Safety & Efficacy of Lowering Lipids in the Elderly

I am bombarded regularly by older patients, their adult children and various elements of the media with complaints that elderly are taking too many medicines. Poly pharmacy is the word they use and the first prescription medications they want eliminated are their cholesterol lowering drugs – either a statin (Lipitor, Zocor, Pravachol, Crestor , Livalo or their generic form), Zetia ( Eztimebe) or the newer injectable PCSK9 inhibitors Repatha and Praluent. Is there an age that we should stop these medications? Is there benefit in the elderly to continue taking them? Should we start these medications in the elderly if we discover they have high cholesterol and vascular disease?

A recent study was published in the prestigious Lancet medical journal. The authors looked at 29 trials with 244,090 patients. From this pool there were 21,492 patients who were at least 75 years old. Half of them were on oral statin drugs and the others were on Eztimebe or PCSK9 inhibitors. They were followed from 2 – 6 years.

The results showed that for every reduction of LDL cholesterol of 1mmol/L there was a 26% reduction of in major adverse vascular events. These numbers were similar to those in younger patients. The data also pointed out that these patients had a significant reduction in cardiovascular deaths, myocardial infarction (heart attacks), strokes and the need for heart surgical revascularizations. It was extremely clear that if you are on a cholesterol lowering drug you should stay on that medication despite your age!

A study in JAMA internal medicine, authored by LC Yourman, answered the question of whether you are too old to start on a cholesterol lowering drug. They found that it took 2.5 years before the cholesterol lowering medicine reduced your risk of a major cardiovascular event. Their conclusion was that if you are 70 or older, and your lifespan appears to be greater than 2.5 years, you should start the medicine.

Distancing, N95 Masks and Eye Covering Protect Against Respiratory Illness

To wear a facial covering or mask, or not, has been turned into a political affiliation and machismo issue in the United States instead of a scientific, medical and public health issue. A publication in the British medical journal Lancet clearly brought the issue into a medical public health category.  The “cliff notes” summary of the study is that for each meter (2.2 meters = one foot) you distance from a contagious individual, the less likelihood you have of becoming infected with that illness.  Facial coverings diminish your risk of catching the disease by about 15% and N95 or KN95 respirator masks work better than surgical masks, bandanas or cloth masks.

The study was a systemic review and meta-analysis of 172 observational studies involving SARS, MERS and COVID-19 spanning six continents with almost 26,000 participants.  Daniel Chu, MD, PhD made it clear, “The risk for infection is highly dependent on the distance to the individual infected and the type of face mask and eye protections worn. Six feet or more away is the optimal distance to maintain. While N95 masks scored best in terms of protection for health care workers, facial coverings of any type reduced the chance of infections from 17.4% to 3.1%. Eye protection reduced the risk of infection from 16% to 5.5%.”

Due to a shortage of personal protective equipment (PPE), the CDC downgraded its requirements for health care workers treating sick infected individuals  to surgical masks, cloth masks or bandanas.  Professor Raina MacIntyre, MBBS, PhD at the Kirby Institute University of New South Wales in Sydney went on to say that recommending anything less than an N95 mask for health care workers is like sending troops into battle “ unarmed or with bows and arrows against a fully armed enemy.”

Many wonder what the difference is between an N95 respirator mask and a KN95 respirator mask. They both are supposed to prevent 95% of the particles of a certain size from penetrating. If the masks are reviewed and approved and certified by USA agencies such as OSHA or the CDC, they are labeled N95.  If they are reviewed by similar agencies in China, they are labeled KN95. In most cases the product is made outside the USA even if the company is an American firm.

Key points to remember are:

  • Distancing works with over six feet best for preventing person to person transmission of respiratory illnesses like Covid-19.
  • Facial coverings reduce the risk of infection.
  • N95 and KN95 are the gold standard for health care workers.
  • Eye covering reduces infections even further. 

This is not a macho or political issue. It’s an infectious disease public health issue.  Be smart and considerate of others. Cover your mouth, cover your eyes and keep six feet or more apart.

Absence of Leadership Is Why COVID-19 Is Destroying The USA

Two articles arrived at my desk discussing the ongoing tragedy of COVID-19. One is written in the New England Journal of Medicine by Dr. Eric Schneider. Dr Schneider sees the ability to test someone quickly and reliably as the only way out of the pandemic and back to some degree of normal life without there being mass casualties and deaths. He is appalled that foreign nations with far less developed scientific communities have developed testing and contact tracing so that they can limit the spread of the disease while safely opening those societies again. 

He cites the failure of the Trump administration to heed warnings, prepare for the arrival of the virus and more importantly to produce, distribute and test the public while collecting and organizing the data as the only reason we are now left with “non pharmacological interventions (NPIs)”   Shutting down society and staying at home is our only successful  NPI option to date.  He goes on to criticize the administration for looking for that magic cure with a medication or a quick vaccine which the scientists working on them insist will take longer than the President claims it will.  While Dr. Schneider believes that NPI’s have been successful, they carry their own price of economic ruin, social isolation and a restless population now demonstrating loudly to resume commerce and normal activities even though the infection rate and death rate will be so much higher. 

An editorial in the revered British Journal The Lancet today discusses the need to revive the CDC. The editorial highlights the history of the Center for Disease Control and its role as a world leader in public health and safety.  It then goes on to illustrate how the Ronald Reagan and George W. Bush administrations, and now the Trump administration, have destroyed its funding and marginalized its role.

The Lancet editorial board first criticizes those administrations for reducing funding when the CDC was leading the fight against HIV disease worldwide. The current administration has eliminated funding and support even further.

The CDC always kept pandemic surveillance personnel in China since Asia has always been a birthplace of new serious viral illnesses such as SARS, Bird Flu and MERS. Funding elimination resulted in the last CDC surveillance officer leaving China in July of 2019.

When the current CDC Director Nancy Meissonier, MD warned the world about the COVID-19 pandemic on February 25, 2020; she was removed from White House briefings and public appearances because of her prophetic statement. “The CDC needs a director who can provide leadership without the threat of being silenced and who has the technical capacity to lead today’s complicated effor. Americans must put a president in the White House come January 2021, who will understand that public health should not be guided by partisan politics.”

Vitamin D Supplements Do Not Reduce Falls, Fractures or Improve Bone Density

Much has been written about the benefits of supplementing Vitamin D in patients. The World Health Organization sets its normal blood level at 20 while in North America it is listed at over 30. Under normal circumstances when your skin is exposed to sunlight your kidneys produce adequate amounts of Vitamin D.

Over the last few years low vitamin D levels have been associated with acute illness and flare-ups of chronic illness. The Vitamin D level is now the most ordered test in the Medicare system and at extraordinary expense. Supplementing Vitamin D has become a major industry unto itself.

The October 4th edition of the Lancet Diabetes and Endocrinology contained an article written by New Zealand researchers that looked at 81 randomized research trials containing almost 54 thousand participants. “In the pooled analyses, researchers found that Vitamin D Supplementation did not reduce total fracture, hip fracture, or falls – even in trials in which participants took doses greater than 800 IU per day.” Vitamin D supplementation did not improve bone mineral density at any site studied (lumbar spine, hip, femoral neck, forearm or total body).

They concluded that there is little justification for the use of Vitamin D Supplements to maintain or improve musculoskeletal health, and clinical guidelines should reflect these findings.

Controversial Study on Body Weight and Development of Dementia

DementiaAs the Baby Boomers age and develop more chronic diseases there is a predicted epidemic of cognitive dysfunction and dementia expected to occur. At the same time the Baby Boomer retirement explosion is occurring the nations of the world are experiencing a significant increase in obesity and its health related problems. In the April 10th issue of The Lancet Diabetes & Endocrinology researchers in Great Britain published a paper suggesting that being overweight might be more protective against the development of dementia than being at a normal weight or underweight. In fact they felt that underweight individuals having a Body Mass Index of < 20 had a far higher risk of developing dementia than normal weight individuals or obese individuals (BMI > 30). The data was collected and analyzed from the United Kingdom Clinical Practice Research Datalink by Nawab Qizilbash, MSc, DPhil, from the London School of Hygiene and Tropical Medicine. The study looked at records of people aged 40 or older between 1992 and 2007.

The author concluded that “If increased weight in midlife is protective against dementia, the reasons for this inverse relationship are unclear at present.” Previous smaller studies on the issue suggested just the opposite that being overweight in midlife was a risk factor for developing dementia. Deborah Gustafson,, PhD, from SUNY Downstate Medical Center in New York cautioned that these results are certainly not the “final word” on the topic.

As a clinician we always advise patients to live a life and eat a diet based on moderation. The study did not make it clear if the protective effect of being overweight extended to the massively obese or not. What is clear is that being at an extreme seems deleterious, while being at normal body weight or mildly overweight may be protective.

Three More Strikes Against Smoking

There is no doubt that cigarette smoking is a practice that contributes to poor health and earlier death. Despite this, the practice is still popular among the young. Over the last three weeks several new research articles have been published that support the concept that smoking is severely detrimental to your health.

An Australian study published in Stroke: Journal of the American Stroke Association pointed out that individuals who had a stroke at the time they were active smokers had a far worse outcome and long term outcome than non- smokers. It additionally showed that smokers had the stroke at a younger age than nonsmokers. The group was followed for another 10 years and had a higher incidence of strokes, heart attacks and deaths than the nonsmoking group. The study emphasized the devastation and cost of “healthy years of life lost” as a consequence of continuing to smoke.

In an online publication in the Lancet, researchers working in the “Great Britain Million Women Study” noted that women who quit smoking lived longer than women who continued – irrespective of the age they decided to stop smoking. They additionally lowered their chances of dying from lung cancer.

A study out of the Mayo Clinic in Rochester, Minnesota looked at the effect of indoor smoking bans on heart attack rates in a community. This study looked at the effect of secondhand smoke on individuals. The Mayo Clinic has an exhaustive and large data base of individuals in the Midwest who have come to their clinic for health care for generations. They believe that in their study population, the number and extent of cardiovascular risk factors has remained fairly constant but, since the institution of strict bans on indoor smoking, the number of heart attacks has dropped dramatically.

Spray on Skin Cells Heal Wounds Fast

Non healing ulcers and wounds in the elderly are a common and severe problem. These skin breakdowns are painful, often get infected and often require wound care teams to treat the problem.  Robert Kirsner, MD, PhD of the University of Miami Miller School of Medicine Division of Dermatology reported in the online edition of the prestigious Lancet magazine that he is using a spray bottle containing a mix of skin cells called keratinocytes and fibroblasts to enhance the rate of healing.

Dr. Kirsner is looking at healing venous stasis ulcers of the legs. It is common to find venous insufficiency of the legs in senior citizens (poor return of blood from the legs through the veins and back towards the heart).  Venous ulceration and skin breakdown occur in 1 – 2.5% of these adults 65 years and older.  Treatment routinely consists of clearing and controlling infection with antibiotics, primary dressings and compression bandages and stockings. This is successful in 30% – 75% of the situations.  The remaining cases require skin grafting and surgical procedures to heal.

To treat this common and persistent problem, Dr Kirsner and associates have been working with a product known as HP802-247 which is a cryopreserved sampling of fibroblasts and keratinocytes derived from neonatal foreskin tissue that is discarded after circumcision of newborn infants. Thawed cells are suspended in a spray for application to a wound.   The researchers created three strengths of the spray and tested all against standard treatment.  All patients in the study, whether receiving the experimental spray or a placebo, received standard and traditional wound care.  Kirsner’s results show that by using the lowest dose of the spray he was able to achieve complete healing in almost a third more patients as compared with the placebo group.  Differences in the healing rate became apparent within the first week of the treatment.

The product, HP802-247, has shown enough improvement in healing rate and total healing to warrant advancing it to Phase III studies which have begun in the United States and Europe.  While the initial studies have looked only at wounds caused by venous insufficiency, it will be interesting to see if similar studies are initiated on additional slow healing wounds common in seniors as well as in burn unit situations.

Statins Reduce Risks, Even in the Lowest Risk Groups

Current guidelines for the use of statins in the USA (Lipitor, Zocor, Crestor, Atoravastatin, Simvastatin, Pravastatin, etc.) call for only treating individuals who have a ten-year risk of major vascular event of at least 20%.

European researchers including Borislava Mihaylova, MSc DPhil, and colleagues on the Cholesterol Treatment and Trialists Collaborators team writing in the Lancet question whether the guidelines should be changed to treat individuals with even lower risks. Their large Meta analysis suggests that statins provide substantial benefits for primary prevention – especially in patients with a 5-10% ten year risk of a major vascular event. They looked at data from 27 trials including over 175,000 participants. When they took into account cost and side effects of statins, such as muscle pain and inflammation, rhabdomyolysis, diabetes and hemorrhagic stroke, they concluded that the benefits still far outweighed the risks. They think that the clear-cut affect on lower risk individuals coupled with the fact that almost 50% of vascular events occur in patients without previous cardiovascular disease necessitates the broadening of USA guidelines for treatment of patients. The researchers go on to hypothesize that as more generic statins enter the market, cost concerns will become far less of a factor in the decision to treat or not treat.

They noted that for each 1 mmol/L reduction in LDL cholesterol, there was a 21% reduction in the relative risk of major vascular events, and all cause death, irrespective of age, baseline LDL or previous cardiovascular disease.

This research makes it clear that there is great value in assessing the statistical cardiovascular risk of each individual and being more aggressive in the use of statins than current national guidelines call for.  Incorporating risk tools such as the Framingham Risk assessment plus looking at newer techniques such as the measurement of carotid artery intimal thickness may be appropriate in the decision to choose a statin or not.

Aspirin – Cardiovascular and Cancer Benefits

In this week’s on line edition of MedPage, a publication of the University Of Pennsylvania Perelman School Of Medicine, they summarize a series of articles published in the prestigious medical journal Lancet, which conclude that taking aspirin daily reduces your risk of cancer.

Aspirin received its notoriety after a Veterans’ Administration study years ago noted that if you took a daily aspirin and were a male over 45 years old you had fewer heart attacks and strokes. That classic study has led to the recommendation over the years that everyone over the age of 45 years old take aspirin daily to prevent cardiovascular events. No one can quite agree on the dosage of a full aspirin (325 mg), a baby aspirin (81 mg), or two baby aspirin?

As more and more people began taking aspirin for cardiovascular benefits researchers noted more frequent episodes of major internal bleeding either in the gastrointestinal tract or in the brain and head. At the same time, it was whispered among professionals that taking aspirin daily reduced adenomatous growths in the colon (pre-malignant polyps) and reduced colon cancer.   In the past few weeks several studies have tried to stratify whether aspirin use daily should be restricted to men as opposed to women, or to individuals with documented heart and vascular disease for secondary prevention of the next heart attack or stroke rather than primary prevention.  They cited the large number of bleeding episodes in individuals trying to protect themselves from their first heart attack or stroke compared to the events prevented and lives saved.

Today’s MedPage review of three Lancet articles claims that daily aspirin use reduces the risk of adenomatous cancer by 38% and cancer mortality by 15%. It reduces the development of metastatic disease by up to 15%.  These studies looked at more than 51 trials, including well over 100,000 participants, leading Dr Peter Rotwell of Oxford University in the United Kingdom to say that the papers “add to the case for the long term use of aspirin for cancer prevention in middle age.”

As a primary care physician I will continue to take my daily 81 mg enteric coated buffered aspirin (2) with food and take my chances with GI bleeding and cerebral hemorrhage.  If my patients do not have any strong contraindications to aspirin ingestion I will continue to make the suggestion that if they are over 45 years old they consider doing the same.

Lancet Study Emphasizes Long Term Benefit and Safety of Statin Use

Richard Bulbulia, MD, of the Heart Protection Study Group reported in the Lancet that statin medications are safe and effective over long periods of time.  They looked at 20,536 patients at high risk for vascular events. They studied patients who were between 40 and 80 years old. These patients were randomized to one group receiving Simvastatin (Zocor) daily at the 40 mg dose or placebo for 5.3 years. They were then followed for another six years during which both groups received the statin.

Researchers found that during the initial 5.3 years of the study there was a 23% decrease in major vascular events and an 18% reduction in vascular mortality in the Simvastatin treated group.

They also looked at complications of therapy over the eleven year period and concluded, “Reassuringly, there was no evidence that any adverse effect on particular causes of non–vascular mortality or major morbidity, including site-specific cancer, was emerging during this prolonged follow-up period.”  In an editorial in the same edition, Payal Kohli, MD and Christopher Cannon, MD of the Brigham and Women’s Hospital in Boston said the results “provide contemporary and confirmatory evidence that extended use of statins is safe with respect to possible risk of cancer and non-vascular mortality.”

It is noted that the dosages used are higher than what the FDA currently recommends for Simvastatin due to the risk of muscle injury at higher doses. Despite that, the Lancet editorialists concluded that “concerns should be put to rest and doctors should feel reassured about the long-term safety of this life saving treatment for patients at increased cardiovascular risk.”