Tag Archives: guidelines

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.

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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.

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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)

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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.

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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

Should I Take A Statin Drug? Risks, Benefits and the New Guidelines

StatinsThe skeptical cardiologist just returned from Washington, DC where he attended the American College of Cardiology (ACC) annual conference and visited Ford’s Theatre. I was hoping to gather more information on diet and cardiovascular disease but most of the discussions on prevention of heart disease centered around the new ACC/AHA guidelines for treating cholesterol.

A recently published analysis of the impact of these guidelines found that

As compared with the ATP-III guidelines, the new guidelines would increase the number of U.S. adults receiving or eligible for statin therapy from 43.2 million (37.5%) to 56.0 million (48.6%). Most of this increase in numbers (10.4 million of 12.8 million) would occur among adults without cardiovascular disease.

If you are a man over the age of 59 (which I just became), even without any cardiovascular disease or diabetes, there is an 87% chance the guidelines would suggest you take a statin drug.

This is a startling increase and consequently there has been a lot of criticism and questioning of the validity of these recommendations.

More importantly, for an individual patient, should you take a statin drug if your doctor recommends it? This is an especially good question if you have no evidence of any atherosclerotic cardiovascular disease (so-called primary prevention). At a minimum, you should have a very detailed discussion with your doctor about the risk and benefits of taking the medication in your particular situation.

What are statin drugs?

Statins are the most powerful, safe and effective drugs available for lowering LDL or bad cholesterol levels. They inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, involved in cholesterol biosynthesis. Low density lipoprotein (LDL) cholesterol concentration is lowered by reducing its production in the liver and increasing removal from the circulation. Statins also have anti-inflammatory effects, improve endothelial function, and reduce thrombus formation.

Common examples of statin drugs are Lipitor which is now available as a generic called Atorvastatin , Pravastatin, and Crestor (Rosuvastatin), which is only available in brand name form.

What are the risks of statin drugs?

When large scale randomized trials of statin drug therapy are analyzed, rates of adverse events (17%) or stopping treatment due to adverse events (12%) are similar in the statin compared to placebo/control groups.

The incidence of cancers, liver enzyme elevations, kidney dysfunction or arthritis was the same in the two groups.

There are only two side effects from taking statins I consider significant and mention to my patients:
1. There does appear to be a 9% increase in the risk of developing diabetes. Most of the patients who develop diabetes on statins were at high risk for this to begin with and the overall benefits of lowering CV disease outweighs the development of diabetes in patients who take statins.
2. Statins definitely can cause muscle aches (myalgias) and this seems to happen in about 10% of patients over time. If these develop, we stop the statin and the myalgias go away if they are due to the drug. There are no reliable studies showing any long term residual muscle weakness or ache. A very, very small number of patients develop rhabdomyolysis, in which there is severe muscle damage. These patients are almost always taking multiple medications which interact with the statins and often have kidney failure to begin with.

Some things you don’t need to be concerned with while on statins:

1. That the drug will give you Alzheimer’s or make you stupid. There is much anecdotal misinformation on the web about this, but no solid evidence of any adverse effect on cognition.
2. That the drug will destroy your liver. A small percentage of patients will develop elevations of their liver enzymes (AST or ALT) but this does not lead to liver damage and is considered so insignificant now that the FDA now longer advises checking liver enzymes in patients on statin drugs.

What are the benefits of statins in people without known heart disease?

They lower all-cause mortality by 14%, combined fatal and nonfatal cardiovascular disease by 25%, and stroke by 22%. They lower the chances that you would need a stent or bypass surgery by 38%.
Another way of looking at the benefits of a treatment is the number needed to treat (NNT).
To save one life, you would need to treat 138 patients for 5 years with statin drugs. This means that 137 patients would have done fine without taking the drug.

The higher your risk of developing atherosclerotic cardiovascular disease  (ASCVD (all the disease that occurs as a result of fatty plaque build up in the body, including heart attack and stroke)), the more likely you will benefit from taking a statin drug.
Thus, the new guidelines utilize a risk estimator that takes into account your total and good cholesterol values, your systolic blood pressure, age and whether you smoke, have diabetes or treated hypertension to calculate your risk of developing clinical ASCVD over the next ten years.

If this ten year risk is over 7.5%, statin therapy should be considered.

I’ve looked over the guidelines carefully, read a lot of the original studies and listened to the discussion and I think this is a reasonable approach. I try to present each patient with the risks and benefits and let them make the decision as to whether they want to take the drug.
Each individual has a different perspective, perhaps heavily influenced by their father having died of a heart attack in his fifties or by a close friend who feels that statins ruined his life.

Two important new concepts from the new guidelines

The new guidelines no longer look at the LDL or bad cholesterol level as a goal or as a level for initiating treatment (unless it is super high, above 190). Thus, the only reason to be checking follow up cholesterol panels on patients who are taking good levels of statin drugs is to verify compliance and an effective reduction in LDL from baseline. I will not try to get your LDL below 100 or 70 and you will not have to worry that it is not at that level.

The new guidelines rightly emphasize statin drugs as the only drug therapy that has good outcomes data (meaning they have been show to reduce heart attacks and strokes) supporting their use in primary prevention.
Ezitimibe (Zetia) is a commonly prescribed drug which lowers LDL cholesterol but is expensive and has never been shown to lower heart attack or stroke risk and, in my opinion, should not be prescribed.

Our goal should be prevention of heart disease, not lowering LDL levels or triglyceride levels.

I believe that we can fine tune which patients will and will not benefit from statin therapy by looking for evidence of what is called “subclinical atherosclerosis.” I plan to review this in a future post.
For now, I leave you with the humorous line from the play “Our American Cousin” that caused the distracting laughter during which John Wilkes Booth shot Lincoln in Ford’s Theatre (which is not far from the Washington Convention Center and well worth visiting!)

“Don’t know the manners of good society, eh? Well, I guess I know enough to turn you inside out, old gal — you sockdologizing old man-trap.”

Tell your cardiologist you will sockdologize him if he doesn’t give you a good discussion of the risks and benefits of the statin drug he is recommending.