Justin Sherman, PharmD

Drs. Menefee and Knox are PharmDresidents, and Dr. Sherman is anassociate professor of pharmacypractice, at the University ofLouisiana at Monroe College ofPharmacy.

More than 1.4 million Americansdie of cardiovascular diseaseeach year, which is 1 deathevery 36 seconds, and more than 79 millionAmericans currently live with a cardiovasculardisease, including hypertension,coronary artery disease, heart failure,myocardial infarction, and stroke.

 Inaddition to certain lifestyle factors, suchas diet and exercise, diabetes mellitus isespecially important when looking atincreased risk of target-organ damagecaused by cardiovascular disease.

Common risk factors for cardiovasculardisease include the following: age >65years, male, genetic predisposition,African American race, smoking, highcholesterol, high blood pressure, physicalinactivity, overweight, and diabetes.Smoking, diet, blood pressure, and diabetesare modifiable risks, while race,age, and genetics are not. Risk increasesproportionally with the number of riskfactors. Two major independent risk factorsare high blood pressure and highblood cholesterol. A 10% decrease intotal cholesterol levels in the US populationoverall, for example, may result in anestimated 30% reduction in the incidenceof coronary heart disease.

 Thus,community pharmacists should encouragereducing modifiable risk factors.

Long-standing hypertension, uncontrolleddiabetes, and high cholesterolcan lead to many complications, suchas kidney damage, heart attack, stroke,limb amputation, and blindness. Animportant consideration in cardiovasculardisease is that many complicationscan occur together and lead toothers. Education and prevention providepharmacists with an importantopportunity to help patients reducetheir risk of cardiovascular events.

Resources for Lifestyle Modifications for Cardiovascular Disease

According to theSeventh Report of theJoint National Committeeon Prevention,Detection, Evaluation,and Treatment of HighBlood Pressure (JNC 7),the American HeartAssociation Guidelines,and the NationalCholesterol EducationProgram Adult TreatmentPanel III (NCEP/ATP III), a nutritiousdiet helps to reduceoccurrence of cardiovasculardisease.Heart failure, hypertension,stroke, andmyocardial infarctionrisk can be decreasedwith weight reduction, smoking cessation,and increased physical activity.

Teaching patients how to read foodlabels, choose alternative salt and sugarsources, and participate in local fitnessprograms could have a major impact ontheir health care. Eliminating sodas, highfructose fruit drinks, bread, and table saltand simply walking for 30 minutes a dayin 10-minute blocks could help withweight, blood pressure, and cholesterolreduction. The benefits of lowering bloodpressure alone equal a 40% reduction instroke occurrence, a 25% decrease inmyocardial infarction, and a 50% decreasein heart failure.

To help reduce cardiovascular disease,pharmacists should encouragemodest weight reduction (approximately10%); a diet rich in fruits, vegetables,and low-fat dairy products; reducedsodium (&#8804;2.4 g per day); limitedalcohol consumption; smoking cessation;and increased physical activity(Table 1). To maximize the reduction oflow-density lipoprotein (LDL) cholesterolthrough diet, NCEP?s TherapeuticLifestyle Change (TLC) Diet recommendsconsumption of <200 mg ofcholesterol per day.

 Although manypatients expect medications to be thecure-all, they are not; rather, theyshould be used along with lifestylemodifications for optimal results.

Pharmacists can have a tremendousimpact on the treatment of cardiovasculardisease. Adherence to evidencebasedtherapies and risk-factor managementimproves cardiac-patient survivaland quality of life.

 Angiotensin-convertingenzyme inhibitors (ACEIs) are effectivein the treatment and prevention ofmany cardiovascular events. An ACEI oran angiotensin receptor blocker (ARB)should be prescribed to all patients withleft ventricular dysfunction (heart failure)and/or post myocardial infarction.7Clinical trials have demonstrated thebenefits of antiplatelet, beta-adrenergicblocker (BB), ACEI, and statin therapy incardiovascular disease.

 According to theAmerican Diabetes Association guidelines,aspirin as a primary and secondarytherapy prevents cardiovascular eventsin diabetic and nondiabetic individuals.

Nearly 1 in 3 adults in the UnitedStates has high blood pressure. For each20-mm increase in systolic readings and10-mm increase in diastolic above115/75 mm Hg, there is a twofold increasein cardiovascular disease.

Recommended medication therapies forhypertension and other cardiovascularcomorbidities from the JNC 7 are listed inTable 2.

Pharmacists also should remind patientsto stay current with their vaccinationsand have blood pressure, blood glucose,and cholesterol levels checked routinely.Influenza vaccine has been shownto reduce diabetes-related hospitaladmission by as much as 79% during fluepidemics. Also, tight glycemic controlhelps to delay or diminish microvascularcomplications.

 Reduced blood pressureand cholesterol decrease morbidity andmortality for patients with hypertensionand hyperlipidemia, respectively. Preventionis the best means of treatmentfor cardiovascular disease.

Compliance and creating the idealenvironment for medications to workcan help prevent and treat cardiovasculardisease. Inform patients of the importanceof taking their medications asdirected. Although many patients expecta quick fix at the doctor?s office or neighborhoodpharmacy, encourage them totake responsibility for their own healthcare and make this a priority. Exercising,eating right, and following their prescribedtreatment regimens are for theirown benefit.

Centers for Disease Control and Prevention. Division for Heart Disease and Stroke Prevention. Addressing the Nation's Leading Killers-At a Glance 2007. Available at: 

www.cdc.gov/nccdphp/publications/AAG/dhdsp.htm

American Heart Association. Risk Factors and Coronary Heart Disease. Available at: 

www.americanheart.org/presenter.jhtml?identifier=4726

National Heart Lung and Blood Institute. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Available at: 

www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.htm

American Diabetes Association. Standards of Medical Care in Diabetes-2007. 

National Heart Lung and Blood Institute. Third Report of the Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Executive Summary. Available at: 

www.nhlbi.nih.gov/guidelines/cholesterol/atp_iii.htm

Updates in Therapeutics: The Pharmacotherapy Preparatory Course

. American College of Clinical Pharmacy; 2007:581-607.

Hertz KT. The continuum of cardiovascular care: championing guideline adherence, optimizing the "teachable moment." 

www.physiciansweekly.com/index.asp?issueid=143

Articles

Adherence to medications can aid in preventing and treating CVD.

Helping Patients Manage Cardiovascular Disease

At least 20% of patients older  than 65 years currently have  diabetes. They make up a  growing segment of the health care  population--a segment that is expected  to grow even more rapidly over the  next few decades.

Treatment approaches should be  highly individualized and dynamic.  Therefore, considering the following  questions will optimize the management  of this special group of patients.

 Should the Same Treatment Goals  Be Used for the Elderly?

The American Diabetes Association  (ADA) guidelines dictate that a goal  level of hemoglobin A1C should be  <7%.

For an ideal patient, clinicians  should aggressively treat to reduce  A1C to <6%. Yet, elderly patients (>65  years), the young (<13 years), and  those with limited life expectancies,  comorbid conditions, or frequent or  severe hypoglycemia may need less  stringent goals.

Thus, the level of control depends on  individually weighing risk versus benefit.  In contrast with their nondiabetic  counterparts, the diabetic elderly are  at risk for increased comorbidity, cognitive  and physical impairment, depression,  falls, and polypharmacy.

Not  all elderly persons with diabetes, however,  have the same risk. Some are  active, with little comorbidity and reasonable  life expectancies. The age of  onset of the diabetes--middle age versus  elderly--also may influence disease  burden and in the future may dictate  different treatment goals.

In addition,  the duration of the diabetes and  other factors influence disease burden.

A general goal, however, is this: manage  diabetes intensively for all who  benefit, regardless of age. Those who  will likely benefit from long-term management  (those with a life span of =10  years) and are cognitively aware,  active, and compliant with intense self-management  should maintain the  same goals as younger patients.

 What Treatment Will Lower the  Risk of Cardiovascular  Complications?

No long-term studies have been conducted  to demonstrate the benefits of  tight glycemic, blood pressure, and  lipid control in the diabetic elderly, and  large-scale trials have been criticized  for excluding the elderly.

Yet, strong  evidence exists to aggressively treat  hypertension--and possibly lipids--rather than treating hyperglycemia  alone.

For example, the blood pressure goal  for the diabetic elderly is still <130/80  mm Hg. The elderly benefit equally, and  perhaps even more so, than their  younger counterparts. In the Heart  Outcomes Prevention Evaluation study,  aggressively treating hypertension  with ramipril lowered the risk for major  cardiovascular events. It showed a 25%  greater benefit for the diabetic elderly.

In the Systolic Hypertension in the  Elderly Program trial, chlorthalidone  reduced the risk of coronary events.

In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart  Attack Trial, chlorthalidone was compared  with amlodipine, lisinopril, and  doxazosin.

The thiazide-like diuretic  (doxazosin) reduced cardiovascular  disease risk and heart failure in the diabetic  elderly. This finding is consistent  with using hydrochlorothiazide for isolated  systolic hypertension, which is  common in the elderly.

However, the Seventh Report of the  Joint National Committee on hypertension  recognizes that angiotensin-converting  enzyme (ACE) inhibitors have  renoprotective effects, and that often 2  or more medications are needed for diabetic patients to achieve target  blood pressure.

Often, comorbidities dictate using  ACE inhibitors or angiotensin receptor  blockers and ?-blockers. Yet, ?-blockers  can mask hypoglycemia, a-blockers  can cause orthostasis, and multiple  medications can cause hypotension.  Although standard doses often help  the elderly reach the goal, initial doses  may need to be lower than those for  younger patients.

Finally, subanalyses of major studies  give indirect evidence that antihyperlipidemia  treatment can reduce myocardial  infarction, coronary death, and  stroke.

Although many older patients  deal with muscle pain, specific muscular  adverse effects with statins--including rhabdomyolysis--are not  age-related. Again, treatment of hyperlipidemia  depends on risk versus benefit.  Because the diabetic elderly have  an increased risk for cardiovascular  disease, ADA guidelines advocate  aggressively managing lipids and using  aspirin unless otherwise indicated.

 What Recommendations Will  Avoid Hypoglycemia?

Of the potential complications from  intensive glycemic control, hypoglycemia  is in the forefront of the clinician's  mind. Common symptoms  include fatigue, headache, difficulty  concentrating, and excessive hunger,  but they can manifest differently in the  elderly (eg, blurred vision and dizziness  often are experienced).

Sometimes,  symptoms are blunted due to impaired  cognition or autonomic neuropathy.  Along with advanced age, factors  increasing hypoglycemia risk include  comorbidities, poor behavioral compliance,  the use of certain medications,  and polypharmacy.

Many elderly patients have not  adapted to their diabetes in terms of  diet. The elderly are satiated more  quickly and food loses its taste, and as  a result the elderly consume fewer  meals. Because patients with diabetes  should eat smaller meals more often,  patients eating 1 or 2 meals daily may  have more postprandial hyperglycemia.

Maladaptive eating behaviors are  compounded when patients take medications  incongruently with meals- especially sulfonylureas and insulin.  Dietary errors account for 53% of hypoglycemic  episodes when the patient  has skipped a particular meal.

Also,  patients may take sulfonylureas and  rapid-acting insulin after meals, and  the result may be postprandial hypoglycemia.  For example, the Diabetes  Outcomes in Veterans Study showed  an increased hypoglycemic risk, depending  on the number of insulin injections  per day and whether rapid-acting  insulin was used.

In fact, hypoglycemia  is 3 times more frequent with  insulin versus oral medications.

Whereas sulfonylureas and fast-acting  insulin can cause hypoglycemia,  thiazolidinediones and metformin generally  do not. Second-generation sulfonylureas  are less problematic than  first-generation agents. These agents  usually are prescribed twice daily, and  doses should be split appropriately (for  example, 10 mg glyburide twice daily  rather than 20 mg once daily). Also,  nonsulfonylurea secretagogues lower  postprandial glucose levels with relatively  less hypoglycemic incidents.  Therefore, the clinician might consider  switching a patient with significant  hypoglycemia (once per week or significant  symptoms) to one of these latter  agents. Still, sulfonylureas reduce A1C  by 1% to 2% and are effective agents,  so any decision to change medications  should be judicious and individualized.

Finally, the need for tight control of  glycemia and comorbidities often leads  to polypharmacy.

Both diabetes and  hypertension frequently require multiple  medications. Thus, polypharmacy  can increase adverse effects and the  potential for medication interactions.  Consequences result when medications  do not achieve goal levels, however,  so stopping medications should  receive careful consideration.

Polypharmacy is compounded when  patients use multiple physicians and  obtain prescriptions from several pharmacies.  Simple measures can prevent  polypharmacy, such as instructing  patients to maintain an active list of  their medications, including OTC drugs  and nutritional supplements. Single  medications that can treat multiple  conditions should be used when feasible.  Patients with multiple providers  should coordinate medications at 1  pharmacy. Education of patients also  is key: they should understand the indications  and possible adverse effects of  each medication, as well as their treatment  goals.

Treatment goals for elderly patients  with diabetes should be individualized,  but in many cases they are no less  aggressive than those for younger patients.  This population is highly susceptible  to cardiovascular complications  and thus should be treated accordingly,  in terms of optimizing medications  and treatment goals. Plans may need  to be changed, however, due to challenges  that are relatively unique to elderly  patients, including severe hypoglycemia  and polypharmacy. 

1. Chau D, Edelman SV. Clinical management of diabetes in the elderly. 

2. American Diabetes Association. Standards of medical care in diabetes-2007. 

   3. Selvin E, Coresh J, Brancati FL. The burden and treatment of diabetes in elderly individuals in the U.S. 

4. McMurdo ME, Witham MD, Gillespie ND. Including older people in clinical research [editorial]. 

5. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. 

6. Curb JD, Pressel SL, Cutler JA, et al. Systolic Hypertension in the Elderly Program Cooperative Research Group. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. 

7. 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). 

8. Chobanian AR, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. 

9. Verny C. Management of dyslipidemia in elderly diabetic patients. 

10. Lecomte P. Diabetes in the elderly: considerations for clinical practice. 

11. Murata GH, Hoffman RM, Shah JH. A probabilistic model for predicting hypoglycemia in type 2 diabetes mellitus: the Diabetes Outcomes in Veterans Study (DOVS). 

12. Good CB. Polypharmacy in elderly patients with diabetes. 

 Dr. Sherman is associate professor of  pharmacy practice at University of  Louisiana at Monroe College of  Pharmacy.

A Q&A on Outpatient Treatment of Elderly Patients with Diabetes

Alzheimer's disease (AD) isthe most common form ofdementia. Age is the greatestrisk factor for dementia. Dementiaaffects ~1% of individualsaged 60 to 64 years and between24% and 33% of individuals over theage of 85.

The main pathologic componentsof the AD brain are neuritic plaquesand neurofibrillary tangles. Theneuritic plaques are composed of?-amyloid peptides, sometimes referredto as ?

. Theneurofibrillary tangles are composedof protein called tau, whichforms insoluble filaments that leadto cell death in large numbers andresult in atrophy of the cerebralhemispheres.

Diagnosis of AD is one of exclusionbased on the presence of certainclinical findings. The primaryclinical finding is a loss of cognitivefunction?a decline from a previoushigher level of functioning that distinguishesdementia from mentalretardation or other developmentaldelays.

The primary cognitive findingis short-term memory loss or, inparticular, the inability to learn anythingnew. AD patients often havedifficulty keeping track of the date,remembering recent conversations,or recalling where they recently leftan item. The diagnosis is made asthese symptoms become more evident,but often after much delay.

AD often is described in stages.The 2 most common staging methodsinvolve a 3-stage system and a7-stage system. Staging of AD providesthe patient and/or familymembers and caregivers a frame ofreference for understanding the diseaseprocess and for future planning.

AD is a continuing diseaseprocess in which individuals maynot experience all symptoms ateach stage, and symptoms mayoccur at different times. After diagnosis,patients live an average of 8years, with a range of 3 to 20 years.

Current drugs used in the treatmentof AD are (1) the cholinesteraseinhibitors donepezil,galantamine, and rivastigmine and(2) memantine, an 

aspartate(NMDA) receptor antagonist.Donepezil is currently indicatedfor mild, moderate, and severe AD,and galantamine and rivastigmineare indicated for mild-to-moderateAD. Memantine is indicated formoderate-to-severe AD. Trials ofcholinesterase inhibitors show thatlong-term use will result in modeststabilization of cognitive and functionalstatus in AD patients for up to1 year.

Memantine can delay symptomprogression in moderate-to-severestageAD patients. One study hasindicated that combination treatmentwith memantine anddonepezil in moderate-to-severe ADis more effective than donepeziltherapy alone.

Therefore, combinationtherapy with memantine and acholinesterase inhibitor may proveto be beneficial.

Data indicate that early and continued therapy with a cholinesteraseinhibitor (possibly combinedwith memantine) can delay or slowthe inevitable cognitive and functionaldecline in AD patients.

Early,continued treatment of AD translatesinto longer periods of higherfunctioning, which may mean increasedquality of life for patients,less caregiver burden or stress, anddelayed institutionalization. Therefore,early recognition of the signsand symptoms of AD is critical tomaximize the benefits of currentdrug treatment for AD.

Although a randomized trial doesnot exist for definitive evaluation,screening programs should be beneficial.The prevalence of undiagnoseddementia, the accuracy ofthe screening tools, the efficacy oftreatment for mild-to-moderate dementia,and whether screeningactually could be harmful are importantfactors in determining the benefitsof a screening program.

Oneevaluation of the body of literatureon undiagnosed dementia foundthat 50% to 66% of all patientswho had not receiveda diagnosis of dementiadid, in fact, have mild-tomoderatedementia.

Thus,a screening program forpatients 65 years and oldercould double the number ofdiagnosed dementia patients.

Among the memoryscreeninginstruments, theMini-Mental StateExamination (MMSE) is themost widely used. It hasbeen used for screening inepidemiologic studies. Itassesses attention, orientation,short-term recall, language,and an ability to followverbal and written commandson a 30-point scale.

The MMSE may be lessaccurate when detectingmild dementia, and it requires specialadjustments for variations inage and educational level

Thegroups most appropriate for the useof the MMSE are Caucasians with atleast a high school education.

Other memory-screening toolsinclude the Memory ImpairmentScreen (MIS) and the Short BlessedTest.

During the MIS, patients aregiven the names of items in 4 differentcategories and are asked toname each item after a short delay.The Short Blessed Test has 6 items:the patient is asked to identify theyear, month, and time of day; tocount from 20 backwards; to recitethe months backwards; and torecall a phrase.

A Web-based ADscreener contains a list of 11 questions,adapted from a validatedquestionnaire that describes symptomsof AD.

The risks of screening programsare relatively few, but they include arisk for causing anxiety or depressionand, of course, adverse effectsfrom medications if drugs are subsequentlyemployed.

Surveys reveal,however, that most patientswith AD want to be told of a dementiadiagnosis.

Another risk is identifying falsepositives. Screening tests may yieldmore than 50% of patients with apositive result that will not meet thecriteria for dementia. Thus, thescreening program must be linkedwith a good referral system to aprovider for follow-up.

When counseling a patient showingsigns of memory impairment, itis important to point out that,although memory impairment is ahallmark feature of AD, it does notmean that the patient has AD. Apatient showing signs of dementiashould follow up with a physician torule out potential reversible causes.Potential medical causes may includedepression, vitamin B

Medications that possess anticholinergicactivity may impair memoryand cognitive functioning, and theiruse in older patients should beavoided if medically possible.

Because drug therapy can delaythe progression of impairment, thepharmacist can play a pivotal role inscreening, educating, and referringpatients to their physician for follow-up. Maximizing the effectivenessof drug therapy for AD includesinitiating early treatment, maximizingthe dose, and continuing treatment.In all 3 areas, the pharmacistcan play an active role. Screeningpatients for memory impairmentand referral can lead to early initiationof therapy. Education of patients,caregivers, and physiciansregarding dose maximization andcontinuation of treatment also canlead to more effective drug treatmentof AD.

Dr. Nickelson is an assistant professor of pharmacy practice and Dr. Sherman is an associate professor of pharmacy practice at the University of Louisiana at Monroe College of Pharmacy.

1. Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphiconsensus study. 

2. Blennow K, de Leon MJ, Zetterberg H. Alzheimer's disease. 

3. Alzheimer disease and other major dementing illnesses. Knopman DS. 

Available at: www.medscape.com/viewarticle/530672. Accessed May10, 2006.

4. Stages of Alzheimer's Disease. Alzheimer's Association Web site. Available at:www.alz.org/AboutAD/Stages.asp. Accessed November 1, 2006.

5. Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I.Memantine treatment in patients with moderate to severe Alzheimer diseasealready receiving donepezil: a randomized controlled trial. 

6. Seltzer B. Cholinesterase inhibitors in the clinical management of Alzheimer'sdisease: importance of early and persistent treatment. 

7. Boustani M, Peterson B, Hanson L, Harris R, Lohr KN. Screening for dementia inprimary care: a summary of the evidence for the US Preventive Services TaskForce. 

8. Stern RG, Mohs RC, Davidson M, et al. A longitudinal study of Alzheimer'sdisease: measurement, rate, and predictors of cognitive deterioration. 

9. Crum RM, Anthony JC, Bassett SS, Folstein MF. Population-based norms for theMini-Mental State Examination by age and educational level. 

10. Buschke H, Kuslansky G, Katz M, et al. Screening for dementia with the memoryimpairment screen. 

11. Katzman R, Brown T, Fuld P, Peck A, Schechter R, Schimmel H. Validation of ashort Orientation-Memory-Concentration test of cognitive impairment. 

12. Alzheimer's and Your Loved One: Concerned a Loved One Has Alzheimer's? EisaiInc. Available at: http://aricept.com/your_loved_one/does_loved_one.aspx. AccessedNovember 8, 2006.

13. Drickamer MA, Lachs MS. Should patients with Alzheimer's disease be told theirdiagnosis? 

14. Jha A, Taber N, Orrell M. To tell or not to tell?comparison of older patients'reaction to their diagnosis of dementia and depression. 