But what do we do for those patients whose HDL’s remain abysmally low despite statin treatment? Low HDL predicts increased CVD risk, and usually correlates with high triglycerides. Two medication strategies to raise HDL and lower triglycerides have a long history in clinical practice, but do they improve patient-oriented outcomes: niacin, and fibrates (gemfibrozil, fenofibrate)?  The answer appears to be “no”.

Niacin raises HDL, is inexpensive, is largely free of serious side-effects (but that flushing is very annoying), and is very cheap. The NIH-sponsored AIM-HIGH trial treated patients with known CVD and low HDL (<40 for men and <50 for women) with a statin (target LDL<80). Most also were on aspirin, a beta blocker, and an ACE-inhibitor. After a run-in to ensure that all could tolerate niacin, patients were randomized to 1500-2000 mg of extended-release niacin daily. After 3 years, the trial was stopped early because there was no suggestion of any cardiovascular benefit, but a trend toward more strokes in the niacin-treated patients. With no evidence for niacin’s benefit in contemporary primary prevention either, we should stop using this vitamin/medication.

Older studies with fibrates (Helsinki Heart Study, VA-HIT) in non-statin-treated patients showed some weak evidence for reduction in coronary events, but likely not in overall mortality. Remarkably, despite lack of evidence of benefit in more recent studies of high-risk patients (FIELD, ACCORD), prescriptions for fibrates are increasing dramatically in the US, but not in Canada! Might this have to do with marketing of brand name fenofibrate  – a 1.5 billion dollar drug in the US? Fibrates do not work for prevention of CVD (at least in statin-treated patients) and should not be used!

Elevated homocysteine levels correlate with cardiovascular disease. And homocysteine lowering is so easy with folic acid, vitamin B6, and vitamin B12 (JAMA 2008 May 7; 299:2027; JAMA 2006 Dec 13; 296:2720-6)! Once again, simple explanations for the complex atherosclerotic process of CVD fail: homocysteine lowering does not work to prevent CVD or reduce all-cause mortality in patients with vascular disease or in primary prevention. Don’t routinely check homocysteine levels for CVD risk-stratification, and don’t use these vitamins for treatment or prevention.

What’s the best treatment for all patients with low HDL’s and high triglycerides? NOT A PILL. Exercise, weight loss, and avoidance of simple sugars in the diet. Exercise and weight loss definitely improve patient outcomes of all kinds, including cardiovascular disease. For patients with CVD (and for those at >20% 10-year risk [http://www.mdcalc.com/framingham-cardiac-risk-score], also use a statin, and other proven strategies like BP control. Let’s be as aggressive prescribing exercise & weight loss as we are in prescribing statins!

-Jeremy Golding, MD

1. Call ‘em like you see ‘em: don’t ignore your patient’s weight. Include BMI as part of your vital signs, and TELL your patient if they are overweight or obese. Just as simply telling our patients to quit smoking increases tobacco cessation rates, telling our patients that they need to lose weight can be powerful motivation.
2. Reality check: perform a 24 hour dietary recall: ask your patient to briefly tell you everything they put in their mouth during the last 24 hours, and write it down in their chart.  Look for skipped meals, fast food, fruit & vegetable servings, and liquid calories- then ask your patient where they think they could commit to make a change.
3. Focus on MORE, not LESS: rather than prescribing specific calorie intakes, encourage your patient to commit to eating a minimum of 5-10 servings of vegetables or fruits each day. (Note- a serving is what you can hold in your cupped hand, so a large salad might be 4 or 5 servings.)
4. Refer your patients to a Registered Dietitian:  yes, it costs money to see a dietitian, but they are the true weight loss experts, and it’s worth it. If our patients can afford smart phones, MP3s, hair highlights and daily Starbucks, they can prioritize paying a dietitian for one of the most important health interventions in their lives.
5. KEEP IT OFF so your 2013 Resolutions don’t start with weight loss! Check out the National Weight Control Registry to recognize the consistent behaviors of over 10,000 people who have maintained at least a 30 pound weight loss for greater than one year. Here’s a hint: don’t skip breakfast, weigh yourself weekly, limit TV to less than 10 hours per week, and exercise every day!

Welcome to 2012! Let’s step up to the plate this year and start with a good, hard look in the mirror.  Do we look like the model of health we’d like our patients to attain? If so, terrific- keep it up!  If not, make 2012 the year to prioritize our own health, so we can lead by example.

-Jill A. Grimes, MD

“If you are healthy, and not pregnant, you will probably not die from Influenza this winter.  The Influenza vaccine is recommended for everyone over the age of 6 months to keep most of us from passing the infection on to someone who will die from it.”

“Do many people DIE from the flu?”  The death rate from illness rarely makes the evening news and is hard to tease out.  The CDC states over 58,000 US citizens died from influenza and pneumonia in the US in 2009.  A subset of those were people who developed pneumonia not secondary to influenza; most estimate the actual number of people who die in the US solely from an influenza infection to be around 15,000/year. 

About 1 in 20,000 US citizens died in 2009 from the flu.  Those that die are the very young and those with co-morbidities who die from secondary pneumonia.  Small communities have less than 20,000 inhabitants; at least one of your neighbors died.  And most deaths are preventable, but only if most everyone gets the vaccine.

These same skeptics will be calling us at 2 AM in mid January, because they are ill and asking for “Theraflu” (they really want oseltamivir, but watch too much TV.)   Remind them influenza’s symptoms are not subtle:  Temp usually > 101 F, chills, myalgias, rhinorrhea, non-productive cough.  They are not typical URI/cold symptoms and low grade fever – the flu makes you feel really ill.

But, even if they have the proper symptom complex, many do not qualify for medications.  Anti viral agents are only effective if started within 48 hours of symptom onset and should be reserved for patients most likely to develop a complication: those with asthma, blood disorders, COPD, cystic fibrosis, diabetes mellitus, heart disease, renal and liver diseases, obesity, neurological disorders or HIV. Populations at risk are: age < 2 and > 64, pregnancy, American Indians and Alaskan natives.

And, for the rest of us?  Be aggressive with fever control (I use 1,000 mg acetaminophen + 800 mg ibuprofen every 8 hours – YES, they can be given together), fluids, maybe a decongestant, and chicken soup (it can’t hurt). 

And, Elderberry Extract Lozenges (175 mg) QID x 2 days (again, if started within 48 hours of symptom onset).  These lozenges are available at most pharmacies and health food stores.  In 3 small trials, this extract was as effective at reducing symptoms as anti-virals  [J Pharmacol Pharmacokin; 2009: 5:23].  It is safe, and may be helpful. 

The wisest route is prevention.   Get everyone immunized, and if you want to learn more, check out our chapter on Influenza.

- Frank J. Domino, MD

Recent meta analysis of the value of aspirin in primary prevention helps us see, in the most discreet of numbers, how most of medical interventions help our overall patient population, and not any individual. 

This study reviewed 9 randomized, controlled trials, and covered over 100,000 patients over about 7 years, to determine if low dose aspirin prevented major cardiovascular events (MCEs) (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), all-cause mortality, and the rate of major bleeding. 

The headline:  there was a risk reduction in the combined end point of MCEs in the aspirin group compared to the placebo group.  But, with slightly deeper review, we find NO reduction in myocardial infarctions, strokes, ischemic strokes, or all-cause mortality and an increased risk of hemorrhagic strokes and major bleeding (most GI). 

Bottom Line:  For every 1000 primary prevention patients taking aspirin for 5 years, aspirin would prevent 2.9 MCEs and cause 2.8 major bleeds.  In short, taking aspirin helps less than 1% of those who take it, and hurts at a rate every so slightly less.

How do I use this information for the primary prevention of CHD?  I tell them to take a 15 minute walk 5 days a week.  The risk reduction from this is huge, and outside of getting hit by a car, the risk is small.  Really. 

If you are still unsure what to do, a huge meta analysis from 2009 found aspirin for primary prevention was useful if the risk of a CHD event was >/= to 10%.  So to maximize benefit and minimize risk – only suggest aspirin to those at high risk for subsequent CV events – those whose risk of having such an event is > 10% in the near future. You can calculate that risk by going to: http://www.mdcalc.com/framingham-cardiac-risk-score. 

-Frank J. Domino, MD

HPV causes over one million reported annual cases of genital warts here in the United States. Obviously, warts affect both sexes, and the true number of cases likely exceeds three million. The health care dollars spent on treating this problem alone are astronomical, not to mention the very serious psychological impact of developing and enduring treatment for genital warts. Additionally, we know we cannot cure these warts, but simply continue to treat new lesions each time they recur.

Cancer is the most serious end point of HPV-related diseases. We know that HPV causes over 12,000 cases of cervical cancer per year (sadly including over 4000 deaths), as well as close to 6000 cases of anal cancer, roughly 1300 cases of penile cancer, and increasing numbers of oral cancers.

Ultimately, our take home message remains: we need to discuss risks of HPV with all of our patients- both male and female- and offer HPV vaccinations to all adolescents.

- Jill A. Grimes, MD

Some things we recommend, like seatbelts, dramatically decrease morbidity and mortality from motor vehicle accidents.  Fluoride in the water decreases dental disease.  Aerobic exercise before and little aspirin after an MI decreases mortality.  You would never recommend something that could lead to an increase in morbidity or mortality to your patients, right?

Last week’s announcement from the Agency for Health Care Quality and Research’s US Preventive Service Task Force making Prostate Cancer Screening a “D-recommend against” (http://www.uspreventiveservicestaskforce.org/draftrec3.htm) is welcome, if not long overdue.  We all know a case where some cancer was identified through screening and the patient felt like their life had been saved by this action.  But screening for Prostate Cancer does not lead to improved outcomes.   In fact, it leads to worse outcomes and always has.

In 2009, the Chief Medical Officer of the American Cancer Society, Otis Brawley, M.D. along with Peter Boyle, the International Prevention Research Institute, published an editorial in the journal “Ca: A Cancer Journal for Clinicians” summarizing the best data we have on the influence of Prostate Cancer Screening.  Here is what they found:

–In 1985 (before mass screening), the risk of prostate cancer diagnosis was 8.7%, and risk of dying from the disease was 2.5%.

–In 2005 (yearly DRE and PSA determination in asymptomatic males over 50), the risk of prostate cancer diagnosis doubled to 17%, and, the risk of death went UP, to 3%.

Reviewing the morbidity data, a man is 48 times more likely to be harmed than saved by screening over 9 years; those harms include impotence, incontinence, and, death. 

Some think this is just a government ploy to save money.  Just like the mammography issue of 2 years back, the government does not make these decisions; we do.  The best of our unbiased peers: physicians, researchers and statisticians review the data and offer advice to the government.  

Even the people who financially benefit from aggressive testing (Dr. Brawley and the American Cancer Society) are telling us to stop trying to relieve anxiety by screening for prostate cancer since; it only makes matters worse.

Work up a patient with a GU problem and find prostate cancer; treating it has better outcomes than finding it by screening.   Like screening for lung cancer or lymphoma, we do not have a good test that identifies the disease early enough to allow an effective treatment to reduce morbidity and mortality.  Maybe we will in the future, but not yet.

So, whose anxiety are you treating when you do PSA testing?  The patients’?  Your own? You became a health care provider to protect your patients from disease; this includes protecting them from unnecessary interventions.  Ordering tests to prevent lawsuits is  more likely to lead to adverse outcomes and patient dissatisfaction, and is based upon blind faith.. 

 A final quote from Dr. Brawley: 

“In the United States, widespread prostate cancer testing is commonly practiced. For nearly 2 decades, testing has been based on blind faith in early detection as opposed to being based on evidence of a decrease in mortality as observed in well–designed clinical trials.  Prostate cancer screening and the treatment of early stage disease is also a profitable industry….  If we are to stem the spiraling costs of health care, we must move toward the use of evidence–based rather than the faith–based or profit–based practice of medicine.”

The evidence is clear.  Encourage seat belts and exercise, and help your patients refrain from believing this test is going to make them live longer or better.  Will diagnostic and treatment of this disease change in time? I believe so.  Prostate cancer is the 2^nd leading cause of cancer death in the US (Lung cancer is still #1).  But till then, screening for prostate cancer does not lead to improved outcomes.    

-Frank J. Domino, MD

Shortly after this FDA communication, a systematic review/meta analysis on varenicline was published and found serious cardiovascular events occurred in 52 (1%) of 4,908 patients on varenicline, but only 27 (0.082%) of 3,308 taking placebo. While this was a statistically significant finding, the resulting absolute risk increase was only 0.024% (2); NNH = 4167.

Given the significant increased risk for serious cardiovascular events and other morbidity associated with smoking, it would seem that an absolute risk increase of 0.02% is an acceptable risk in helping smokers quit.   

The CDC tells us the leading cause of accidental death in the first 25 years of life is due to motor vehicle accidents.  Yet, they do not warn us about the hazards of using a car.  While the FDA is under a different mandate to the US citizens, it seems ironic they found it necessary to provide this safety communication without keeping in perspective the benefits of smoking cessation in this high risk population.  For example, if a 55-year-old male with controlled hypertension smokes, his 10-year risk of a CHD event is 21%; without smoking, this risk drops to 11%.

Varenicline appears to be the most effective drug available for the treatment of nicotine addiction. I will continue to prescribe this medication to my patients along with motivational interviewing, supportive counseling and referral for cognitive behavioral therapy as needed, in an attempt to help my smoking patients improve their overall health.

-Robert A. Baldor, MD

They found intensive treatment (generally, target HgbA1c <7%) did NOT affect all-cause mortality, but lowered risk of non-fatal MI about 15% (but with increased rates of severe hypoglycemia). They estimate over 5 years, about 135 people would need to be treated intensively to prevent one non-fatal MI, but 1 in 33 patients so-treated would have a severe hypoglycemic episode over the same 5 years. When they included only the best quality trials in the analysis, all evidence of benefit disappeared, and the risk of heart failure increased 47%!

The authors conclude, “The absence of benefits from intensive glucose lowering treatment further illustrates why relying on surrogate end points for treating people is a fallacy. Marketing new drugs based only on evidence that they decrease glucose or HbA_1c plasma levels, or both, should not be allowed. Practitioners (and patients) should not rely on either blood glucose targets or HbA_1c targets or the concept of ‘the lower the better.’ “

Many diabetologists argue the trials included mostly patients with more advanced diabetes, with diabetic and cardiovascular complication. They suggest trials that look at newly diagnosed Type 2 DM will be more favorable… but we really don’t know. It’s a reasonable hypothesis. The American Diabetes Association, along with the American College of Cardiology and the American Heart Association recommend tailoring the A1C goal to the patient’s co-morbidities. They outline their more aggressive HgbA1c-targeted approach in papers in Diabetes Care (Diabetes Care 2009; 32:193,  and  Diabetes Care 2009; 32:187).  If the patient is newly diagnosed, active, and has no other complications, an A1C goal of < 7.0 is reasonable.  But if obese, not exercising, and other multiple co-morbidities are present, a goal of > 7.0 is preferred. 

What’s a primary care clinician to do? Available data suggest metformin is the most outcomes-effective oral treatment for glycemic control in overweight people with diabetes. Metformin helps patients lose weight, does not cause hypoglycemia, and probably works independent of its affect on A1C. So – use metformin, and avoid the newer, expensive, unproven diabetes medications that may have unforeseen bad effects in years to come. Beyond that, focus on the strategies that really do matter – blood pressure control, statins, exercise, and probably aspirin.

Now, if we can only convince the insurance companies that HgbA1c is NOT a good indicator for assessing the quality of primary care of diabetics!

 - Jeremy Golding, MD

Since 2003, the American Academy of Pediatrics (AAP) has recommended that exclusively breastfed infants be supplemented with vitamin D to prevent rickets [level of evidence B].  In 2008, the AAP updated its recommended daily intake of vitamin D in infants from 200 to 400 IU and revised the start of therapy from 2 months of age to the first few days of life  (Pediatrics. 2008 Nov;122(5):1142-52; Am Fam Physician. 2010 Mar 15;81(6):745-8). Infants can take a 1 ml dropperful per day of a vitamin supplement such as Poly-Vi-Sol or Vi-Daylin.  Vitamin D supplementation should be continued until one year when vitamin D-fortified milk is introduced.

Vitamin D is not that controversial any more.  However, the newer recommendations that iron supplementation for exclusively breastfed infants should begin at 4 months of age still are (Pediatrics. 2010 Nov;126(5):1040-50. Epub 2010 Oct 5).  Recent basic research demonstrates that iron deficiency can have long-lasting detrimental effects on neurodevelopment.  As such, in 2010, the AAP recommended adding supplementation for breast-fed infants with oral iron 1 mg/kg per day beginning at age 4 months until the infant begins eating complementary food (or formula) that supplies 2 mg/kg of iron [level of evidence B].

Since formula-fed babies do not require any supplementation, families may falsely believe that formula is better than breast milk for their babies. So how should physicians counsel families on infant nutrition?  Breastfeeding is still the healthiest option by far.  If I had a newborn in 2011, I would exclusively breastfeed, supplement my baby with both vitamin D and iron in a liquid daily multivitamin, and not freak out when I forgot a dose or two!

  -Julie Scott Taylor, MD, MSc

The major change in criteria reflects the understanding that Alzheimer’s disease represents a slow, steady progression of pathophysiologic changes for years before any clinical symptoms appear. This initial stage is called “Preclinical Alzheimer’s disease” followed by progression to the next two stages – Mild Cognitive Impairment and finally, Alzheimer’s Dementia.

In the Preclinical stage, which is diagnosed only in research settings, the patient  has changes in biomarkers found through CSF assays and brain imaging.  Beta Amyloid levels are decreased in the CSF, while amyloid tracer retention increases in the brain scans.  Subsequently, CSF tau proteins rise and structural MRI’s show cortical thinning and hippocampal atrophy.  The patient would still test in the “normal” range on cognitive tests, but it may represent a decline for that patient.

The second stage is Mild Cognitive Impairment (MCI), where there are early memory and other cognitive changes, but these developments do not significantly impair the person’s ability to perform daily tasks.

The final stage is Dementia, where the memory, orientation and judgment difficulties reach a level that they affect the patient’s daily life.

Biomarkers represent a very exciting future for Alzheimer’s disease research and treatment. Right now, these tests are not readily available to those of us in private practice, and even if they were, we have not established solid reference points to allow for their accurate interpretation.  The importance is this- just like we can measure and treat cholesterol levels before someone has a cardiovascular event, elevated AD biomarkers may warn us of impending AD. Obviously, the next step is to develop medications that will prevent the full development of dementia, if initiated early enough.

The Alzheimer’s Association website has links to full recommendations of the National Institute on Aging and the Alzheimer’s Association. The four papers are packed with information, but lack simple flow charts or outlines for quick reference for the practicing clinician. Dementia will increasingly become part of our practice.  For more information, check out our chapter: Alzheimer Disease.

-Jill A. Grimes, MD