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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Managing the Hypertensive Patient with Diabetes: What Should Every Practitioner Know?


GOAL
To provide cardiologists, family physicians, internists, and other relevant physicians with up-to-date information on the management of hypertensive patients with diabetes.

TARGET AUDIENCE
This activity is designed for cardiologists, family physicians, internists, and other physicians involved in the care of patients with hypertension.
No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, participants should be able to:

  • Define the relationship between hypertension and diabetes, focusing on the role of the renin-angiotensin-aldosterone system.
  • Discuss risk assessment methods and approaches to slowing the progression of renal disease in patients with hypertension, using information from recently published articles and the RENAAL study.
  • Examine the prevalence and risk factors for stroke in patients with hypertension and comorbid diabetes.
  • Outline primary and secondary stroke prevention methods, applying information from different studies.
  • Identify risk factors and various treatment goals for hypertensive patients with metabolic syndrome and prediabetes.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity. The estimated time to complete this educational activity: 2 hours.

Release date: November 15, 2005.
Expiration date: November 15, 2007.

This activity has been reviewed and is acceptable for up to 2 Prescribed credit(s) by the American Academy of Family Physicians. AAFP accreditation begins 11/15/05. Term of approval is for two-year(s) from this date, with option for yearly renewal.

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 combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Merck and Company.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Directors and Participating Faculty reported the following:

PROGRAM DIRECTOR

Sherita Hill Golden, MD, MHS
Assistant Professor of Medicine and Epidemiology
Division of Endocrinology and Metabolism
Johns Hopkins University School of Medicine
Department of Epidemiology
Johns Hopkins University Bloomberg School of Public Health
Baltimore, Maryland
Dr Golden reports receiving honoraria from Pfizer Inc.

PARTICIPATING FACULTY

Lawrence M. Brass, MD
Professor of Neurology, Epidemiology, and Public Health
Department of Neurology
Yale University School of Medicine
New Haven, Connecticut
Dr Brass reports receiving grants/research support from Bristol-Myers Squibb Company and Sanofi Synthelabo Pharmaceuticals; serving as a consultant for AstraZeneca, Bayer, Bristol-Myers Squibb, Merck and Company, ONO Pharmaceuticals, Sanofi Synthelabo Pharmaceuticals, Solvay Pharmaceuticals, and Wyeth; and being on the speaker's bureau for Bristol-Myers Squibb Company, Sanofi Synthelabo Pharmaceuticals, Solvay Pharmaceuticals, and Wyeth.

John Palmer, DO
Resident Physician
Department of Internal Medicine
University of Missouri Health Sciences Center
Columbia, Missouri
Dr Palmer reports having no financial or advisory relationships with corporate organizations related to this activity.

James R. Sowers, MD, FACE, FACP, FAHA
Thomas W. and Joan F. Burns Missouri Chair in Diabetology
Director, MU Diabetes and Cardiovascular Center
Associate Dean for Clinical Research
Professor of Medicine, Physiology, and Pharmacology
Department of Internal Medicine
University of Missouri Health Sciences Center
Columbia, Missouri
Dr Sowers reports having no financial or advisory relationships with corporate organizations related to this activity.

Matthew R. Weir, MD
Professor of Medicine
Head, Division of Nephrology
University of Maryland Medical Center
Baltimore, Maryland
Dr Weir reports receiving honoraria from Bristol-Myers Squibb Company, MSD, Novartis, and Sanofi-Aventis.

Adam Whaley-Connell, DO
Postdoctoral Fellow
Division of Nephrology
Department of Internal Medicine
University of Missouri Health Sciences Center
Columbia, Missouri
Dr Whaley-Connell reports having no financial or advisory relationships with corporate organizations related to this activity.

Notice: The authors have indicated that this CME activity contains no mention of unlabeled/unapproved uses of drugs or devices.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Managing the Hypertensive Patient with Diabetes: What Should Every Practitioner Know?
Sherita Hill Golden, MD, MHS*

More than 18 million people in the United States have diabetes, and approximately 75% of these patients are affected by hypertension.1 The coexistence of diabetes and hypertension additively increases the risk of life-threatening cardiovascular events—heart disease and stroke accounting for approximately 65% of deaths among patients with diabetes.1 Hypertension also substantially increases the risk of other macrovascular and microvascular complications, including nephropathy, in this population.

The increasing prevalence of diabetes and hypertension has been accompanied by a substantial increase in the prevalence of stroke. Stroke is the leading cause of death and severe long-term disability in the United States.2 Control of high blood pressure contributes to the prevention of stroke, in addition to the prevention or reduction of other target-organ damage, including clinical coronary heart disease, congestive heart failure, and renal failure.

Type 2 diabetes and cardiovascular disease appear to share common metabolic antecedents, including impaired glucose tolerance, hypertension, dyslipidemia, and abdominal obesity.3-5 The clustering of these risk factors is thought to be a manifestation of an underlying insulin resistance syndrome, also referred to as the metabolic syndrome.6,7 Although there is some debate as to whether elevated blood pressure is a consistent feature of the metabolic syndrome, the coexistence of insulin resistance in the setting of hypertension is very likely central to the development of cardiovascular disease.8 In a population-based cross-sectional analysis, hypertension was one of the components of the metabolic syndrome that was most strongly associated with subclinical atherosclerosis.7 An integral component to reducing the risk of cardiovascular and renal outcomes in patients with the metabolic syndrome is the aggressive management of the individual components of the syndrome, including hypertension. Initial therapy should focus on lifestyle modifications, such as smoking cessation, dietary modifications, increased physical activity, and weight loss.

Pharmacologic therapy is a critical step in the management of patients with diabetes and hypertension. Recent guidelines emphasize the need for early and aggressive reduction of blood pressure in patients with diabetes.9,10 All of the available classes of antihypertensive agents, including thiazide diuretics, b blockers, and calcium channel blockers, are effective in reducing blood pressure in patients with diabetes and result in reduced cardiovascular morbidity and mortality.11-13 Recent studies have shown that treatment with antihypertensive agents that target the renin-angiotensin-aldosterone system (RAAS), including angiotensin- converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), may also improve cardiovascular, renal, and cerebrovascular outcomes.14-23

Matthew R. Weir, MD, examines the underlying causes and progression of renal disease in patients with diabetes and hypertension. Optimal metabolic control can help to prevent not only microalbuminuria, the earliest manifestation of nephropathy, but also the accelerated progression of renal disease in patients with diabetic nephropathy. The RAAS plays a critical role in the pathogenesis of hypertension and renal complications. Although ACE inhibitors and ARBs target the RAAS, the ARBs may offer more complete angiotensin II inhibition by acting selectively with the receptor site. Healthcare professionals must recognize patients who are at risk of or who have chronic kidney disease and implement strategies, including initiating therapy that targets the RAAS, to optimize blood pressure control and reduce the incidence of end-stage renal disease, particularly among patients with type 2 diabetes.

Lawrence M. Brass, MD, reviews the different subtypes of stroke, in addition to the risk factors for stroke. There have been many advances in the treatment of stroke in recent years. However, a significant number of individuals continue to be affected by stroke each year. The prevention of stroke is an important strategy that can help to reduce the burden of the disease. Management of modifiable risk factors, particularly hypertension, has the greatest impact on primary prevention of stroke and should also be part of the strategy for secondary prevention. Agents that target the RAAS have also been shown to be effective in primary and secondary prevention of stroke.

Adam Whaley-Connell, DO, James R. Sowers, MD, FACE, FACP, FAHA, and John Palmer, DO, describe the key components of the metabolic syndrome. Hypertension is frequently associated with the metabolic syndrome and with diabetes and is a risk factor for cardiovascular disease and renal disease. Individual components of metabolic syndrome should be treated to targets that prevent or delay the onset of type 2 diabetes and its complications. Nonpharmacologic treatment approaches, such as lifestyle modifications, have been shown to be effective in preventing diabetes among patients with impaired glucose tolerance.24 Recently, the focus of pharmacologic therapy has shifted toward inhibition of the RAAS. Most patients with hypertension require multiple antihypertensive agents to achieve optimal blood pressure control. The Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure recommends using a combination of 2 agents, one of which should be a diuretic, when a single agent in adequate doses fails to achieve the blood pressure goal.

The articles in this monograph will help practitioners to improve their understanding of the relationship between hypertension and diabetes; the role of the RAAS in the pathogenesis of hypertension and renal disease; the risk assessment methods and approaches to slowing the progression of renal disease; the prevalence and risk factors for stroke in patients with hypertension and diabetes, and primary and secondary stroke prevention methods; and the risk factors and treatment approaches for patients with hypertension, metabolic syndrome, and prediabetes.

REFERENCES

1. Centers for Disease Control and Prevention. National Diabetes Fact Sheet. Available at: http://www.cdc.gov/diabetes/pubs/estimates.htm. Accessed July 30, 2005.
2. American Heart Association, American Stroke Association. Heart Disease and Stroke Statistics-2005 Update. Dallas, Tex: American Heart Association; 2005.
3. Haffner SM, Stern MP, Hazuda HP, et al. Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA. 1990;263:2893-2898.
4. Stern MP. Do non-insulin-dependent diabetes mellitus and cardiovascular disease share common antecedents? Ann Intern Med. 1996;124:110-116.
5. Haffner SM, Mykkanen L, Festa A, et al. Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state. Circulation. 2000;101:975-980.
6. Reaven GM. Role of insulin resistance in human disease. Diabetes. 1988;37:1595-1607.
7. Golden SH, Wang N, Klag MJ, et al. Blood pressure in young adulthood and the risk of type 2 diabetes in middle age. Diabetes Care. 2003;26:1110-1115.
8. Reaven GM. Insulin resistance/compensatory hyperinsulinemia, essential hypertension, and cardiovascular disease. J Clin Endocrinol Metab. 2003;88:2399-2403.
9. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206-1252.
10. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28(suppl 1):S4-S36.
11. Huang ES, Meigs JB, Singer DE. The effect of interventions to prevent cardiovascular disease in patients with type 2 diabetes mellitus. Am J Med. 2001;111:633-642.
12. United Kingdom Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998;317:713-720.
13. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981-2997.
14. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet. 2002;359:995-1003.
15. Lindholm LH, Ibsen H, Dahlof B, et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet. 2002;359:1004-1010.
16. Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomized trial. Lancet. 2004;364:2022-2031.
17. Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345:870-878.
18. Viberti G, Wheeldon NM. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus. A blood pressure independent effect. Circulation. 2002;106:672-678.
19. Bakris GL, Weir MR, Shanifar S, et al. Effects of blood pressure level on progression of diabetic nephropathy. Arch Intern Med. 2003;163:1555-1565.
20. Barnett AH, Bain SC, Bouter P, et al. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med. 2004;351:1952-1961.
21. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. 2000;355:253-259.
22. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851-860.
23. Brenner BM, Cooper ME, Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861-869.
24. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.

*Assistant Professor of Medicine and Epidemiology, Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.

Address correspondence to: Sherita Hill Golden, MD, MHS, Assistant Professor of Medicine and Epidemiology, Welch Center for Epidemiology, Prevention, and Clinical Research, 2024 East Monument Street, Suite 2-600, Baltimore, MD 21205.
E-mail:
sahill@jhmi.edu.





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