Lipoprotein(a): Normal vs. High + Improving Heart Health

Although not known as well as its cousins LDL and HDL, lipoprotein(a) may be just as important for health. Like LDL cholesterol, high levels have been linked to an increased risk of heart disease and stroke. Lp(a) levels are largely determined by genetics. However, emerging studies have found that lifestyle and dietary modification can positively affect Lp(a). Read on to learn more about this test, when and why doctors order it, and what to do if your levels are high.

What is Lipoprotein(a)?

Lipoproteins are a mesh of proteins and fats that help carry cholesterol in the blood. Examples include low-density lipoprotein (LDL), which carries “bad cholesterol” and high-density lipoprotein (HDL), which carries “good cholesterol” [1].

Lipoprotein(a), or Lp(a) is a type of LDL. It contains LDL and a protein called apolipoprotein(a) (not to be confused with apoA). Lp(a) is made in the liver and carries fats and other lipids such as cholesterol around the body [1, 2].

The exact function of Lp(a) is still an active area of research. What we do know is that high levels pose a health risk. In particular, higher Lp(a) levels have been associated with heart disease and stroke [3, 4, 5, 6, 7, 8].

Researchers think Lp(a) is involved in wound healing, tissue repair, immune response, and inflammation. However low or even undetectable Lp(a) levels are common and do not appear to have any negative health effects [9, 10, 11].

Lp(a) levels are largely determined by genetics and remain more or less stable throughout your life. However, some conditions can increase Lp(a), including hormonal imbalances, inflammatory diseases, metabolic issues, and kidney disease [12, 11, 13].

Although largely genetic, some newer studies suggest that certain lifestyle and dietary interventions may help slightly reduce lipoprotein(a) levels [12, 11, 13].

Lipoprotein(a) Test

Lipoprotein(a) levels are measured with a blood test. You don’t need to prepare for the test. However, you will need to fast for 9-12 hours before getting a blood draw if you are doing a lipid panel along with Lp(a).

This test is not a routinely ordered test. Your doctor will usually order it if you have other risk factors for heart disease, such as [14]:

• Heart disease runs in your family
• You have a genetic condition that causes high cholesterol levels (familial hypercholesterolemia)
• Your heart disease is worsening despite treatment with statins

Lp(a) test helps your doctor determine your heart disease risk.

Typically, Lp(a) test is only done once, because it’s pretty constant across your lifetime. On occasion, your doctor may order a second Lp(a) test to confirm the first one:

• If it was measured when you were ill
• After menopause, because Lp(a) levels increase as estrogen levels drop

Normal Range

The normal range for Lp(a) is <75 nmol/L or <30 mg/dL [15].

About 70% of people fall within this range [14].

Studies suggest that Lp(a) levels are higher in people of African descent than in people of European or Asian descent [16, 17].

Causes of High Lipoprotein(a) Levels

Lipoprotein levels above 75 nmol/L or 30 mg/dL indicate an increased risk of hardening of the arteries (atherosclerosis), heart disease, and stroke. Your doctor will interpret this test, taking into account your medical history, symptoms, and other tests.

Causes shown below have been associated with high Lp(a). Work with your doctor or another health care professional to get an accurate diagnosis.

1) Genetics

Lp(a) levels are largely determined by genetics. Mutations in the LPA gene can lead to high levels [11].

Mutations in this gene can result in different sizes of apolipoprotein(a). Research has found that people with smaller apolipoprotein(a) particles have higher Lp(a) levels [11].

Familial hypercholesterolemia is a genetic disorder that results in high cholesterol levels, and frequently, high Lp(a) levels as well [18, 19, 20].

2) Pregnancy

Researchers found that Lp(a) levels temporarily increase during pregnancy but return to baseline levels following childbirth [21].

Preeclampsia is a condition in which pregnant women develop high blood pressure during pregnancy that can damage the liver or kidneys. Lp(a) levels increase in preeclampsia, possibly as the body’s attempt at injury repair. In severe cases of preeclampsia, Lp(a) drop, likely because its reserves are emptied [21, 22].

3) Underactive Thyroid

People with an underactive thyroid often have high lipoprotein(a) levels, possibly because they produce more Lp(a) while breaking down less. Treatment with thyroid hormones restores their levels to normal [23, 24, 25, 26].

4) Low Testosterone and/or Estrogen Levels

Men with low testosterone levels have higher Lp(a) levels and are at an increased risk of heart disease. Studies suggest that testosterone replacement therapy, even in men with normal testosterone levels, decreases Lp(a) [27, 28, 29, 30, 31].

Low estrogen levels can also increase Lp(a). In women, estrogens are mainly produced in the ovaries. One study found that Lp(a) increased by 90% three months after surgical removal of the ovaries [32, 33].

Turner syndrome is a genetic condition that can severely damage the ovaries and drastically reduce estrogen levels. Lp(a) levels are frequently high in women with Turner syndrome [34].

In menopause, Lp(a) levels increase due to the large drop in estrogen. In a study of 1.4k women, those in menopause had 8% greater Lp(a) levels. Researchers found that estrogen replacement therapy reduces Lp(a) levels in menopausal women [35, 36, 37, 38, 39, 40].

5) Tissue Damage

Lp(a) may rise in response to serious inflammation and tissue damage, such as after surgery or heart attacks. Within the first week after a heart attack or surgery, Lp(a) can be spike 10-fold. Levels may stay high for a month but return to normal within about 2 months [41, 42].

The rise in Lp(a) follows an increase in damaging inflammatory compounds. Lp(a) probably increases to aid tissue repair [41].

6) Autoimmune Diseases

Inflammation is common to both autoimmune diseases and heart disease. Inflammatory compounds such as IL-6 can increase Lp(a) levels [43, 44, 45].

Various chronic inflammatory and autoimmune diseases have been linked to high Lp(a), including [46, 47, 48, 49, 50, 51]:

• Rheumatoid arthritis
• Crohn’s disease
• Lupus
• Psoriasis

7) Kidney Disease

People who have kidney disease can have higher Lp(a) levels which decrease with proper treatment [52].

8) Polycystic Ovary Syndrome

Women with polycystic ovary syndrome (PCOS) have high testosterone levels, often along with high Lp(a). However, higher-than-normal testosterone is not what causes Lp(a) to rise. Instead, inflammation is the likely culprit [53, 54, 55, 56].

9) Certain Drugs

Although statins are effective for lowering LDL levels, studies suggest they may actually increase Lp(a) levels [57].

Other drugs that can increase Lp(a) levels include:

• Insulin [58]
• Pioglitazone (Actos), Troglitazone (Rezulin), and metformin (Glumetza, Glucophage), used to treat type 2 diabetes [59, 60]
• Anti-seizure drugs [61]
• Growth hormone [62, 63]
• Finasteride (Propecia), used to treat an enlarged prostate (BPH) [64]

Health Effects of High Lipoprotein(a) Levels

Heart Disease

Like LDL, lipoprotein(a) can build up in blood vessels, leading to fatty plaques, calcium deposits, and hardened arteries (atherosclerosis). Hardened arteries cannot properly expand. As a result, high Lp(a) levels are linked with an increased risk of heart disease [65, 66, 67, 68, 4, 5, 6, 7, 8, 69]

Another hazard is that Lp(a) is similar to a protein called plasminogen. The body converts plasminogen into plasmin, which dissolves blood clots that can lead to heart attack and stroke. Lp(a) interferes with the conversion, lowering plasmin [70, 71, 72].

Multiple studies have found that high Lp(a) levels are linked to an increased risk of heart disease. A meta-analysis of 31 studies found that levels above 50 mg/dL increased the risk of heart disease by 50% compared to levels below 5 mg/dL [3, 4, 5, 6, 7, 8].

Lp(a) is an independent risk factor: its link with heart disease still holds even after other risk factors – such as cholesterol, obesity, and smoking – are accounted for [73].

In heart failure, the heart doesn’t pump blood as well as it should. In a study of over 98k people, compared to those with Lp(a) levels below 8 mg/dL, people with levels above 68 mg/dL had a 50% increased risk of heart failure [74].

Higher Lp(a) levels increase the risk of both milder and deadly heart attacks [75, 76].

In those who already suffered a heart attack, higher Lp(a) levels were associated with an increased risk of suffering another heart attack, as well as stroke, hospitalization, and death [77, 78].

Chronic Kidney Disease

Higher Lp(a) levels are linked to worse kidney function [79].

In one study of 560 people with diabetes, those with Lp(a) levels above 31 mg/dL were at two times higher risk of developing chronic kidney disease than those with levels below 9 mg/dL [80].

High Lipoprotein(a) Levels? What’s Next?

The most important thing is to work with your doctor to devise a strategy for lowering your heart disease risk. If there’s a condition other than genetics that is increasing your Lp(a), work with your doctor on treating it.

So far, studies suggest that because Lp(a) is mainly dependent on genetics, it’s difficult to change. Instead, your doctor will likely want to focus on minimizing other risk factors, such as “bad” cholesterol, in order to help decrease your overall heart disease risk.

We summarized strategies that can help decrease your heart disease risk below. Some of them may even have a slightly positive impact on lowering Lp(a). Discuss the lifestyle changes listed below with your doctor. None of these strategies should ever be done in place of what your doctor recommends or prescribes!

Diet and Lifestyle

1) Healthy Diet

To improve your heart health, eat a healthy, balanced diet low in saturated fats and processed carbs [81, 82, 83]:

• Mediterranean diet is a good example of a healthy diet rich in monounsaturated fats. It includes lots of fruits and vegetables, fatty fish, olive oil, and nuts [84, 85, 86, 87].
• DASH diet is another type of diet that can help decrease cholesterol levels [88, 89]. This diet is used to lower blood pressure. DASH is, similarly to the Mediterranean diet, rich in vegetables, fruits, lean meats, nuts, and beans. It’s high in fiber and low in fat.

A study suggests that eating more vegetables, fruits, and nuts may even help decrease Lp(a). A diet high in these foods reduced Lp(a) levels by 24% in a 2-week study of 10 people [90].

Flaxseed is rich in beneficial fiber and omega-3s. In one 6-week study of 38 people with high Lp(a) levels, ground flaxseed lowered Lp(a) levels by ~7%. In another 10-week study of 62 people, Lp(a) decreased by 14% [91, 92].

Several studies have found that eating pecans, almonds, and walnuts may also help reduce Lp(a) levels [93, 94, 95].

On the other hand, you should avoid low-fat (<20% of calories) high-carbohydrate diets. Several studies found that these diets increased Lp(a) levels [96, 97, 98].

Studies looking at the effect of dietary changes on Lp(a) are small and few. We need more solid evidence from larger and well-designed trials to conclude that these are truly effective in the general population.

However, we already know that these changes are beneficial when it comes to heart health, based on the effect they have on other risk factors such as “bad” cholesterol and triglyceride levels.

2) Weight Loss

Being overweight and obese is a risk factor for heart disease [99]. Keep your weight in healthy limits.

3) Exercise

Exercise is extremely beneficial when it comes to heart health and overall health in general.

A study in 15 men showed that high-intensity interval training may actually reduce Lp(a) levels [100]. This type of exercise involves short periods of intense exercise followed by short periods of rest.

However, you may not need to take up high-intensity interval training to see benefits. Just walking for 30 minutes a day for at least 5 days a week also lowered Lp(a) levels in another study of over 300 people with heart disease [101].

4) Quitting Smoking

Smoking is a known risk factor for heart disease [99].

In addition, one study of 35 habitual smokers, those who stopped saw a 12% reduction in Lp(a) after a week [102].

5) De-Stressing

Stress has a negative effect on our overall health, including heart health. Studies suggest that chronic stress contributes to heart disease. For example, people who experience work-related stress and those who are socially isolated or lonely have an increased risk of adverse heart-related events (e.g. heart attack) [103].

Therefore, remember to slow down, unplug, and destress. It’s important to engage in activities you love. Also, surround yourself with people whose company you enjoy. A massage, yoga session, meditation, gardening, and walk in the park are just a couple of examples that can help you unwind.

6) Decreasing Blood Pressure

High blood pressure is another independent risk factor for heart disease [99]. If your blood pressure is elevated, work with your doctor on decreasing it.

Supplements

Discuss the following foods and supplements with your doctor. Initial research has shown they may help decrease Lp(a) levels:

• Niacin. Multiple trials of over 29k people have found that niacin (vitamin B3) decreases Lp(a) levels by up to 28% and on average 20%. The effect was greater in those with higher levels [104, 105, 106, 107, 108, 57]. However, niacin needs to be taken under medical supervision because it can increase blood sugar levels and the risk of diabetes.
• CoQ10. A meta-analysis of 7 trials and more than 400 people found that CoQ10 reduced Lp(a) levels by 3.5 mg/dL on average. Higher doses worked better, while people with Lp(a) levels above 30 mg/dL saw an impressive 11.7 mg/dL reduction in their levels [109].
• L-carnitine. L-carnitine supplements reduced Lp(a) by about 8.8 mg/dL, according to a meta-analysis of 7 trials and 375 people [110].
• Turmeric. Curcuminoids are a group of bright-yellow compounds found in turmeric, curcumin being the main one. Curcuminoids taken with piperine (to increase their absorption) reduced Lp(a) levels by up to 16% (two studies of 50 and 180 people) [111, 112].
• Red yeast rice extract. It reduced Lp(a) levels by 23% in a 6-week study of 60 people with heart disease and high Lp(a) [113].
• Red wine in moderation (a glass/day) [114]. Discuss your alcohol consumption with your doctor
• Vitamin D + Calcium. The combination of vitamin D and calcium reduced Lp(a) levels by up to 25% in two different trials [115, 116].
• Estrogen-like isoflavones (in women). Isoflavones from red clover reduced Lp(a) levels by 63% in overweight postmenopausal women over 3 months (53 total people). Women with a healthy weight saw a more modest 15% reduction [117].

Remember, always speak to your doctor before taking any supplements, because they may interfere with your health condition or your treatment/medications!

Keep in mind that most of these studies are small, and there is insufficient evidence that any of these would actually work in a larger population. We’ll update the list as new studies emerge.