Photo Credit: Heart Attack by Nick Youngson CC BY-SA 3.0 Alpha Stock Images
A risk factor for heart disease that we cannot control? Yes, you read that right, and it is called lipoprotein (a) or Lp (a). Scientists and physicians around the world are puzzled by this "silent" cardiac risk factor. Lp (a) is primarily determined by genetics, does not produce any symptoms, and is largely unaffected by lifestyle habits. If that isn’t enough, it’s being linked to heart disease in young adults as well.
So, what is Lp(a)? It is a subtype of LDL cholesterol, often referred to as “bad” cholesterol by doctors, but this particular type is even more concerning. Lp(a) is known to be significantly more damaging to the lining of blood vessels and is a major contributor to plaque buildup compared to other types of LDL cholesterol. Let’s explore Lp(a): what we know about it, what is currently being studied, and what actions we can take in response.
Why is Lp (a) called a “silent” risk factor?
Lp(a) is often referred to as a “silent” risk factor for heart disease because, despite high levels, most people do not experience any noticeable symptoms. Additionally, individuals with elevated Lp(a) can still have normal levels of other known cardiac risk factors, such as blood sugar and blood pressure. This is not a routine blood test, which adds to the uncertainty surrounding it. However, as awareness of Lp(a) increases and research expands, some cardiologists now recommend that everyone be tested for Lp(a) at least once in their lifetime. The American Heart Association recommends screening for Lp(a) in individuals who have a known family history of elevated Lp(a), a personal or family history of heart disease, premature cardiovascular disease, or a diagnosis of Familial Hypercholesterolemia, which is a genetic condition that affects the recycling of LDL cholesterol. Therefore, discussing your potential need for screening with your doctor is essential. Additionally, since Lp(a) levels are genetically determined, it is crucial to encourage your family members to be screened as well if you are found to have elevated Lp(a) levels.
Age and Lp (a)
Research studies have concluded that Lp (a) levels peak by age 5, and remain stable thereafter. Thus, by age 5, we can determine if we have a normal or elevated Lp (a) level which will remain as such into adulthood. However, levels can be influenced by acute illness, menopause, and changes in the functioning of your kidneys and thyroid gland – all leading to increased Lp (a). Furthermore, Lp (a) has also been found to be a risk factor for plaque buildup and subsequent heart disease, termed premature Atherosclerotic Cardiovascular Disease (ASCVD), in young adults. This alone has heightened the awareness of and need for continued research into Lp (a).
Racial and Ethnic Differences in Lp (a) Levels
A study recently published in the journal Atherosclerosis concluded that the Black population was found to have the highest levels of Lp (a), followed by South Asians, Whites, Hispanics, and East Asians. Therefore, they deemed that defining what “elevated” means for Lp (a) in each ethnic group is an important topic of future research. Furthermore, they concluded that in all ethnic groups Lp (a) was found to be a risk factor for heart disease.
Lp (a) Levels and Cardiovascular Risk
According to ongoing research, it is estimated that globally, it is likely that 1.5 billion people have elevated Lp (a) levels. An elevated level, which according to the American Heart Association is defined as greater than 50 mg/dL or 125 nm/L, increases your risk of heart attack, stroke, peripheral artery disease, and additional heart conditions as well. Additionally, these levels are not related to lifestyle habits and diet. Now, this does not mean to ignore these factors. The current landscape of research is highlighting that Lp (a) is, on its own, a risk factor for heart disease. It is best, however, not to add additional risk factors for heart disease by doing all one can to follow healthy eating and lifestyle habits, preventing the development of other known risk factors such as diabetes and high blood pressure.
Detection, Prevention, and Treatment
As was mentioned, some Cardiologists are now recommending screening for Lp (a) levels once in your lifetime, while other heart experts are recommending it only in certain situations as listed above. Additionally, as discussed, while not much can be done to change one’s Lp (a) level at the moment, we can manage our overall risk of heart disease by following healthy lifestyle habits to prevent the development of other known risk factors – such as diabetes, high cholesterol, and high blood pressure.
Nonetheless, there is a myriad of research currently investigating potential therapeutics to target elevated Lp (a) levels. Zerlasiran, known as a “gene silencing” drug as it stops a gene from producing Lp (a), is being investigated by the Cleveland Clinic in what is being called the ALPACAR trial. Promisingly, the drug was found to reduce levels of Lp (a) by more than 80%. In doing so, and with minimal side effects, the ALPACAR trial has opened the door to potential new and promising therapeutic agents for elevated Lp (a) levels. The downside, though, is that it is an injectable medication, and not everyone is fond of this route of administration. However, the KRAKEN trial has found that Muvalaplin, an oral medication, may be able to reduce Lp (a) levels safely. Muvalaplin is the first oral medication developed to decrease elevated levels of Lp (a), and it works by preventing Lp (a) from assembling properly. While there are currently no FDA-approved medications to lower Lp (a) levels, many are in development and offer a promising outlook to treating this “silent” risk factor for heart disease. For now, all one can do is speak to their healthcare provider about the need for screening, control all known potential risk factors such as blood sugar and blood pressure, and follow a healthy lifestyle. The future, though, seems bright for further research to turn up the volume on this silent risk factor.
###