP in preventing new-onset hypertension and cardiovascular events was also explored.

The first study by Marin et al1 was a prospective, observational study of 1889 individuals without elevated blood pressure, referred for nocturnal polysomnography between January 1, 1994, and December 31, 2000. Among these individuals, 1579 subjects were diagnosed with OSA. In this cohort, 824 were eligible for and adhered to CPAP treatment, whereas the remaining 755 were either ineligible for CPAP treatment according to national treatment guidelines, or were eligible but declined CPAP therapy, or were eligible and started CPAP but were nonadherent.

The investigators found that in the median follow-up period of 12.2 years, 37.3% (n = 705) developed hypertension. The study found that when compared with individuals without OSA, treatment with CPAP was associated with a lower risk of new-onset hypertension, whereas untreated OSA was associated with an increased risk of new-onset hypertension (Tables 1 and 2). This study suggests that OSA may be a modifiable risk factor for hypertension.

The study by Barbé et al2 evaluated the impact of CPAP treatment on the incidence of hypertension or cardiovascular events in 725 individuals with OSA (as evidenced by an apnea-hypopnea index of >20 per hour) who lacked symptoms of daytime somnolence (as evidenced by an Epworth Sleepiness Scale score of 10 or less).

The main outcomes were incidence of either systemic hypertension (BP>140/90 mmHg or taking antihypertensive drug therapy) or cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, hospitalization for unstable angina or arrhythmia, heart failure, or cardiovascular death).

In this randomized, controlled multicenter trial, there were 357 adults in the CPAP treatment group and 366 in the control group (usual care); the median follow-up duration was 4 years. During this period there were 68 cases of new hypertension and 28 cardiovascular events in the CPAP group, compared with 79 cases of new hypertension and 31 cardiovascular events in the control group. The incidence of new hypertension or cardiovascular events per 100 person-years in the CPAP group was

9.20 (95% CI, 7.36-11.04), whereas in the control group the incidence of new hypertension or cardiovascular events per 100 person-years was 11.02 (95% CI, 8.96-13.08) (incidence density ratio 0.83; 95% CI, 0.63-1.1; P = 0.20).

Therefore, in the CPAP group there was, at best, a trend toward a reduction in the incidence of hypertension and cardiovascular events that did not reach statistical significance. A post hoc analysis suggested that CPAP therapy may reduce the incidence of hypertension or cardiovascular events in individuals with CPAP adherence of 4 hours or longer every night.

1. Marin JM, Agusti A, Villar I, et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012;307:2169-2176.

2. Barbé F, Durán-Cantolla J, Sánchez-dela- Torre, et al; for the Spanish Sleep and Breathing Network. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA. 2012;307:2161-2168.

3. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572.

The Impact of CPAP Obstructive Sleep Apnea

Both studies are important in that they better define the impact of CPAP in individuals with OSA. The study by Marin et al1 clearly suggests there is a causal role between OSA and hypertension and, more importantly, suggests that modifying OSA with CPAP therapy not only reduces blood pressure but favorably reduces the risk of developing hypertension. The study by Barbé et al2 is an important hypothesis-generating study because it suggests that treating OSA with CPAP therapy in patients without excessive daytime somnolence may reduce the risk of hypertension. The post-hoc analysis also suggested that CPAP therapy >4 hours duration every night was associated with a 3-mm reduction in systolic blood pressure. This is a significant change because a 3-mmHg reduction in systolic blood pressure is associated with an 8% reduction in stroke-related annual mortality, a 5% reduction in coronary heart disease- related annual mortality, and a 4% reduction in total annual mortality (Table 3).3

However, there are several issues that remain to be addressed: (1) predicting which patients with OSA are at risk of developing hypertension, secondary pulmonary hypertension, heart failure, and atrial fibrillation; (2) predicting which patients with OSA will favorably respond to CPAP (the responders); (3) finding the optimal duration of CPAP to have a significant therapeutic effect; (4) defining the risks and benefits of CPAP therapy in those without daytime sleepiness; and (5) discovering the mechanism

of blood pressure reduction with CPAP. To address these questions, a large multicenter, randomized, controlled trial will be required, with particular attention not only to the quality of life but also to morbidity (including hypertension, pulmonary hypertension, atrial fibrillation, and heart failure) and mortality in this cohort.

Ragavendra Baliga, MD, MBA, FACP, FRCP (Edin), FACC, is Chief Mentor Officer for Clinical Faculty and Vice- Chief/Assistant Division Director, Division of Cardiovascular Medicine, Wexner Medical Center, and Professor of Internal Medicine at The Ohio State University in Columbus. He received his MD from St John’s Medical College in Bangalore, India, and completed his Internal Medicine residency at Victoria Hospital in Bangalore. He completed his Cardiology fellowship from Hammersmith Hospital, London, UK, and advanced fellowships from Brigham & Women’s Hospital/Harvard Medical School, Boston University Medical Center, and UT Southwestern Medical Center, Dallas, TX. He is board-certified in internal medicine and cardiovascular diseases. He was a faculty cardiologist at the University of Michigan and received an MBA from the Stephen Ross School of Business. Dr Baliga joined The Ohio State University in 2005.

Sleep Apnea and Hypertension: The Impact of CPAP Treatment

D’Elia L, Cairella G, Garbagnati F, Scalfi L, Strazzullo P. Moderate coffee consumption is

associated with lower risk of stroke: meta-analysis of prospective studies. Presented at the

European Society of Hypertension, May 11, 2012, London. [Abstract e107].

Stroke is a devastating disease that constitutes the third leading cause of death in the United States. Even though the prevalence of stroke has decreased dramatically in the last 20 years due to better diagnosis and control of hypertensive patients, there are still many aspects of the disease that remain to be improved, including prevention and effective treatment strategies.

Coffee is one of the most widely consumed drinks in the world, but has been associated with drawbacks such as high concentrations of caffeine, transient increase in blood pressure, and long-term increases in low-density lipoprotein cholesterol levels.1 On the other hand, coffee contains beneficial antioxidants, and recent reports of the association between its consumption and decreased total mortality have been encouraging.1 A new meta-analysis by European researchers on the 

association between low and moderate coffee consumption and lower risk for stroke adds to myriad beneficial effects for human health reported previously.2

The main goal of D’Elia et al’s metaanalysis was to provide a systematic review of studies conducted from 1966 to 2011 published in major online databases that evaluated baseline coffee consumption and risk of stroke in a general population. Patients were divided according to the amount of coffee ingested: Moderate (1 to 3 cups/day), High (3 to 6 cups/day), and Very High (>6 cups/day) and were compared with a reference category (0 to 1 cups/day). A total of 10 cohorts, which encompassed

442,098 participants with a follow-up of 2 to 24 years, had 6962 stroke events. Those in the category of Moderate consumption had a significantly decreased risk of stroke (relative risk [RR], 0.82; 95% confidence interval [CI], 0.74-0.90; P <0.001). In the High consumption group, after excluding one single cohort, there was also a significant

trend toward diminishment of the risk of stroke (RR, 0.79; 95% CI, 0.68-0.92; P <0.003). However, the Very High consumption group was not associated with decreased risk for stroke [RR, 1.00; 95% CI, 0.76-1.32 (P = 0.97)]. The authors also performed an evaluation of publication bias and quantified the heterogeneity between the studies. Subgroup and meta-regression analysis did not detect identifiable sources of heterogeneity.

The authors concluded that moderate coffee consumption was associated with a statistically significant reduction in risk for stroke in the general population, independent of most identifiable confounders.

1. Freedman ND, Park Y, Abnet CC, et al. Association of coffee drinking with total and cause-specific mortality. N Engl J Med. 2012;366:1891-1904.

2. Lopez-Garcia E, Rodriguez-Artalejo F, Rexrode KM, et al. Coffee consumption and risk of stroke in women. Circulation. 2009;119:1116-1123.

3. Lopez-Garcia E, van Dam RM, Qi L, et al. Coffee consumption and markers of inflammation and endothelial dysfunction in healthy and diabetic women. Am J Clin

4. Huxley R, Lee CM, Barzi F, et al. Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis. Arch Intern Med. 2009;169:2053-2063.

5. Larsson SC, Orsini N. Coffee consumption and risk of stroke: a dose-response meta-analysis of prospective studies. Am J Epidemiol. 2011;174(9):993-1001.

6. Larsson SC, Virtamo J, Wolk A. Coffee consumption and risk of stroke in women. Stroke. 2011;42:908-912.

7. Umemura T, Ueda K, Nishioka K, et al. Effects of acute administration of caffeine on vascular function. Am J Cardiol. 2006;98:1538-1541.

8. Bohn SK, Ward NC, Hodgson JM, et al. Effects of tea and coffee on cardiovascular disease risk. Food Funct. March 29, 2012.

This study added stronger flavor to a growing body of knowledge that suggests major beneficial effects on cardiovascular health are associated with moderate coffee consumption. Those benefits include, but are not limited to, improvement in serum biomarkers of inflammation; decreased insulin resistance;3 lower rates of diabetes,4 injuries, and accidents; and even reductions of total all-cause mortality.1

Other studies have investigated the relationship between coffee and risk of stroke. A similar 2011 study by Larsson and Orsini5 was a meta-analysis of prospective  studies conducted to quantitatively assess the association between coffee consumption and stroke risk. Pertinent studies were identified by searching PubMed and Embase from January 1966 through May 2011. Prospective studies in which investigators reported stroke risk reduction for 3 or more categories of coffee consumption

were included. Results from individual studies were pooled using a randomeffects model. Eleven prospective studies, with 10,003 cases of stroke and 479,689  participants, met the inclusion criteria. There was some evidence of a nonlinear association between coffee consumption and risk of stroke (P for nonlinearity = 0.005). Compared with no coffee consumption, the RRs of stroke were 0.86 (95% CI, 0.78-0.94) for 2 cups of coffee per day, 0.83 (95% CI, 0.74-0.92) for 3 to 4 cups/day, 0.87 (95% CI, 0.77- 0.97) for 6 cups/day, and 0.93 (95% CI, 0.79-1.08) for 8 cups/day. Findings from this meta-analysis indicated that moderate coffee consumption may be weakly inversely associated with risk of stroke.5

Interestingly enough, the same authors published data early in 2011 about low or no coffee consumption and increased risk of stroke among 34,670 women without a history of cardiovascular disease or cancer at baseline in 1997 from the Swedish Hospital Discharge Registry.6 During a mean follow-up of 10.4 years, and after adjustment for other risk factors, coffee consumption was associated with a statistically significant lower risk of total stroke, cerebral infarction, and subarachnoid hemorrhage, but not intracerebral hemorrhage. The multivariable RRs of total stroke across categories of coffee consumption (<1 cup/day, 1 to 2 cups/day, 3 to 4 cups/

day, and ≥5 cups/day) were 1.00, 0.78 (95% CI, 0.66-0.91), 0.75 (95% CI, 0.64-0.88), and 0.77 (95% CI, 0.63-0.92, respectively; P for trend = 0.02).6

What would be the mechanism(s) behind these benefits? In a randomized, controlled trial, Japanese authors suggest that the acute administration of caffeine augments endothelium-dependent vasodilatation in healthy young men through an increase in nitric oxide production. 7 In addition, a number of factors such as an improved glucose metabolism, increased reverse cholesterol transport and inhibition of foam cell formation, inhibition of oxidative stress, and effects on platelet function (adhesion and activation, aggregation and clotting) have been suggested to be among coffee’s benefits.8

However, an acute increase in blood pressure, hypercholesterolemia, and increased risk of myocardial infarction keeps open the debate as to whether there should be a clear recommendation for coffee drinkers. It is estimated that 150 million people in the United States drink coffee, and we need more data on the type of coffee consumed

(caffeinated versus decaffeinated), additives used in it (sugars, cream), genetic variations in metabolism, and many other confounders that need to be adjusted before we can definitively say that our stimulating, aromatic, energy-infusing morning cup of coffee is also protecting our brain from strokes. In the meantime, the healthiest thing to do is to avoid extremes like either not drinking any coffee or having more than 5 to 6 cups/day. We are eager to hear more about this coffee paradox! It would be a well-deserved honor for an international, all-time favorite drink to be found to have such benefits.

Jimena A. Blandon, MD, is a third-year resident instructor in the Department of Internal Medicine at Texas Tech University Health Sciences Center in El Paso. She received her MD at Universidad del Valle, in Cali, Colombia. Dr Blandon is currently involved in a study of the prevalence and predictors of contrast-induced nephropathy among patients undergoing angiography at the University Medical Center at El Paso, TX, in a predominantly Hispanic population.

Impact of Coffee Consumption on Stroke

Chen Z-Y, Chiang C-H, Huang C-C, et al. The association of tooth scaling and decreased cardiovascular

disease: A nationwide population-based study. Am J Med. 2012;125:568-575.

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