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Medical Complications of Aging With HIV
Aging affects us all -- something that was unfortunately not true for most of the HIV-positive population until recently. But thanks to the wonders of modern science, many HIV-positive Americans are joining the march to older age together with millions of their fellow citizens. In the year 2000, 34 million people in the United States were older than 65 years; by 2025, this number will almost double. And, given effective antiretroviral therapy, HIV-positive people will face the same burdens of diseases of aging as everyone else, with the added problems of HIV/AIDS and the complications of drug-drug interactions -- the effects of antiretroviral drugs on drugs used to treat diseases that affect the elderly and vice versa.
In the following paragraphs, a few ailments common in older people will be discussed. They include high blood pressure (hypertension), heart disease, high cholesterol and triglycerides (hyperlipidemia), colorectal cancer, prostate cancer, and osteoporosis (reduction in bone mass). A bit about each condition and how being HIV-positive affects its treatment will be presented. Of particular concern are the interactions between the drugs used to treat these ailments and the antiretrovirals used to treat HIV.
Hypertension (High Blood Pressure)
Hypertension affects over 60% of people aged sixty or above. It is the most common reason people visit internists and a major risk factor for heart disease -- people with high blood pressure are more likely to have heart disease than people with normal blood pressure. Hypertension increases the risk of heart attacks, strokes, heart failure, and early death. When people are successful in lowering their blood pressure to normal, the risk of developing any of these complications is also lowered.
Blood pressure can be lowered in two ways -- by living a more healthy life and with drugs. By a healthier life, I mean by losing weight if one is overweight, stopping smoking if one smokes, reducing one's alcohol consumption if one drinks, and moderate exercise. These changes are often enough to treat mild hypertension.
There are a large number of antihypertensive drug options for patients whose blood pressure does not respond to these interventions. Frequently, both a healthier way of life and antihypertensive drugs are needed.
Definitions of hypertension continue to change. For me, a person needs to be treated if their blood pressure is above 135/85 mm mercury. The first number is known as the systolic reading. It is the pressure measured in the arteries when the heart is contracting. The diastolic reading, or second number, is the pressure measured in the arteries when the heart is no longer in contraction. The contracting state is called systole and the relaxed state is called diastole. Thus, a blood pressure of 135/85 means that the systolic blood pressure is 135 and the diastolic is 85.
People with high blood pressure usually remain symptom free for years before they develop the complications of stroke, heart attack, heart failure and renal failure. The time course for developing these complications is sped up by abnormal levels of lipids, or fats, in the blood (dyslipidemia), cigarette smoking, diabetes mellitus, obesity, lack of exercise, high salt diet, and situational stress.
Clinical trials have shown that the more weight one loses, the greater the fall in blood pressure. Even a weight loss of several pounds may be enough to enable one to do without drugs or to reduce the amount of drugs needed to control blood pressure. If weight gain recurs, hypertension may return.
Exercise also helps reduce high blood pressure. After exercise, blood pressure may fall as much as 6 to 7 mm Hg, independent of any weight changes. It has been shown that moderate-intensity exercise is as effective as higher-intensity exercise. A 20 to 30 minute daily walk may be just as effective at lowering one's blood pressure as an intensive workout.
A recently published clinical trial done in people with mild hypertension showed that increasing fruits and vegetables in one's diet resulted in a moderate reduction of blood pressure. The reduction in blood pressure was almost doubled if one also reduced their dietary fat intake. Some patients who were on a high fruit and vegetable and low fat diet had normal blood pressure after only eight weeks.
Salt restriction has been shown to reduce the need for drug therapy in hypertension. This seems to occur with or without weight reduction. The problem most patients have is maintaining a low salt diet over time. I usually tell my patients to do the best they can but not get crazy over it.
Alcohol Restriction and Smoking Cessation
Reducing alcohol intake to less than two shots of liquor or 8 ounces of wine a day is effective in reducing blood pressure and may even help prevent the disease. And, while stopping smoking may not affect blood pressure levels, it does eliminate an additional risk factor for cardiovascular disease.
Stress Reduction/Relaxation Training
Stress reduction has not been shown conclusively to be effective in reducing blood pressure when used as the main treatment. Also, it has not been proven that a high-stress job by itself is enough to produce high blood pressure. Current thinking is that it is how one copes with stress that may cause hypertension rather than the stress itself.
Different physicians use different drugs, usually choosing the one that best suits the particular patient and with which the prescribing physician is most familiar. In general, most physicians start with a diuretic, then add either a beta blocker, ace inhibitor, or calcium channel blocker. Further changes depend on the patient's response.
High Cholesterol and Triglycerides (Hyperlipidemia)
Based on years of clinical trials and experience, it is becoming clearer and clearer that a large number patients who are at risk for heart disease because of high cholesterol levels in their blood will benefit from having their cholesterol lowered. Of course, this is in addition to losing weight, reducing dietary fat intake, exercising, controlling blood pressure, and stopping smoking. Since most HIV-positive patients over 50 have one or more risk factors for cardiovascular disease, they are prime candidates for changing their habits and lowering their cholesterol.
Lipids are fatty substances in the blood. The one most everyone knows is cholesterol. There is the good cholesterol, called HDL (high density lipoprotein), and the bad cholesterol, called LDL (low density lipoprotein). Total cholesterol is the sum of these two components plus a few others that are present in much smaller amounts. HDL helps remove cholesterol from the body, while LDL helps deposit it in the walls of blood vessels where it can cause heart disease and strokes. A study published in the April 8, 2004 issue of The New England Journal of Medicine showed that the lower one's LDL, the lower the risk of further heart disease in people who already have heart disease. Up until this study, health guidelines called for lowering LDL in the blood to 100 mg/dL in people with risk factors for heart disease. Now, most physicians are trying to get their patients to go even lower. One result is that more people will need to be placed on statin drug therapy, which, together with a low fat diet, is the most effective way today to reduce LDL levels (see chart below for cholesterol ranges).
Statins are very effective and powerful cholesterol-lowering drugs, which reduce the formation in the body of cholesterol, among other things. These are generally well tolerated. Usually a single dose, taken at bedtime, is enough to lower one's LDL significantly. The most common side effects are mild gastrointestinal complaints and headaches. Liver enzyme elevations occur in 1% to 2% of users and resolve when the drug is stopped. Sore or weak muscles with elevated blood muscle enzymes occur in less than 0.5% of users. It is estimated that currently only a third of the 40 million or so people who need to be on statins in this country are actually receiving them. Lipitor (atorvastatin), the drug used in the study mentioned above, costs around $1,400 annually for the 80 mg a day dose used in the study.
A variety of statins is currently available. Lipitor (atorvastatin) is probably the most effective LDL cholesterol-lowering statin, achieving reductions of LDL in the blood of up to 55%. Pravachol (pravastatin) and Lescol (fluvastatin) achieve reductions of about 34% at their highest doses, while Mevacor (lovastatin) and Zocor (simvastatin), at their highest doses, produce a further 6% and 12% decrease, respectively. These reductions are much greater than those achieved by a low fat diet alone, which usually produces a reduction ranging from 5-15%.
Patients With HIV
Lipid abnormalities are common in HIV-positive patients, especially in those on protease inhibitors and some other antiretrovirals. The risk of having high cholesterol increases with the length of time on medications. Most commonly, we see an increase in LDL cholesterol and triglycerides (another lipid found in the blood). Only a few controlled studies have been done looking at the relationship of heart disease to high cholesterol in HIV-positive patients. These studies suggest a correlation of having heart disease and increased cholesterol levels. However, there is no evidence to suggest that the strong correlation of increased cholesterol and heart disease in the HIV-negative population is any different in the HIV-positive population. Certainly, all patients with cardiac risk factors such as smoking, hypertension, a family history of heart disease, age, and a sedentary life style need to reduce their cholesterol levels.
Along with antiretroviral agents and statins, HIV-positive patients may be taking a range of drugs to treat or prevent opportunistic infections and conditions associated with HIV and AIDS. Many of these drugs are broken down by the body in ways affected by statins and vice versa. This means that some drugs may increase statins to toxic levels, resulting in increased adverse effects from the statins, particularly the breakdown of muscle tissue. These effects vary by drug, so the choice must be individualized according to what other drugs the patient is taking (See table below). Grapefruit juice can also increase the levels of some statins, so it's probably best to talk to your healthcare provider about this possible interaction if you're taking a statin.
Probably the statin with the fewest interactions with antiretrovirals is Pravachol as it is broken down in the body by a mechanism not affected by protease inhibitors. Given that the strongest statin is Lipitor, many HIV-positive patients will probably prefer using this statin. Therapeutic drug monitoring (checking blood levels of drugs being taken to try to avoid high levels that could be toxic or low levels that might not work) may be useful until the necessary drug interaction studies are done.
Cancer of the colon and rectum rises in prevalence in people over 50, from a rate of 15 cases per 100,000 people who are between 40 and 50 years of age to 400 cases per 100,000 people who are over 80. These rates can be greatly reduced by screening. There is no evidence that the rate of this cancer is higher in HIV-positive patients than in the HIV-negative population, but as the HIV-positive population ages, this may change. I routinely suggest to all of my patients who are over 50 that they have a colonoscopy -- a test done under sedation, usually as an outpatient in the hospital. In this test, a flexible tube (colonoscope) with a light at the end is passed under direct vision through the anus and rectum into the colon and the entire length of the colon is visualized. Preparation for this test involves cleaning out one's colon the night before the test by drinking large amounts of a liquid preparation that causes a lot of diarrhea.
In this procedure, the doctor is looking for polyps (small benign growths that have the potential to turn cancerous), which can be removed through the colonoscope with special instruments. Since cancers of the colon can come from these polyps, removing them before this happens prevents the disease. The rate of major complications from this procedure, such as bleeding or perforating the colon, is less than 1%, and fewer than one out of a thousand people who have a colonoscopy die from complications.
The most common cancer occurring in men is prostate cancer. Indeed, over 80% of men who died for reasons other than prostate cancer and then had autopsies were found to have cancer in their prostate glands that had not spread. This means that most men who have localized prostate cancer will not die of it but with it. The problem for physicians and patients is identifying which patients will have the aggressive, life threatening cancers that spread out of the prostate. Prostate cancer is more common in older men, with over 80% of the disease being diagnosed in men over 65. Men with a history of prostate cancer in their families and African-American men are at higher risk. Again, whether or not HIV-positive men have a higher rate of this disease will only become apparent as the over 50 HIV-positive population grows.
The most common test for screening for prostate cancer is the rectal exam. Although it is an inexpensive test, it is not all that sensitive. This test picks up only about two thirds of cancers in men who don't have any symptoms.
The PSA (prostate-specific antigen) test is a blood test that was first used to monitor the spread of prostate cancer and is now being used as a screening test. PSA is a protein made by the prostate and is found normally in the blood. The amount of this protein in the blood increases in men who have prostate cancer. The PSA test is more sensitive than the rectal exam but often detects cancers that will not spread. Recent reports show that some men have cancer with low levels of PSA in their blood and other men with high levels do not have cancer. Illnesses such as prostatic inflammation or enlargement can cause elevated levels. Once someone is found to have an elevated PSA level, a needle biopsy of the prostate gland is usually done and, if cancer is found, an operation may be suggested. Whether or not surgery is recommended depends on many factors including the patient's age and the appearance of the cancer cells under the microscope.
Patients should not undergo PSA testing lightly. Because a high PSA level often leads to biopsies and surgery which may not always be necessary and can cause serious complications, it is important that all of this be explained to the patient before they have the test, in fuller detail than space allows here. Sort of like the informed consent one gets before having an HIV test. The complications of surgery include impotence and urinary incontinence -- and, although not everyone gets these complications, not everyone with prostate cancer needs surgery. The subject is a complicated one, much more knowledge needs to be gathered, and patients should be well informed before they embark on screening tests for prostate cancer. Some physicians recommend that only high-risk patients undergo such screening.
Osteoporosis (Reduction in Bone Mass)
The most common bone disease is osteoporosis. In this disease, the structural integrity of the bone is affected, the density of bone is lower, and bones become more fragile -- they break more easily. This disease results in over 1.3 million bone fractures a year in the United States; about half are vertebral fractures, 25% occur in the hips and 25% in the wrists. Women over 50 are three times as likely as men to have vertebral or hip fractures and six times as likely to have wrist fractures.
Bone density has been reported to be lower in both HIV-positive men and women when compared to the HIV-negative population. However, the differences shown have not been significant and may not be related to age. It has been shown to occur regardless of whether or not patients are on antiretroviral therapy. A recent study from Spain suggests that the longer one is HIV-positive, the greater the loss of bone density. The significance and validity of this study will become apparent as the HIV population over 50 increases and more studies are done.
This article is not meant to be and is by no means exhaustive in its discussion of diseases and conditions that affect the HIV-positive population over 50. What should be clear, however, is that the diseases of aging will become more prevalent in the HIV-positive population as it itself ages. It does not seem that being HIV-positive protects anyone from these illnesses. Whether these diseases will be less or more prevalent and how, if at all, their characteristics will differ from their manifestations in the HIV-negative population remains to be seen. The interactions between drugs used by someone with HIV and those used to treat the diseases of aging need further exploring. And, of course, the added costs of these medications will continue to be a problem for most Americans.
Jerome Ernst, M.D. is ACRIA's Medical Director and sees both HIV-positive and negative patients in his medical practice.
This article was provided by AIDS Community Research Initiative of America. It is a part of the publication ACRIA Update. Visit ACRIA's website to find out more about their activities, publications and services.