Monday, June 22, 2020

Lowering cholesterol? How, why?

This post was suggested by a reader, who had read enough about the coronavirus, and it is a topic that merits attention. Cardiovascular disease remains by far the number one killer in the developed world and is rapidly rising to that spot in the developing world as well, and our ability to prevent heart attacks is in large part related to lowering cholesterol.

The first point to note is that cholesterol is not arsenic – cholesterol is part of normal cells, and no one dies of cholesterol. It has, however, been known for many decades that an elevated level of cholesterol, along with high blood pressure and smoking, increases the risk of developing coronary disease. Norwegian researchers in 1939 described families with abnormally high levels of blood cholesterol and premature heart attacks. This led, beginning in the 1950s, to attempts to lower cholesterol with diet and medication. Most of the medications which were then available, which included nicotinic acid, fibrates and cholestyramine, were not very effective and/or were difficult for people to take for any time, and their use did not reduce the risk of heart attack by a large amount.

A breakthrough in cardiology occurred with the development of the class of drugs technically known as HMG-CoA reductase inhibitors and widely known as “statins.” The first in this class, lovastatin, was discovered in 1978 and first tested in humans in 1980. Multiple similar drugs followed, and we now have seven on the American market. They vary in potency, but all work in a very similar way. The first major trial of using a statin to prevent CV death was conducted in the west of Scotland, among men at high risk of heart attack. Participants were enrolled between 1989 and 1991 and the results of the trial were published in 1995. Those taking the active drug, which in this trial was pravastatin, had about 31% fewer heart attacks, and there was about a 9% reduction in total mortality (from 38.6% to 34.7%) over an extended 20-year follow-up. Multiple later trials, done in lower risk patients, all showed similar results: fewer heart attacks and a trend to lower overall deaths in statin-treated groups.

I do not own stock in any healthcare companies, so have no conflict of interest in stating that the statins as a class are one of the best medicines in our armamentarium. Most are now available generically and are dirt-cheap in the big picture of pharmaceutical products; they are well-tolerated by most people; and have very few bad side effects. There was a flurry of concern a few years back about them contributing to dementia, but this has been disproven by many large studies. They do seem to slightly hasten the onset of diabetes in people prone to it, but the benefit far outweighs the risk.

There is one fly in the ointment: many people develop muscle aches from taking a statin. Only a tiny number have muscle damage (which can be measured with a blood test), and in my opinion if you fall in that tiny number you should never take any statin, but 5-10% complain of muscle aching that goes away when you stop the drug. In some cases, taking a different statin can be done without the problem recurring, but some get the same reaction to every statin they try. What options are available if you are in this group?

The first step is to decide with your doctor if you truly need to have your cholesterol lowered. While statins seem to have a similar relative reduction in heart attack risk in all groups, there is a difference between relative and absolute risk. Let’s say that taking a moderate dose of a statin reduces your risk of having a heart attack in the next 10 years by 25%. If that risk is 40%, then reducing it by 25% means you have reduced your odds by 10%. If that risk is 4%, reducing it by 25% means your actual benefit is a 1% risk reduction – perhaps not worth it in your mind. There are on-line risk calculators that will help you calculate your personal risk.

If you feel that lowering your cholesterol is important and cannot take a statin, there are several choices available, but NONE of them has been studied for risk reduction when taken alone – all have been shown to lower your risk of heart attack when added to a maximally-tolerated dose of a statin.

Ezetimibe (Zetia) inhibits absorption of cholesterol from the intestine and reduces cholesterol by about 18% (compared to 25-60% reduction with a statin). There are two new injectable drugs, called PCSK9 inhibitors, that are very potent, but are extremely expensive and require self-injection every 2-4 weeks. Unless you have a very high risk, your health insurance company is likely to balk at paying for these. The newest entry is bempedoic acid (Nexletol), which also lowers cholesterol by about 18%, and it has also only been tested as an add-on.

Finally, do not forget lifestyle changes: a better diet, weight loss, moderate aerobic exercise. If you are a smoker, quitting will do more to reduce your heart attack risk than any pill.

Prescription for Bankruptcy. Buy the book on Amazon

Saturday, June 6, 2020

Health care: black and white

The Covid-19 pandemic has brought into sharp relief the failings of the U.S. health care system to give adequate priority to public health: our woeful performance in testing, contact tracing and availability of personal protective equipment. It has also highlighted the marked social disparities in how we deliver health care.

Across the United States, the death rate from Covid-19 per 100,000 among non-Hispanic whites is 22.7, among Asian-Americans 24.3, among Hispanics 24.9 and among African Americans 54.6. The strikingly higher death rate reflects many factors. Blacks are more likely to live in crowded housing, making “social distancing” more difficult; they are more likely to have to depend on crowded public transportation; they have a higher incidence of such medical conditions as hypertension and diabetes that increase mortality; and they are more likely to work in such “essential” jobs as meat packing, nursing homes and home health care and grocery stores, and less likely to be able to work from home.

The racial disparity in health care exposed by the pandemic is not new. Overall deaths per 100,000 in the U.S. in 2018 were 725 for non-Hispanic whites and 852 for African Americans. The maternal death rate in this country has been (or should have been) an embarrassment for a long time. While the death rate per 100,000 live births in most of the western world ranges from 5 to 8 and has been falling, in the U.S, during the decade 2007-2016, it rose from 15 to 17. Here too there was a marked racial disparity. The maternal death rate among white women averaged 12.7/100,000 in the most recent figures, while it was 40.8 among black women. Poverty alone is not the explanation; among women with at least a college degree, the maternal death rate of black mothers was 5.2 times that of whites.

Too often, minority populations live in the least safe housing, are less likely to have health insurance and have less access to health care.

As detailed in Prescription for Bankruptcy, some 80% of a nation’s health, as measured by factors such as our life expectancy at birth, is determined by social factors rather than the traditional health care delivery system. To lead healthy lives, people need safe housing, access to healthy food, green spaces, educational opportunity, social support and, most important of all, a living wage.

Whether through development of a vaccine or the gradual development of effective treatment and herd immunity, the pandemic will end. The racial disparity in health and health care will not unless we make a conscious decision to make societal change.

Prescription for Bankruptcy. Buy the book on Amazon

Tuesday, June 2, 2020

What do Covid-19 tests tell us?

To understand what various tests for Covid-19 mean, you must first accept one important fact: medical tests are not perfect. Even the most accurate tests we have at our disposal may say that someone has a disease when they do not (a “false positive”) or that they do not have the disease when they do (“false negative”). All tests must be interpreted together with the clinical findings and the likelihood of someone having the disease in question.

Let’s look at how Covid-19 is diagnosed. The “gold standard” is detection of the virus’ RNA in specimens from the respiratory tract of a sick person. These tests go by the highfalutin label of “reverse transcriptase-polymerase chain reaction” or RT-PCR, and this describes a technique by which the presence of viral RNA is measured and quantified. This technique can be used on any specimen, but the earliest and still most common specimen has been a swab taken from the very back of the nasal passage. It has also been used on sputum (spit), throat culture, stool samples and even semen.

In most people who develop symptoms of Covid-19, viral RNA becomes detectable in the nasopharyngeal swab as early as day 1 of symptoms and in over 98% within the first week. Detection falls off after week 3, though positive tests have been reported as late as six weeks after symptoms begin. Tests for Covid-19 RNA in the stool and semen have also been found positive long after patients recover. It appears that late tests often do NOT indicate that the person is still contagious, and that they may simply be shedding decayed viral remnants.

The RT-PCR is highly accurate when positive. False negative tests do occur because of technical problems: the specimen may have not been taken properly or not transported properly to the lab, or there may have been a problem with the way the test was conducted.

The other type of test about which you will read is the antibody test. When we are exposed to an infectious agent (or a vaccine), our immune system gears up to fight it off by producing proteins called antibodies that both directly fight the infectious agent and call in various cells to do the same. It takes time for antibodies to be produced, so they are unlikely to be found very early in an illness. In the case of Covid-19, some antibodies have been found as early as 4 days into symptoms, but it is generally in week 2 or 3 that they are reliably found. First to appear are a group called IgM antibodies, that fall off by week 6, while IgG antibodies appear slightly later but persist, for months or years.

Antibodies are commonly measured in blood samples and provide proof of prior exposure to an infectious agent. In many, but not all, cases, presence of antibodies indicates at least some immunity to the agent against which they are targeted. The degree to which the presence of antibodies means immunity to the disease varies a lot. If you have measles antibodies, you are safe, but that is less true for whooping cough or for the coronaviruses that cause the common cold. We simply do not yet know if antibodies against Covid-19 will protect one from re-infection. It is clearly premature to use these tests to offer “immune passports.”

The other major problem with current Covid-19 antibody tests is that many of the tests now available are far from reliable. Many were rushed to market with limited testing and have a high number of both false positives and false negatives. Remember that Covid-19 is one of a group of coronaviruses, many of which cause the common cold, and a poorly designed antibody test may simply be detecting a prior exposure to one of these other viruses.

Bottom line: until we have more consistently reliable antibody tests, and until we know if the presence of antibodies is a reliable way to guarantee immunity to re-infection, I would not be in a hurry to get tested.

Prescription for Bankruptcy. Buy the book on Amazon