cardiovascular disease

Understanding Lipoprotein(a) and the Risk for Cardiovascular Disease

Author:
Anne Danahy, MS, RDN
Scottsdale, Arizona

 

A person’s risk of heart disease and stroke is usually determined by low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels. For most of the general population, these numbers, along with an assessment of risk factors, such as blood pressure, body mass index (BMI), and smoking status, are a good determination of risk. Over the past few years, more emphasis has been placed on the role of lipoprotein(a), or Lp(a), which greatly increases the risk for premature cardiovascular disease (CVD), especially when it is combined with other risk factors.

Lipoproteins and Cholesterol

Lipoproteins are particles that carry cholesterol and triglycerides through the bloodstream. Chylomicrons (which carry triglycerides), VLDL, LDL, and HDL are all types of lipoproteins, and each of these has subtypes of lipoproteins. Lp(a) is a subtype of LDL lipoprotein that is associated with increased inflammation and atherosclerosis. It is found in very small amounts in most people, but about 1 in 5 individuals worldwide, or about 63 million people in the United States1 has a genetic trait that causes them to have much higher levels of Lp(a). 

Because Lp(a) is easily deposited in the arteries, it fuels the development of atherosclerosis, or hardening of the arteries, and it is considered an independent risk factor for CVD. Lp(a) levels are not currently routinely tested. A person can have a normal fasting lipid profile, with LDL levels within normal limits, and appear to be at low risk for CVD while having high Lp(a) levels. A normal Lp(a) level is lower than 30 mg/dL. Those with inherited Lp(a) tend to have much higher levels. Lp(a) greater than 30 mg/dL confers 2 to 4 times greater risk of heart attack, stroke, or aortic stenosis before age 55 years for men and 65 years for women.1,2 A meta-analysis of 5436 participants demonstrated that compared with those who had Lp(a) levels in the bottom third, those with Lp(a) levels measured in the upper third were 70% more likely to develop coronary heart disease.3

Who Is at Risk?

Inherited Lp(a) is caused by a genetic mistake or Single Nucleotide Polymorphism (SNP) in the apo(a) LPA gene.4 It affects all ethnic groups but is more common in African Americans and South Asians.1 Those with a family history of early CVD or heart attack in men younger than 50 years and women younger than 60 years are at greatest risk.

Other risk factors include:1,5

  • A family history of diabetes, hypertension, stroke, or kidney disease
  • Dyslipidemia
  • Elevated fasting blood glucose
  • BMI greater than 28 kg/m2
  • Waist circumference more than 35" for women and more than 40" for men
  • Sedentary lifestyle
  • Smoking
  • Migraines with aura


Anyone who carries the Lp(a) SNP is at increased risk for heart attack or stroke, including children (although CVD is rare in young children) and young adults. In a study that examined the relationship of Lp(a) to cases of unexplained ischemic stroke in patients aged 18 to 64 years, the researchers determined that higher concentrations of Lp(a) are an independent risk factor for premature stroke in young and middle-aged adults.5 Those with the highest Lp(a) levels had double the odds of unexplained stroke compared with those with low levels.

It is important to understand that with hereditary Lp(a), CVD risk is elevated, even in a person who appears to be at low risk (e.g., normal BMI, normal labs, healthy diet).

Next Page: Pharmacological Treatment and Dietary Intervention

Pharmacological Treatment and Dietary Intervention

There is currently no medication available to inhibit Lp(a), so pharmacological treatment is focused on:

  • Statins to improve LDL cholesterol, if needed;
  • Niacin to improve HDL cholesterol and reduce Lp(a) levels by approximately 20%6 (although some studies suggest additional benefit); and
  • Low-dose aspirin therapy.


In the Women’s Health Study, low-dose aspirin therapy, which is commonly prescribed to patients with CVD risk, had more benefit in preventing CVD in those with elevated Lp(a) than in those without.7

Generally, Lp(a) does not respond to changes in diet or exercise in the same way that total or LDL cholesterol does, but because elevated LDL cholesterol along with elevated Lp(a) has a synergistic effect, the importance of diet and exercise on lipids should not be overlooked. To date, the most important research has been on the potential benefits of unsaturated fats and fish oil.

Several small studies have shown that in healthy adults, eating a low-fat, high-carbohydrate diet increases Lp(a) levels.8,9 Contrary to expectations, a study by Dr Marja-Leena Silaste and colleagues showed that healthy women who consumed a low-fat diet with polyunsaturated fat as the main fat source had increases in Lp(a).

As part of the OMNI Heart Trial, researchers conducted a randomized crossover study on 155 participants who followed DASH-style diets that were high in unsaturated fat, protein, or carbohydrates. They determined that Lp(a) levels were increased with each test diet pattern, and most significantly in blacks vs whites. However, they noted that the smallest increase in Lp(a) was from the diet that was higher in unsaturated fat.10

The effect of fish and omega-3 on Lp(a) has also been examined, because of a larger population study that compared Lp(a) levels in two Bantu populations in Tanzania.11 In one group, 622 people living near a lake consumed primarily freshwater fish. In the second group, 686 people living in a farming area ate primarily a vegetarian diet. After analyzing Lp(a) levels, the researchers noted that they were significantly lower in the fish-eating group. While numerous studies support the benefits of eating fish for CVD prevention, studies on the use of omega-3 supplements have been mixed.

Implications for Practice

The heightened risk for heart attack and stroke that inherited Lp(a) places on an individual is a good reminder of why it is so important for RDNs to ask about family history when assessing a patient. Patients who are genetically predisposed to CVD should be educated about their increased risk and ways to improve any modifiable risk factors, especially diet. For these patients, a Mediterranean or DASH diet that is rich in omega-3 and other unsaturated fats from fish, nuts, seeds, avocados, and other heart-healthy fats may be especially beneficial.

Anne Danahy, MS, RDN, is a registered dietitian nutritionist in Scottsdale, Arizona; a nutrition communications specialist; and author of Craving Something Healthy.

 

References:

  1. Understand inherited lipoprotein(a). Lipoprotein(a) Foundation. https://www.lipoproteinafoundation.org/page/UnderstandLpa. Accessed August 21, 2018.
  2. Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2016;32(11):1263-128
  3. Danesh J, Collins R, Peto R. Lipoprotein(a) and coronary heart disease: meta-analysis of prospective studies. Circulation. 2000;102(10):1082-1085.
  4. Saeedi R, Frohlich J. Lipoprotein(a), an independent cardiovascular risk marker. Clin Diabetes Endocrinol. 2016;2(1):7.
  5. Beheshtian A, Shitole SG, Segal AZ, et al. Lipoprotein(a) level, apolipoprotein(a) size, and risk of unexplained ischemic stroke in young and middle-aged adults. Atherosclerosis. 2016;253:47-53.
  6. van Capelleveen JC, van der Valk FM, Stroes ES. Current therapies for lowering lipoprotein(a). J Lipid Res. 2016;57(9):1612-1618.
  7. Chasman DI, Shiffman D, Zee RY, et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis. 2009;203(2):371-376.
  8. Faghihnia N, Tsimikas S, Miller ER, Witztum JL, Krauss RM. Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet. J Lipid Res. 2010;51(11):3324-3330.
  9. Silaste ML, Rantala M, Alfthan G, et al. Changes in dietary fat intake alter plasma levels of oxidized low-density lipoprotein and lipoprotein(a). Arterioscler Thromb Vasc Biol. 2004;24(3):498-503.
  10. Haring B, von Ballmoos MC, Appel LJ, Sacks FM. Healthy dietary interventions and lipoprotein(a) plasma levels: results from the Omni Heart Trial. PLoS One. 2014;9(12):e114859.