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Friday, April 15, 2011

Understanding Cardiovascular Risk

Many express hesitation when it comes to the idea of taking cholesterol medication, or “statins.” This is despite their well documented record of efficacy and safety in the prevention of cardiovascular disease (CVD).  Guidelines for the treatment of high cholesterol are based on one’s LDL (or “bad cholesterol”) level in combination with one’s determined CVD risk.  

According to the National Cholesterol Education Program’s most recent Adult Treatment Program Report (ATP III for those at lowest risk, medication may not be indicated until the LDL cholesterol is greater than 160 to 190. However, for those at highest risk, medication may be suggested when the LDL level is over 100, or even lower for some. 

Who is at highest risk and how should asymptomatic adults be screened for CVD?

Recent guidelines by ACCF and AHA have been issued in 2010. Those with existing cardiovascular disease (history stroke, aortic aneurysm, coronary artery disease or peripheral vascular disease) are at highest risk for future events.  Certain diseases are also considered “coronary artery disease equivalents,” because of the very high rates of cardiovascular disease in those affected. Diabetes and chronic renal insufficiency are the two most common conditions that fall into this category.  

One widely used CVD risk calculator is called the Framingham Risk Score (FRS).  Use of this tool is endorsed by the American Heart Association and the American College of Cardiology, and numerous other medical professional groups.  The FRS uses traditional cardiac risk factors to calculate a score of one’s ten year risk of having a cardiovascular event.  The major risk factors for CVD are: 
  • Cigarette smoking
  • Hypertension (BP greater than or equal to 140/90 mm Hg or on antihypertensive medication)
  • Low HDL cholesterol (less than 40 mg/dL),
  •  Family history of premature CHD (CHD in male first-degree relative less than 55 years; CHD in female first-degree relative less than 65 years)
  • Age (men greater than or equal to 45 years; women greater than or equal to 55 years)

High risk is defined as a person whose likelihood of having a cardiovascular event is over 20% within ten years.  Low risk is defined as a person whose likelihood of having a cardiovascular event is less than 10 %. Those at intermediate risk have a 10 to 20% chance of having a cardiovascular event within 10 years.  Some further stratify intermediate risk into moderate risk (FRS of <10% but two CHD risk factors) and moderately high risk (FRS >10% and two CHD risk factors). Furthermore, some use a cut-off of 6% as the upper limit of “low risk.”  

The Framingham Risk Score works well for those over 40 years old, and may work better for men than women.  The key is to identify those who are at higher risk and to take action to modify that risk—lowering their blood pressure and treating their cholesterol.  There are supplementary tests that can be particularly useful in patients who are intermediate risk and might benefit from more intense monitoring and intervention.

Here some tests that have clinical utility:

“HS-CRP” (C-reactive protein) is an inflammatory marker that may be helpful to guide decision-making for men over 50 and women over 60 who are at intermediate cardiac risk.  CRP can be lowered by interventions that improve other cardiovascular risk factors, such as exercise, weight loss, smoking cessation, statins, and antihypertensive treatments.  In the JUPITER trial rosuvastatin (Crestor) 20 mg/d versus placebo was studied in the primary prevention of cardiovascular events in men and women without diabetes with LDL cholesterol > 130 mg/dL and CRP > 2 mg/L.  After a median follow-up of 1.9 years, rosuvastatin was associated with a significant reduction in cardiovascular events.

Hemoglobin A1C
Hemoglobin A1C is a measure of glycemic control over several months.  It is most commonly used to diagnose and monitor diabetes. However, studies have shown that in non-diabetic patients increased hemoglobin A1C levels (even within normal range) are associated with increasing risk of cardiovascular disease. 

Urinalysis for the detection of microalbumin
Urine microalbumin detection is recommended annually in diabetic patients. The test is inexpensive and easy to perform. The presence of microalbuminuria has also been linked to increased cardiovascular risk in patients with hypertension and in asymptomatic adults who are at intermediate risk of cardiovascular disease.

Carotid Intima Media Thickness (IMT) by Ultrasound
This is the thickness of the vascular lining of the carotid artery. The risk of CHD events increases in a continuous fashion as carotid intima media thickness increases (RR increases approximately 15% per 0.10-mm increase in carotid IMT). This test is not performed at all centers.

Ankle Brachial Index (ABI)
The ABI is performed by doppler measurement of blood pressure in all 4 extremities at the brachial, posterior tibial, and dorsalis pedis arteries. The highest lower-extremity blood pressure is divided by the highest of the upper-extremity blood pressures, with a value of < 0.9 indicating the presence of peripheral arterial disease, which is defined as > 50% blockage. When defined in this way, the ABI has both a high sensitivity and specificity for anatomic blockage.  An abnormally low ABI has also been shown to be a predictor of cardiovascular events.

Exercise ECG
 An Exercise ECG, a form of cardiac “stress test,” may be useful for risk assessment in intermediate-risk asymptomatic adults (including sedentary adults considering starting a vigorous exercise program).  Probably the most powerful risk marker obtained during routine exercise testing is exercise capacity; studies have consistently found that depressed exercise capacity is associated with increased cardiovascular risk.

Computed Tomography for Coronary Calcium
A cardiac CT or EBCT may be used to detect and quantify coronary calcium (CAC), a marker of atherosclerosis.  It may be useful in persons at intermediate risk (6 to 20%). This test is not recommended for men less than 40 or for women less than 50 due to the very low prevalence of detectable calcium in these demographics. 

In pooled data from six clinical trials, study subjects who had calcium scores of zero were found to have a low rate of cardiovascular events (0.4%) over the subsequent 3 to 5 years after testing. In subjects with high calcium scores, 400 to 1000 and >1000, the rates of cardiovascular events over the 3 to 5 year period were 4.6% and 7.1% respectively.

The recently released EISNER study found that study subjects who received cardiac CT for coronary artery calcium score were more likely than control subjects who received counseling alone to modify their cardiovascular risk profile over a 4 year period.  In contrast study subjects who received calcium scoring by CT were not found to incur higher downstream medical testing or health care costs. The implication being that the test could be an effective strategy for early detection, without increasing overall cost. 

Cardiovascular disease remains the most common cause of death in the American population.  In the last century we have developed effective therapeutics that help prolong life, reduce and delay the risk of cardiovascular illness.  Doctors should help patients understand their individual risk profiles, which are not static, but worsen with age, so that appropriate behavioral change or medication is prescribed when it is indicated.

Sunday, April 3, 2011

Difficult Access and Lack of Continuity Delays Making a Correct Diagnosis

A close friend of mine is hospitalized.  What happened to him merits a blog.  Several weeks ago my friend developed numbness in his hands, feet and tongue.  Not one who particularly fancies seeing doctors, he called his primary care physician, who he had recently seen for a check-up in honor of his 50th birthday. His own doctor was not available urgently so he saw his doctor’s partner in the same practice, who he had never met.  A history, neurological exam and a battery of blood tests were performed, revealing a low vitamin B12 level of 170.  My friend was told that vitamin B12 deficiency was the likely the source of his troubles, and was started on oral supplements.  However, over the next several days he developed worsening numbness and weakness in his legs.  Two days later he was felt increasingly unwell—now also lightheaded and faint with standing.  Unable to speak with his physician, he went to the emergency room on Friday afternoon.  After many hours he was assessed by a neurology resident who consulted with a senior neurologist by phone.  My friend, who described lightheadedness and muscular weakness, apparently did not have many findings on exam, but lacked proprioception (position sense), which was the reason he was told he was having difficulty walking.  He was sent home and instructed to take B12 injections.  On Monday he called his PCP back for an appointment, alarmed by rapidly evolving symptoms of numbness and weakness. He was told that no appointments were available, so he decided to walk in to the office and asked to receive an injection of B12, which he believed would make him better.  He left without being assessed by a physician.  Throughout the course of the week he became progressively weaker in his legs and was not able to drive to work.   By the end of the week he fell when he tried to get up from a chair and noticed a change in his voice.  On Sunday, ten days after his first symptoms developed, my husband called to see if my friend could play tennis.  As my friend declined, explaining the problem, it became readily apparent to us (who are both physicians) that this was not B12 deficiency.  We pulled some strings and managed to get him seen by his own primary care physician the following day (he had been given a follow up appointment in ten more days).  We were suspicious that this was Guillain-Barre Syndrome, which was the confirmed diagnosis two days later, after a thorough history, physical exam, lumbar puncture, electromyogram and nerve conduction studies were performed. Guillain-BarreSyndrome is an uncommon condition (1-2:100,000) where the body’s own immune response attacks one’s nerves, causing “demyelination.”  In severe cases paralysis and respiratory failure can occur. My friend is now unable to walk and is receiving intravenous immunoglobulin therapy.  Needless to say he has received ample good attention while in the hospital and, being very easy going, he has nothing but good things to say about his physicians and care.  The prognosis for Guillain-Barre Syndrome is very good, but can require up to 6 to 12 months for a full recovery.
In my view, there are several lessons here.  These were all excellent doctors that my friend encountered.  So what was the problem?  I have only heard my friend’s point of view, but here are some thoughts:
  • He was not seen by his own primary care doctor for his urgent complaint.
  • His primary care physician had met him only twice. Though a patient of this physician for at least five years, he had seen 3 or 4 different providers within the practice for all previous urgent issues because of a lack of available appointments with his personal physician.
  • His initial diagnosis may not have been presented as a hypothesis.
  • He may not have been given adequate instruction about what to do if his condition worsened.
  • He was not seen in the emergency room by an attending neurologist.
  • He was not given neurology follow-up.
  • His complaint of weakness may not have been taken seriously because it was not clearly perceived on his physical exam.
  • When he worsened no one initially questioned the accuracy of the diagnosis of B12 deficiency.
  • When my friend came to the primary care office for a second time, after his ER visit, with worsening symptoms, he was seen only by a nurse for the B12 injection (there was no MD appointment available).
  • The ER did not communicate directly and promptly with either the physician who had seen him several days prior, or his primary care physician.
  • My friend trusted the original diagnosis and that the system would take care of him adequately.
  • My friend did not want to be perceived as a difficult patient or as a hypochondriac, so decided to wait it out.
This case is a near miss.  My friend got the care that he needed, but there was delay, inefficiency and poor communication.  It’s a shame that we, as primary care physicians, have become so busy that we cannot care for our patients’ urgent needs. Fortunately, my friend was well-connected.  Making a diagnosis like Guillain-Barre Syndrome and helping a patient receive timely and appropriate care is fascinating and is what makes primary care potentially so interesting and rewarding.  However, when access is limited, there are ineffective channels of communication, and continuity is lacking it’s tough for even excellent doctors to function well.  Atul Gawande has proposed checklists and team work as measures to improve hospital based care.   In the primary care world I can see that the majority of mishaps occur at times of care transitions because of poor communication between office visits.  Part of the problem is the ever expanding patient panels of primary care physicians who are so busy seeing their 20 to 30 patients daily that they are unable to manage any event that occurs outside of the context of an office visit.  Personally, I am not sure that even the best checklists, care teams, or electronic systems can make up for this lack of adequate time to spend with a single physician, who knows a patient well and is able to oversee care continuously throughout health and illness.