Michael J. Koronkowski, Pharm.D.
Spring 1998
Michael J. Koronkowski, Pharm.D.
Spring 1998
Cardiovascular Diseases and the Geriatric Patient
Assigned Readings:
Suggested Readings:
Note: Preliminary drafts of the sixth report have been presented at National meetings with subsequent publication due out early 1998.
Learning Objectives:
I. Significance of Cardiovascular Disease
A. Mortality
1. Cardiovascular and cerebral vascular disease rank as the #1 and #3 causes of death in people ³ 65.
2. If cardiovascular (CV) disease was eliminated, people >65 would gain an estimated average of 16 years life expectancy. By comparison, the elimination of neoplasms would add 1.2 years to this populations life expectancy.
B. Risk Factors and Their Modification
1. According to the Framingham Study, persons ³ 70 without risk factors (normal BP, serum lipids, fasting blood sugar, nonsmoker, no left ventricular hypertrophy) for CV disease, only 10% will develop CV disease over the next 8 years; compared to 70-80% of persons in the poor risk group.
2. You are never too old to your reduce risks. Over the past 20 years, the reduction in atherosclerotic-related death has been as great in persons >85 as for middle age adults.
II. Physiologic Changes In The Cardiovascular System with Aging
A. Atrial Stiffness Pressure
1. Changes in the vascular media decrease elasticity
2. Aortic wall stiffening and thickening do to a reduction in the amount of elastic tissue and an increase in the amount of collagen.
3. A decrease in vascular distensibility leads to a increase arterial pulse pressure.
NET EFFECT: Increased aortic impedance to blood flow.
Is this increase in vascular stiffness a manifestation of aging or lifestyle? Studies in China looked at two populations with different dietary sodium intake: a high sodium diet in the Beijing population and a low sodium diet in the Guanzhou population. The Beijing population had significantly accelerate vascular stiffening and an increased arterial pressure.
In the U.S., a significant increase in systolic arterial pressure with age has been reported, however, there is wide scatter among individuals.
B. Cardiac Structure and Function
1. Progressive left ventricular hypertrophy - Heart mass increases on average of 1gm/year in men and 1.5gm/year for women between the ages of 30-90 years. Echocardiographic studies show an increase diastolic and systolic left ventricular wall thickness with age in men and women. The hypertrophy noted is moderate and a successful adaptation to the increased arterial pressure in order to maintain normal heart volume and pump function.
2. Decreased early diastolic compliance secondary to incomplete relaxation during early diastolic filling. Enhance filling later in diastole is an adaptive mechanism to maintain adequate filling volume. The net affect is that end-diastolic filling volume of the left ventricle is preserved.
3. Cardiac output (CO)
At rest, CO may decrease slightly or remain unchanged due the mechanisms described above. However, the heart's adaptive mechanism to exercise, postural or pressor stress in the older adult differs from younger individuals. Instead of maintaining CO by increasing heart rate in the face of a decreased stroke volume, the older adult has a greater reliance on the Frank- Starling mechanism, [i.e., an increased end-diastolic volume and lower maximum heart rate]
III. Presentation of Common Cardiac Illness in the Older Adult
A. Coronary Heart Disease
1. >50% of acute myocardial infarction are in persons >65 years of age and is commonly triggered by other medical problems such as infection, acute blood loss, hypotension or hypoglycemia. The presentation of an acute MI in this population is often atypical and frequently "silent" (without pain). Dyspnea, syncope, abdominal pain, congestive heart failure, acute changes in mental status may be the major presenting characteristics of a acute myocardial infarction.
2. Angina is less often activity-related and may increase in attack frequency during other acute illnesses such as infection.
3. Congestive heart failure (CHF) can present with coexisting conditions that tipped the patient into CHF. Infections are an excellent example, particularly pneumonia which can missed because of the CHF and visa versa - Diastolic dysfunction is overlooked in favor of the more common ventricular systolic dysfunction. Diastolic dysfunction should be ruled out in older patients without cardiac enlargement in the presence of a history of hypertension or hypertrophic cardiomyopathy.
IV. Hypertension (See assigned readings)
A. Definition by the National Heart, Lung and Blood Institute's Advisory Committee:
Isolated Systolic Hypertension (ISH) - SBP >140mmHg and DBP <90mmHg
Systolic-Diastolic Hypertension (SDH) - SBP >140-160mmHg and DBP >90mmHg
B. Prevalence of Hypertension in Persons >65
STUDY TYPE OF HTN RACE CUT-OFF VALUE (mmHg) #of READINGS PREVALENCE EST.%
HANES SDH W/B DBP>95 1 >40/>50 HDFP SDH W/B DBP>90 2 >11/>26 SHEP ISH W SBP>160 2 >10
1. Prevalence of both SDH and ISH have both been overestimated and over treated in the elderly.
a. Diagnosis is often made on too few blood pressure readings.
b. "White coat" isolated systolic hypertension has been reported to be as high as 42% in older patients. White coat hypertension refers to blood pressure readings in the physicians office or hospital that are greater than those taken in the patient's home due to anxiety.
c. Pseudohypertension - exact incidence is unknown, but thought to be uncommon or rare.
C. Risks of HTN
1. CHF, sudden death, MI, angina, stroke, and arterial aneurysms
D. Pathophysiology
1. Vascular systems - arteriosclerosis and decreased distensibility leading to increased peripheral vascular resistance.
2. Renin-angiotensin system has a minimal role
3. Cardiovascular hemodynamics
E. Treatment Considerations
1. Efficacy of treatment (See assigned readings)
2. Goal of treatment
a. Diastolic hypertension a DBP < 90 mmHg
b. Isolated systolic hypertension
* If SBP > 180 mmHg, reduce to < 160 mmHg initially
* If SBP 160 - 179 mmHg, a 20 mmHg decline
* Individuals whose SBP is 140 - 160 mmHg attempt lifestyle modifications
ß
The value of pharmacologic management for these individuals has not been established and the decision to initiate drug therapy should be individualized.
3. Treatment Strategies
a. Nonpharmacologic Measures
* sodium restriction * alcohol (less than 3 drinks/day) * weight loss * exercise (walk 30minutes/day)
b. Pharmacologic Measures
Remember to consider co-morbid disease states (CHF, angina arrhythmias), medications and cost!
Co-morbid Condition Preferred Antihypertensive Diabetes *insulin dependent thiazide diuretic, calcium channel blocker, ACE Inhibitor, hydralazine Diabetes *noninsulin dependent calcium channel blocker, ACE inhibitor, beta-blocker Ischemic heart disease calcium channel blocker, beta blocker, nitrates Post- Myocardial Infarction beta blockers, ACE inhibitors Heart Failure diuretics, ACE inhibitor, hydralazine, nitrates, peripheral alpha blockers Bradyarrhyhtmias diuretic, calcium channel blocker {dihydroperidine}, hydralazine, peripheral alpha blockers Tachyarryhytmias calcium channel blockers, beta blockers Orthostasis beta blocker, ACE inhibitor, calcium channel blocker COPD/Asthma diuretic, calcium channel blocker Chronic renal disease diuretic {loop}, calcium channel blocker, ACE inhibitor Peripheral vascular disease calcium channel blocker, diuretic, ACE inhibitor Gout/Hyperuricemia calcium channel blocker, ACE inhibitor Sexual Dysfunction ACE inhibitor, calcium channel blocker Depressed /Impaired cognitive fx. diuretic, calcium channel blocker, ACE inhibitor
V. Antihypertensives by Class and Individual Agents
Diuretics - inexpensive, well tolerated
(1) Hydrochlorothiazide (HCTZ) or other thiazides
Dose: initial 12.5 mg qam, 20% will respond to this dose, double the dose in 2 to 4 weeks if necessary. As the dose is increased so does the risk for electrolyte abnormalities.
Maximum dose 50mg qam (rarely needed)
Positives:
* the decrease in calcium excretion may benefit those at risk for osteoporosis
* A reduction in morbidity and mortality from isolated systolic hypertension has been demonstrated
* because of the renal changes associated with aging, hypokalemia often does not occur.
* cost
Diuretic Negatives:
* may aggravate urinary incontinence, particularly fast acting loop diuretics.
* increased risk for hypovolemia and hypomagnesemia
Calcium channel blockers
These agents undergo extensive first pass metabolism. Their clearance and elimination half-lives have been shown to be decreased and increased, respectively, in the elderly. As result their antihypertensive effects may be prolonged. In addition, their effects on blood pressure are increased in the elderly.
Positives as a class:
* probably as effective as diuretics without their metabolic effects
* do not affect lipid profile
* useful in man co-morbid disease states
Negatives as a class:
* effect on morbidity and mortality in ISH are unknown
* constipation
* avoid the use of diltiazem and verapamil in conjunction with other agents that negatively affect the AV conduction system, (i.e., beta blockers, digoxin).
* cost+++
(1) Diltiazem
Dose: initial 30mg bid or tid immediate release, increase gradually (60-90 mg/day every 7-14 days); convert to SR or CD product when stable. Maximum dose 360-480 mg/d.
[effects on the AV node may limit its use]
(2) Verapamil
Dose: initial 40mg bid or tid immediate release, increase gradually (80-120 mg/day every 7-14 days); convert to SR product when appropriate. Maximum dose 480 mg/day
* negative effects on heart rate and contractility
(3) Nifedipine
Dose: initial 10mg tid, increase gradually (30 mg/day ever 7-14 days); switch to XL product when appropriate
* orthostatic hypotension, primarily with the immediate release product
* peripheral edema may limit use
* nocturia can be a problem
* reflex tachycardia is uncommon
* cognitive impairment has been reported
(4) Isradipine Dose: 2.5 - 10 mg/day
(5) Amlodipine Dose: 2.5 - 10 mg/day
(6) Felodipine Dose: 5.0 - 20 mg/day
Angiotensin Converting Enzyme (ACE) Inhibitors
Despite an age associated decline in the renin~aldosterone system, these are effective in the elderly. Chronic angiotensin II blockade in the kidney results in increased sodium and water excretion, thus decreasing blood pressure. Hence, maximal effect on BP may take weeks.
Positives:
* little impact on quality of life
* do not affect lipid profile
* useful in many co-morbid disease states
Negatives:
* limited role as monotherapy since only » 15% respond
* hyperkalemia and renal azotemia particularly in volume depleted (diuretics) patients or those also taking a nonsteroidal antiinflammatory agents.
* cough
(1) Captopril
Dose: initial 12.5 mg bid-tid, increase by 25-37.5 mg/day after 7-14 days; maximum dose 150 mg/day.
(2) Enalapril
Dose: initial 2.5 mg/day as a single dose, increase by 2.5-5 mg/day, after 7-14 days; maximum 40 mg/day in two divided doses. Do not use in patients with hepatic dysfunction or decompensated CHF.
(3) Benazepril Average Daily Dose: 10-40 mg qd Max. 40mg
(4) Fosinopril Average Daily Dose: 10-40 mg qd Max. 80mg
(5) Lisinopril Average Daily Dose: 10 mg qd Max. 40mg
(6) Quinapril Average Daily Dose: 5-80 mg qd Max. 80mg
(7) Ramipril Average Daily Dose: 1.25-20 mg qd Max. 20mg
Angiotensin II Inhibitors
(1) losarten Average Daily Dose: 25-100 mg qd Max. 100mg
Note: may be dosed twice daily if trough blood pressure control is lost, no dose adjustment is needed for the elderly, combination product with hydrochlorthiazide is available
Beta-blockers
Due to the age associated decrease in the number receptors and response by beta-adrenergic autonomic nervous system, beta-adrenergic blockade may result in less hemodynamic response than seen in younger adults. Studies indicate that despite a decreased sensitivity to the chronotropic effects of beta blockade with age, there appears to be an increased myocardial sensitivity to the negative inotropic effect during stress, (i.e., exercise). Controlled trials have shown the overall response rate for propranolol to be only 20% to 50% in elderly hypertensives. Therefore, all beta-adrenergic blocking agents may result in a decreased reponse as compared to younger adults.
First pass metabolism has been found to be reduced in the elderly. Consequently, the systemic bioavailabilty of acebutolol, metoprolol, propranolol, and timolol may be increased by as much as two-fold. As a result, serum and tissue concentrations may be higher and beta-1 selectivity for acebutolol and metoprolol may be compromised. Therefore, lower maintenance doses may be needed. For the same reasons, doses for acebutolol, atenolol, cartelol, and nadolol need to be adjusted for reduced renal function.
Positives:
* protection against initial infarction and reinfarction
* useful in many co-morbid disease states
* little orthostasis
Negatives:
* negative inotropic and chronotropic effects can decrease cardiac output and exercise capacity and increase fatigue
* drug-induced depression and cognitive impairment
(1) Acebutolol
Dose: Usual 400-800 mg/day 2 divided doses; Max 1200 mg/day
ClCr 25-49 ml/min - decrease by 50%
ClCr <25 ml/min - decrease by 75%
(2) Atenolol
Dose: Initial 25 mg/day as single dose; usual 50-100mg/day
ClCr 15-35 ml/min - 50 mg/day maximum
ClCr<15 ml/min - 50 mg qod
(3) Metoprolol
Dose: Initial 25 mg/day as a single daily dose; usual 25-300 in 1-2 doses
(4) Propranolol
Dose: Initial 20-40 mg bid, increase every 3-7 days;
dose <320mg/day in 2-3 doses or qd with SR formulation
(5) Betaxolol Average Daily Dose: 5-40 mg qd Max. 40mg
(6) Bisoprolol Average Daily Dose: 5-20 mg qd Max. 20mg
(7) Carteolol Average Daily Dose: 2.5-10 mg qd Max. 10mg
(8) Nadolol Average Daily Dose: 20-40 mg qd Max. 240mg
(9) Pindolol Average Daily Dose: 10-60 mg qd Max. 60mg
(10) Timolol Average Daily Dose: 10-20 mg bid Max. 80mg
Hydralazine
Dose: 10 to 25 mg bid-tid; maximum 150-200 mg/day
* reflex tachycardia often not a problem without prior beta blockade
* may have role as a second-line agent when combined with a diuretic
CNS Sympathomimetics
Limited role due to their unfavorable CNS adverse effects profile (sedation, depression), bradycardia, and other agents are available for the treatment of co-morbid conditions simultaneously.
(1) Reserpine: 0.05-0.lmg qd
Positives:
* very inexpensive
* better tolerated by the elderly than methyldopa
* depression, weight gain, and sedation are uncommon in the low doses currently used today
Negatives:
* contraindicated in persons with a history of depression, dementia, peptic ulcer disease
* not effective as a first line agent, use with a diuretic
(2) Methyldopa:
Initial 125-250 mg at bedtime, increase by 125-250 mg/day every 3-4 weeks (certainly not faster than every week). Keep a single bedtime dose until 500-750 mg, afterwards 2-3 divided doses.
(3) Clonidine:
Initial 0.05-0.1 mg at bedtime, increase by 0.05-0.1 mg/day every 3-4 weeks (certainly not faster than every week). Keep as single bedtime dose until 0.5-0.6 mg, afterwards 2-3 divided doses.
*** Compliance is essential for all of the CNS antihypertensive agents (all carry potential for withdrawal)
caution patients regarding abrupt discontinuation and missing doses.
REFERENCES AND READINGS
Mr. A.M. is a 72 yo WM who has no history of any medical problems. He recently participated in a hypertension screening program where his blood pressure was 180/86. He was told to see his physician for follow-up. During the last 6 weeks he has been seen 3 times and his blood pressures have been 184/88, 168/84, an 170/84, respectively. All other vital signs have been within normal limits. He is 5’9" and weighs 210 lbs.
Questions - Based upon the definitions of the National Heart, Blood and Lung Institute, What type of hypertension does Mr. A..M. have?
Questions - Based upon the findings of the SHEP trial what are your goals in terms of blood pressure lowering?
Question - How would you begin to manage Mr. A M’s hypertension? If drug therapy was required, what would you choose and why?
Mrs. EG is an 85 BF whose past medical history is significant for essential hypertension x 30 years, adult onset diabetes mellitus x 20 years, CHF x 5 years, and osteoarthritis x 15 years. Her current medications include the following:
- Furosemide 40mg bid
- Ibuprofen 600mg tid
- Digoxin 0.25mg qam
- Aspirin 325mg qam
- KCL 20mEq qam
- Glyburide l0mg bid
- Milk of Magnesia 30ml bid prn constipation
On this clinic visit her blood pressure is 145/100 mmHg (similar to the two previous visits), pulse 70 and regular, Labs: BUN 11 mg/dl, SCr 1.1 mg/dl, Na 140 mEq/L, K 4.4 mEq/L, Cl mEq/L 101, CO2 24 mEq/L, and fasting glucose 120 mg/dl. Her physical exam is essentially normal: no JVD, rales, trace of edema. She denies any dizziness or weakness or falls. Her physician adds Verapamil 80mg q8 hours to further lower her blood pressure and tells her to return in 1 month.
Two weeks later Mrs. EG comes into clinic with the assistance of her daughter and granddaughter. She gives a history of progressive dyspnea even at rest, a new 2 pillow orthopnea, swelling in her feet, ankles and lower legs, being less ambulatory, feeling tired, has little appetite and at times nauseous. She states that she has been compliant with her medications, except that she did not take her digoxin the morning and that her daughter even given her an extra furosemide for a couple of mornings. On physical exam her BP is 128/88, pulse 60, bilateral rales are heard, and she has 2+ pitting edema to the knees and one plus to the thighs. Labs are as follows: BUN 40, SCr 1.4, Na 138, K 3.9, Cl 99, CO2 30 mEq/L, a random glucose of 334 mg/dl, and a digoxin level 2.3 ng/ml. Her chest X-ray revealed bilateral pleural effusions and cardiomegaly. Her EKG shows a second degree AV block.
CASE #2 Questions
Questions - Based upon the above, what do you think has caused the exacerbation of Mrs EG’s CHF? What evidence supports your conclusion? Could it have been avoided? How?
Questions - Discuss the advantages, disadvantages and risks of the alternative antihypertensive agents listed below in reference to Mrs. EG’s case
Hydralazine
Angiotensin-converting enzyme inhibitor
Nifedipine
Questions - On top of her CHF, what possible iatrogenic illness could Mrs. EG be experiencing?
KEY TO CASE #1
Mr. A.M.'s mean blood pressure for the last 3 clinic visits is 174/85.3 mmHg, therefore he has isolated systolic hypertension.
According to the SHEP study the goal to lower Mr. A.M.’s systolic blood pressure at least 20 mmHg or £ 154mmHg without minimizing organ perfusion..
Mr. A.M. has isolated systolic hypertension and he is overweight, therefore initial treatment should be aimed at weight loss. A diet and moderate aerobic exercise should be prescribed. If these interventions prove ineffective or the patient can not comply with them, then pharmacologic treatment should be prescribed. A low dose of a thiazide diuretic would be indicated, such as 12.5mg of hydrochlorothiazide every morning. Diuretics are proven to be effective in lowering peripheral vascular resistance and systolic blood pressure. They are also inexpensive, can be taken once a day and have proven long term benefit. A calcium channel blocker such as nifedipine 30mg XL every morning is an alternative. Calcium channel blockers can be taken once or twice daily depending on the product, lower systolic blood pressure, an are less likely to cause electrolyte abnormalities. Their cost limits their use.
KEY TO CASE #2
The addition of verapamil to lower her blood pressure pressure probably put Mrs. EG in congestive heart failure. The mechanism is most likely the negative inotropic and chronotropic effects of verapamil. Her EKG shows a 2nd degree AV block from verapamil and digoxin and her pulse is 60, compared to 70 prior to verapamil. Yes, this could have been prevented by choosing an alternative drug would both lower her blood pressure and be good for her CHF.
Hydralazine - Advantages include: effectively lowers diastolic blood pressure (DBP) > systolic blood pressure (SBP), decreases afterload > preload, less likely to see reflex tachycardia in an older patient. Disadvantages include: postural changes in blood pressure.
ACE Inhibitor - Advantages include: effective blood pressure lowering when combined with a diuretic, decreased afterload, proven efficacy in heart failure Disadvantages in this patient include: concurrent use with a potassium supplement and nonsteroidal-antiinflammatory agent (ibuprofen) which may lead to hyperkalemia and renal toxicity.
Nifedipine - Advantages include: effectively lowers blood pressure as well as afterload, once daily dosing, and no effect on the AV node. Disadvantages include: may cause peripheral edema which may be confused with worsening CHF and postural hypotension.
Digitalis intoxication secondary to the addition of verapamil and or CHF with decreased digoxin clearance.
 Previous |
 Next |
 Syllabus |
| The College of Pharmacy | UICPHARM@uic.edu | |
| The University of Illinois at Chicago | Last modified: Jan 6, 1998 | |