Should you be on cholesterol medication? How the new guidelines are different

Cardiovascular disease—including coronary atherosclerosis and cerebrovascular disease, remains the number one cause of mortality in the United States. One out of three people in this country will die of cardiovascular causes.  Although I can’t say that the other top causes of mortality are particularly attractive--cancer, chronic lung disease, accidents and dementia—premature cardiovascular death can certainly be very devastating and it makes sense to do our best to prevent it.

In November 2013 updated guidelines for the treatment of high cholesterol were released by the American College of Cardiology-American Heart Association.  These guidelines were the subject of significant controversy. In contrast to the previous guidelines from 2002, the current guidelines do not suggest treatment based primarily on numerical cholesterol targets. Rather, the guidelines stratify people according to determined cardiovascular risk and recommend either high intensity statin treatment, moderate intensity statin treatment, or no statin treatment. The guidelines do not support using other types of cholesterol-lowering drugs because at this point there is not good data to suggest that using other types of treatments is beneficial in terms of preventing actual cardiovascular outcomes (heart attack, stroke or cardiovascular death). This is despite the fact that there are treatments out there that do lower one’s cholesterol numbers.

How is cardiovascular risk determined? With the new guidelines, a new risk calculator was proposed. In my clinical practice in the past I’ve used the Framingham Risk Calculator and the Reynolds Risk Calculator . The new risk calculator released with the 2013 guidelines is a bit different. Some experts have suggested that it overestimates risk. With the new risk calculator, if one’s ten year risk of a cardiovascular event exceeds 7.5% then treatment with a statin is recommended.

The new guidelines divide people into the following groups of patients between ages 40 and 75 years who are in need of treatment with statins, or so called “statin benefit groups.”

·         Those with LDL over 190mg/dL (high intensity statin treatment is recommended)

·         Those with a ten year risk of >7.5% (moderate intensity statin treatment is recommended)

·         Those with established cardiovascular disease (high intensity statin treatment is recommended)

·         Those with diabetes, in which 10 year risk is >7.5% (high intensity statin treatment is recommended)

·         Those with diabetes, in which 10 year risk is <7 .5="" font="" intensity="" moderate="" statin="">treatment is recommended)

Click here to calculate your risk. What qualifies as high intensity statin treatment? LDL lowering of 50% or greater. What is moderate intensity statin treatment? LDL lowering of 30-50%.

The guidelines suggest that particular statins may be better than others at achieving these goals and good outcomes: atorvastatin, simvastatin, and rosuvastatin.  Other statins are typically used when patients experience unwanted side effects, like muscle pain.

How are things different with the new guidelines?

Let’s take an example.    A 71 year old white female, non-smoker, non-diabetic, with a history of hypertension, asked me whether or not she should be treated for high cholesterol.  She is concerned about her risk of heart disease, as her mother had a stroke in her 60s and then sudden death, presumed cardiovascular, at age 83. My patient’s most recent total cholesterol level was 204 mg/dL with an LDL level of 121 mg/dL and an HDL level of 64 mg/dL.  A couple of years ago I calculated her Framingham Risk score, which is 6% with these risk factors. This represents low to intermediate risk. To get further information I also ordered a coronary calcium score, which was found to be zero.  Last year, based on these numbers and the older guidelines, I recommended against treatment with a statin.  However, now, based on the new risk assessment tool, the same patient has a ten year risk of 16%.  With the new guidelines she would unequivocally qualify for moderate dose statin.   At this point, I am not exactly sure what to do with the coronary calcium score, which probably projects that her risk is lower than the 16% that the new equation came up with.  Nonetheless, I am not sure that coronary calcium scoring entirely predicts all cardiovascular risk—for example risk related to small vessel disease and stroke, so perhaps she should receive treatment.  Low dose, statin treatment might be a good compromise here.

Interestingly, based on this new risk calculator virtually every 71 year old, even with optimal risk factors, would qualify for treatment with a statin.  Herein lies the controversy with this tool.

Nonetheless, my own view of the new guidelines is mostly favorable. To me it simplifies things based on what we know from numerous well designed studies. Treatment, with an emphasis on statins, is based on risk projection and less attention is paid to absolute numbers.  I hope that the next decade will continue to bring more a nuanced understanding of risk.

 

 

 

 

 

Preventing Shingles

Shingles is a common disorder.  It’s caused by the reactivation of the chicken pox virus, varicella zoster virus, which remains dormant in one’s nerves after infection with chicken pox. Anyone who has had chicken pox is at risk.  Shingles is an unpleasant illness.  It causes prodromal nerve irritation, followed by the appearance of a blistering rash that follows the distribution of a nerve root. The rash can be painful and itchy, and can be the source of subsequent bacterial infection.  In some cases, cranial nerves, including nerves that supply the eye and ear, may be affected and this may lead to loss of vision or hearing.

The most unpleasant complication of shingles is the occurrence of “post-herpetic neuralgia,” defined as pain in the distribution of the shingles rash (or affected nerve root), which persists for more than three months after the shingles goes away--this may occur in 10 to 20% of cases.  Early treatment with antiviral therapy may reduce the risk of post-herpetic neuralgia.

One’s risk of developing shingles, and post-herpetic neuralgia as a complication, increases with age.  Immune deficiency, such as infection with HIV/AIDS or treatment with cancer chemotherapeutic drugs, also increases one’s susceptibility to shingles.  It is uncertain how the use of the chicken pox vaccine, now standard in children, will affect their adult risk of shingles compared with those who are unvaccinated.

A vaccine for shingles, Zostavax®, was FDA approved in 2006. In 2008 the CDC recommended that persons over the age of 60 receive the vaccine.  This recommendation is based on the relatively higher prevalence of shingles and its related complication in this age bracket. However, the shingles vaccine is also effective in healthy adults ages 50-59.  At this time the CDC has not recommended routine vaccination of this age group, which is likely related to lower disease incidence (about 4.6% annually in 50 year olds, compared with 7% annually in 60 years olds ,and 9 to 11% in 70 and 80 year olds).

Here are some common questions that patients ask me about the shingles vaccine:

1.       If I have already had shingles should I get a vaccine?

The shingles vaccine has not been tested in those who have already had shingles once. It is speculated that having the condition increases one’s immunity and helps prevent future recurrences. However, there is some research  indicating that those who have already been afflicted may continue to be at significant risk for recurrence. Therefore, it may be reasonable for this population to be vaccinated.

2.       What are the most common side effects related to the shingles vaccine?

According to the CDC, redness, pain, itching, and swelling at the site of the vaccine may occur in 1 out of 3 who receives the vaccine. Headache may occur in 1 out of 70.  More serious allergic reactions to the vaccine components including fever, difficulty breathing and throat swelling, are infrequent.

3.       Will it be safe for me to be around babies, pregnant women, and those with immune compromise after I have had the shingles vaccine? 

Yes, although it is a live attenuated virus vaccine, there have been no described cases of the chicken pox virus being transmitted in this manner from a person inoculated with Zostavax ®to a person who is not immune.

4.       In what population is the shingles vaccine contraindicated?

Although shingles is more common in those with immune compromise, the shingles vaccine is contraindicated in this population, which includes patients with HIV/AIDS, patients on cancer chemotherapy, patients on drugs that affect their immune system (such as oral steroids), and pregnant women. There are case reports describing disseminated shingles resulting from the vaccine in patients with established immune deficiency.

5.       I’m not sure if I had chicken pox, Should I have a shingles vaccine?

Persons who are unsure of whether or not they have had chicken pox should have blood work done to determine their immunity. If there is no evidence of previous exposure then a chicken pox vaccine (Varicella) should be administered in those who are eligible, not a Zostavax®.

6.       After 60, how often does one need a shingles vaccine?

Currently a single vaccine at or after age 60 is recommended.  The shingles vaccine is also FDA approved for patients ages 50-59 years.  However, given the lower disease prevalence and risk in this population the cost and health-benefit is not as well established and at this time the CDC does not specifically recommend it.  It remains uncertain how long the immunity conferred by a single shingles vaccine will last.

7.       What is the cost of a shingles vaccine?

A shingles vaccine costs approximately $200. Many health insurance plans, including Medicare Part D and private insurers, cover the immunization after (but not before) age 60.

For more information visit http://www.cdc.gov/shingles/index.html or http://nihseniorhealth.gov/shingles/aboutshingles/01.html .

 

 

 

Andropause?

Everyone has heard of menopause, but is there a male equivalent? Two weeks ago at Personalized Primary Care Atlanta we discussed treatment of testosterone deficiency, or so called "andropause," in an evening health talk. PPC was happy to host Dr. Wayland Hsiao, Assistant Professor of Urology from Emory University as our discussant. Dr. Hsiao pointed out that declining testosterone levels are normal as men age and that while some men may be asymptomatic, others may suffer with symptoms that may negatively impact quality of life.

What are the symptoms of testosterone deficiency?  Loss of energy, decreased strength, reduced exercise capacity and erectile dysfunction are some. Testosterone deficiency may also contribute to metabolic syndrome, loss of lean muscle mass, and osteoporosis.  The ADAM questionnaire is a validated tool that can help identify symptomatic men.  Morley et al. Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism. 2000;49(9):1239-1242.

Testosterone deficiency may be diagnosed on the basis of blood tests. Dr. Hsaio pointed out that saliva tests are not accurate.  Typically total testosterone and free testosterone levels are measured.  Free testosterone is the active version of the hormone.  If levels are low and men are deemed symptomatic treatment involves supplementation with testosterone, which is available in various delivery systems including transdermal gels, patches and pellets (implanted beneath the skin of the buttocks). Dr. Hsiao is of the opinion that injections of testosterone are not as well tolerated as the other delivery methods as they produce hormonal peaks and troughs that are associated with more adverse effects including flushes. 

Given the common nature of some of the described symptoms of testosterone deficiency it is not always clear who should be treated. One approach, for symptomatic men who have low or borderline testosterone levels, is a three month trial of treatment to see if symptoms improve.

What is the downside of testosterone replacement? One large clinical trial reported in the New England Journal of Medicine in 2010 demonstrated increased cardiovascular events in men who were randomized to treatment, and the trial was terminated early because of these adverse outcomes. However, Dr. Hsiao is skeptical that these risks translate to all men, and he noted that the population studied was primarily elderly, frail, and immobile.

Another concern with testosterone therapy is whether it has potential to promote prostate cancer growth in a man who may have subclinical prostate cancer or prostate cancer that has not yet been detected, and also whether it can cause enlargement of benign prostate tissue and contribute to worsening of urinary symptoms in men. Benign prostatic hypertrophy is another common condition that impacts quality of life in men as they age by causing reduced ability to urinate.  Dr. Xiao felt that evidence is lacking to suggest that either of these prostate conditions is affected much by testosterone therapy and sited data supporting this viewpoint.

It’s good to know that testosterone therapy exists as an option to help men with symptoms of andropause, which can adversely affect quality of life. However, those of us who have doctored through the era of the Women’s Health Initiative, which studied the effects of hormonal therapy for menopause, have to be somewhat cautious about prescribing treatment for a condition that affects a huge segment of the population. In the case of estrogen and progestin therapy in women, as discussed in a recent blog,  the pendulum has swung for, then against, and now recently partially back in favor of a cautionary approach to post-menopausal hormone replacement for symptom management during the time immediately following menopause in women.

To date testosterone therapy has been less well studied, and it could be years before the safety data for testosterone replacement in men is as good as the data for hormone replacement in women, which has been the subject of intense research in the previous decade.

Are Annual Physical Exams Necessary

Recently a physician reporter for the New York Times, Elisabeth Rosenthal, argued in the cover article of the Sunday Review that routine physicals are in many ways pointless, and perhaps even dangerous.  In the article, entitled “Let’s Not Get Physicals,” Dr. Rosenthal goes on to point out that many routine tests performed during physicals --EKG’s, pap smears and blood work, are unnecessary. In my opinion, Dr. Rosenthal’s front page skepticism of the utility of the annual ritual misses the key point and sets a dangerous tone.  As every good primary care physician knows, the key benefit of an annual check-up (aka “physical”) is not the litany of tests ordered, but the opportunity it provides to do a complete review of a patient’s medical history and risk factors.  The “annual physical” also provides an opportunity for healthy people to get to know their physicians and vice versa, so that when illness arises, as it always will, the physician will understand a patient’s personality and healthy baseline.  

After years of criticism by proponents of prevention Medicare recently started to cover an annual exam, which is referred to as a “Wellness Exam.”  The Medicare preventive exam, which became a covered benefit in 2011, emphasizes history-taking as opposed to testing, which in my view is appropriate.   The Affordable Care Act also regulates the provision of preventive care by health plans requiring that plans provide a core set of preventive services without requiring a co-pay, co-insurance, or deductible.

While the physician author of the New York Times piece surely understands many of her own personal risk factors for disease and also the signs and symptoms of potentially serious underlying conditions, the general public does not have this expert knowledge. Why shun a once a year, hour-long (or, as is more often the case these days, 20 minute-long) visit to a medical expert to review one’s personal health profile, risk factors and family history?  I suppose that Dr. Rosenthal’s point is to de-emphasize the testing component.  In my view, if anything many individuals could benefit from more frequent (biannual or quarterly) preventive checks to keep them on track with their health goals and risk factors—perhaps this would keep more folks out of the ER and hospital.  As to the “testing” component of the annual physical, the visit provides an opportunity for patient and physician to discuss the state of the art, information that the patient might be reading online, and the evidence for and against screening for particular conditions. Which screening tests health insurance should pay for is a separate question. The issue here may be semantic—should it be called a "physical,"  a "wellness visit," or a "preventive check-up--" but, let’s not get rid of the annual visit.

Who Should Take Aspirin for Prevention?

The answer is not entirely straightforward.  Aspirin has been shown to reduce the risk of cardiovascular disease, including heart attack and stroke. Aspirin inhibits the function of platelets, the blood cell line responsible for clot formation.  When a heart attack or stroke occur the cholesterol plaque that lines an artery ruptures and platelets aggregate, resulting in a cascade that results in acute occlusion of a blood vessel.  Patients who are treated with aspirin are less likely to clot.  However, the effects of aspirin are not entirely benign. With its platelet inhibition it also confers a higher risk of bleeding—in particular gastrointestinal bleeding and hemorrhagic stroke, which also may be life threatening.

Clinical trials have looked at aspirin intake, cardiovascular outcomes, and bleeding risk. Aspirin for acute cardiovascular events and for “secondary prevention” (prevention after the diagnosis of coronary artery disease or cerebrovascular disease has been established) is undisputed.  Trials suggest that the benefits of therapy outweigh the risks of bleeding. 

However, whether or not aspirin should be prescribed for “primary prevention” (prevention in a person who is disease-free) is more ambiguous.  In 2009 a meta-analysis of existing study data looking at this question was published in Lancet.  The analysis found that aspirin reduced the risk of non-fatal myocardial infarction by one fifth, but that aspirin therapy also significantly increased risk of major gastrointestinal and extracranial bleeding and did not improve overall mortality.  In 2009 the US Preventive Services Task Force (USPSTF) reviewed the existing data and concluded that while aspirin reduces the risk of myocardial infarction in men and ischemic stroke in women, it increases the risk of major extracranial bleeding.  The USPSTF recommended that the decision to use aspirin therapy for the purpose of primary prevention should take into account an individualized assessment of cardiovascular risk and also bleeding risk. Patients with higher cardiovascular risk may benefit most from therapy.  

Patients considering aspirin therapy for primary prevention should assess their cardiovascular risk profile with their personal physician. The Framingham Risk Calculator is a recommended tool for estimating one’s ten year risk of having a major cardiovascular event.   However, Framingham may not be as useful for women as it is for men, and some recommend use of the Reynolds Risk Calculator. The Reynolds Calculator incorporates the inflammatory marker hs-crp into its calculation of ten year risk.

In a similar vein, in 2010 the American Diabetes Association, the American Heart Association, and the American College of Cardiology issued a joint statement revising their recommendations for use of aspirin for thepurpose of primary prevention amongst diabetic patients.  In contrast to old guidelines, the new recommendations do not advise that all diabetics over age 40 receive aspirin therapy.  Rather, they advise aspirin therapy for primary prevention in male diabetics under 50 and female diabetics under 60 only if one additional cardiac risk factor is present (hypertension, high cholesterol, smoking, family history, microalbuminuria) The new recommendation is based in part on a subgroup analyses of diabetic patients in the meta-analysis of the Antithrombotic Trialists’ Collaboration showing  that diabetic patients benefited less from aspirin therapy than non-diabetics. In addition, several smaller studies conducted specifically on diabetics and looking at primary prevention failed to demonstrate a significant benefit of aspirin therapy in those without diagnosed cardiovascular disease.  Further study is ongoing to research the issue of primary prevention of cardiovascular disease with aspirin in diabetic patients.  For now the therapy is recommended for diabetics who are determined to be intermediate to high risk (Framingham risk of 10% or higher).

Who is most likely to suffer a complication related to daily use of aspirin? Risk factors for gastrointestinal bleeding with aspirin therapy have been identified:

• Non-steroid anti-inflammatory (NSAID) use (in particular, high dose NSAID use)
• Chronic steroid use
• Prior history of peptic ulcer disease (PUD)
• Advanced age (>60-65 years old)
• GERD or dyspepsia (less risk than PUD)
• Concomitant use of another anti-coagulant

Treatment with a proton pump inhibitor, or the prostaglandin E analog misoprostol, can reduce one’s risk of gastrointestinal bleeding from NSAIDS.  By contrast, H2 blockers are not effective in this regard.  In addition, using enteric coated aspirin does not reduce its gastrointestinal toxicity.  It is unclear what dose of aspirin is best for primary prevention, but most recommend low dose aspirin (81-162mg), which appears to be equal in efficacy to higher doses (though it has not been demonstrated to be safer).

It’s interesting to me that simultaneous with a growing emphasis on incorporating population-based strategies into healthcare delivery we are also becoming increasingly aware of the importance of identifying personalized risk factors in order to best counsel individual patients on medical care and prevention.  Aspirin therapy for primary prevention is an example of how a one-size-fits-all population-based strategy is hard to apply.  We have seen similar recent trends with mammography screening recommendations, using PSA for prostate cancer screening, and will likely soon be hearing more about using a personalized approach to recommending statins for the purpose of primary prevention of cardiovascular disease (given recent associations between statin use and reversible cognitive complaints and diabetes). How population medicine, its associated quality reporting, and pay-for-performance on the one hand, and personalized medicine on the other, are reconciled in medical practice will be a challenge to be dealt on the level of policy, practice, and reimbursement in years to come.