eDiabetesReview Volume 1, Issue 3

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eDiabetes Review
VOLUME 1, ISSUE 3

CVD RISK FACTORS IN PATIENTS WITH T2D

In this Issue...

Cardiovascular disease is the primary cause of morbidity and mortality in people with diabetes, and preventive therapies to control hyperlipidemia and hypertension have long been considered critical aspects of proper patient care. New evidence has led to the recent release of new guidance, challenging widely held beliefs and common practices.

In this issue, we review recent publications describing:

New cholesterol guidelines from the American Heart Association and the American College of Cardiology (released at the end of 2013) that recommend a significant departure from the previous guidance
The long-awaited JNC 8 blood pressure guidelines (published in January 2014) that have created controversy about blood pressure goals in various patient groups
The concern that statins, the evidence-based drug of choice for LDL-C reduction, may increase the risk of developing diabetes
The role of other lipid-lowering drugs on the residual risk of CVD events after optimal LDL – C reduction

LEARNING OBJECTIVES

After participating in this activity, the participant will demonstrate the ability to:

		Explain the implications of recent guidelines for cholesterol management.

		Describe recent clinical trials related to CVD outcomes in patients with diabetes.

		Summarize the recent blood-pressure guidelines and controversy among experts.
*The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.*

PLANNER DISCLOSURES

Program Begins Below


	As a provider approved by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine Office of Continuing Medical Education (OCME) to require signed disclosure of the existence of financial relationships with industry from any individual in a position to control the content of a CME activity sponsored by OCME. Members of the Planning Committee are required to disclose all relationships regardless of their relevance to the content of the activity. Faculty are required to disclose only those relationships that are relevant to their specific presentation. The following relationship has been reported for this activity:

Om P. Ganda, MD, discloses that he has received grant/research funding from Amarin Pharma,Inc., and has served on advisory boards for Amgen and Sanofi.
No other planners have indicated that they have any financial interest or relationships with a commercial entity whose products or services are relevant to the content of their presentations.

IMPORTANT CME/CE INFORMATION

IN this issue


		COMMENTARY from our Guest Author

		THE 2013 ACC/AHA GUIDELINES FOR CHOLESTEROL MANAGEMENT

		APPLYING 2013 CHOLESTEROL GUIDELINES TO THE U.S. POPULATION

		STATIN-INDUCED DIABETES—A META-ANALYSIS

		EFFECT OF NIACIN ON CARDIOVASCULAR EVENTS IN PATIENTS WITH LOW HDL-CHOLESTEROLS

		JNC 8 HYPERTENSION GUIDELINES

		APPLYING JNC 8 HYPERTENSION GUIDELINES TO THE US POPULATION

Program Directors

Nestoras Mathioudakis, MD
Assistant Professor of Medicine
Division of Endocrinology and Metabolism
Associate Director, Inpatient Diabetes Management
The Johns Hopkins University School of Medicine
Baltimore, Maryland

Om P. Ganda, MD
Associate Clinical Professor of Medicine
Harvard Medical School
Senior Physician and Director, Lipid Clinic
Chair, Clinical Oversight Committee Joslin Diabetes Center
Boston, Massachusetts

Susan Porter, MSN, CRNP, CDE
Clinical Nurse Practitioner and Certified Diabetes Educator
The Johns Hopkins University School of Medicine
Baltimore, Maryland

GUEST AUTHOR OF THE MONTH

		Commentary:
		Om Ganda, MD Associate Professor of Medicine Harvard Medical School Senior Physician and Director, Lipid Clinic Chair, Clinical Oversight Committee Joslin Diabetes Center Boston, Massachusetts

Guest Faculty Disclosures

Om Ganda, MD has indicated that he has received grants/research funding from Amarin Pharma, Inc., and has served on advisory boards for Amgen and Sanofi.

Unlabeled/Unapproved Uses

Dr. Ganda has indicated that there will be no references to unlabeled/unapproved uses of drugs or products.

Program Directors' Disclosures


	Program Information CME Info Accreditation Credit Designations Intended Audience Learning Objectives Internet CME Policy Faculty Disclosures Disclaimer Statement Length of Activity 1.0 hour Physicians 1.0 contact hour Nurses Launch Date May 29, 2014 Expiration Date May 28, 2016


	TO ACCESS THE POST-TEST Step 1. Review the CE Information and study the educational content. Step 2. Click the post-test link at the end of the newsletter. Step 3. Follow the instructions to access a post-test.

COMMENTARY

Globally, cardiovascular events are the major cause of morbidity and mortality in patients with diabetes. The good news is that the major complications of diabetes have declined substantially during the past two decades, with a 68% decline in rates of myocardial infarction and ~50% decline in stroke and amputations.¹ This is likely the result of a combination of better access to care, health promotion efforts, and advances in treatment. However, obesity and diabetes continue at epidemic rates: some 24 million adults in the United States have diabetes;² the number of patients with diabetes worldwide soared to some 382 million in 2013; and cases are projected to reach 592 million by 2035.³ Thus, the task of improving CVD outcomes in patients with diabetes will continue to remain a major challenge.

Elevated LDL-cholesterol (LDL-C) and hypertension are the key risk factors for atherosclerotic cardiovascular disease (ASCVD), including coronary disease and stroke. Efforts to improve their control have been a major focus during the past 20 years, thanks to the evolution and application of cholesterol and blood pressure guidelines in the US and elsewhere. Recently, the AHA (American Heart Association) and ACC (American College of Cardiology) published their revised guidelines on cholesterol management, and the JNC 8 panel published their revised blood pressure guidelines. Although both documents based their recommendations strictly on the basis of strong evidence from clinical trials, strong controversy has arisen.

The cholesterol guidelines are a significant departure from the past and provide an increased emphasis on the use of statins rather than any other cholesterol-lowering drug not proven to reduce CVD events. They recommend a more intensive therapy, even in primary prevention, for those at risk with or without diabetes and provide an updated risk calculator based on longitudinal data from several population cohorts. The lack of evidence for the CVD benefit of combining statins with other cholesterol-lowering drugs, including ezetimibe and bile acid sequestrants, was also reviewed recently by Gudzune et al.⁴ Another major change is that these recommendations provide no defined goals for LDL-C or non-HDL-C, if sufficiently intensive statin therapy is used.

In the new blood pressure guidelines, the JNC 8 panel recommends a less intensive approach compared to those used in the past. Specifically, a more liberal systolic blood pressure goal has been recommended for those ≥ 60 years of age without diabetes or renal disease, which is different from that recommended by other major blood pressure guidelines from the American and International Societies of Hypertension, and others, including some of the authors of the JNC-8 itself.⁵

The impact and projections of the new cholesterol and blood pressure guidelines to the US population is discussed in the articles reviewed in this issue; in summary, these extrapolations find that some 13 million additional adults in the US are candidates for statin therapy, especially men > 60 years, and that some 13.5 million adults previously considered not at blood pressure goal by JNC 7 criteria would now be considered at goal.

One of the issues that has emerged recently is the impact of statin therapy on the development of diabetes. The risk is relatively small as reported in several studies and meta-analyses and mainly affects those already at increased risk for or have pre-diabetes; the risk/benefit ratio favors the use of statins even in those who develop diabetes. The largest meta-analysis of 17 trials is summarized in this issue (Navarese et al); it suggests that the risk of diabetes may be less pronounced with less potent statins, such as pravastatin, compared to than with more potent statins, such as rosuvastatin. The latter is, however, recommended by the new cholesterol guidelines as a preferred statin for those at the highest risk of CVD. Further, the interactions of specific statin molecules with the mechanisms of diabetes development remain incompletely understood.

The final topic discussed in this issue has to do with the residual CVD risk in patients treated with statins. It is well recognized that despite intensive statin therapy, many patients, particularly those with diabetes and metabolic syndrome, remain at considerable residual risk of subsequent CVD events. In the past, we have been using fibrate drugs and niacin to improve the dyslipidemia (characterized by high triglycerides and low HDL-C) often encountered in patients with type 2 diabetes — with limited evidence of their benefits in such patients. In the ACCORD-lipid study, addition of fenofibrate in patients treated with statins resulted in possible, but inconclusive, benefit in the that patient subgroup.⁶ The AIM-HIGH trial discussed here (Boden et al) randomized patients with diabetes and/or metabolic syndrome and with pre-existing CVD and low HDL-C to extended-release niacin or placebo. These patients were all optimally treated with intensive therapy to a LDL-C goal of < 70 mg/dl. In this setting, the addition of niacin resulted in no cardiovascular benefit despite the significant increase in HDL-C. Similar lack of benefits with niacin were recently reported in another larger trial (HPS2-THRIVE).⁷ These findings have raised the possibility that HDL-C as a static measure may not be very helpful in determining the functionality of HDL, and point to a need to develop drugs that might directly improve HDL function. Thus, it appears that intensive statin therapy should remain the mainstay of lipid management in our armamentarium.

References
1. Gregg, EW, Li, Y, Wang, J et al. Changes in Diabetes-Related Complications in the United States, 1990–2010. N Engl J Med. 2014;370: 1514-1523.
2. Selvin E, Parrinello CM, Sacks DB, Coresh J. Trends in prevalence and control of diabetes in the United States, 1988–1994 and 1999–2010. Ann Intern Med. 2014;160:517-525.
3. The IDF Diabetes Atlas, 6th edition.
4. Gudzune, KA, Monroe, AK, Sharma, R et al. Effectiveness of Combination Therapy With Statin and Another Lipid-Modifying Agent Compared With Intensified Statin Monotherapy A Systematic Review. Ann Intern Med. 2014;160:468-476.
5. Wright JT Jr, Fine LJ, Lackland DT, Ogedegbe G, Dennison Himmelfarb CR. Evidence supporting a systolic blood pressure goal of less than 150mmHg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014;160:499-503.
6. The ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563-74.
7. Armitage J. HPS2-THRIVE: randomized placebo-controlled trial of ER niacin and laropiprant in 25,673 patients with pre-existing cardiovascular disease. Presented at: American College of Cardiology Annual Scientific Sessions; March 9, 2013; San Francisco, CA.

THE 2013 ACC/AHA GUIDELINES FOR CHOLESTEROL MANAGEMENT

Stone NJ, Robinson J, Lichtenstein AH, et al. ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 November 12 (Epub ahead of print).


		Link

This landmark article, authored by the Expert Panel Members of the American College of Cardiology (ACC) and the American Heart Association (AHA) Task Force on Practice Guidelines, provides a summary of the long-awaited guidelines for cholesterol management. The full report appeared simultaneously as a separate article.¹ There has been substantial progress in our understanding of the evidence-base for cholesterol management since the last set of guidelines were published by the Adult Treatment Panel III of the National Cholesterol Education Program in 2002² and updated in 2004.³

In addition to recommending that all individuals age > 21 years have LDL-C measured and other cardiovascular risk factor screened, with the exception of those with heart failure (NYHA Class II-IV) and end-stage renal disease (on hemodialysis), the guidance defines four distinct groups of people likely to benefit from LDL-cholesterol (LDL-C) reduction by treatment with HMG-CoA reductase inhibitors (statins), in addition to lifestyle recommendations:

1. For patients with established atherosclerotic cardiovascular disease (coronary, cerebrovascular, or peripheral vascular): treat with high-intensity statin therapy;
2. For patients with LDL-C ≥ 190 mg/dl: treat with high-intensity statin therapy;
3. For patients with diabetes (type 1 or 2), age 40-75 and LDL–C 70-189 mg/dl: treat with moderate-intensity statin if the 10-year risk of ASCVD is < 7.5%, or high-intensity statin if the 10-year risk of ASCVD is ≥ 7.5%; 4. For patients without diabetes, age 40-75 years and LDL-C 70-189 g/dl: treat with moderate– to high-intensity statin if the 10-year risk of ASCVD is ≥ 7.5%. In some cases where the 10-year risk 5 to ≤ 7.5%, moderate statin therapy may be considered.

The 10-year risk of atherosclerotic CVD may be calculated with the use of the new 10-year risk calculator available at my.americanheart.org/cvrisk calculator. This tool was developed from the longitudinal data from several community cohorts of white and African Americans. According to these recommendations, high-intensity statin treatments are aimed at LDL-C reduction of ≥ 50%, and moderate-intensity statin treatments aimed at achieving a 30 to < 50% reduction from the baseline. Specific examples include atorvastatin 40-80 mg or rosuvastatin 20-40 mg for high-intensity treatment, and atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, pravastatin 40-80 mg, fluvastatin 40-80 mg, and pitavastatin 2-4 mg for moderate-intensity treatment.

For patients unable to tolerate high-intensity statin treatment because of statin intolerance, concomitant drug interactions, age > 75 years, unexplained elevations in ALT, or other reasons, an attempt should be made to prescribe at least a moderate-dose statin before considering any other cholesterol-lowering drugs. For risk assessment, CRP determination, ankle/brachial ratio, or coronary calcium score is not recommended. Finally, a major difference in the new guidelines is the lack of specific treatment targets for LDL-C or non- HDL-C.

Two concerns are that 1) many individuals under the age of 40 years who have considerable elevation of LDL-C with or without additional risk factors will not receive statin treatment until age 40; and 2) many individuals in the older age group might be "over-treated."⁴

References
1. Stone NJ, Robinson J, Lichtenstein AH, et al. ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 November 12 – Full Panel Report Supplement (Epub ahead of print).
2. National Cholesterol Education Program (NCEP) ExpertPanel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143-421.
3. Grundy S. et al. for the Coordinating Committee of the National Cholesterol Education Program Endorsed by the National Heart, Lung, and Blood Institute, American College of Cardiology Foundation, and American Heart Association. Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation. 2004;110:227–239,.
4. Baum SJ, From the "Ivory Tower" to the trenches: A Practical Approach to the 2013 ACC/AHA Cholesterol and Risk Assessment Guidelines. J Clin Lipidol. 2014 Mar-Apr;8(2):231-233. doi: 10.1016/j.jacl.2013.12.010. Epub 2014 Jan 27.

APPLYING 2013 CHOLESTEROL GUIDELINES TO THE U.S. POPULATION

Pencina MJ, Navar-Boggan AM, D'Agostino RB Sr., et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med. 370; 1422-1430.


		View journal abstract

In this article, Pencina et al compare the eligibility for statin treatment as described in the 2013 ACC/AHA cholesterol guidelines¹ to the previous guidelines from the Adult Treatment Panel (ATP III)², using the data from the National Health Examination and Nutrition Survey (NHANES) sample of 2005-2010. Their findings were extrapolated to the 115.4 million US adult population age 40-75 years.

Compared to ATP III criteria, the 2013 ACC/AHA guidelines will increase the number of people eligible for statin therapy from 43.2 million to 56.0 million. Most of this increase will occur in people without prior cardiovascular disease, ie, in primary prevention, and in those in the age range of 60-75 years. Among this latter group, 87.4% of men and 53.6% of women would be eligible for statin treatment, compared to 30.4% and 21.2%, respectively, by the ATP III criteria. Moreover, most of this increase will result from clinical application of the new 10-year risk calculator. The newly eligible candidates will have generally higher blood pressure and lower cholesterol. Among the patients with diabetes, those eligible for statin treatment in the 40-75 year age group will increase from 13.3 to 16.4 million. The calculated 10-year risk increased from 10.7 to 15.5% in the 40-59 year age group, and from 9.9 to 18.0% in the 60-75 year age group, using the ATP III and ACC/AHA criteria, respectively.

Thus, the new cholesterol guidelines overall have a greater sensitivity and a lower specificity for projecting new cardiovascular events.

One of the limitations of such analyses is that the data were extrapolated from only 3773 subjects included in the NHANES population and the information on atherosclerotic events other than coronary disease was not available. In a 2013 report in Lancet, Ridker et al compared the predicted CVD events based on the ACC/AHA risk estimates with the observed event rates in 5 primary prevention cohorts.³ They found an overall 40-50% over-estimation of eligibility using the recommended risk calculator, although a substantial number of people in these particular cohorts may have been relatively healthier.

References
1. Stone NJ, Robinson J, Lichtenstein AH, et al. ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 November 12 (Epub ahead of print).
2. National Cholesterol Education Program (NCEP) ExpertPanel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143-421.
3. Ridker PM, Cook NR. Statin guidelines and the prevention of cardiovascular disease. Lancet. 2013; 382:1762-1765.

STATIN-INDUCED DIABETES—A META-ANALYSIS

Navarese, EP et al. Meta-Analysis of Impact of Different Types and Doses of Statins on New-Onset Diabetes Mellitus. Am J Cardiol. 2013; 111: 1128-1130.


		View journal abstract

A significantly increased risk of new-onset diabetes in patients on statin therapy has been well-recognized since the 2008 Jupiter trial reported a 25% increase with rosuvastatin 20 mg compared to those on placebo.¹ Since then, several meta-analyses have confirmed a smaller but significant increase with various statins; in particular, the 2010 analysis by Sattar et al showed a 9% overall risk in 13 RCTs.² Of note, the risk-benefit ratio for CVD still clearly favors statin therapy in people at high-risk, and even those who develop diabetes during statin therapy have better CVD outcome compared to those on placebo.^2,3

The precise mechanism for statin-induced diabetes remains unclear, although the majority of patients developing diabetes have prediabetes or features of metabolic syndrome, indicating a high risk for diabetes at baseline.³ It has also been controversial whether intensive statin therapy or particular statin agents are more likely to precipitate diabetes. In the 2011 analysis of 5 RCTs by Preiss et al, dose-dependent intensive statin therapy led to a greater increase in diabetes with an odds ratio (OR) of 1.12 (CI 1.04-1.22).⁴ However, this was not confirmed in a propensity score-matched cohort of patients with MI who were prescribed intensive or moderate dose statins and followed for five years (new diabetes in 13.6% vs 13%).⁵

This article by Navarese et al is the largest meta-analysis to date (17 RCTs including > 113,000 patients). The study compared new onset diabetes in patients receiving statin versus placebo, as well as high dose versus moderate dose statin. Pravastatin 40 mg, compared to placebo, was associated with the lowest risk (OR 1.07, CI 0.83-1.30), whereas rosuvastatin 20 mg showed the highest risk (OR 1.25; CI 0.82-1.90), and atorvastatin 80 mg was intermediate (OR 1.15, CI 0.9-1.50)—even though none of these differences achieved statistical significance. Simvastatin also appears to be associated with higher risk compared to pravastatin. The differences among various statins persisted after adjustments for cholesterol reduction. These findings suggest the possibility of molecule-specific effects on diabetogenesis, although the data thus far are inconclusive. The effects of the newest statin, pitavastatin, were not available in a large-enough cohort for inclusion in this report.

References
1. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195-2207.
2. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010; 375:735-742.
3. Ridker PM, Pradham A, MacFayden JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380565-571.
4. Preiss D, Seshasai SRK, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305:2556-2564.
5. Ko, DT et al. Diabetes Mellitus and Cardiovascular Events in Older Patients With Myocardial Infarction Prescribed Intensive-Dose and Moderate-Dose Statins. Circ Cardiovasc Qual Outcomes. 2013; 6: 315-322

EFFECT OF NIACIN ON CARDIOVASCULAR EVENTS IN PATIENTS WITH LOW HDL-CHOLESTEROL

Boden W et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. NEJM. 2011; 365: 2255-2267.


		View journal abstract				View full article

Armitage J. HPS2-THRIVE: randomized placebo-controlled trial of ER niacin and laropiprant in 25,673 patients with pre-existing cardiovascular disease. Presented at: American College of Cardiology Annual Scientific Sessions; March 9, 2013; San Francisco.


			View full article

Haynes R, Jang L, Hopewell JC, et al. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013;34:1279–91.


		View journal abstract				View full article

An inverse relationship between HDL-C and CHD, based on epidemiologic studies, has been well-recognized for several decades. Patients with type 2 diabetes are frequently characterized by low HDL-C and high triglycerides (TG), which often persist after statin treatment. This has been assumed to play a role in the residual CV risk after statin treatment. The most effective drug to raise HDL-C in those with low HDL-C is nicotinic acid (niacin). In angiographic studies, niacin was shown to be associated with atherosclerotic plaque regression, generally in the setting of suboptimal control of LDL-C at baseline,¹ and in the Coronary Drug Project (a secondary prevention RCT), niacin led to a reduction in coronary events compared to placebo.² However, whether niacin will reduce the residual risk of CVD events in patients with optimal LDL-C after statin treatment had never been studied until the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial.

In this study, the AIM-HIGH investigators randomized 3414 very high-risk patients with established CVD and optimal LDL–C but low HDL-C already on simvastatin 20-40 mg (with ezetimibe if needed) to extended-release niacin or placebo. At baseline, 34% of the patients had type 2 diabetes and 81% had metabolic syndrome. During the trial, mean HDL-C in the niacin group increased significantly by 20% (35 to 42 mg/dl) (P < 0-001), triglyceride declined by 25% (164 to 122 mg/dl), and LDL-C declined by 10% (74 to 62 mg/dl). The study was stopped at a mean follow-up of three years because of lack of efficacy (HR 1.02 (CI 0.87-1.21). There was an unexpected (but nonsignificant) increase in the number of ischemic strokes (27 vs 15), which could be a chance finding.

Thus, despite a significant increase in HDL-C, the addition of niacin did not result in any further benefit in patients with established CVD and optimal LDL-C at baseline.

The futility of adding niacin to intensive statin therapy was recently confirmed in the HPS-2 THRIVE study. In this much larger trial in Europe and China (n = > 25,000 with established CVD; 32% with diabetes), in patients with a baseline mean HDL-C ~ 43 mg/dl, LDL-C ~ 64 mg/dl on simvastatin (and ezetimibe if needed), the addition of extended-release niacin–laropiprant vs placebo resulted in no benefit in CVD outcomes (HR 0.96, CI 0.09-1.02). Moreover, those randomized to niacin had a number of adverse events including gastrointestinal side-effects, skin rashes, infections, and increased number of new cases of diabetes during the trial. Thus, these studies have kindled a valid controversy about the utility of the HDL-raising drug, niacin, in the setting of an intensively lowered LDL-C.

It is interesting to note that in a small subgroup analysis of 100 patients from the AIM-HIGH trial, in both highest tertile of TG ( > 198 mg/dl) and the lowest tertile of HDL-C ( < 33 mg/dl), there was a trend toward CVD benefit ( HR 0.74; P = 0.073).³ This finding raises the possibility of some uncharacterized nonlipoprotein mediated adverse effects of niacin overall, with a possible benefit in a subgroup.

References

1. Canner PL, Furberg CD, McGovern ME. Benefits of niacin in patients with versus without the metabolic syndrome and healed myocardial infarction (from the Coronary Drug Project). Am J Cardiol. 2006; 97(4):477-479
2. Phan, BAP et al. Effects of Niacin on Glucose Levels, Coronary Stenosis Progression, and Clinical Events in Subjects With Normal Baseline Glucose Levels (< 100 mg/dl): A Combined Analysis of the Familial Atherosclerosis Treatment Study (FATS), HDL-Atherosclerosis Treatment Study (HATS), Armed Forces Regression Study (AFREGS), and Carotid Plaque Composition by MRI During Lipid-lowering (CPC) Study. Am J Cardiol. Published online Nov 17, 2012. doi: 10.1016/j.amjcard.2012.09.034.
3. Guyton, JR et al. Relationship of Lipoproteins to Cardiovascular Events The AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes). J Am Col Cardiol. 2013; 62: 1580-1584.

JNC 8 HYPERTENSION GUIDELINES

James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520.


		View journal abstract				View full article

This article presents the long-awaited revised guidelines for treating hypertension in a report from the panel members appointed to the Eighth Joint National Commission 8 (JNC 8). These guidelines are relevant to adults in the general population as well as in various subgroups, including ethnic backgrounds, diabetes, and renal disease. Strong evidence led the panel to recommend raising the goal of blood pressure to < 150/90 mm Hg for all people 60 years of age or older (Grade A). For people younger than 60 years, the panel could not find strong evidence for a definite goal, and recommended a goal of < 140/90 mmHg based on expert opinion (grade E). Similarly, based on expert opinion (grade E), a goal of < 140/90 mmHg was recommended for people with kidney disease or those with diabetes age 18 and above.

The revision of BP goal in the diabetes population from < 130/80 in the past to < 140/90 was based on a lack of sufficient evidence from several trials, including the most recent blood-pressure sub-study of the ACCORD trial, which showed the control group with SBP goal of < 140 had similar outcomes to the group with lower goal.¹ Similarly, the panel could not find support for a diastolic goal of < 80 mmHg.

These recommendations for a higher goal in persons age 60 or greater has caused considerable controversy among the experts, and in fact, even among the JNC8 panel members. In a separate publication, five of the 17 JNC 8 authors have expressed a contrarian view:² in particular, they highlight the concerns of possible harm in people in the age group 60-80 years with increased CVD risk and comorbidities and recommend keeping the systolic goal of < 140 in people less than 80 years of age. This recommendation of < 140 systolic is also in line with those of several other guideline organizations from Europe, Canada, and United Kingdom and the AHA, as well as the American and International Hypertension Societies (ASH/ISH).²

Regarding the choice of antihypertensive drug therapy in patients with diabetes and the non-African American population, the panel recommended either a thiazide-type diuretic, a calcium channel blocker (CCB), or an ACEI or ARB alone or in combination (grade B). In the African American population, a thiazide-type diuretic or CCB is preferred, either alone or in combination, before adding other drugs. In patients with CKD, regardless of race or diabetes status, an ACEI or ARB are preferred as the initial therapy, followed by drugs from other classes. Beta-blockers are currently not recommended among the initial choice of drug unless other drug combinations are inadequate, as they are less likely to prevent stroke than the other major classes; however, they are the drugs of choice in patients with history of myocardial infarction or heart failure.³

References
1. Cushman WC, Evans GW, Byington RP, et al. ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575-1585.
2. Wright JT Jr, Fine LJ, Lackland DT, Ogedegbe G, Dennison Himmelfarb CR. Evidence supporting a systolic blood pressure goal of less than 150mmHg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014;160:499-503.
3. Weber, MA et al. Clinical Practice Guidelines for the Management of Hypertension in the Community. A Statement by the American Society of Hypertension and the International Society of Hypertension. J Am Soc Hypertension. 2014. DOI: 10.1111/jch.12237.

APPLYING JNC 8 HYPERTENSION GUIDELINES TO THE US POPULATION

Navar-Boggan AM, Pencina MJ,Williams K, Sniderman AD, Peterson ED. Proportion of US adults potentially affected by the 2014 hypertension guideline. JAMA. 2014; 311: 1424-1429.


		View journal abstract				View full article

In this article, the authors compared the eligibility of US adults for hypertension treatment according to the 2014 JNC 8 guidelines¹ vs the JNC 7 guidelines available since 2003.² They extrapolated data from 16,372 adults in the NHANES survey between 2005-2010. In this analysis, the proportion of treatment-eligible adults decreased slightly (from 20.3% to 19.2 %) in the 18-59 year old age group, whereas a larger decrease (from 68.9% to 61.2%) occurred in older adults (≥ 60 years) due to the revised goal of < 150/90 mm Hg. Moreover, as expected, the new 2014 guidelines resulted in an increase in the proportion of adults meeting BP goals from 41.2 % to 47.5 % in the 18-59 year old age group, and more substantially from 40.0% to 65.% in adults ≥ 60 years of age.

Extrapolating these results to the adult US population, some 13.5 million people not previously considered at BP goal by the JNC-7 criteria would now be considered at goal (41.5 million under JNC 8 vs 28.0 million under the JNC 7 criteria). A majority of the adults meeting the revised 2014 goal are 60 years or older, and many have diabetes and/or CKD, recalling that the JNC goal for adults with these comorbidities was previously < 130/80 mm Hg, but is now < 140/90 mm Hg.² However, it is especially important to note that, despite some limitations in the NHANES survey, more than 50% of the eligible adults under both JNC 7 and JNC 8 guidelines in this analysis were untreated, indicating the considerable on-going burden of untreated hypertension in the US.

This revision of the systolic blood pressure goal in adults ≥ 60 years to 150 mm Hg in JNC 8 is being debated by some of the dissenting authors of the JNC 8 panel (in a separate publication),³ as other professional society guidelines,^3-5 recommend the > 150/90 target only for those age 80 or greater.

References
1. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520.
2. Chobanian AV, Bakris GL, Black HR, et al. National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. 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(19):2560-2572.
3. Weber, MA et al. Clinical Practice Guidelines for the Management of Hypertension in the Community. A Statement by the American Society of Hypertension and the International Society of Hypertension. J Am Soc Hypertension. 2014;DOI: 10.1111/jch.12237
4. Wright JT Jr, Fine LJ, Lackland DT, Ogedegbe G, Dennison Himmelfarb CR. Evidence supporting a systolic blood pressure goal of less than 150mmHg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014;160:499-503.
5. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al; Task Force Members. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31:1281-357.


	COMPLETE THE POST-TEST Step 1. Click on link to download instructions for the post-test and evaluation

IMPORTANT CME/CE INFORMATION

Accreditation Statements
Physicians
This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the Johns Hopkins University School of Medicine and The Institute for Johns Hopkins Nursing. The Johns Hopkins University School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

Nurses
The Institute for Johns Hopkins Nursing and the American Nursing Credentialing Center do not endorse the use of any commercial products discussed or displayed in conjunction with this educational activity.

credit designation STATement
Physicians
eNewsletter: The Johns Hopkins University School of Medicine designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Podcast: The Johns Hopkins University School of Medicine designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Nurses
eNewsletter: This 1 contact hour educational activity is provided by The Institute for Johns Hopkins Nursing. Each newsletter carries a maximum of 1 contact hour or a total of 6 contact hours for the six newsletters in this program.

Podcast: This 0.5 contact hour educational activity is provided by The Institute for Johns Hopkins Nursing. Each podcast carries a maximum of 0.5 contact hours or a total of 3 contact hours for the six podcasts in this program.

successful completion
To successfully complete this activity, participants must read the content, and then link to the Johns Hopkins University School of Medicine's website or the Institute for Johns Hopkins Nursing's website to complete the post-test and evaluation. A passing grade of 70% or higher on the post-test/evaluation is required to receive CE credit.

Launch Date
May 29, 2014; activities expire 2 years from the date of publication.

Internet CME Policy
The Office of Continuing Medical Education (CME) at the Johns Hopkins University School of Medicine is committed to protecting the privacy of its members and customers. The Johns Hopkins University SOM CME maintains its Internet site as an information resource and service for physicians, other health professionals, and the public.

Continuing Medical Education at the Johns Hopkins University School of Medicine will keep your personal and credit information confidential when you participate in an Internet-based CME program. Your information will never be given to anyone outside of the Johns Hopkins University School of Medicine's CME program. CME collects only the information necessary to provide you with the services that you request.

Disclaimer Statement
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of the Johns Hopkins University School of Medicine name implies review of educational format design and approach. Please review the complete prescribing information of specific drugs or combination of drugs, including indications, contraindications, warnings, and adverse effects before administering pharmacologic therapy to patients.

Statement of Responsibility
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.

Statement of Need


	Clinicians do not appropriately intensify therapy as necessary to maintain glycemic control.
	Conflicting data about the safety of incretin agents may unduly deprive patients of treatment benefits.
	Clinicians are not aware of and/or are not implementing strategies to maximize the value of SMBG readings to improve patient outcomes.
	Clinicians do not adequately understand or treat to control CVD risk factors in their patients with T2D.
	Clinicians do not have a sufficiently current knowledge base to effectively consult patients about potential T2D therapeutic advances.
	Clinicians do not adequately counsel and treat their overweight/obese patients with T2D.

Intended Audience
The target audience for this initiative includes: endocrinologists, primary care clinicians, nurse practitioners, physician assistants, Certified Diabetes Educators, and other health care practitioners whose work/practice includes treating patients with T2D.

Policy on Faculty and Provider Disclosure
It is the policy of the Johns Hopkins University School of Medicine that the faculty and provider disclose real or apparent conflicts of interest relating to the topics of this educational activity, and also disclose discussions of unlabeled/unapproved uses of drugs or devices during their presentation(s). Johns Hopkins University School of Medicine OCME has established policies in place that will identify and resolve all conflicts of interest prior to this educational activity. Detailed disclosure will be made in the newsletters/podcasts.

Guest Author Disclosures

Confidentiality Disclaimer for Conference Attendees
I certify that I am attending a Johns Hopkins University School of Medicine CME activity for accredited training and/or educational purposes.

I understand that while I am attending in this capacity, I may be exposed to "protected health information," as that term is defined and used in Hopkins policies and in the federal HIPAA privacy regulations (the Privacy Regulations). Protected health information is information about a person's health or treatment that identifies the person.

I pledge and agree to use and disclose any of this protected health information only for the training and/or educational purposes of my visit and to keep the information confidential.
I understand that I may direct to the Johns Hopkins Privacy Officer any questions I have about my obligations under this Confidentiality Pledge or under any of the Hopkins policies and procedures and applicable laws and regulations related to confidentiality. The contact information is Johns Hopkins Privacy Officer, telephone: 410-735-6509, e-mail: HIPAA@jhmi.edu.

"The Office of Continuing Medical Education at The Johns Hopkins University School of Medicine, as provider of this activity, has relayed information with the CME attendees/participants and certifies that the visitor is attending for training, education and/or observation purposes only."

For CME Questions, please contact the CME Office at (410) 955-2959 or e-mail cmenet@jhmi.edu.

For CME Certificates, please call (410) 502-9634.

Johns Hopkins University School of Medicine
Office of Continuing Medical Education
Turner 20/720 Rutland Avenue
Baltimore, Maryland 21205-2195

Reviewed and Approved by
General Counsel, Johns Hopkins Medicine (4/1/03)
Updated 4/09

Hardware & Software Requirements
Pentium 800 processor or greater, Windows 98/NT/2000/XP/7 or Mac OS 9/X, Microsoft Internet Explorer 5.5 or later, 56K or better modem, Windows Media Player 9.0 or later, 128 MB of RAM, sound card and speakers, Adobe Acrobat Reader, storage, Internet connectivity, and minimum connection speed. Monitor settings: High color at 800 x 600 pixels.