Taking BP Medications at Night More Efficacious Than in the Morning

The European Heart Journal published the Hygia Chronotherapy Trial which followed hypertensive patients in Spain for a decade between 2008 and 2018. There were 19,000 participants of whom 10,600 were men, all older than 18 and all being treated for high blood pressure.  The group was randomly selected to either take their blood pressure medications at bedtime or in the morning.  They were followed with frequent blood pressure checkups plus 48-hour ambulatory blood pressure monitoring to assess their sleep time blood pressures.

The study was performed only on Caucasian participants who went to sleep on what would be considered a normal day/night schedule.  The results were significant and important.

Those who took their blood pressure medications at bedtime saw the risk of dying from a heart or blood vessel related problem drop by two-thirds compared to those who took their meds in the morning.  Night time administration of blood pressure medications resulted in a 44% drop in heart attack risk, a 40% drop in the need for coronary artery revascularization, a 42% drop in the risk for heart failure and a 49% drop in stroke risk.  The overall reduction in risk for cardiovascular death was 45%.

This is a significant study which must now be performed in patients of color who tend to have higher night time blood pressures.  While these studies are in progress, it appears that taking your blood pressure medication before bed is the correct choice.

Healthy Aging – Adjustments for Living & Reality

For several years now my wife has been complaining that I do not hear her when she talks.  I have gone for regular ENT checkups with audiology testing and while there is clearly a drop in hearing certain frequencies, my word discrimination and comprehension put me in a position of delaying using hearing aids for another year.

I was aware I had trouble hearing my middle adult daughter’s voice frequency.  I was missing words on TV especially when foreign accents were present leading to the purchase of TV Ears which solved the problem.  Still I knew that without auditory stimulation your brain deteriorates at a faster rate.

Last year the ENT doctor sent me home with a pair of hearing aids to try.  “Your wife called and said that if you don’t try them she may find me and kill me in my sleep.”  I was so angry with my wife for interfering that I made a point of pretending not to hear her every time she addressed me and I had the hearing aides in.  Those hearing aids were returned within the 30-day trial period because I could not use my stethoscope with them in.

One year later I was back again and this time my hearing test showed some drop in my word discrimination. They suggested trying a blue tooth compatible pair of hearing aids and even took out a stethoscope to show me how my hearing was enhanced using the stethoscope thus eliminating my favorite argument.   I wore them home and frankly they are wonderful.

The next day I had an appointment for my six-month eye exam. My acuity was off and I suspected my visual field in one eye had diminished based on driving and athletic pursuits.  The test confirmed my suspicions with my ophthalmologist diagnosing “normal pressure glaucoma” in my right eye.  “We need to lower the pressure by 3% with the drops I am prescribing and if the pressure doesn’t decrease we will recommend a laser surgery procedure in three weeks.  You are not going blind, but we want to preserve your visual field.”

The look on my face advertised my disappointment.  “It’s not so bad, you have sent me hundreds of patients with this situation and we helped them all. Why are you so troubled over this?  Looking at your med sheet and problem list at least you aren’t complaining about ED.”    When I didn’t answer her there was a long pause and she said, “Oh, I am sorry if I brought up a difficult topic.”   The best I could mutter was that in geometry what was once an acute angle is now an obtuse one.”

I tried to sell the fact that my dermatologist had me on a short-term course of prednisone which was raising the ocular pressure, but she wasn’t buying that argument.  New glasses, nightly eye drops and hearing aides all in a 72-hour period.

Instead of being grateful and thankful that I had minor correctable issues, and I could afford to spend the $6000 plus dollars for hearing aides and new trifocal lenses, I was moaning and groaning about the trials and tribulations of healthy aging. It was like running into the ocean surf on a hot day preparing to dive in to the surf and cool off and an unexpected wave smacks you down and stuns you before you can dive below its crest and avoid the strong impact.  I was devastated.

It took about 72 hours to adjust.  At my regular Friday night dinner with friends my buddy said, “Steve you seem to be hearing much better tonight. We did not have to repeat anything. What are you doing?”   I told him I was wearing new hearing aids which he had not noticed.  I hear better through my stethoscope than I did before.  When I walk my dogs or take my daily walk I hear the birds chirping, the children playing, the sprinklers initiating their watering cycle. These are all sounds I had forgotten about.  At lectures and movies I am hearing clearer. The blue tooth connection to my cellphone makes calls easier to complete.  My new trifocals allow me to read up close far more easily and see distance much better.

As a physician and geriatrician, I stress eye exams, hearing tests and evaluations to determine our ability to stay independent and functional. I cannot explain why I was so resistant to applying the same principles to my own health.

My day-to-day life has improved markedly with the hearing enhancement and new glasses. I hope my patients and students will look at my stubbornness and reluctance to accept healthy age-related changes as an example of how hard we cling to our independence and how reluctant we are to give up pieces of it even when we know it is for the best.

Hypertension Guidelines Versus Life Experiences

One of the advantages of practicing clinical medicine, and seeing patients daily for many years, is you develop your own long-term study regarding certain medical health issues. In the area of hypertension, I have been taught by the best since my internship with pioneers such as Eliseo Perez Stable and Barry Materson at the University of Miami affiliated hospitals, Jackson Memorial Program, ensuring that their trainees were up to the task.

The goals and guidelines have changed. Lifestyle changes including salt restriction (sodium chloride), weight reduction, smoking cessation, reducing alcohol intake and regular exercise will always be mainstays of non-pharmacologic treatments.  We used to be taught to keep the systolic blood pressure at less than 140 and the diastolic blood pressure at less than 85.  These numbers have changed over the years, having been lowered, with everyone over 120 systolic now being classified as having some degree of increased risk of cardiac, cerebrovascular or vascular disease and hypertension.

We originally were taught to start with a diuretic and keep raising the dosage until the blood pressure was controlled or the patient developed adverse effects. We learned that when we used one medication, pushing it to its limit inducing adverse effects along the way, patients just stopped taking their medications. This resulted in a change in strategy to using several medicines each with another pathway to controlling blood pressure but all at a lower dosage which did not produce any ill feeling adverse effects.  The downside of more medications was additional costs and more pills to remember to take.  As hypertension experts pushed us to lower systolic blood pressure to 120 or less in our geriatric population I was concerned that lowering the pressure that much would again create adverse effects which were as or more troublesome than the risk  of having a BP between 120 and 140 systolic.  An article in JAMA Internal Medicine looked at this issue. They looked at patients over 65 years of age who were hospitalized for non-cardiac related problems and whose blood pressure was over 120. They studied these patients at Veterans Administration hospitals over two year period. Patients with elevated blood pressure above 120 were given more medications and higher dosages to bring their pressure down to meet the more stringent guidelines. The result was that there were no fewer cardiac events than anticipated and no better blood pressure control at a year.  In addition, these patients suffered from an increased number of re-admissions to the hospital and “serious“ adverse events within 30 days.

The new guidelines for blood pressure control may be applicable in a younger healthier population.  In the geriatric population we may need to readjust our goals to account for the physiologic changes that occur in men and women who age in a healthy manner. More specific data on why there were more re-admissions and what serious adverse effects occurred needs to be made public to determine if the effort to tightly control blood pressure is to blame.

Antibiotic Use – Independent of Physician Prescribing

A recent article in the Annals of Internal Medicine looked at individuals who took antibiotics without them being prescribed by physicians at a visit.  The authors looked at 31 published studies between January 2000 and March 2019.  The medications came from family and friends, online distribution sites, drugs prescribed for their animals by their veterinary doctors and those stored after a previous indicated use.   When asked about it, and the reasons why these patients took these medications, the main factors cited were lack of health insurance or lack of healthcare access, cost of physician visits or medications, long waiting times in clinics, embarrassment for needing antibiotics, lack of transportation and/or easy availability of antibiotics  from other sources.

We are currently going through an antibiotic resistance crisis in the world.  Most of the fault lays with agricultural industry feeding livestock tons of antibiotics to fatten them up. Patterns of resistance develop on the farms and are passed species to species.

To remedy this, the US agriculture industry, especially in chicken production, has cut back drastically on this process.  At the same time, we are requesting physicians to work with infectious disease doctors in stewardship programs to reduce their use of ineffective antibiotics and to prescribe with precision when these medications are needed.  It works. Studies are beginning to show the benefits of these programs.

Despite this, the pressure from patients to be given something when they pay for, and invest in, a medical evaluation for an infection is overwhelming. In the setting of telemedicine, as well as walk-in and urgent care centers, reviews and patient satisfaction survey results are tied to whether the patient was given an antibiotic whether it was indicated or not.

As bacteria become resistant to common and inexpensive antibiotics, pharmaceutical manufacturers are not being incentivized to produce newer more efficacious medications.  At the same time, older useful antibiotics which do not generate much of a profit are not even being ordered and stored by chain pharmacies that lose money each time the older generics are prescribed.

To begin solving this problem, an improvement of our health literacy is required. Education in schools and in public health announcements, both in print and social media, need to realistically address the issue. This education will not replace the need for access to health care and health, but it is a beginning to make individuals understand how, when and why these “miraculous” medications can and should be used.

Heartburn, Indigestion & Protein Pump Inhibitors

I have seen multiple adult patients with intractable heartburn, reflux, indigestion and chest pressure all related to food and digestive enzymes kicking back up the esophagus from the stomach through a lax group of muscles known as the lower esophageal sphincter.  All these patients receive a fiber optic upper endoscopy (EGD) at some point and are observed and biopsied to eliminate the possibility of ulcers, cancer, gastric polyps, esophageal cancer, potential esophageal cancer and Helicobacter Pylori bacteria as the cause.

They are all treated with weight control suggestions, avoiding a host of foods, most of which are quite healthy from a cardiovascular standpoint plus limits on alcohol, elimination of tobacco and other indulgences of adults. We ask these patients to wear loose clothing at the waistline, avoid reclining for three hours after eating and take a host of medicines including proton pump inhibitors (PPI) such as Nexium, Protonix, Prilosec.  Drugs like Tagamet, Zantac (H2 Receptor Blockers), Tums, Rolaids are far less effective.

In recent years, numerous articles have appeared in medical journals stating that protein pump inhibitors, when taken regularly, can predispose to increased and early death, pneumonia and dementia.  A large review article from a prominent GI group in Boston, and published in the New England Journal of Medicine, tried to eloquently refute these claims but the doubt about long term safety lingers buoyed by numerous lay periodicals and online internet sites sensationalizing the down sides of these medicines.

To allay the patients fears, doctors and patients work together to try and stop the PPIs and substitute the older standbys like Tagamet and Zantac but they just don’t provide the symptom relief that the PPI’s do. Patient’s face the dilemma of taking the medicine that works best and incurring the potential risks or suffering.

In a recent edition of the journal Gastroenterology, Paul Moayyedi, MB ChB, PhD from McMaster University in Canada followed 17,000 patients for three years with half the group taking PPI’s. Those taking a PPI (Protonix) for three years had no more illness or adverse effects than those taking a placebo.  L. Cohen, MD, a reviewer at Mount Sinai School of Medicine in NY, concluded that the study provided strong evidence of the safety of PPIs for patients taking the drug for three consecutive years.

The controversy will continue. I am sure next week someone will produce data revealing some additional horrible consequences of taking these medications to relieve heartburn. It will ultimately come down to individual decisions about quality of life versus potential risks because the lifestyle changes necessary to control this problem are difficult for human beings to sustain over a long period of time.

Alzheimer’s Disease – More Insight

The August 1, 2019 issue of the journal Neurology carried a report of a team of researchers who have developed a blood test that can detect the presence of amyloid in the brain with 94% accuracy.  Amyloid is one of the chemical constituents found to be tangling up the neuron nerve communication pathways in humans with Alzheimer’s disease.

The article emphasizes this is currently a strict research tool. It is not a laboratory test that your physician or clinic can order or use to detect this form of dementia early. The results of the blood test correlate well with imaging studies currently in use. It is one small step in the investigation of the causes of this progressive, and fatal, heartbreaking disease and hopefully will allow us to evaluate Alzheimer’s at its earliest stages.

In a journal specifically dedicated to this disease entitled Alzheimer’s and Dementia, researchers at the University of California, San Francisco discussed the increased tendency of patients with Alzheimer’s disease to nap and sleep inappropriately and ineffectively. Previously it was felt that this inappropriate sleep pattern when observed was in fact a risk factor and marker for the development of the disease.

Lea Grinberg, MD and her co-authors feel it is a symptom of the disease instead. They believe that the disease process has already destroyed or inhibited those neurons (brain nerve cells) responsible for wakefulness and alertness. In the absence of this stimulation, patients nap and sleep ineffectively and inappropriately.

Imaging of these areas is difficult to obtain because of their location in the skull and brain but, on detailed studies, more tau protein deposition in these wakefulness areas is visualized.   This concept now allows researchers to zero in on other brain chemicals associated with wakefulness, alertness and sleep as a potential form of treatment of Alzheimer’s disease in addition to those chemicals in the cholinergic system that most medications attack.

Is TMAO the New LDL CHOLESTEROL?

Prevention of heart disease has centered on smoking cessation, controlling blood pressure, achieving an appropriate weight, regular exercise, control of blood sugar and control of your cholesterol.  Despite addressing and controlling these items individuals still have heart attacks and strokes and vascular events. Researchers are now directing their attention to a dietary metabolite of red meat called trimethlamine N-oxide or TMAO.

Recent peer reviewed and published studies have shown an association between high blood levels of TMAO and increased risk of all-cause mortality and cardiovascular disease.  A 2017 study published in the Journal of the American Heart Association found a 60% increased risk of a major cardiovascular event and death from all causes in individuals with elevated TMAO.  Other research has linked high TMAO levels to heart failure and chronic kidney disease.

Our bodies make TMAO when choline and L-carnitine are metabolized by our gut bacteria in the microbiome. Red meat is particularly high in L-carnitine.  A study group at the Cleveland Clinic found that red meat raised the TMAO levels more than white meats or non-meat protein. They also discovered that red meat allowed more bacteria in the gut microbiome to be switched to producing TMAO. Of interest was the fact that the amount of fat in the food, particularly saturated fat, made no difference on the TMAO levels obtained.   Stanley Hazen, M.D. PhD, section head of preventive cardiology at the Cleveland Clinic, feels the TMAO pathway is “independent of the saturated fat story.”  The important issue to Dr Hazen is the presence of the gut bacteria to produce the TMAO from foods eaten.

Not all scientists buy into the TMAO theory of cardiovascular disease because of the relatively high level of TMAO found in many fish.  Some experts believe the beneficial effects of omega 3 fatty acids in fish offset the negative effects of TMAO. The leading researcher on TMAO says it is an evolving study and he is supported by experts who believe TMAO is “atherogenic, prothrombotic and inflammatory” per Kim Williams, M.D., chief of cardiology at Rush University Medical Center in Chicago.

There is even a blood test to measure TMAO levels developed by the Cleveland Clinic and available through Quest Labs.  Do not get too excited about asking your physician to order it on your blood because it requires eliminating meat, poultry and fish plus other food items for several days in advance of the test.

For many years researchers at the Cleveland Clinic and Emory University recognized that 50% or more of heart attacks occurred in men who followed all the risk reduction guidelines including stopping smoking, controlling blood pressure and lipids, losing weight and getting active. Perhaps the answer as to why will be in the TMAO research and the solution will be changing the gut bacteria or their ability to convert L-carnitine to TMAO.