Category Archives: atherosclerotic cardiovascular disease

A Voodoo Coronary Calcium Scan Could Save Your Life

The skeptical cardiologist received this reader comment recently:

So I went and got a Cardiac Calcium Score on my own since my cardiologist wouldn’t order one because he says they are basically voodoo.. Family History is awful for me.. I got my score of 320 and I’m 48 years old.. Doc looked at it and basically did the oh well.. so I switched docs and the other doc basically did the same thing.. I try so very hard to live a good lifestyle..I just don’t understand why docs wait so long to actually take a look at your heart.. I would have thought a score of 320 would have brought on more testing.. It did not..

I was shocked that a cardiologist practicing in 2019 would term a coronary artery calcium (CAC) scan (aka, heart scan or calcium score) “voodoo.”

I’m a strong advocate of what I wrote in a recent post with the ridiculously long title, “Prevention of Heart Attack and Stroke-Early Detection Of Risk Using Coronary Artery Calcium Scans In The Youngish“:

It’s never too early to start thinking about your risk of cardiovascular disease. If heart disease runs in your family or you have any of the “risk-enhancing” factors listed above, consider a CAC, nontraditional lipid/biomarkers, or vascular screening to better determine where you stand and what you can do about it.

Here’s what I told this young man:

If your cardiologist tells you coronary calcium scores are voodoo I would strongly consider changing cardiologists.

A score of 320 at age 48 puts you in a very high risk category for stroke and heart attack over the next 10 years.

You need to find a physician who understands how to incorporate coronary calcium into his practice and will help you with lifestyle changes and medications to reduce that risk


Let’s analyze my points in detail and see if these off the cuff remarks are really justified

1,  Changing cardiologists.

Recent studies and recent guideline recommendations (see here) all support utilization of CAC in this kind of patient. If you have a strong family history of premature heart disease or sudden death you want a cardiologist who is actively keeping up on the published literature in preventive cardiology,  Such cardiologists are not dismissing CAC as “voodoo” they are incorporating it into their assessment of patient’s risk on a daily basis.

2. High risk of CAC score 320  at age 48

I plugged normal numbers for cholesterol and BP into the MESA risk calculator (see my discussion on how to use this here) for a 48 year old white male.

As you can see the high CAC score puts this patient at almost triple the 10 year risk of heart attack and stroke.

Immediate action is warranted to adjust lifestyle to reduce this risk! This high score will provide great motivation to the patient to stop smoking, exercise, lose excess weight, and modify diet.

Hidden risk factors such as lipoprotein(a),  hs-CRP and LDL-P need to be assessed.

Drug treatment should be considered.

3. Find physician who will be more proactive in preventing heart disease

This may be the hardest part of all my recommendations. On your own you can get a CAC performed and advanced lipoprotein analysis.

However, finding progressive, enlightened, up-to-date preventive cardiologists can be a challenge.

We need a network of such cardiologists.

I frequently receive requests from readers or patients leaving St. Louis for recommendations on cardiologists.

If you are aware of such preventive cardiologists in your area email me or post in comments and I will keep a log and post on the website for reference.

Voodoophobically Yours,

-ACP

Is An Unneeded Beta-Blocker Making You Feel Logy?

The skeptical cardiologist saw a patient recently who  had undergone stenting of a 95% blocked right coronary artery. Mr Jones had presented  a year ago to our ER 2 days after he first began experiencing a light pressure-type discomfort in his left shoulder and scapular region. This pain persisted, waxing and waning, without a clear relationship to exertion or position or movement of his shoulder.

Upon arrival in the ER, his ECG was normal but his cardiac enzymes were slightly elevated (troponin peaking 0.92), thus he was diagnosed with a non-ST elevation myocardial infarction (MI).

He’s done great since the stent procedure fixed the coronary blockage that caused his infarct and chest pain, but during our office visit he related that since his hospitalization he had been feeling “logy.” 

Being a lover of words, my ears perked up at this new-to-me adjective, and I asked him to describe what he meant by logy. For him, loginess was a feeling of fatigue or lacking energy.

Indeed, the online Merriam-Webster dictionary defines logy as sluggish or groggy. It is pronounced usually with a long o and a hard g.

The origin is unclear but has nothing to do with rum:

Based on surface resemblance, you might guess that “logy” (also sometimes spelled “loggy”) is related to “groggy,” but that’s not the case. “Groggy” ultimately comes from “Old Grog,” the nickname of an English admiral who was notorious for his cloak made of a fabric called grogram – and for adding water to his crew’s rum. The sailors called the rum mixture “grog” after the admiral. Because of the effect of grog, “groggy” came to mean “weak and unsteady on the feet or in action.” No one is really sure about the origin of “logy,” but experts speculate that it comes from the Dutch word log, meaning “heavy.” Its first recorded use in English, from an 1847 London newspaper, refers to a “loggy stroke” in rowing.

Fatigue is a common, nonspecific symptom that we all feel at times. It is more common as we age and it can be challenging for both patients and physicians to sort out when it needs to be further evaluated.

Occasionally, fatigue is the only symptom of a significant cardiac condition, but more frequently in the patient population I see it is either noncardiac (low thyroid, anemia, etc.) or iatrogenic

When a patient tells me they are feeling fatigued I immediately scan their med list for potential logigenic drugs.

In this case, my patient had been started on a low dosage of the beta-blocker carvedilol (brand name Coreg) after his stent, and I suspected this was why he had felt logy for the past year.

In cardiology, we utilize beta-blockers in many situations-arrhythmias, heart failure, and heart attacks to name a few, and they are well-known to have fatigue as a common side effect. There was a really good chance that Mr. Jones’s loginess was due to the carvedilol.

It’s important to review all medications at each patient visit to check for side effects, interactions and benefits, and in the case of Mr. Jones’ carvedilol, loginess.

Do All Patients Post-Revascularization or Post-MI Need To Take Beta-Blockers

Beta-blockers (BBs) are frequently started in patients after a stenting procedure or coronary bypass surgery, and continued indefinitely. However, the evidence for their benefit in such  patients with normal LV function long term is lacking.

If any post-revascularization population benefits from BBs, it is those, like Mr. Jones who have had a myocardial infarction (MI, heart attack) prior to the procedure, however the smaller the infarct, the less the benefits.

And with the widespread use of early stenting to treat MI, infarcts are much smaller and dysfunction of the left ventricle (LV) less likely.

In those patients with minimal damage and normal LV function, the benefits appear minimal. For this reason in the last 5 to 10 years I’ve been stopping BBs in this population if there are any significant side effects.

An “Expert Analysis” published in JACC in 2017 noted that:

A 2015 meta-analysis of 10 observational acute MI studies including more than 40,000 patients showed that beta-blockers reduced the risk of all-cause death  However, the benefit of these agents was not found in all subgroups and seemed confined to the patients with reduced LVEF, with low use of other secondary prevention drugs, or NSTEMI.

In a study of almost 180,000 patients post MI with normal LV systolic function in the UK between 2007 and 2013 there was no difference in mortality at one year in patients discharged with or without beta-blockers.

The only way to answer this question definitely would be with a randomized controlled trial and, to my surprise and delight, such a study (CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) was published in PLOS One in August of 2018.

I’ll save readers the details, but the bottom line is that patients treated with optimal contemporary therapy for acute MI, whose LV function was not significantly impaired, did not benefit in any way from treatment with carvedilol, the beta-blocker my patient was taking.

It’s rare that we get such definitive evidence for a change in treatment that reverses what is in current guidelines. This has the potential to affect tens of thousands of patients and improve their quality of life. It should be trumpeted far and wide. The cynic in me suspects that if it were a study demonstrating the benefits of a new drug, physicians would be bombarded with the new information.

Helping Patients Feel Less Logy

We will be ordering an echocardiogram on Mr. Jones, and if his LV function is normal we will stop his carvedilol and see if he feels significantly better.  

I feel like stopping a drug that is not beneficial and that is causing a lifetime of loginess is an incredibly important intervention a cardiologist can make. It’s not as life-saving as stenting for acute MI, but saving quality of life is something this non-invasive cardiologist can do every day for every patient.

Skeptically Yours,

-ACP

N.B. The summary of the recent CAPITAL-RCT:

STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) ≥40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06).

 

 

 

 

Is It Time To Stop Eating Deadly Eggs Or Time To Stop Putting Nutritional Epidemiology In The Headlines?

After carefully ingesting the new JAMA egg study that has gotten the media and many patients in a tizzy I consumed a three egg (of course with yolk) omelette.

I am happy to report that I survived the incident and am not concerned at all that my longevity has been compromised.

My 2013 summary of eggs, dietary cholesterol and heart disease (see here) is still valid and I highly recommend patients and readers read that post plus my updates on eggs with newer data (see here and here) rather than information related to the new egg study.

Although CNN and other news outlets lead with an inflammatory headline suggesting that eating those 3 eggs increased my risk of heart disease the new egg study could not possibly prove causation because it was an observational study.

Nutritional epidemiology has come under considerable criticism in the last few years for churning out these weak observational studies .John Ionaddis has been particularly vocal about these limitations, writing:

A large majority of human nutrition research uses nonrandomized observational designs, but this has led to little reliable progress. This is mostly due to many epistemologic problems, the most important of which are as follows: difficulty detecting small (or even tiny) effect sizes reliably for nutritional risk factors and nutrition-related interventions; difficulty properly accounting for massive confounding among many nutrients, clinical outcomes, and other variables; difficulty measuring diet accurately; and suboptimal research reporting. Tiny effect sizes and massive confounding are largely unfixable problems that narrowly confine the scenarios in which nonrandomized observational research is useful

This egg study contains the usual flaws that render it inconclusive:

First, the study relies on data collected from a food frequency questionnaire. Have you ever sat down and tried to recall exactly what you ate in the previous week? How accurate do you think your estimate of specific food items would be?

Ed Archer has written about the inaccuracy of the food frequency questionairres extensively. Here’s a sample from one of his devastating critiques;

In lieu of measuring actual dietary intake, epidemiologists collected millions of unverified verbal and textual reports of memories of perceptions of dietary intake. Given that actual dietary intake and reported memories of perceptions of intake are not in the same ontological category, epidemiologists committed the logical fallacy of “Misplaced Concreteness.” This error was exacerbated when the anecdotal (self-reported) data were impermissibly transformed (i.e., pseudo-quantified) into proxy-estimates of nutrient and caloric consumption via the assignment of “reference” values from databases of questionable validity and comprehensiveness. These errors were further compounded when statistical analyses of diet-disease relations were performed using the pseudo-quantified anecdotal data. These fatal measurement, analytic, and inferential flaws were obscured when epidemiologists failed to cite decades of research demonstrating that the proxy-estimates they created were often physiologically implausible (i.e., meaningless) and had no verifiable quantitative relation to the actual nutrient or caloric consumption of participants.

In addition to unreliable initial data the subjects were followed up to 30 years without any update on their food consumption. Has your food consumption remained constant over the last 30 years? Mine hasn’t. I went from avoiding eggs to eating them ad lib and without concern for my cardiovascular health about 5 years ago after looking at the science related to dietary cholesterol.

It’s Hard To Get Around Confounding Variables

Observational studies like this one try to take into account as many factors as they can which might influence outcomes. Invariably, however, there are factors which are unaccounted for, indeed unknowable, which could be influencing the results.

Individuals who were avidly trying to follow a healthy lifestyle in 1985 likely had drummed into their heads the message when these questionnaires were filled out that they needed to limit egg consumption. These individuals were also likely following other healthy habits, including exercising more, smoking less, and eating more fruits and vegetables and less junk food.

Observational studies cannot account for all these confounding variables.

At science-media centre.org they do a fantastic job of having independent experts in the field present their evaluation of scientific studies which have been popularized in the media. For the JAMA egg study their analyses can be found here.

Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University emphasized the problem with residual confounding :

That’s because, for instance, there will be many other differences between people that eat many eggs and people that eat few other than their egg consumption.  These other differences might be what’s causing higher death rates in people who eat a lot of eggs, rather than anything to do with the eggs themselves.  The researchers point out that this has been a particular problem in some previous studies, and that this may have been a reason for inconsistency in the results of those studies.  They have made considerable efforts to allow statistically for other differences in the new study.  But they, correctly, point out that their own study is still not immune from this problem (known as residual confounding), and that therefore it’s impossible to conclude from this new study that eating eggs, or consuming more cholesterol in the diet, is the cause of the differences in cardiovascular disease rates and overall death rates that they observed.

For observational epidemiological studies like this egg study which show increased risks that are only “modest” it is highly likely that the next such study will find something different.

Eggs Are Not Eaten In Isolation

Finally, It’s important to remember that eggs, like most foods, are rarely consumed without accompanying food. This accompaniment is often bacon in the US. Eggs are often cooked in oil or butter and unless you cook them yourself you are unlikely to know the nature of the oil.

Eggs are frequently components of recipes.

We have no idea how these factors play into the results of the egg study.

So, rather than drastically cutting egg consumption I propose that there be a drastic cut in the production of weak observational nutrition studies and a moratorium on inflammatory media coverage of meaningless nutritional studies.

Eggsponentially Yours,

-ACP

N.B. For a good article on this topic read Julia Volluz of Vox on why nutritional science is so messy

The MESA App-Estimating Your Risk of Cardiovascular Disease With And Without Coronary Calcium Score

Yesterday, I laid out the case for utilizing coronary artery calcium score (CACS) to further refine the assessment of youngish patients risk of developing cardiovascular disease (ASCVD). I referenced the ACC/AHA ASCVD risk estimator tool (app available here) as the starting point but if I have information on my patient’s CACS I use a new and improved tool called the MESA risk score calculator.

It is available online and through an app for Apple and Android (search in the app store on “MESA Risk Score” for the (free) download.)

The MESA tool allows you to easily calculate how the CACS effects you or your patient’s 10 year risk of ASCVD.

The Multi-Ethnic Study of Atherosclerosis (MESA) is a study of the characteristics of subclinical cardiovascular disease (disease detected non-invasively before it has produced clinical signs and symptoms) and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease. MESA researchers study a diverse, population-based sample of 6,814 asymptomatic men and women aged 45-84. Approximately 38 percent of the recruited participants are white, 28 percent African-American, 22 percent Hispanic, and 12 percent Asian, predominantly of Chinese descent.

To use the score you will need information on the following risk factors:

age, gender, race/ethnicity, diabetes (yes/no), current smoker (yes/no), total and HDL cholesterol, use of lipid lowering medication (yes/no), systolic blood pressure (mmHg), use of anti-hypertensive medication (yes/no), any family history of heart attack in first degree relative (parent/sibling/child) (yes/no), and a coronary artery calcium score (Agatston units).

In many cases the CACS dramatically lowers or increases the risk estimate.

In this example a 64 year old man with no discernible risk factors has a CACS of 175
The 10 year risk of a CHD event almost doubles from 4.7% to 7.6% when the CACS is added to the standard risk factors and moves into a range where we need much more aggressive risk factor modification.

On the other hand if we enter in zero for this same patient the risk drops to a very low 1.9%.

It’s also instructive to adjust different variables. For example, if we change the family history of heart attack (parents, siblings, or children) from no to yes, this same patient’s risk jumps to 7.2% (2.6% with zero calcium score and to 10.4% with CACS 175.)

It can also be used to help modify risk-enhancing behaviors. For example if you click smoker instead of non-smoker the risk goes from 4.7% to 7.5%. Thus, you can tell your smoking patient that his risk is halved if he stops.

Discussions on the value of tighter BP control can also be informed by the calculator. For example, if  our 64 year old’s systolic blood pressure was 160 his risk has increased to 6.8%.

How Does Your CACS Compare To Your Peers?

A separate calculator let’s you see exactly where your score stands in comparison individuals with your same age, gender, and ethnicity

The Coronary Artery Calcium (CAC) Score Reference Values web tool will provide the estimated probability of non-zero calcium, and the 25th, 50th, 75th, and 90th percentiles of the calcium score distribution for a particular age, gender and race. Additionally, if an observed calcium score is entered the program will provide the estimated percentile for this particular score. These reference values are based on participants in the MESA study who were free of clinical cardiovascular disease and treated diabetes at baseline. These participants were between 45-84 years of age, and identified themselves as White, African-American, Hispanic, or Chinese. The current tool is thus applicable only for these four race/ethnicity categories and within this age range.

The calculator tells us that 75% of 64 year old white males have a zero CACS and that the average CACS is 61.

Unlike SAT scores or Echo Board scores you don’t want your CACS percentile status to be high. Scores >75th percentile typically move you to a higher risk category, whereas scores <25th percentile move you to a lower risk category, often with significant therapeutic implications.

Scores between the 25th and 75th percentile typically don’t significantly change the risk calculation.

Exploring Gender Differences In CACS

If we change the gender from male to female on our 64 year old the risk drops considerably from 4.7% down to 3.3%. This graph demonstrates that over 20% of women between the ages of 75 and 84 years will have zero calcium scores.

The graph for men in that same range shows that only around 10% will have a zero CACS.

I’ve been asked what the upper limit is for CACS but I don’t think there is one. I’ve seen numerous patients with scores in the high two thousands and these graphs show individuals in the lowest age decile having scores over 2981.

If you want to be proactive about the cardiovascular health of yourself or a loved one, download the MESA app and evaluate your risk. Ask your doctor if a CACS will help refine that risk further.

Antiatherosclerotically Yours,

-ACP

Prevention of Heart Attack and Stroke-Early Detection Of Risk Using Coronary Artery Calcium Scans In The Youngish

Since 1/3 of Americans die from atherosclerotic cardiovascular disease (ASCVD, mostly heart attacks and strokes) and dropping dead is often the first symptom of ASCVD it’s incredibly important to identify early, “subclinical” ASCVD and begin measures to reduce risk.

How early to begin that process is open to debate. The recent sudden death of the 41-year old son of a patient of mine, however, has reinforced to me how crucial it is to begin risk assessment and potential treatments as early as possible, especially in individuals with a strong family history of premature ASCVD.

We use standard risk factors like lipids, smoking, age, gender and diabetes to stratify individuals according to their 10 year risk of ASCVD (using this online risk calculator) but many apparent low risk individuals (often due to inherited familial risk) drop dead from ASCVD and many apparent high risk individuals have no subclinical ASCVD and don’t need preventive therapy.

Recent studies provide compelling support for the early utilization of cardiac imaging in to identify high risk individuals.

Heart attacks and most sudden cases of sudden death are due to rupture of atherosclerotic plaques. Thus, it makes sense to seek out  such plaques, a process I call searching for subclinical atherosclerosis. There are a number of ways to search for sublinical plaques but the two most widely studied are carotid ultrasound screening and coronary artery calcification (CAC) measurement.

I’ve been utilizing CAC (also termed  heart scan, coronary calcium score, or cardioscan) to help assess my patient’s risk of ASCVD for years although the procedure is not covered by insurance and until recently was not strongly endorsed by major guidelines. (For a complete description of the test and the risks/benefits see here). As I pointed out here, in November the new ACC/AHA guidelines finally embraced CAC for

adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels ≥70 mg/dL- 189 mg/dL (≥1.8-4.9 mmol/L), at a 10-year ASCVD risk of ≥7.5% to 19.9%, if a decision about statin therapy is uncertain

Typically, if we have calculated (using the ASCVD risk estimator) a 10 year risk >7.5% we have a discussion with the patient about beginning drug treatment to reduce risk.

To inform the decision and help us “get off the fence” I usually recommend a CAC. To see how this works in a typical sixty something see my posts here and here.

Significant Of CAC Score

As the new ACC/AHA guidelines state:

If CAC is zero, treatment with statin therapy may be withheld or delayed, except in cigarette smokers, those with diabetes mellitus, and those with a strong family history of premature ASCVD.

A duo of studies from Walter Reed Army Hospital have provided more support for the value of the zero CAC for risk prediction and identifying who should get treatment for prevention of both heart attacks and strokes.

Over 10,00 subjects underwent CAC and were assessed for the primary outcomes of all-cause mortality, incident MI, stroke, and the combination of major adverse cardiovascular events (MACE), defined as stroke, MI, or cardiovascular death over an average 11.4 years

Patients were classified on the basis of the presence or absence of calcium and further subdivided into CAC score groups of 0, 1 to 100, 101 to 400, and >400

Patients without a zero CAC had a very low number of events , with a 1.0% rate of mortality and 2.7% rate of MACE over a 10-year period.

On the other hand subjects without any traditional risk factors (n = 6,208; mean age 43.8 years), the presence of any CAC (>0) was associated with a 1.7 fold increased risk of MACE after adjustment for traditional risk factors.

f2.large-3
Patients with CAC who were prescribed a statin had a significantly reduced risk of MACE (aSHR: 0.76; 95% CI: 0.60 to 0.95; p = 0.015), whereas patients without CAC had no associated MACE reduction (aSHR: 1.00; 95% CI: 0.79 to 1.27; p = 0.99). p = 0.097 for interaction between statin treatment and CAC presence. aSHR = adjusted subhazard ratio; CAC = coronary artery calcium; CI = confidence interval; MACE = major adverse cardiovascular event(s)

The red line of the >400 score individuals has a much higher risk of death, stroke and heart attack (myocardial infarction) than the blue (CAC 1-100) or the gray line of the zero CAC scorers.

Furthermore, when these investigators looked at outcomes in those individuals who received statins versus those who didn’t, the zeros didn’t benefit from statin therapy over the 10 year follow-up.

f3.large
Benefit of statin therapy was significantly related to CAC group with benefit in patients with CAC score >100 but not in patients with CAC <100. aSHR = adjusted subhazard ratio; CAC = coronary artery calcium; CI = confidence interval; MACE = major adverse cardiovascular event(s).

But there was a tremendous reduction in bad CV events in those with scores >100 who received statin (red line) versus those who did not (blue line).

Here’s the figure which encapsulates both the risk prediction power of the CAC (and the benefits of statin treatment restricted to those with >0 (blue lines)

f2.large-4

 

Benefits of CAC Testing In The Young

So these new studies provide powerful data supporting the use of CAC in younger individuals to help us refine risk estimates and target the individual at high risk of MI and sudden death. It seems highly appropriate to consider CAC testing beginning at age 40 years as the AHA/ACC guidelines suggest.

But what about the individual who has a strong family history of premature CAD and is age say 35 or 39 years of age. Do we ignore advanced risk assessment? Very few individuals die in their 30s from ASCVD but I have a number of patients who suffered heart attacks in their forties. In addition, the earlier we can start risk modification the better as the process begins very early in life and accumulates over time.

The Coronary Artery Risk Development in Young Adults (CARDIA) Study published in 2017 has demonstrated the early development of nonzero CAC score in the youngish and the predictive value of the high CAC score for mid life ASCVD events.  It was  a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014.

The conclusions:

Any CAC in early adult life, even in those with very low scores, indicates significant risk of having and possibly dying of a myocardial infarction during the next decade beyond standard risk factors and identifies an individual at particularly elevated risk for coronary heart disease for whom aggressive prevention is likely warranted.

screen shot 2019-01-19 at 12.36.44 pmI read CAC scans every day and it is not uncommon to see a non-zero scores in individuals in their late 30s or early 40s.

The two sons of another one of my patients both in their late 50s with unremarkable risk factor profiles and both developing anginal type symptoms limiting their activities each underwent multi vessel stent procedures in the last month. If I had seen them  10 to 20 years ago we would have identified the subclinical atherosclerosis building up in their coronaries, started treatment and avoided the need for invasive, expensive procedures.

Other Risk-Enhancing Factors To Consider In The Young

The ACC/AHA guidelines list some “risk-enhancing factors” some of which I find useful.

screen shot 2019-01-19 at 7.33.39 am

Clearly family history of premature ASCVD is important but the devil is in the details. What relatives count? What was the event in the family member? If it was sudden death was an autopsy done?

What about nontraditional lipid/biomarkers?  I consider an assessment of Lp(a) and some more sophisticated measurement of atherogenic dyslipidemia (apoB, LDL-P) and inflammation (CRP) essential.

Interestingly the guidelines include ABI (which I do not find helpful) but not carotid vascular screening which has frequently guided me to earlier therapy in youngish individuals with abnormal biomarkers or strong family history.

Vascular screening in young subjects may detect subclinical atherosclerosis as measured by thickening of the carotid wall (IMT) or early carotid plaque prior to the formation of calcium in the coronary arteries. Advanced IMT precedes the formation of soft plaque in arteries and only later is calcium deposited in the plaque.

It’s never too early to start thinking about your risk of cardiovascular disease. If heart disease runs in your family or you have any of the “risk-enhancing” factors listed above, consider a CAC, nontraditional lipid/biomarkers, or vascular screening to better determine were you stand and what you can do about it.

Included in my discussions with my patients with premature ASCVD is a strong recommendation to encourage their brothers, sisters and children to undergo a thoughtful assessment for ASCVD risk. With these new studies and the new ACC/AHA guideline recommendations if they are age 40-75 years there is ample support for making CAC a part of such assessment.

Hopefully very soon, CMS and the health insurance companies will begin reimbursement for CAC. As it currently stands, however, the 125$ you will spend for the test at my hospital is money well spent.

Skeptically Yours,

-ACP

Has REDUCE-IT Resurrected Fish OIl Supplements (And Saved Amarin)?

The answers are no and yes.

There is still no reason to take over the counter fish oil supplements.

In fact, a study published Saturday found that fish oil supplementation (1 g per day as a fish-oil capsule containing 840 mg of n−3 fatty acids, including 460 mg of eicosapentaenoic acid [EPA] and 380 mg of docosahexaenoic acid [DHA]

did not result in a lower incidence than placebo of the primary end points of major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type.

However, another study  published Saturday (REDUCE-IT) and presented at the annual American Heart Association Scientific Sessions to great fanfare found that an ethyl-ester formulation (icosapent ethyl) of eicosapentanoic acid (EPA, one of the two main marine n-3 fish oils)  reduced major cardiovascular events by 25% in comparison to placebo.

When I wrote about Icosapent ethyl (brand name Vascepa) in a previous blog post in 2015 there was no data supporting its use:

A fish oil preparation, VASCEPA,  available only by prescription, was approved by the FDA in 2012.

Like the first prescription fish oil available in the US, Lovaza, VASCEPA is only approved by the FDA for treatment of very high triglycerides(>500 mg/dl).

This is a very small market compared to the millions of individuals taking fish oil thinking that  it is preventing heart disease.

The company that makes Vascepa (Amrin;$AMRN)would also like to have physicians prescribe it to their patients who have mildly or moderatelyelevated triglycerides between 200 and 500 which some estimate as up to 1/3 of the population.

The company has a study that shows that Vascepa lowers triglycerides in patients with such mildly to moderately elevated triglycerides but the FDA did not approve it for that indication.

Given the huge numbers of patients with trigs slightly above normal, before approving an expensive new drug, the FDA thought, it would be nice to know that the drug is actually helping prevent heart attacks and strokes or prolonging life.

After all, we don’t really care about high triglycerides unless they are causing problems and we don’t care about lowering them unless we can show we are reducing the frequency of those problems.

Data do not exist to say that lowering triglycerides in the mild to moderate range  by any drug lowers heart attack risk.

In the past if a company promoted their drug for off-label usage they could be fined by the FDA but Amarin went to court and obtained the right to promote Vascepa to physicians for triglycerides between 200 and 500.

Consequently, you may find your doctor prescribing this drug to you. If you do, I suggest you ask him if he recently had a free lunch or dinner provided by Amarin, has stock in the company (Vascepa is the sole drug made by Amarin and its stock price fluctuates wildly depending on sales and news about Vascepa) or gives talks for Amarin.

If he answers no to all of the above then, hopefully, your triglycerides are over 500.

And although elevated triglycerides confer an elevated CV risk nearly all prior trials evaluating different kinds  of triglyceride-lowering therapies, including extended-release niacin, fibrates, cholesteryl ester transfer protein inhibitors, and omega-3 fatty acids have failed to show reductions in cardiovascular events

REDUCE-IT, Amarin trumpeted widely in September (before the actual data was published)  now provides impressive proof that it prevents cardiovascular disease. Has the skeptical cardiologist changed his mind about fish oil?

Vascepa Is Not Natural Fish Oil

Although Amarin’s marking material states “VASCEPA is obtained naturally from wild deep-water Pacific Ocean fish” the active ingredient is an ethyl ester form of eicosapentoic acid (EPA) which has been industrially processed and distilled and separated out from the other main omega-3 fatty acid in fish oil (DHA or docosohexanoieic acid).

Natural fish oil contains a balance of EPA and DHA combined with triacylglycerols (TAGS).

So even if the REDUCE-IT trial results can be believed they do not support the routine consumption of  over the counter fish oil supplements for prevention of cardiovascular disease.

Does REDUCE-IT  Prove The Benefit of Purified High Dose EPA?

REDUCE-IT was a large (8179 patients) randomized, double-blind placebo controlled trial

Eligible patients had a fasting triglyceride level of 150 to 499 mg per deciliter  and a low-density lipoprotein (LDL) cholesterol level of 41 to 100 mg per deciliter  and had been receiving a stable dose of a statin for at least 4 weeks. In 2013 the protocol was changed and required a triglyceride level>200 mg/dl.

Participants were randomized to icosapent ethyl (2 g twice daily with food [total daily dose, 4 g]) or a placebo that contained mineral oil to mimic the color and consistency of icosapent ethyl and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group.

More importantly, the hard end-points of CV death, nonfatal stroke and heart attack were also significantly lower in the Vascepa arm compared to the “placebo” arm.

These results are almost unbelievably good and they are far better than one would have predicted given only a 17% reduction in triglycerides.

This makes me strongly consider prescribing Vascepa (something I heretofore have never done) to my higher risk patients with triglycerides over 200 after we’ve addressed lifestyle and dietary contributors.

Perhaps the high dose of EPA (4 grams versus the 1 gram utilized in most trials) is beneficial in stabilizing cell membranes, reducing inflammation and thrombotic events as experimental data has suggested.

Lingering Concerns About The Study

Despite these great results I have some concerns:

  1. The placebo contained mineral oil which may not have been neutral in its effects. In fact, the placebo arm had a significant rise in the LDL cholesterol.
  2. Enrolled patients were predominantly male and white. No benefit was seen in women.
  3. Higher rates of serious bleeding were noted in patients taking Vascepa
  4. Atrial fibrillation developed significantly more often in Vascepa patients (3.1%) versus the mineral oil patients (2.1%)

Finally, the trial was sponsored by Amarin Pharma. This is an aggressive company that I don’t trust.  The steering committee consisted of academic physicians (see the Supplementary Appendix), and representatives of the sponsor developed the protocol,  and were responsible for the conduct and oversight of the study, as well as the interpretation of the data. The sponsor was responsible for the collection and management of the data. All the data analyses were performed by the sponsor,

After i wrote my negative piece on Vascepa in 2015 a number of Amarin investors attacked me because Vascepa is the only product Amarin has and any news on the drug dramatically influences its stock price. Here is the price of Amarin stock in the last year.

The dramatic uptick in September corresponds to the company’s announcement of the topline results of REDUCE-IT. Since the actual results have been published and analyzed the stock has dropped 20%.

High Dose Purified and Esterified EPA-Yay or Nay?

I would love to see another trial of high dose EPA that wasn’t totally under the control of Amarin and such trials are in the pipeline.

Until then, I’ll consider prescribing Amarin’s pills to appropriate patients* who can afford it and who appear to have significant residual risk after statin therapy*.

But, I will continue to tell my patients to stop paying money for useless OTC fish oil supplements.

Megaskeptically Yours,-

ACP

N.B.* Appropriate patients will fit the entry criteria for REDUCE-IT described below.

Patients could be enrolled if they were 45 years of age or older and had established cardiovascular disease or were 50 years of age or older and had diabetes mellitus and at least one additional risk factor. Eligible patients had a fasting triglyceride level of 150 to 499 mg per deciliter (1.69 to 5.63 mmol per liter) and a low-density lipoprotein (LDL) cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter) and had been receiving a stable dose of a statin for at least 4 weeks;

So either secondary prevention (prior heart attack or stroke) or primary prevention in patients with diabetes and another risk factor.

 

 

Coronary Artery Calcium Scan Embraced By New AHA/ACC Cholesterol Guidelines: Will Insurance Coverage Follow?

The skeptical cardiologist has been utilizing coronary artery calcium (CAC) scans to help decide which patients are at high risk for heart attacks, and sudden cardiac death for the last decade. As I first described in 2014, (see here) those with higher than expected calcium scores warrant more aggressive treatment and those with lower scores less aggrressive treatment.

Although , as I have discussed previously, CAC is not the “mammography of the heart” it is incredibly helpful in sorting out personalized cardiovascular risk. We use standard risk factors like lipids, smoking, age, gender and diabetes to stratify individuals according to their 10 year risk of atherosclerotic cardiovascular disease (ASCVD) but many apparent low risk individuals (often due to inherited familial risk) drop dead from ASCVD and many apparent high risk individuals don’t need statin therapy.

Previously, major guidelines from organizations like the AHA and the ACC did not recommend CAC testing to guide decision-making in this area. Consequently, CMS and major insurers have not covered CAC testing. When my patients get a CAC scan they pay 125$ out of their pocket.. For the affluent and pro-active this is not an obstacle, however those struggling financially often balk at the cost.

I was, therefore, very pleased to read that the newly updated AHA/ACC lipid guidelines (full PDF available here) emphasize the use of CAC for decision-making in intermediate risk patients.

 

 

 

 

 

 

 

 

For those patients aged 40-75 without known ASCVD whose 10 year risk of stroke and heart attack is between 7.5% and 20% (intermediate, see here on using risk estimator) the guidelines recommend “consider measuring CAC”.

If the score is zero, for most consider no statin. If score >100 and/or >75th percentile, statin therapy should be started.

I don’t agree totally with this use of CAC but it is a step forward. For example, how I approach a patient with CAC of 1-99 depends very much on what percentile the patient is at. A score of 10 in a 40 year old indicates marked premature build up of atherosclerotic plaque but in a 70 year old man it indicates they are at much lower risk than predicted by standard risk factors. The first individual we would likely recommend statin therapy and very aggressive lifestyle changes whereas the second man we could discuss  taking off statins.

Neil Stone, MD, one of the authors of the guidelines was quoted  as saying that the imaging technique is “the best tiebreaker we have now” when the risk-benefit balance is uncertain.

“Most should get a statin, but there are people who say, ‘I’ve got to know more, I want to personalize this decision to the point of knowing whether I really, really need it.’ … There are a number of people who want to be certain about where they stand on the risk continuum and that’s how we want to use it,”

Indeed, I’ve written quite a bit about my approach to helping patients “get off the fence” on whether or not to take a statin drug.

I recommend reading “Are you on the fence about taking a statin drug” to understand the details of using CAC in decision-making and the follow up post on a compromise approach to reducing ASCVD risk.

Deriskingly Yours,

-ACP

Full title of these new guidelines includes an alphabet soup of organization acronyms

2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol

N.B. For your reading pleasure I’ve copied the section in the new guidelines that discusses in detail coronary artery calcium.

Two interesting sentences which I’ll need to discuss some other time

-When the CAC score is zero, some investigators favor remeasurement of CAC after 5 to 10 years

CAC scans should be ordered by a clinician who is fully versed in the pros and cons of diagnostic radiology.

In MESA (Multi-Ethnic Study of Atherosclerosis), CAC scanning delivered 0.74 to l.27 mSv of radiation, which is similar to the dose of a clinical mammogram 

-4.4.1.4. Coronary Artery Calcium

Substantial advances in estimation of risk with CAC scoring have been made in the past 5 years. One purpose of CAC scoring is to reclassify risk identification of patients who will potentially benefit from statin therapy. This is especially useful when the clinician and patient are uncertain whether to start a statin. Indeed, the most important recent observation has been the finding that a CAC score of zero indicates a low ASCVD risk for the subsequent 10 years (S4.4.1.4-1–S4.4.1.4-8). Thus, measurement of CAC potentially allows a clinician to withhold statin therapy in patients showing zero CAC. There are exceptions. For example, CAC scores of zero in persistent cigarette smokers, patients with diabetes mellitus, those with a strong family history of ASCVD, and possibly chronic inflammatory conditions such as HIV, may still be associated with substantial 10-year risk (S4.4.1.4-9–S4.4.1.4-12). Nevertheless, a sizable portion of middle-aged and older patients have zero CAC, which may allow withholding of statin therapy in those intermediate risk patients who would otherwise have a high enough risk according to the PCE to receive statin therapy (Figure 2). Most patients with CAC scores ≥100 Agatston units have a 10-year risk of ASCVD≥7.5%, a widely accepted threshold for initiation of statin therapy (S4.4.1.4-13). With increasing age, 10- year risk accompanying CAC scores of 1 to 99 rises, usually crossing the 7.5% threshold in later middle age (S4.4.1.4-13). When the CAC score is zero, some investigators favor remeasurement of CAC after 5 to 10 years (S4.4.1.4-14–S4.4.1.4-16). CAC measurement has no utility in patients already treated with statins. Statins are associated with slower progression of overall coronary atherosclerosis volume and reduction of high-risk plaque features, yet statins increase the CAC score (S4.4.1.4-17). A prospective randomized study of CAC scoring showed improved risk factor modification without an increase in downstream medical testing or cost (S4.4.1.4-18). In MESA (Multi-Ethnic Study of Atherosclerosis), CAC scanning delivered 0.74 to l.27 mSv of radiation, which is similar to the dose of a clinical mammogram (S4.4.1.4- 19). CAC scans should be ordered by a clinician who is fully versed in the pros and cons of diagnostic radiology.

Downloaded from http://ahajournals.org by on November 11, 2018

from Grundy SM, et al.
2018 Cholesterol Clinical Practice Guidelines

Heart Healthy Breakfast Choices?: Cheerios, Honey-Nut Cheerios and Soluble Fiber Revisited

A reader commenting on my Plant Paradox post questioned nutritional  recommendations to consume fiber. This has prompted me to revisit a post I wrote in 2014 on Cheerios and Soluble Fiber.

I mentioned at that time that Honey-Nut Cheerios was the #1 selling ready-to-eat breakfast cereal and Cheerios #4. This update Screen Shot 2018-07-15 at 7.22.55 AMindicates little has changed in the rankings or consumption of breakfast cereal since then despite a more widespread recognition that added sugar is the major toxin in our diet and that these food items are basically a vehicle for sugar.

Apparently, Americans believe honey is not sugar. But Honey Nut Cheerios contain 9 times as much sugar as cheerios. Here are the top ingredients:

Whole Grain Oats, Sugar, Oat Bran, Corn Starch, Honey, Brown Sugar Syrup, Salt, Tripotassium Phosphate, Rice Bran Oil and/or Canola Oil,

General Mills tries to emphasize the healthiness of Honey Nut Cheerios, focusing on their close relationship with bees and the natural goodness of honey in its advertising along with other factors that we now know are not important (low fat, 12 vitamins and minerals, source of iron).Screen Shot 2018-07-15 at 7.56.32 AM

Little has changed with respect to the science supporting fiber consumption to reduce cardiovascular disease since 2014.  It is still weak and based on observational studies and surrogate biomarkers.

Between the lines below is my original post with current annotations in red.


The skeptical cardiologist usually eschews the breakfast offerings in the Doctor’s lounge. I’m not really interested in consuming donuts, muffins, or bagels with their high carbohydrate load. As I’ve ranted out about previously, the only yogurt available is Yoplait low fat , highly sugared-up yogurt which is arguably worse than starting the day with a candy bar.

A selection of breakfast cereals is available including Cheerios, Raisin Bran, and Frosted Flakes. Occasionally, when I have neglected to bring in my own full-faty yogurt, granola and/or fruit I will open up one of the Cheerios containers and consume a bowl mixed with 2% milk (full-fat, organic milk which I passionately advocate here and here is not available) (2018 update, I have said “cheerio” to all breakfast cereals and no longer eat Cheerios in the doctor’s lounge). 

Pondering the Cheerios packaging and the cute little O’s made me wonder whether this highly processed and packaged food with a seemingly endless shelf life was truly a healthy choice.

The “Ready-To-Eat”  And Allegedly Heart-Healthy Cereal

Cheerios and Honey-nut cheerios were  the #4 and #1 breakfast cereals in the US in 2013, generating almost a billion dollars in sales. Both of these General Mills blockbusters undoubtedly have reached their popularity by heavily promoting the concept that they are heart healthy.

The Cheerios label is all about the heart. The little O’s sit in a heart-shaped bowl. A prominent red heart with a check inside it attests to the AHA having certified Cheerios as part of its checkmark.heart.org program. Additional text states “low  in Saturated fat and cholesterol” and “diets low in saturated fat and cholesterol may reduce the risk of heart disease.”

Is The Fiber In Cheerios “Heart-Healthy” ?

Beta-glucan is a soluble fiber primarily located in the endosperm cell wall of oats. Early studies showed that oats and beta-glucan soluble fiber could reduce total and LDL (bad cholesterol) levels. The mechanism isn’t really known. (see the end of post for possible mechanisms). The Quaker oats web site oversimplifies the mechanism thusly :

“In your digestive tract, it acts as a sponge, soaking up cholesterol and carrying it out of the body”

This narrative fits with the oversimplified and now discredited descriptions of atherosclerosis which attribute it directly to consumption of cholesterol and fatty acids. See here if you’d like to appreciate how complex the process truly is.

The FDA Sanctions Oats As Heart Healthy

In 1997, the FDA reviewed 33 studies (21 showing benefit and 12 not) and decided to allow a health claim for foods that contain oats and soluble fiber. A minimum dose of 3 grams/day of oat beta-glucan was suggested for a beneficial reduction in blood cholesterol and (presumably, although never documented) a subsequent decline in coronary heart disease.

In 1998 Johnson, et al, published the results of a study funded by a grant from General Mills that showed that  inclusion of whole grain oat ready to eat cereal providing 3 grams of beta-glucan as part of a low fat diet reduced  LDL cholesterol by 4% after 6 weeks. HDL was unchanged. Patients in this study consumed 45 grams (1.5 oz) of cheerios at breakfast and then again in the evening. There was a total of 3 grams of soluble fibre in this amount of Cheerios. A control group consumed corn flakes in a similar fashion without change in LDL.

General Mills took this weak data and ran with it and began posting on Cheerios the following statements

 “Did you know that in just 6 weeks Cheerios can reduce bad cholesterol by an average of 4 percent? Cheerios is … clinically proven to lower cholesterol. A clinical study showed that eating two 1 1/2 cup servings daily of Cheerios cereal reduced bad cholesterol when eaten as part of a diet low in saturated fat and cholesterol.”

Although the FDA had approved verbiage indicating oats may reduce heart disease “when eaten as part of a diet low in saturated fat and cholesterol” the agency objected to General Mills claiming that Cheerios lowers cholesterol “when eaten as part of a diet low in saturated fat and cholesterol”.

The FDA  issued a warning letter to General Mills in 2009 in which the agency alleged “serious violations” of the FDC Act in the label and labeling of Cheerios cereal.

Based on claims made on your product’s label, we have determined that your Cheerios® Toasted Whole Grain Oat Cereal is promoted for conditions that cause it to be a drug because the product is intended for use in the prevention, mitigation, and treatment of disease.

Lowering Cholesterol Is Not The Same As Preventing Heart Disease

The FDA was telling General Mills that it was OK to say that Cheerios may reduce heart disease but not that it can reduce cholesterol because that made it a drug. It makes no sense.

The only thing that had been demonstrated for oat soluble fiber and Cheerios in particular was a reduction in cholesterol. There has never been a study with oats showing a reduction in heart disease..

It’s the heart disease, the atherosclerosis clogging our arteries and causing heart attacks and strokes that we want to prevent. We could care less about lowering cholesterol if it doesn’t prevent atherosclerosis.

A recent review of studies since the FDA ruling shows that 70% of studies show some reduction in LDL with beta-glucan. Interstingly, the studies which added beta-glucan to liquids were generally positive whereas addition to solids such as muffins usually did not show benefit.

I’m going to accept as evidence-based the claim that whole oats can lower your LDL about 7% if you consume a very large amount of them on a daily basis.

However, the critical question for any drug or dietary intervention is does it prevent atherosclerosis, the root cause of heart attacks and strokes. There has been in the past an assumption that lowering cholesterol by any means would result in lowering of atherosclerosis.

This theory has been disproven by recent studies showing that ezetimibe and niacin which significantly lower LDL do not reduce surrogate markers of atherosclerosis or cardiovascular events any more than placebo when added on to statin drugs. (There is now weak evidence that ezetimibe does lower cardiovascular events ). The recently revised cholesterol guidelines endorse the concept of treating risk of atherosclerosis rather than cholesterol levels.


 

I do like the food writer Michael Pollan’s simple rules to “Eat Food. Mostly Plants. Not Too Much.” and this NY Times piece summarizes much of what is in his short, funny and helpful Food Rules book:

you’re much better off eating whole fresh foods than processed food products. That’s what I mean by the recommendation to eat “food.” Once, food was all you could eat, but today there are lots of other edible foodlike substances in the supermarket. These novel products of food science often come in packages festooned with health claims, which brings me to a related rule of thumb: if you’re concerned about your health, you should probably avoid food products that make health claims. Why? Because a health claim on a food product is a good indication that it’s not really food, and food is what you want to eat.

If you follow Pollan’s dictum you will get plenty of fiber, soluble or otherwise and you will avoid the necessity to obsess over the macronutrients in your diet, fiber or otherwise. Throw in some Cheerios and oatmeal every once in a while if you like them;  in their unadulterated state they are a heart-healthy food choice.

Cheerio,

-ACP

Mitigating Sarcopenia In The Elderly: Resistance Training Is A Powerful Potion

While researching afib-detection apps recently, the skeptical cardiologist stumbled across an article with the title “Resistance training – an underutilized drug available in everybody’s medicine cabinet”

This brief post from the British Journal of Sports Medicine blog nicely presents the rationale for using strength training to improve the overall health of the elderly. I have reblogged it below.

Americans spend billions on useless supplements and vitamins in their search for better health but exercise is a superior drug, being free  and without drug-related side effects

I’ve spent a lot of time on this blog emphasizing the importance of aerobic exercise for cardiovascular health but I also am a believer in strength and flexibility training for overall health and longevity.

As we age we suffer more and more from sarcopenia-a gradual decrease in muscle mass.

Scientific reviews note that loss of muscle mass and muscle strengh is quite common in individuals over age 65 and is associated with increased dependence, frailty and mortality

Specific information on progressive resistance training for the elderly is sparse but I found this amusing and helpful video on a Canadian site that provides some guidance for beginners.

 

And below is the referenced blog post:

Resistance training – an underutilised drug available in everybody’s medicine cabinet

By Dr Yorgi Mavros @dryorgimavros

As we get older we begin to lose muscle mass, approximately 1% every year. But more importantly, the decline in muscle strength declines at a rate 3-times greater [1]. The consequences of this decline in strength are significant, with lower muscle strength being associated with an increased risk dementia[2], needing care, and mortality[3]. But should we accept this as our fate, or is there anything we can do prevent, reverse or at least slow this age-related decline?

In 1990, a type of exercise called progressive resistance training, commonly known as strength training, was introduced to 9 nonagenerians living in a nursing home, specifically to treat the loss of muscle mass and strength, and the functional consequences of disability [4]. After just 8 weeks, these older adults saw average strength gains of 174%, with 2 individuals no longer needing a cane to walk. In addition, one out of the three individuals who could not stand from a chair, was now able to stand up independently. Just take a moment to think about the results of that study. If I told you there was a medicine that you or a loved one could take, and it could make either of you strong enough to now get out of a chair, would you take it?

What if you or a loved one had a hip fracture, and I told you that same medicine could help reduce the risk of mortality by 81%, and the risk of going in to a nursing home by 84%, as was shown in this study [5]. Currently, the only way to take this medicine is by lifting weights, or pushing against resistance.

A recent study from Britain, [6] showed an association between adults who participated in 2 days per week of strength training and a 20% reduction in mortality from any cause, and a 43% reduction in cancer mortality. Data from the Women’s Health Study in the US published at a similar time were very similar, with women reporting up to 145 minutes per week of strength training having a 19-27% reduced risk of mortality  from any cause [7].

So where does the benefit of strength training come from? First and foremost, it is anabolic in nature (meaning that it can stimulate muscle growth) making it the only type of exercise that can address the age-associated decline in muscle mass and strength. Within our laboratory at the University of Sydney, we have shown that we can use this type of exercise to improve cognitive function in adults who have subjective complaints about their memory [8]. What’s important though, is that there was a direct relationship between strength gains and improvements in cognition, and so maximizing strength gains should be a key focus if you want to maximize your benefit [9]. This type of exercise has even been taken into hospitals and used in adults with kidney failure undergoing haemodialysis, where it was shown to reduce inflammation, and improve muscle strength and body composition [10].

Other laboratories around the world have also used strength training to increase bone strength in postmenopausal women [11], help manage blood sugar levels in adults with type 2 diabetes [12], as well as to counteract the catabolic side effects of androgen-deprivation therapy for men with prostate cancer [13]. Not to mention its benefits to sleep [14], depression  [15] and recovery from a heart attack  [16].

So it is no surprise to see that the  Australian [17] and UK [18] public health guidelines for physical activity recommend we take part in activities such as strength training 2-to-3 days per week. Unfortunately however, these recommendations lack detail and guidance on intensity and frequency.

A key theme in all the randomized controlled studies discussed above, is that not only were exercises performed at least 2 days per week, but they were fully supervised, used machine and/or free weights, and were done at a high intensity, which is commonly set to 80% of an individual’s peak strength. It is for this reason I like to focus on the guidelines put forward by The American College of Sports Medicine (ACSM) [19]. The ACSM advises that everyone, including older adults do at least 2 days of progressive resistance training, which is to be performed at a moderate (5 – 6) to high/hard (7 – 8) intensity on a scale of 0 to 10, involving the major muscle groups of the body. So if you are looking to maximise the benefit from your time in the gym, or looking to make a positive change to your lifestyle, remember that there is medicine you can take; Try lifting some weights or doing other forms of strength training, 3 days a week, and importantly, make sure it feels moderate to hard. Not only will it add years to your life, but life to your years.


Since college I have regularly done weight training 3 times per week As I get  dangerously close to age 65 and joining the ranks of the “elderly” I have ramped up the intensity of my workouts, working hard to forestall the sarcopenia that will ultimately be my fate.

Antisarcopenically Yours,

-ACP

***************************

Video credit: Produced for the University of British Columbia’s (UBC) Department of Physical Therapy, the Aging, Mobility, and Cognitive Neuroscience Laboratory, the Centre for Hip Health and Mobility and the Brain Research Centre at Vancouver Coastal Health and UBC
hiphealth.ca/news/preventing-dementia

 

What You Should Know About Lipoprotein(a) And Heart Attack Risk

If you have had a heart attack at an early age or one of your parents did but your standard risk factors for coronary heart disease are normal you should consider getting tested for Lipoprotein(a) or Lp(a).

The standard lipid profile that most patients get checks LDL (bad) HDL (good) and total cholesterol along with  triglycerides. While these are useful, I have many patients who have normal standard values but have developed advanced coronary heart disease at an early age despite following a perfect lifestyle (not smoking, regular aerobic exercise, healthy diet.)

The skeptical cardiologist tests such patients for Lp(a) (pronounced LP little a)  and it is quite frequently elevated.

For patients, these are the facts to know about Lp(a)

  1. It is the strongest single inherited (monogenetic) risk factor for the early development of coronary artery disease, heart attacks and strokes.
  2. In addition to increasing risk of atherosclerosis, high Lp(a) is strongly associated with the development of calcific aortic valve disease which can result in narrowing of the aortic valve and aortic stenosis.
  3. Depending on the cut-off used  up to one in five individuals may have elevated Lp(a)
  4. Levels of Lp(a) can be measured with a simple blood test that should cost no more than 50 to 100$. This is not included in standard lipid or cholesterol testing.
  5. Risk for heart attack starts to rise with levels above 30 mg/dl and Canadian guidelines from 2016 (see here)) consider >30 mg/dl to be a risk factor and they recommend measuring Lp(a) in those with a family history of premature CAD or those at intermediate risk.
  6. The European Atherosclerosis Society (EAS, 2010), suggested levels of <50 mg/dl as optimal. The EAS advised measuring Lp(a) once in all patients with premature CVD.
  7. As levels get even higher risk also rises as these graphs show

 

 

 

 

Treatment For High Lp(a)

The lifestyle changes (both exercise and diet) that improve bad and good cholesterol levels have no effect on Lp(a). Our best drugs, the statins, for reducing risk of heart attack and stroke also don’t lower Lp(a) levels.

Only niacin has been shown to reduce Lp(a) across broad populations but there is no evidence that Lp(a) lowering by niacin lowers cardiovascular risk so it cannot be recommended for treatment.(In the AIM-HIGH study niacin did not reduce cardiovascular events in patients with Lp(a) with levels>50 mg/dl, despite achieving a mean Lp(a) reduction of 39%.)

Cholesteryl ester transfer protein inhibitors which raise HDL levels also reduce lipoprotein(a) concentrations, but three such inhibitors have not shown a clinical benefit.

In fact, currently there are no studies showing that lowering Lp(a) with any drug will effectively lower the associated risk of heart attack, stroke and aortic stenosis.

In the not too distant future, effective therapies may emerge. There are promising newer agents (antisense oligonucleotides or ASOs) currently in clinical trials and in limited populations the PCSK9 inhbitors, mipomersen and estrogen have lowered Lp(a) levels.

Why Test For Lp(a)?

If we have no effective therapies that work by lowering Lp(a) why recommend testing for it?

I test Lp(a) for  two reasons.

First, since it is inherited, patients with high levels should consider having first degree relatives tested for Lp(a) to identify those who are going to be at high risk. This provides an early warning of who in the family is most at risk for cardiovascular complications early in life. Such patients should be considered for early screening for subclinical atherosclerosis. In addition, they should be additionally motivated to do everything possible to reduce their elevated risk by lifestyle changes.

Second, I tend to recommend  more aggressive cholesterol lowering in patients who have evidence for early plaque build up for atherosclerotic events early in life than I otherwise would be.     I tend to agree with the approach diagrammed below:

 

With this approach for patients who have had events related to atherosclerosis or advanced CAC for age we work super aggressively on optimizing all risk factors. I try to lower LDL to <70 with statins and with the addition of ezetimibe or PCSK9 inhbitors if needed.

If the patient has more problems with atherosclerotic events despite optimizing risk factors and Lp(a) >60 mg/dl, some experts recommend using apheresis a technique which runs the patient’s blood through a filter which removes LDL and Lp(a). Personally, I have not sent any patients for apheresis and await better studies proving its benefit.

Antiproatherogenically Yours,

-ACP

For those patients seeking more detailed information and references I recommend Dr. Siggurdson’s excellent post on Lp(a)

There is a Lipoprotein(a) Foundation with reasonably informative and accurate website you can peruse here for more information.

Finally, if you want to delve deeply into the data check out this recent JACC review here.

The graphs above and this figure
showing the proposed pro-inflammatory, pro-atherogenic and pro-thrombotic pathways of Lp(a) are from that article.