Tag Archives: family history heart disease

Should You Get Tested For Lipoprotein(a), The “Hidden” Risk Factor For Cardiovascular Disease?

The skeptical cardiologist wrote about the importance of testing patients with premature atherosclerosis or strong family history of cardiovascular disease for Lipoprotein(a) here.

The National Lipid Association (NLA) published their scientific statement on Lipoprotein(a) (Lp(a)) (Use of Lipoprotein(a) in Clinical Practice: A Biomarker Whose Time Has Come) last summer (summarized nicely here) and I’ve listed their key recommendations below.

  1. For diagnosing high Lp(a) they chose a universal cut point of >100 nmol/L (approximately >50 mg/dl) which is at the 80th percentile in white Americans. This cut-off is not written in stone and may vary depending on risk, ethnicity, and comorbidities. Some labs report out Lp(a) in mg/dl, others in nmol/L. Pay attention to the units.
  2. An individual’s Lp(a) level is 80-90% genetically determined in an autosomal codominant inheritance pattern with full expression by 1-2 years of age and adult-like levels achieved by approximately 5 years of age. Outside of acute inflammatory states, the Lp(a) level remains stable through an individual’s lifetime regardless of lifestyle.

  3. High-quality evidence supports a link between Lp(a) levels and a variety of cardiovascular-related outcomes. See Table 1. The risk of heart attack and aortic stenosis is increased 3 to 4 fold.

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4. The following populations should be considered for testing.Screen Shot 2020-02-16 at 6.26.11 AM

5. Neither diet nor lifestyle influences Lp(a) levels.

6. PCSK9 inhibitor drugs and niacin lower Lp(a) levels and but there are no data showing this changes clinical outcomes.

7. Similar to my approach, “the authors recommend initiating a moderate- to high-intensity statin therapy in adults aged 40-75 years with a 10-year ASCVD risk of 7.5% to ≤20% with a Lp(a) ≥100 nmol/L. High-risk patients with LDL-C ≥70 mg/dL (non-HDL-C ≥100 mg/dL) and a Lp(a) ≥100 nmol/L on maximally tolerated statin should be considered for more intensive therapies (ezetimibe and PCSK9 inhibitors) to lower LDL-C.”

8. Currently, novel therapies are being studied that selectively target Lp(a). A phase 2 trial of AKCEA apo(a)-LRx, an apo(a) antisense oligonucleotide, reduced Lp(a) up to 80%. A phase 3 study is being planned. Additionally, an oxPL antibody that binds and inactivates the pro-osteogenic activity of Lp(a) has promising in vitro data. These therapies, while promising, require additional research prior to becoming mainstream therapies.

The cost of the blood test for Lp(a) should be minimal. Medicare reimburses $14 for it. You can order it from Boston Heart Diagnostics for $11. Unfortunately, there is no telling what your local hospital lab will charge.

Since Lp(a) 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.

Proantiatherogenically Yours,

-ACP

N.B. In 2018 the Centers for Disease Control and Prevention (CDC) approved two ICD-10 codes for the diagnosis of elevated Lipoprotein(a), or Lp(a). The ICD-10 diagnosis codes help to identify asymptomatic patients with elevated Lipoprotein(a) (E78.41) and a family history of elevated Lipoprotein(a) (Z83.430)

N.B.2. Don’t confuse Lp(a) with Apolipoprotein A1 which is the major protein component of HDL particles in plasma. Also, please note that WordPress converted my little a into a capital A in the title and I have no idea how to prevent that conversion.

Dealing With The (Cardiovascular) Cards You’ve Been Dealt

The skeptical cardiologist was in Atlanta recently  visiting  his Life Coach (LCOSC). Oddly enough, the wife of the LCOSC (who I’ll call Lisa) had just undergone a coronary calcium scan  and it came back with a high score.  Most women her age (58 years old) have a zero score but hers came back at 208 .

What is the significance of a calcium score of 208 in this case?

The CT scan for calcium (discussed by me in more detail here) focuses entirely on quantifying the intense and very specific kind of x-ray absorption from calcium. The three-dimensional resolution of the scan is such that the coronary arteries which supply blood to the heart can be accurately located and the amount of calcium in them very accurately and reproducibly added up. Calcium is not in the arteries normally and only accumulates as atherosclerotic plaque builds up over time. The build up of fatty plaque (atherosclerosis) is the major cause of coronary artery disease (CAD, sometimes termed coronary heart disease (CHD)) which is what causes most heart attacks and most death in both men and women in the U.S.

We can enter Lisa’s numbers into the online MESA calculator to see how she compares to other white 59 year old women. The calculator tells us that 72% of her peers have a zero calcium score and a score of 208  is higher than 95% of her peers. Although the 95th percentile is a good place to be for SAT scores it is not for atherosclerosis. This means substantial amount of fatty atherosclerotic plaque has built up in the arteries and puts the individual at significantly greater risk for heart attack and stroke. A calcium score of 100-300 confers a 7.7 times increased risk compared to an individual with similar risk factors with a zero calcium score.

Most of the risk factors that we can measure to assess one’s risk of heart attack (blood pressure, diabetes, smoking) were absent in Lisa. Her cholesterol levels had risen in the last 10 years but when I entered her numbers (total cholesterol 221, HDL 68) into the ASCVD risk estimator her 10 year risk came back at 2.5%. This is considered low and no treatment of cholesterol would be advised by the new guidelines.

The only clue that her cardiologist would have that Lisa has advanced premature atherosclerosis is that her mother had coronary heart disease at an early age, something we call premature CAD. Her mom at the age of 62 suffered a heart attack and had a stent placed in one of her coronary arteries. The occurrence of significant premature CAD in a parent or sibling  substantially increases the chances that a patient will have premature CAD and the earlier it occurred in the parent or sibling the higher the risk.

Some of this excess risk is transmitted by measurable risk factors such as hypertension and hyperlipidemia and some through lifestyle factors but the majority of it is through genetic factors that we haven’t fully identified.

How much of an individual’s risk for heart attack  is determined by genetics versus lifestyle?

A large Swedish study found that adopted men and women with at least one biological parent with CHD were 1.5 times more likely to have CHD than adoptees without. In contrast, men and women with one adoptive parent were not at increased risk.

Since 2007 an intense project to identify genetic factors responsible for CAD has been underway at multiple academic centers. Thus far 50 genetic risk variants have been identified. According to Dr. Robert Roberts

” All of these risk variants are extremely common with more than half occurring in >50% of the general population. They increased only minimally the relative risk for coronary artery disease. The most striking finding is that 35 of the 50 risk variants act independently of known risk factors, indicating there are several pathways yet to be appreciated, contributing to the pathogenesis of coronary atherosclerosis and myocardial infarction. All of the genetic variants seem to act through atherosclerosis, except for the ABO blood groups, which show that A and B are associated with increased risk for myocardial infarction, mediated by a prolonged von Willebrand plasma half life leading to thrombosis”

 How well do the standard risk factors capture the individuals risk for heart attack?

The standard approach to estimating risk fails in about 25% of individuals as it does not accurately convey the high risk of the patient with family history and it overestimates risk in many elderly individuals who have an excellent family history.

It is in these patients that testing for the actual presence of atherosclerosis, either by vascular screening or coronary calcium is helpful.

Reducing The Excess Risk of Premature CAD

For many individuals there are clear-cut lifestyle changes that can be implemented once advanced CAD is identified: cigarette smoking cessation, weight loss through combinations of diet and exercise with resulting control of diabetes, However, many patients like Lisa, are non-smokers, living a good lifestyle, eating an excellent diet with plenty of fresh fruit, vegetables, fish and healthy oils and  without obesity or diabetes. There is no evidence that modifying lifestyle in this group is going to slow down an already advanced progression of atherosclerosis.

Patients like Lisa have inherited predisposition to CAD, it is not due to their lifestyle.

Lisa’s cardiologist  suggested she get a copy of Dr. Esselstyn’s book “Prevent and Reverse Heart Disease”. This book, based on the author’s experience in treating 18 patients with advanced CAD espouses an ultra low fat diet. The author declares that “you may not eat anything with a face or a mother (meat/poultry/fish)” and bans  full fat dairy products and all oil (“not even a drop”)

Such “plant-based diets” (codeword for vegan or vegetarianism) lack good scientific  studies supporting efficacy and are extremely hard to maintain long term. There is nothing to suggest that Lisa’s long term risk of heart attack and stroke would be modified by following such a Spartan dietary regimen.

Her cardiologist did recommend two things proven to be beneficial in patients with documented advanced CAD: statins and aspirin.

Taking a statin drug will arrest the atherosclerotic process and reduce risk of heart attack and stroke by around 30% as I’ve discussed here and here.

An aspirin is now indicated since significant atherosclerosis has now been documented to be present as I’ve discussed here.

We can blame a lot of heart disease on lifestyle: poor diets and lack of exercise are huge factors leading to obesity, diabetes, hypertension and hyperlipidemia, but in many patients I see who develop heart disease at an early age, lifestyle is not the issue, it is the genetic cards that they have been dealt.

Until we develop reliable genetic methods for identifying those at high risk it makes sense to utilize methods such as vascular screening or coronary calcium to look for atherosclerosis in individuals with a family history of premature CAD.

Once advanced atherosclerosis is identified, we have extremely safe and effective medications that can help  individuals like Lisa deal with the cardiovascular cards they have been dealt.