I used to think that lisinopril cough always started in the first month or so of using lisinopril, but it’s clear that a small minority of patients will develop a lisinopril cough months or longer after starting lisinopril. In addition although most patients find their lisinopril cough decreasing shortly after stopping lisinopril and resolving within a few weeks, there are patients where the cough can persist for many weeks or even months.

Although most people think of cough as a symptom of a respiratory infection or an allergic problem like asthma or hay fever, it is becoming increasingly clear that esophageal acid reflux is a common cause of cough. Cough related to reflux can either be due to occult minor aspiration of gastric contents into the trachea or from irritation of the esophagus leading to cough without aspiration. Reflux related cough is another type of cough can take a long time to resolve even on aggressive anti-reflux therapy, and so be difficult to diagnose with certainty. If a patient is also on lisinopril the sorting out which problem is causing the cough can be a challenge.

Lisinopril is used primarily for the treatment of high blood pressure and congestive heart failure. It is also used for prevention of kidney disease in patients with diabetes. All of these conditions are seen more often in older adults, obese patients and often in patients with multiple complex medical conditions. This can make physicians reluctant to discontinue lisinopril because every medication change in a complex patient can upset a delicate balance, so if a patient is doing well except for the cough it is tempting to now want to make any medication changes.  Thankfully now switching to an angiotensin receptor blockers is a fairly easy medication alternative, especially with losartan now available as an inexpensive generic ARB with losartan soon to follow.

Lisinopril cough is felt to happen because the site of action of lisinopril is in the lungs where it prevents the conversion of angiotensin I into angiotensin II.  It is not completely clear what causes the cough but the known fact that angiotensin converting enzyme inhibitors function at a cellular level in the lung seems to be the key. Angiotensin I is produced in the kidney and released to the circulation. The angiotensin I in the bloodstream circulates through the lungs where it is converted into angiotensin II in a process requiring an enzyme called angiotensin converting enzyme. ACE inhibitors like lisinopril block the site where angiotensin I fits at the angiotensin converting enzyme therefore blocking the production of angiotensin II which is the active form of angiotensin. Angiotensin II works in the peripheral arterioles to cause constriction of the tiny arteries and therefore elevation of blood pressure. The angiotensin receptor blockers (ARB) function at this receptor in the peripheral arterioles and so ARB medications are much less commonly associated with cough.  Unfortunately cough is an occasional but very infrequent cause of cough which can further complicate trying to decide whether the cough was related to lisinopril if it doesn’t resolve quickly and switching medications.

The incidence of lisinopril cough is almost certainly higher than the incidence noted in the original studies of lisinopril quoted at 1% for patients with congestive heart failure 3.5% for patients with hypertension, but the exact incidence of lisinopril cough is really unclear.

When I see a patient on lisinopril with cough I first try to put the cough into perspective. If the cough started as part of a typical upper respiratory infection with congestion, fever or chills, sore throat or other similar symptoms I will tend to advise the patient that the cough will likely resolve as the illness passes.  Problems like post-bronchitic bronchospasm, where cough persists for weeks or months after an episode of acute bronchitis can be a challenge sometimes, but usually this approach works. On the other hand if the cough is a fairly mild cough that persists or gradually progresses to be much more annoying then I usually suggest that we stop the lisinopril and use an alternative medication, usually a generic ARB like losartan.  Then we wait and see if cough resolves over the next few weeks. If cough persists more than a few weeks it comes a bit trickier. If the cough seems to be gradually diminishing I usually try to convince the patient with a longer.  If the cough is not improvingat all we need to look harder for another cause.

Most of the time lisinopril cough is usually fairly simple problem to diagnose and manage because most physicians recognize cough as among the most common of lisinopril side effects, but like almost everything in medicine things are sometimes more complicated than they appear and cough is a symptom that can be a diagnostic and therapeutic challenge.

1. West Virginia (18.4)                      >30%                               25% (tie for 8^th highest)
2. Tennessee (16.9)                          >30%                              25% (tie for 8^th highest)
3. Alabama (16.9)                             >30%                              25% (tie for 8^th highest)
4. Kentucky (16.5)                             30%                               29% (alone w/top rate)
5. Arkansas (16.4)                            >30%                              26% (6 way for 2^nd)
6. South Carolina (16.3)                     25%-29%                        24% (4-way tie for 12^th)
7. Mississippi (15.9)                            >30%                             26% (6-way tie for 2^nd)
8. Iowa (15.3)                                  25%-29%                        22% (3-way tie for 17^th)
9. Missouri (15)                                 >30%                              26% (6-way tie for 2^nd)

For reference there are nine states with 2009 rates of obesity > 30% of which 7 are here in the top 9 most medicated states. The national average rate of smoking is 21% and all 9 of the states with the highest rates of medication use are in the top 17 states for rates of smoking.

I cannot access the SDI data to see what the rates of obesity are in the states with the lowest incidence of obesity are  but here are some other health related statistics and their relationship to a relative lower obesity rate.

1)      Colorado is alone as the only state in the US with a 2009 rate of obesity at <20%.   Why doesn’t Colorado rank at the very top for the lowest for death rates in adults?  Possibly because of a smoking rate of 20% (tie for 28^th highest leaving it pretty good but with  a death rate of 709/100,00 (11^th best).

2)      The fifteen states with obesity rates from 20-25% (the best except for Colorado) are listed below in alphabetical order:

                                                      Death rate (rank)                             Smoking Rate (rank)

a)      Alaska                               742 (2oth)                           24% (Tie for 12^th highest)

b)      California                         660 (4^th)                                15% (50^th highest, i.e. 2^nd lowest)

c)       Connecticut                   691 (8^TH)                               18% (tie for 38^th highest)

d)      Hawaii                               590 (1^st)                                16% (49^th, i.e. 3^rd lowest)

e)      Idaho                                 723 (16^th)                             18% (tie for 38^th highest)

f)       Minnesota                        675 (5^th)                                17% (tie for 44^th highest)

g)      Montana                           786 (33^rd )                            20% (tie for 29^th highest)

h)      New Jersey                     717 (14^th)                             18% (tie for 38^th highest)

i)        New York                        676 (6^th)                                19% (tie for 32^nd highest)

j)        Oregon                              748 (22^nd)                             18% (tie for 38^th highest)

k)      Rhode Island                   749 (23^rd)                             20% (tie for 28^th highest)

l)        Utah                                    659 (3^rd)                               11% (51^st highest, i.e. lowest)

m)    Vermont:                           721 (15^th)                             18% (tie for 38^th highest)

n)      Virginia                              762 (25^th)                             19% (tie for 32^th highest)

o)      Wyoming                           773 (29^th)                             21% (tie for 21^st highest)

Looking at this data you may note that 4 of the 5 states with the lowest death rates are in the 15 states with the lowest rates of obesity, and that none of them are worse than the 44^th highest smoking rates. (only Arizona is missing, in the next 25%-29% obesity rate and at a tie for 21^st in rate of smoking)  You may also note that the only two states in the top 15 for lower obesity rates ranking in the bottom half for death rates have smoking rates ranking at 21^st and 29^th.

Contrast this with the five states with the highest death rates:

1. West Virginia with >30% obesity and 25% smoking rate (tie for 8^th highest)
2. Mississippi with > 30% obesity and 26% smoking rate (tie for 2^nd highest)
3. Oklahoma with >30% obesity and 26% smoking rate (tie for 2^nd highest)
4. Alabama with > 30% obesity and 25% smoking rates (tie for 8^th highest)
5. Louisiana with >30% obesity and 26% smoking rate (tie for 2^nd highest)

In contrast the states with the lowest death rates have the opposite statistics for obesity and smoking rates:

1. Hawaii with 20-24% obesity and 16% smoking rate (3^rd lowest).
2. Arizona is the exception in these states with 25-29% obesity and a smoking rate of 21% (right at the national average and ranking in a 6 way tie for 20^th highest in the U.S.
3. Utah with in the 20-20% obesity and the lowest smoking rate in the U.S. at 11%.
4. California with 20-24% obesity and 16% smoking, second only to Utah.
5. Minnesota with 20-24% obesity and in a tie for 4^th lowest smoking rates at 17%.

It appears that states where citizens choose not to smoke and trend to be less obese have both lower rates of medication use and lower death rates. My guess is that the observation of lower death rates and lower rates of medication use are the result of lower rates of diabetes, hypertension, COPD, cardiovascular disease in these same states.   Yes these other health markers also trend directly with obesity and smoking rates.

So what can you as an individual learn from this?  Get fit, avoid obesity and don’t smoke.  No surprises here.

You may also enjoy:

Belly Fat is Bad for Our Health

Just How Fat are Americans?

CDC Widgets  - Go Here to calculate your own BMI and see other cool calculators

Some states have taken measures to reduce tobacco use, you can use this CDC widget to see how your state is doing, and what other states have done.

High blood pressure. The words don’t exactly strike fear into most American’s hearts. After all, it’s not painful, like cancer. It doesn’t sound deadly, like heart disease. But it’s literally a time bomb in our blood vessels that threatens our heart, brain and kidneys. Make no mistake – it’s a killer! So what makes our blood pressure rise? Too much salt, extra body weight and spending too much of your time sedentary. But wait! Don’t blame it all on the salt shaker. Only 7% of the excess salt in the average American’s diet comes from the salt shaker. The remaining 93% comes from all the processed and convenience foods we buy at the vending machine, at the local corner store, at the grocery store (for quick dinners) and at fast food and dine-in restaurants.

If your doctor has told you to cut back on your salt intake…you will have to do more than put the salt shaker away.

As for extra body weight (lose weight) and inactivity (begin a modest exercise program and spend less of your day sedentary), applying the following tips may help you on your quest to lower your blood pressure.

Here are some sodium-cutting tips you can try today:

Introduce additional flavor to your foods with herbs and spices like garlic, oregano, basil, pepper, thyme and sesame. These all add flavor without the extra sodium. If a recipe calls for salt, cut the amount called for in half and taste it before adding more.

Make healthy choices at the grocery store. Processed foods (anything in a box or bag) tend to be high in sodium because it helps preserve foods longer and increase flavor. Always read labels for the foods you buy, including the sodium content on the nutrition facts label and the ingredients list.

Remember that “low-fat” or “low-calorie” doesn’t mean healthy. These diet foods can also be higher in sodium because manufacturers hope that added sodium, a flavor-enhancer, will bring back the flavor that is missing since fat and other higher-calorie ingredients are removed. This is especially true for frozen dinners, which are often loaded with extra salt.

Choose low-, no- or reduced-sodium versions of your favorite soups, frozen meals, canned foods, and snacks. Even butter is available without added salt!

Choose fresh or frozen veggies over canned varieties, which often contain added salt to help increase shelf life. If you can’t find sodium-free varieties of canned vegetables, rinse the can’s contents in a colander under water before cooking to remove excess salt.

Olives, pickles and other items packed in brine are saturated in salt, as are many smoked and cured meats, like salami and bologna. Limit your intake of these high-sodium foods and be on the lookout for lower-sodium varieties.

Fast foods are high in more things than just fat. Many of these meals, sandwiches and fries contain more than your daily recommended intake of sodium in just one serving. When consulting restaurant websites to make healthy choices, pay attention to sodium levels as well. By keeping your portions in check (order a junior burger or small French fry instead of the big burgers and super fries) will help control your sodium (and caloric) intake.

Thanks much to Brooke for returning as our first-of-the-month guest contributor.  She does a great job with nutrition advice, so if you are concerned about your or a loved one’s blood pressure give her a call. Did you know that your insurance might cover several visits with a Registered Dietitian? Let Brooke help you navigate the insurance maze to determine whether your insurance will pay for you to having some nutrition coaching with a Registered Dietitian. You can find her at Nutrition Authority.

You may also enjoy this CDC widget:

Essentially all of the evidence used to support the belief that gum disease is a risk factor or a cause of atherosclerosis was from observational studies.  In an observational study it is observed that condition A is present more often in people with condition B than in persons without condition B.  Many studies showed that patients who had heart attacks are more likely to have bad oral health than patients who have not had heart attacks.  This is far different from saying that gum disease causes heart attacks.  In an extensive evaluation of all of the studies showing a relationship between gum disease and cardiovascular disease a panel including both dentists and physicians concluded that the evidence simply does not support the conclusion that there is a causative relationship. The problem appears to be that several other risk factors for cardiovascular disease are also put patients at risk for gum disease.  These include tobacco use and low socioeconomic status, as well as age and diabetes mellitus.  In a controlled study these confounding variables would be considered and “controlled” for in any analysis.  In an observational study this is much more difficult to take into account

The association of periodontal disease and atherosclerosis was so in synch with our bedside observations that it was intuitive to accept the association as dogma. For me at least it never occurred to seriously question the relationship. This was in part because of the widespread acceptance of the test hsCRP (highly sensitive C-reactive protein), a test for low-grade systemic inflammation as an independent risk factor for coronary disease.  It was easy to infer that because periodontal disease is a chronic inflammatory condition, can lead to bacteremia, and is a potential cause of systemic inflammatory marker elevation, that is “just made sense” that it is a cardiovascular risk factor.

I hope this 20 year walk down the path of least resistance is one I and others will remember when presented with an observational study purporting to show a relationship. Although I tell patients frequently that just because one factor precedes or coexists with another that it does not automatically follow that one causes the other, I too am obviously guilty of falling into this trap.

Sometimes as a medical community we are criticized for insisting on controlled, randomized, blinded studies to prove efficacy of our treatments, tests and procedures. It can be an expensive, time consuming and sometimes frustratingly tedious process.  Still, without solid scientific controlled studies we will be at risk of taking what seems to make sense as factual.  Bleeding sick patients was accepted as dogma in centuries prior to use of the scientific method, and we need to beware believing everything we see.

Certainly don’t go out and start using all the drugs mentioned in the interview, but it is fun to watch and get you thinking.  Enjoy.

You may also like these previous posts:

Aspirin:  Should You Take One a Day?

Statin Side Effects:  Add Type 2 Diabetes

One other comment is that the video implies that only if a large heart attack occurs is cardiac arrest likely.  Actually even small heart attacks, and likely even episodes of coronary ischemia not severe enough to cause actual death of cardiac tissue can lead to cardiac rhythm disturbances, a.k.a. cardiac arrhythmias that may cause cardiac arrest and sudden death.

The key to preventing coronary artery disease, heart attacks, heart failure and cardiac arrest is to lower your risk of developing atherosclerosis.  The primary risk factors are tobacco use, high blood pressure, diabetes, lipid abnormalities like high LDL cholesterol and low HDL cholesterol, obesity and sedentary lifestyle. In some cases other familial factors play a role, but most often a strong family history of heart disease is because of a hereditary tendency to one or more of these risk factors.

So what do you do? In order of importance in my opinion:

• Don’t smoke.  If you do smoke quit now.
• If you have high blood pressure be sure it is well controlled.
• If you have diabetes do everything you can to control your blood sugars.
• If you have high LDL cholesterol and other risk factors discuss use of a statin or other lipid lowering medications with your doctor.
• Stay fit.  Exercise regularly, reduce your dietary animal fat intake, and lose weight if you are overweight or obese.
• If you already have atherosclerotic vascular disease, i.e. if you have had a heart attack, stroke, or peripheral artery disease even more aggressive treatment of risk factors like high cholesterol, high blood pressure, obesity, and diabetes is important.  Ask your doctor about how to accomplish these things.
• Ask your doctor about taking an aspirin daily.

Why don’t I do a better job?  I suspect it is a combination of factors.  I think the first is that this is rarely high on a patients list of topics they want to discuss at an office visit.  It is easy to put off this discussion when seemingly more pressing issues are the patient’s expressed reason for the office visit.  Even at physical exam visits, or in the medical coding lingo “preventative care” or “health maintenance” visits, it is alluring to focus on topics that lead to a longer or healthier life rather than a better death experience.  Here is the list of the physician-related barriers to completion of an advance directive listed in the AFP article:

• Discomfort with the topic.
• Lack of institutional support.
• Lack of reimbursement.
• Lack of time.
•  Waiting for the patient to initiate the discussion.

In my case it is certainly not discomfort with the subject, and I am not intentionally waiting for the patient to bring up the subject, but lack of time and reimbursement undoubtedly play a role.

In addition most patients really don’t need my help in working through this decision process if they address the issue before there is a crisis. Although there are cultural, personal and ethnic variables that shape our decision making, most of my patients can  really quite quickly and easily work through the process of completion of both a very functional living will and a durable power of attorney without my assistance.  So why doesn’t everyone just do it themselves?  Here are the barriers listed in the AFP article that are patient related:

• Fear of burdening others, i.e. family or friends.
• Health Literacy
• Lack of interest or knowledge of the subject.
• Spiritual, cultural or racial traditions.
• Waiting for their physician to initiate the discussion.

So how can you just “Do it yourself?” It’s really easy.  Obvoiusly since you are reading this article you have access to the internet, and everything you need is just a few clicks away.  I encourage you, if you have not already completed these documents, to DO IT NOW:

1. Down load your state’s Advance Directives at the caringinfo.org site.  This is really easy and you can get everything you need by selecting your state from the list here.
2. Many states have a form called a POLST form.  This stands for physician orders for live sustaining treatment.  If you use a search engine like Google, and you type in your state + POLST form you will easily find a form to download if your state has a POLST form.  You can get the Washington State form to download easily at WA POLST download.  Many physician offices have these available, just ask your doctor.
3. For some people a form to help you ascertain your values on this subject and to make your values clear to the individual you choose to have your medical power of attorney is helpful.  The University of New Mexico  Institute for Ethics has published online a non-copyright protected form for you to download.  Some patients will find it helpful to attach this to their advance directive as guidance to their proxy in making decisions in line with their values.

There you have it.  You have no more valid excuses to keep you from completing your own advance directive and living will.  Once you complete it be sure to not keep it a secret.  Give a copy to your physician, to the person you choose as your DPA, and keep a copy handy at your home.   Don’t be a victim of your own procrastination or discomfort with this topic.  If you find it helpful ask questions on the subject up with your personal physician.  Be sure to let them know you have these documents completed.

In my best cheer-leading mantra:  You can do it!  Go – Go – Go!

Look at both the subcutaneous fat and the fat inside the abdominal cavity in this overweight patient at laparotomy.

My cadaver for dissection  in medical school was an old man, who was quite thin and had very minimal visceral fat, and when I saw my first few general surgical abdominal cases I was impressed by the amount of fat in the epiploical fat in the omentum and around the mesentery of many patients. I somehow had thought that most of our belly fat was just between the skin and the abdominal cavity, i.e. subcutaneous fat. In obesity a part of out abdominal girth is made up of intraperitoneal (inside the abdominal cavity) fat.

A Nov. 2008 NEJM article reported on a very large study of biometric measurements and showed that the rates of death were clearly related to “abdominal adiposity.” The study showed that increasing abdominal circumference and an increased ratio of abdominal circumference to hip circumference were both significantly related for a higher death rate. This correlation held up even when controlled for BMI, a general measure of height for weight. In other words if you have more belly fat that is a bigger health risk factor than if you carry your weight in your thighs, buttocks or breasts. Those of us with belly fat as opposed to having a fat in other places have long been known to be at higher risk of heart attacks, and recent research suggests correlation of belly fat with diabetes, and possibly some cancers.

So why does increased intra-abdominal fat, also called visceral fat, correlate with heart disease. Animal studies in mice show that increased visceral fat leads to higher rates of inflammation. There is considerable evidence that measures of low-grade inflammation, like highly sensitive C-reactive protein (h-CRP) are indicators of higher risk of coronary heart disease. A condition called metabolic syndrome is defined by having increased belly fat, an abdominal circumference of more than 40 inches (measure the smallest abdominal circumference, usually just above the umbilicus while standing at rest) along with borderline or high blood pressure, low HDL cholesterol and borderline or slightly high fasting blood sugar. Metabolic syndrome is felt to be a pre-diabetic condition and is a risk factor for the same types of cardiovascular conditions as diabetes.

Unfortunately we don’t really get to choose where we become obese. Don’t believe the headlines or web sites promising a secret fix to lose your belly fat, or any other particular fat you dislike. There is no believable evidence to support specific exercises to lose weight in specific areas. We can get stronger muscles in areas we exercise, but cannot specifically lose our belly fat, or any other fat by any means other than overall reduction of body fat, i.e. weight loss. Weight loss is not easy, and maintaining weight loss is arguably even harder than losing weight. I have patients who truthfully assure me that they have lost hundreds of pounds, they have just gained it all back and more.  Still reduction of total body fat is the only way to reduce belly fat, so I know I need to keep up my exercise and my efforts to eat better to lose my belly fat. Wish me success in my ongoing fight to lose my belly fat.

I’ve heard from patients and red in the news about the fact that Pradaxa cannot be reversed with vitamin K like warfarin can. I think this is a seriously flawed argument. The Pradaxa half-life is short enough that requires twice daily dosing (12-17 hours) and within about 36 hours after the last dose of Pradaxa it’s anticoagulation effect should be largely gone in patients with normal renal function. When using vitamin K as an antidote warfarin it takes a day or two for significant hepatic metabolism of the coagulation factors inhibited by warfarin and I seriously doubt if use of vitamin K leads to a reversal of the anti-coagulation in warfarin patients any faster than or even as fast as simply discontinuation of Pradaxa therapy. It’s true that in major emergencies either fresh frozen plasma or other coagulation factor products can be used as an infusion to reverse the quite neuropathy in warfarin use. Pradaxa works directly as an inhibitor of coagulation, so its anticoagulation effect should be less responsive  to this type of therapy. Still I suspect that the argument that there’s no antidote for Pradaxa is less important clinically than it sounds in newsprint.

It will be interesting to see how the aftermarket evaluation of Pradaxa and the other newer anticoagulants bears out. Patients taking Pradaxa seem to certainly appreciate not needing to have frequent coagulation clinic visits to monitor their quite elation status necessary with warfarin use, and so far thankfully I’m not aware of any of my patients who have had bleeding complications from Pradaxa. I seem to see the current local cardiologists still prescribing Pradaxa fairly frequently and my expectations are that as more data comes to bear on the situation Pradaxa will be found to have a bleeding complication rate fairly similar to warfarin. Stay tuned for more updates regarding Pradaxa side effects and efficacy as they become available.

How Doctors Die by Ken Murray a FP at USC.  

It is largely anecdotal, but is a really an interesting perspective on how at least some physicians choose to forgo futile end-of-life treatments because they know the limits of modern medicine first hand.

Also Enjoy:

Octogenerian’s Letter to Santa

I want to weigh in briefly on all the headline news on the review in the online Archives of Internal Medicine about the increased incidence of type 2 diabetes in older women taking statins.  In this analysis of the data from the Women’s Health Initiative an increase of about 50% in the incidence of new cases of diabetes was found in women taking a statin when compared to women not taking a statin.  At first glance this sounds terrible.  Giving people at high risk of cardiovascular disease a drug that increases their risk of developing diabetes when the leading cause of death in diabetic patients is cardiovascular disease may seem odd.

For me this is really a call to reason.  I hear jokes about putting statins in the water supply as if they are a magic medication that patients really need a reason not to take.  The bulk of the evidence is clear that statins are indeed a terrific class of medications. In patients with cardiovascular disease, and in patients at high risk of cardiovascular disease, statins have proven to reduce rates of death and cardiac events like heart attack and stroke in study after study.  Still, even drugs with all the positive outcome data of the statins is not without risk.  The potential for statin side effects especially myalgia are well-known. Now we can probably add an increased risk of developing diabetes to the long-term statin risks.

I suspect that when the dust settles on this issue we are going to continue to encourage the use of statins for patients with elevated LDL cholesterol when their whole profile of risks (looking at other factors like smoking, blood pressure and diabetes in addition to just their LDL cholesterol) puts them at high risk.  I also suspect that we will become more circumspect about advising statins for patients with moderately high cholesterol and few other risks.

It looks like our water supplies are safe from added statins for the time being.  We can probably add an increased risk of type 2 diabetes to the list of statin side effects.

See also:  Simvastatin vs. Lipitor and Any Advantages or is Livalo Just One More Statin?

Click on this Image to Go to the Million Hearts Site Now!

• A= Aspirin for those people at high risk. This generally means adults with high blood pressure, diabetes, any type of vascular disease like peripheral vascular disease, coronary disease, carotid disease etc, smokers, people with high cholesterol or high blood pressure, and those with a strong family history of heart attack or stroke.
• B= Blood Pressure Control: Sounds obvious, but less than half of Americans with high blood pressure have it adequately controlled. Don’t settle for suboptimal blood pressure control. Work with your doctor to do what it takes to gain control. Also focus on the non-medication things you can do like salt restriction, weight loss and more exercise.
• C= Cholesterol management: Goals vary for different people, but ask your physician what your goal cholesterol should be, and if needed use medication plus diet to get to that goal.
• S= Smoking Cessation: If you smoke quitting is probably the number one thing you can do to reduce your chances of a heart attack or stroke. People always correlate smoking with cancer and lung disease, but the leading way smoking kills is from cardiovascular diseases like heart attacks and stroke. Do whatever it takes to find a way to quit.
So this year give the most precious gift of all, yourself through improved health and longer life, to your loved ones.

Add Some Red to Black Friday and I’ll give some Green to the American Cancer Society

Millions of Americans shop for Christmas gift bargains on Black Friday every year.  I encourage you to give a gift on Black Friday that costs you nothing more that a little time, and which can help you feel you have truly given life and hope during this holiday season.

My readers will know that I’m a big proponent of regular blood donations.  Kay, my wife has ovarian cancer and has been a recipient of donated blood when her blood counts get low from chemotherapy.  Cancer patients are among the highest users of donated blood products from red blood cells to platelets.  I’m donating regularly to be sure our family puts more blood into the blood banking system than we take out. I want you to join with me on the Friday after Thanksgiving this year by paying a visit to your local blood donation center.  There are even potential blood donation health benefits.

I’m putting out a challenge to readers, your friends and anyone else you can contact.  Black Friday is a day when many of us are out and about shopping and getting ready for the holidays.  The holiday season is also a time when blood donations tend to fall behind need.  Here is the challenge:

I’ll donate $1. (up to $1000) for every comment to this post or tweet me @DoctorPullen telling me that you have or intend to go to your local blood donation center on Black Friday and donate blood. $1. may sound like chump change, but I want to get 1000+ people who would otherwise not donate blood to do so this Friday.  We are in a world of easy communication, and I bet everyone who reads this knows 10 people who are in a position to get to their blood donation center this black Friday and donate.  Just do it!

Take a break from shopping, get off your feet, and relax while you give one special holiday gift.  Use the twitter or facebook links to send this off to your friends, tell your coworkers, shout from the roof tops, whatever but let’s make this Black Friday blood red with our generosity.

My daughter, son and I plan to go to the local Cascade Regional Blood Bank center in Puyallup Friday. I checked and they are open 7:30 AM – 5:00PM.  I’ll try to keep a counter going on the site to let you all know how we are doing.

They Turned Me Away Today

Egg on my face.  I went today to donate, but was turned away because I went to Belize on vacation a couple of months age, an area with malaria exposure potential.  I’m now ineligible for a year, joining a majority of the rest of Americans.  If you are among the 37% who are eligible donors get to your blood donation center and give.  Keep our blood supply safe and plentiful.  Happy Thanksgiving.

Don’t miss a post.  Subscribe using the right sidebar feature.

You may also enjoy:

Actual Causes of Death in the U.S.: Not What You’d Think

Leading Preventable Cause of Death in America

An argument can be made that knowing when not to do screening for a disease or condition is as important as knowing when to do screening.  The USPSTF makes recommendations to physicians and patients about what screening preventative services should be done in asymptomatic patients, and which should not be done routinely. The USPSTF is an evidence based decision making body. They carefully review the evidence and make recommendations for or against screening based solely on the available evidence which helps keep emotional and arbitrary recommendations from becoming the mandate. The recommendations are separated into 5 grades:

• A Recommendation: The USPSTF recommends the service. There is high certainty that the net benefit is substantial.
• B Recommendation: The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.
• C Recommendation: The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.
• D Recommendation: The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.
• I Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

I thought it was timely to list a few of the screening services that the USPSTF recommends against, or finds insufficient evidence to make a recommendation for or against. This list is not intended to be comprehensive. See the USPSTF site for a complete list of their screening recommendations.
Cancer Screening Recommendations:

• The USPSTF recommends against routine testicular cancer screening in adolescent and adult males. D recommendation.
• The USPSTF recommends against routine ovarian cancer screening. D recommendation.
• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of using a whole-body skin examination by a primary care clinician or patient skin self-examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer in the adult general population. I recommendation.
• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of prostate cancer screening in men younger than age 75 years. I Recommendation.
• The USPSTF recommends against screening for prostate cancer in men age 75 years or older.  Grade: D Recommendation.
• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for bladder cancer in asymptomatic adults.  Grade: I Statement.

Heart and Vascular Disease Recommendations:

• The U.S. Preventive Services Task Force (USPSTF) recommends against screening for asymptomatic carotid artery stenosis (CAS) in the general adult population.  Grade: D Recommendation.
• The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening with resting electrocardiography (ECG), exercise treadmill test (ETT), or electron-beam computerized tomography (EBCT) scanning for coronary calcium for either the presence of severe coronary artery stenosis (CAS) or the prediction of coronary heart disease (CHD) events in adults at low risk for CHD events.  Grade: D Recommendation.
• The USPSTF found insufficient evidence to recommend for or against routine screening with ECG, ETT, or EBCT scanning for coronary calcium for either the presence of severe CAS or the prediction of CHD events in adults at increased risk for CHD events.  Grade: I Statement

Other Recommendations:

• The U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening adults for glaucoma. I recommendation.
• The USPSTF recommends against screening adults for chronic obstructive pulmonary disease (COPD) using spirometry. D Recommendation

These recommendations are for screening in asymptomatic persons. They are not recommendations against testing for a disease in the presence or symptoms or other factors where making a diagnosis may alter management decisions.
At first glance these recommendations  may seem disappointing. Intuitively it seems like early diagnosis of cancer, glaucoma, coronary disease or chronic lung disease should lead to better outcomes. Unfortuntely the data does not lead to those conclusions. In some cases like prostate cancer screening the early diagnosis may lead to more morbidity and problems from testing and treatment than benefits of the earlier diagnosis provide. In other situations like screening for coronary disease screening the high incidence of false positive tests and the low prevalence of disease make screening impractical. In still other situations like COPD making the diagnosis does not lead to effective interventions that alter the course of the disease.
I am grateful that the USPSTF puts out these recommendations, and am hopeful that they will become more active again after political pressure of late seems to have slowed the pace of their production to a point where new recommendations are needed in important areas like PSA screening.

by Charles Boren

The ancient Greeks used running as a form of training and competition. It was a way to test personal fortitude and improve physical health. Many of the health benefits of running were known even in those ancient times. In modern times, many start running for the same reasons. They run to improve their physical endurance, lose weight and build muscle. While these common health benefits of running influence many to start running, runners are surprised to learn just how extensive the health benefits are. Running improves the quality of sleep, fights off depression and anxiety, and improves joint health and stability.

Sleep disorders affect a surprising percent of the population today. There is good news to those who suffer from them. Running can actually improve the decrease the symptoms of sleep disorders and improve the quality of sleep. It also appears to help people sleep more efficiently. That is, the amount of time spent actually sleeping while in bed increases. Running helps people fall asleep more quickly, toss-and-turn less through the night, and wake up more rested than those who do not run.

The runner’s high is a well-documented phenomenon, and major benefit, of running. This is a unique feeling often reported during long, strenuous amounts of exercise. The feeling can range from relaxed and peaceful to intensely euphoric. It is produced when endorphins flood the brain as part of a stress response to running. These endorphins are the natural drugs of the body. They reduce pain and are responsible for the happy and content feelings similar to many those produced by narcotics. While many runners experience this phenomenon, many do not realize the long-term positive effect that is has. Over time, the regular doses of endorphins to the brain can combat both anxiety and depression. In fact, many studies have shown that following a regular running program markedly reduces the symptoms of these disorders.

A common misconception is that the high-impact nature of running negatively affects the joints in the body. The truth is that running may actually improve joint health and stability. (1) This is done in a number of ways. First, running helps keep excess weight off. Just a ten-pound increase in body weight can cause a 45-pound increase in stress on the knees (2).  Second, running causes cartilage to expand and contract with the natural movements created while running. This forces nutrients and oxygen into the cartilage cells. Without this, the cells will slowly die from oxygen depletion and starvation. Third, running strengthens the tendons and ligaments that support and stabilize joints. This prevents injury in the long-term. Overall, running greatly improves joints and prevents the onset of arthritis.

Building muscle, losing weight, and strengthening the heart are the health benefits that motivate people to start running. However, it is the unspoken benefits that keep them running. As a whole, runners have better sleep, improved mental states, and healthier joints. Many runners feel that they are taking responsibility for their health by running. They physically feel better, less stressed and they have peace of mind. This is a reward all in itself.

Bio: Charles spends much of his free time running. On the side he also runs an automotive company, where he purchases vehicles.

Tabex was reported in the prestigious New England Journal of Medicine to be more effective than placebo for help in quitting smoking.  Sounds great until you read the actual numbers.  Tabex was shown in a single fairly small study including only 740 patients that was conducted in Poland to have a 1 year success rate of 8.4% as compared to a 2.4% success rate with placebo.  Admittedly this sounds like it is helpful in a small percentage of patients, but at best only about 1 in 12 patients using Tabex will be successful in quitting smoking.

Still having an inexpensive and over the counter product patients can use to try to get help in quitting smoking is exciting.  Studies show that most smokers would like to quit smoking.  Smoking rates have decreased significantly in the United States over the last couple of decades, but many patients in my practice just cannot seem to quit smoking.  Chantix has been quite helpful for many patients, but significant Chantix side effects including cardiovascular concerns, vivid dreams, depression and even suicidality have been deterents to Chantix use. The high price of Chantix is also a major deterrent to widespread use.  Bupropion, originally marketed as Zyban for smoking cessation, is sometimes helpful, but far from a panacea.

Tabex, chemical name cytosine, is structurally similar to nicotine, and functions as a nicotinic acetylcholine receptor agonist.  It is an extract of the seeds of Golden Rain acacia (Cytisus laborinum) and Chantix is actually a derivative of cytosine and has been approved for smoking cessation in the U.S. since 2006.  Tabex has b een used in Europe for nearly 40 years for smoking cessation and has been produced by a Bulgarian company Sopharma AD.

In the NEJM study Tabex was used on a 25 day tapering schedule, taking 6 tablets daily for the first 3 days, five tablets on days 4-12, and then tapering more quickly by taking 4 days on 4/day, 4 days on 3/day, until stopping on day 25 after 2 days of two tablets daily.  At this dose toxicity seemed minimal, although the authors admit the study was too small to find uncommon adverse effects of Tabex.   Cytisine has been documented to have serious side effects at much higher doses, so users should not take more than this regimen used in the NEJM study.

Tabex appears to be inexpensive, on E-bay I found vendors selling #100 1.5 mg tablets for $13.35 USD.  This would amount to enough pills for a person to take the recommended 25 day regimen and have just a few pills left over.  This compares to Chantix which costs about $179/ month at Drugstore.com.

This small NEJM study implies that this inexpensive, seemingly fairly safe drug, available without a prescription, is marginally effective for helping smokers quit the habit.  I think it may be worth a try for smokers who have been unable to quit using nicotine replacement systems, cannot tolerate, cannot afford or have reasons not to use Chantix, and are motivated to quit.  The long term adverse health effects of continuing to smoke seem to far outweigh the risks of essentially all of the smoking cessation aides for patients without specific contraindications to their use.

In European use for over 40 years there does not seem to have been much in the way of serious problems with Tabex use, and I anticipate the use of Tabex to increase significantly in the U.S since the NEJM article has given more validity to its use.

There is really little to no evidence that the other SSRI drugs like citalopram or sertraline help patients to quit smoking.

The abstract of the NEJM article is available here.

Tagline:  But Not By Much, and at a High Cost.

July 20, 2011 AstraZenica received FDA approval for their new antiplatelet agent Brilinta (ticagrelor) for use in acute coronary syndrome.  Brilinta joins an increasingly crowded market of antiplatelet agents that includes the longstanding leader in the class Plavix and Effient, which came to market July 10, 2009.  Effient has not become terribly popular, likely due to its higher rate of bleeding complications including life threatening bleeding and an increased incidence of stroke in patients with previous stroke.  These risks seem to have held sway over the modestly reduce rate of restenosis of coronary artery stents seen in Effient vs. Plavix patients when used post coronar artery stent placement.

The primary selling point of Brilinta is that in the PLATO clinical trial the mortality rate in patients with acute coronary syndrome was stastically significantly lower in patient using Brilinta (9.8%) vs. Plavix (11.7%) P<0.001.  Patients on Brilinta had lower death rates from heart attack and stroke, but had higher rates of non-fatal bleeding complications. The reversible mechanism of action of Brilinta has its drawbacks though, requiring twice daily dosing vs. daily dosing with Plavix.

The primary issue with Brilinta is whether this statistically significant reduction in death rates in acute coronary syndrome is practically significant, and whether the potential drawbacks of twice daily dosing and the non-compliance issues this may engender will erode those benefits when used for longer periods of time.  When the Plavix patent expires soon and generic clopidogrel becomes available the benefits of Brilinta and its current high cost of $7.24/day will need to be enough to make that cost difference palatable.  Plavix has been an effective, well tolerated and extremely popular drug. It is the third highest gross sales drug in the US  (2009 data) and is anticipated to be available as an inexpensive generic in about May 2012.

These are some of the pros and cons that patients and physicians will need to consider when making a decision between Plavix and Brilinta

Brilinta, like Plavix and Effient works as a platelet aggregation inhibitor, but acts with a slightly different mechanism of action, binding at a site different from the ADP receptor it blocks.  It is a reversible receptor inhibitor, and Brilinta, unlike Plavix does not require hepatic activation which may be a potential advantage in some patients. The importance of the hepatic metabolism issue in overall efficacy is unclear, and this may be just a theoretic issue of little clinical significance.

Brilinta currently has a black box warning similar to that with Plavix warning against use in patients with active bleeding, a history of intracranial hemorrhage, and tha bleeding should be suspected in any patient with hypotension who has had a recent procedure like CABG, coronary angiography or any other surgery.  Unlike Plavix the black box warning also includes an increased risk of cardiovascular events if Brilinta is discontinued, making the twice daily dosing and compliance an even larger concern.  The black box warning also noted the reduced effectiveness of Brilinta if aspirin at doses higher than 100 mg daily are used.  This could easily be done inadvertently in patients taking OTC aspirin products.  If you do not personally have a history with Aspirin usage, consider this resource about aspirin side effects.

An unexpected issue with Brilinta is a much higher incidence of dyspnea (13%) vs Plavix (7%).

In summary I expect Brilinta to be a niche product used in uncommon circumstances once clopidogrel becomes available as an inexpensive generic.

All of the drugs released so far work as direct inhibitors at one point or another in the coagulation cascade, unlike warfarin which as a vitamin K antagonist works by reducing the production of key clotting factors.  Apixaban and Xarelto are factor Xa (X as the Roman numeral for 10, and “a” for activated) inhibitors, and Pradaxa is a direct thrombin inhibitor.  They are immediately active in their functional roles after being absorbed from the gut, and so the speed of action of these drugs is much faster than the speed of action of warfarin.  This is likely to play a key role in looking at the overall cost of use of these drugs.  Warfarin use requires several days to take effect, and the necessary dose is highly variable.  From significant personal experience I can say that when quick anticoagulation is needed as in DVT management there are two major drawbacks to warfarin use.  First it is necessary to treat patients with heparin initially in order to get prompt anticoagulation.  Secondly it is very common to take a week or more to achieve therapeutic levels of anticoagulation. Often the initial dose chosen is either too high or too low. The prothrombin time, or more commonly the INR, is used to measure the degree of anticoagulation with warfarin.  Dosing of warfarin can be anywhere from <1 mg daily to 15 mg daily, and is difficult to predict.  It is not uncommon to have patients significantly over anti-coagulated a week after starting warfarin requiring that the dose be reduced, only to then to reduce the dose and a few days later find that they are now significantly under anti-coagulated.  This yo-yo effect necessitates frequent INR monitoring and visits to have INR testing.  Essentially all of the new drugs work within one to two days, and are twice a day dosed because of relatively short half-lives.  Although twice daily dosing may seem a drawback due to patient compliance issues (vs. once daily warfarin dosing),  I see it a potential benefit because its corollary is that the drug will be out of the system quickly so that any bleeding complications will likely be short lived when they do occur.

Warfarin can be reversed with vitamin K or fresh frozen plasma, but the use of vitamin K takes at least a couple of days, and use of fresh frozen plasma exposes patients to human blood product risks.  I see the faster onset and faster loss of efficacy of apixaban and Pradaxa as significant benefits.

This combined with superiority in three major measures of efficacy and safety for apixaban make it likely that when this drug is approved for use in the U.S. that it will become a very popular new drug.  Pradaxa is already gaining traction among cardiologists in stroke prevention in atrial fibrillation patients, but I suspect that unless Pradaxa can show superiority rather than its current “non-inferiority” claims to warfarin that apixaban may quickly gain favor among physicians and patients. Another drug rivaroxiban is already on the market in Europe and has shown non-inferiority to warfarin in stroke prevention, superiority in bleeding risk, but did not improve overall survival in comparison to warfarin.

Apixaban is in phase three clinical trials and is expected to receive FDA approval by the end of 2011. Some market analysts anticipate that apixaban may end up the overall winner in the competition for the leading position among the new anticoagulant drugs. I suspect that they are correct because to this point only apixaban can claim significant superior efficacy and safety in comparison to warfarin.  I expect warfarin use to be significantly impacted because in addition to the increased efficacy and increased safety, its use eliminates the need for INR monitoring. The real question is going to be whether the first-to-market advantage of Pradaxa is enough to hold off apixaban, and whether insurance companies perceive there is an overall cost benefit to paying for the new drugs.

Another issue is that Pradaxa is only approved for use in non-valvular atrial fibrillation for stroke prevention, and Xarelto is only approved at this time for post-operative DVT prevention in total joint replacement patients. It is likely that apixaban will only get an indication for stroke prevention in non-valvular atrial fibrillation.  I expect wider indication approvals to be forthcoming for this class of drugs as there is little reason to expect that they will not also work for therapy of DVT and DVT prophylaxis in hypercoagulable states.  Stay tuned to see if apixaban gains the popularity that some predict it is destined to have.

So what are the benefits of resistance exercise?  Actually they are multiple, some obvious and others less obvious.

• Resistance Exercise Builds Strength:  This is one of the obvious benefits, but some aspects may not be appreciated. One aspect that some may not fully appreciate is that this benefit does not go away with age.  One study of the elderly (average age 87) showed that an 8 week program of resistance training 3x/ week increased strength by over 100%, increased walking speed by 12%, and reduced the incidence of falls.  With the sedentary life style many jobs enforce, and the lack of outdoors physical work by many of us, resistance training can make a huge difference in the way we feel, in our functional capacity to do tasks without hurting ourselves, and in our overall functional capacity.
• Resistance Training Builds Bone Strength:  Bones are a living tissue, constantly remodeling based on the stress loads placed upon them.  Resistance training while bearing weight can lead to increased bone strength and help prevent the fractures of osteoporosis as we age.
• Resistance Training Helps Lower Mild Hypertension:  Aerobic exercise is the backbone of maintaining cardiovascular health, but resistance training also helps reduce blood pressure to at least some degree.
• Resistance Training can Increase Metabolic Rate:  Aerobic exercise is again the mainstay of weight control and maintenance, but there is considerable evidence that resistance training when combined with aerobic training leads to higher metabolic rate and more weight loss than aerobic training alone.
• Improved Self Image:  This is just my opinion and experience, but I believe that maintaining strength, physical capability and muscle mass is has a positive effect on self-image.  I know I feel better about myself when I feel strong and fit.  Resistance exercises are a key to this for me.

If you believe in the benefits of resistance exercise how should you go about setting up a program?  First be real with yourself.  Set goals that you believe are possible, sustainable and affordable.  You can go to a gym, buy free weights or machines for home, or simply do exercises using your own body weight like pushups, pull-ups, and squats.  Rubber band type resistance equipment is inexpensive and very effective.  Secondly aim for 3 days a week for resistance exercise.  Taking a day between training sessions gives the muscles exercised time to recover and grow.  Third learn from Milo of Croton in that progressive overload is the principle behind steadily increasing strength. You don’t need a calf to carry every day until it has grown.  Just start with exercises where 8-15 repetitions lead to fatigue.  Once this is easy, slightly increase the resistance.  Keep increasing the resistance as the exercise becomes easy.  Last if a certain exercise leads to persistent pain, change something rather that thinking you can work through the pain.  Often some minor change may avoid an overuse injury.

Add resistance training to your regular exercise to reap the full benefits of exercise.  Enjoy.