Tag Archives: coronary artery calcium

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.

 

Calcium Supplements: Would You Rather Have a Hip Fracture or a Heart Attack?

ct_calcium
Does taking extra calcium pills contribute to the deposition of calcium into the coronary arteries that we see in CT scans like this?

Since I’ve been utilizing coronary calcium CT scans to detect early atherosclerotic plaque (see here) in my patients, I have frequently been asked about the relationship between calcium supplements and heart attack risk.

For example, Mrs. Jones has just found out that she has a very high calcium score and that it reflects the amount of atherosclerotic plaque lining and potentially clogging the coronary arteries to her heart. She has also been taking calcium and Vitamin D supplements recommended to her to prevent bone thinning and fractures in the future.

Did all that extra calcium she was consuming end up depositing in her coronary arteries, thus increasing her risk of heart disease?

This is a complex and not fully settled issue, however, there is enough evidence to suggest that we be cautious about calcium supplements.

A recent meta-analysis (Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691) of cardiovascular events in randomized, placebo controlled trials of calcium supplements (without vitamin D co-administration) showed that calcium supplements significantly increased the risk of myocardial infarction by 31% in five trials involving 8151 participants.

A recent meta-analysis of trials involving calcium and Vitamin D supplements found a similar increased risk of cardiovascular disease in the subjects randomized to taking calcium and Vitamin D.

These authors concluded

“in our analysis, treating 1000 patients with calcium or calcium and vitamin D for five years would cause an additional six myocardial infarctions or strokes (number needed to harm of 178) and prevent only three fractures (number needed to treat of 302”

How Might Calcium Supplements Increase Cardiovascular Risks?

Calcium supplements acutely and chronically  increase serum calcium concentration. Higher calcium levels are associated with more carotid artery plaque, aortic calcification, and  a higher incidence of heart attack and death.

Just like atherosclerosis, the process of calcium deposition into the arteries is very complex. Higher calcium levels could alter certain regulators of the process, such as fetuin A, pyrophosphate and bone morphogenic protein-7 or bind to calcium receptors on vascular smooth muscle cells lining the arteries

Higher calcium levels may also promote clot formation.

Bone Fracture versus Heart Attack

The informed doctor would have to tell Mrs. Jones that her calcium supplements may have contributed to her advanced coronary calcium and raised her risk of heart attack and stroke.

As with all medications, she and her doctor are going to have to discuss the relative risks and benefits.

If she has great concerns about fractures and has very low bone mineral bone density (osteoporosis) along with no family history of premature heart disease then the calcium supplementation may be appropriate.

Conversely, if she has high risk factors for coronary heart disease and/or a strong family history of premature coronary heart disease and only slightly low bone mineral density, avoiding the calcium supplements would be appropriate.

Preventing Fractures and Heart Attacks

It’s best to get calcium from the foods we eat rather than a sudden concentrated load of a supplement. Full fat dairy products like yogurt and cheese are heart healthy (see here and here) and they are an excellent source of calcium.

Weight-bearing exercise (such as running/jogging/hiking) and strength-building exercise (lifting weights, resistance machines, etc.) are also important for strengthening bones.

Thus, eating full fat dairy and aerobic exercise will help prevent both a fracture and a heart attack.

Searching for Subclinical Atherosclerosis: Coronary Calcium Score-How Old Is My Heart?

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. I’ve talked about using high frequency ultrasound of the carotid arteries to the brain to look for plaque and for carotid IMT in earlier posts here and here.

There is a third method that looks directly at the coronary arteries, which supply blood to the heart.  It is variously called a heart scan, coronary calcium score, or cardioscan, and it is more widely utilized amongst physicians who are serious about preventing cardiovascular disease.

This technique utilizes the ionizing radiation inherent in X-rays to perform a CT examination of the chest. It does not require injection of any dye or the puncture of any arteries; thus, it is considered noninvasive and has no risk or pain associated with it.

When atherosclerosis first begins to form in the arteries, it generally takes the form of “soft” plaques. Soft plaques are initially full of lipids, but after a period of time, the plaques undergo change: calcium begins to deposit into this plaque.

There is a direct relationct_calciumship between coronary artery calcium (CAC) and the amount of atherosclerotic plaque in the coronary arteries.

CT scans are very accurate in identifying small amounts of calcium in the soft tissue of the body. Calcium score tests essentially look for blobs of calcium that are felt to be within the coronary arteries, count up the intensity and distribution of them, and calculate a total score that reflects the entire amount of calcium in the coronary arteries.

A large body of scientific literature has documented that higher calcium scores are associated with higher risk of significantly blocked coronary arteries and of heart attack.

You can read the NHLBI clinic’s info for patients here on the test.

How Is The Calcium Score Used To Help Patients?

The calcium score can be utilized (in a manner similar to the carotid IMT and plaque) to help determine whether a given individual has more advanced atherosclerosis than we would predict based on their risk factor profile. A score of zero is consistent with a very low risk of significantly blocked arteries and confers an excellent prognosis. On the other hand, scores of >400 indicate extensive atherosclerotic plaque burde , high risk of heart attack, and high likelihood of a significantly blocked coronary artery.

The calcium score (similar to the carotid IMT) increases with age and is higher in males versus females at any given age. We have very good data on age and gender normals. The average 50-59 year old woman has a zero score, whereas a man in that age range has a score of 30. The average man has developed some CAC by the fourth decade of life whereas the average woman doesn’t develop some until the sixth decade. More advanced CAC for age and gender is a poor prognostic sign. You can plug your own age, gender, race and CAC score into a calculator on the MESA (Multi-ethnic Study of Atherosclerosis) website here.

2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk says the following

 If, after quantitative risk assessment, a risk based treatment decision is uncertain, assessment of 1 or more of the following—family history, hs-CRP, CAC score, or ABI—may be considered to inform treatment decision making

This guideline recommended utilizing a  CAC score of >300 Agatson Units or >75th percentile for age, gender and ethnicity as a cut-off.

CAC Score Identifies Those At Very High  Risk

A forty-something year old man came to see me for palpitations. He had a stress echo which was normal except for the development of frequent PVCs and a brief run of non sustained ventricular tachycardia.  His risk factor profile was not particularly bad: no diabetes, hypertension, or cigarette smoking and an average lipid profile. When I calculated his 10 year risk of ASCVD using my iPhone app it came out at 7%: below the level at which statin treatment would be recommended.  Because his father had a coronary stent in his fifties (this does not qualify as a family history of heart disease according to the new guideline, by the way)  I recommended he get a CAC test done.

His CAC score came back markedly elevated, almost 1000.  .  A subsequent cardiac catheterization demonstrated a very high-grade coronary blockage iwhich was subsequently stented. I started him on high intensity statin therapy and he has done well.

CAC score identifies Those At Very Low Risk

Many individuals with high cholesterol values do not develop atherosclerosis.  A zero CAC score in a male over 50 or a woman over 65 (or non-zero CAC score that is <25th percentile for age, gender, ethnicity) indicates that they are not developing atherosclerosis and makes it less likely that they will benefit from statin therapy to lower cholesterol.

Some Caveats About CAC score testing

-Like carotid vascular screening, there is no reason to get a CAC test if you already have had problems related to blocked coronary arteries such as a heart attack or coronary stents or coronary bypass surgery.

-CAC score testing is not covered by insurance (except in Texas) and costs somewhere between $125 and $300 out of pocket.

-The CT scan leads to a small amount of radiation exposure-approximately 1 – 2 milliseiverts of radiation (mSv). To puts things in perspective, the annual radiation dose we receive from natural sources is around 3 mSV per year.

Some of the other approximate radiation doses for tests commonly used in medicine are:

Chest X-ray ( )            0.1 mSV
Routine CT chest:  10 mSV
CT abdomen: 10 mSV
Nuclear stress test: 10 to 20 mSV