Fatty liver disease and cardiovascular risk

While fatty liver disease is named after the liver, its actual impact extends well beyond that organ, with an increasingly well-documented link to cardiovascular risk.

One figure sums up the stakes well. In people with MASLD, the leading cause of death isn't liver disease, but cardiovascular disease. That's what the American Heart Association pointed out in a scientific statement published in 2022. For the vast majority of affected people, the heart and blood vessels are therefore a more immediate concern than the liver itself. Only a minority, those who develop advanced fibrosis, see liver risk move to the forefront.

This holds true everywhere. In France, cardiovascular disease remains the second leading cause of death, with about 140,000 deaths a year. In the United States, it is the leading cause of death. Worldwide, the World Health Organization (WHO) attributes about 18 million deaths a year to it. Fatty liver disease, which affects nearly one adult in three worldwide, sits at the intersection of these two epidemics.

A marker of metabolic syndrome rather than an isolated factor

Fatty liver disease rarely appears on its own. It's most often part of a cluster of interconnected metabolic disturbances: abdominal obesity, type 2 diabetes, high blood pressure, abnormal cholesterol. This is why fatty liver disease is often considered a marker or a consequence of metabolic syndrome rather than a strictly independent cardiovascular risk factor, unlike smoking or hypertension, which act directly on blood vessels.

Metabolic syndrome is diagnosed when several abnormalities occur together in the same person: a large waist circumference, high blood pressure, elevated fasting blood sugar, high triglycerides, and low “good” cholesterol (HDL). Under the most widely used definition, three of these five criteria are enough. The common thread is insulin resistance: when cells respond poorly to insulin, the body compensates by producing more insulin, and the entire management of sugar and fat becomes dysregulated. The liver is both a victim, since it stores the excess fat, and a player, since it in turn worsens the imbalance.

Whether fatty liver disease adds a risk of its own, beyond these factors, is the subject of genuine scientific debate. Two types of studies shed light on this debate, and their results don't quite point in the same direction.

On one hand, observational studies suggest an independent effect. A large meta-analysis published in 2021 in The Lancet Gastroenterology & Hepatology (Mantovani et al.) pooled 36 studies and nearly 5.8 million people. People with fatty liver disease had a roughly 45% higher risk of a cardiovascular event, fatal or not, even after accounting for other risk factors. With advanced fibrosis, the risk reached about 2.5 times that of people without fatty liver disease.

On the other hand, genetic studies add nuance to this picture. Certain genetic variants, notably in the PNPLA3 and TM6SF2 genes, increase fat in the liver without going through metabolic syndrome. Yet people carrying these variants don't have more heart attacks. Some even have slightly lower LDL cholesterol and a slightly reduced coronary risk, because their liver retains fat instead of sending it into the bloodstream. This finding suggests that it's mainly the metabolic backdrop that damages the arteries, not liver fat itself. The most reasonable synthesis today is therefore that metabolic fatty liver disease is a cardiovascular risk marker, with a possible independent contribution that remains debated.

A cardiovascular risk that is nonetheless documented

This nuance doesn't mean fatty liver disease carries no cardiovascular consequence. Studies show that affected people have an increased risk of cardiovascular disease, largely because fatty liver disease shares the same underlying causes as the main risk factors, rather than acting through a completely separate mechanism.

This risk touches several aspects of the cardiovascular system. The first concerns the arteries. A fatty liver produces more small, dense cholesterol particles, especially capable of penetrating artery walls, and releases inflammatory signals. Affected people more often have plaque in the carotid and coronary arteries. The second concerns the heart itself. Fatty liver disease is associated with thickening of the heart muscle, poorer heart relaxation, heart failure, and atrial fibrillation, a common rhythm disorder. The third is hypertension and kidney involvement: fatty liver disease is associated with the onset of hypertension and chronic kidney disease, itself a cardiovascular risk factor.

The degree of liver fibrosis appears to be a better indicator of this risk than the amount of fat. Several studies have shown that a high FIB-4 score is associated with greater cardiovascular risk, even after accounting for other factors.

Why this distinction has practical value

Understanding that fatty liver disease reflects a broader metabolic imbalance, rather than being itself the direct cause of cardiovascular risk, shapes the care strategy. Acting on the underlying metabolic factors (weight, blood sugar, blood pressure, cholesterol) treats both fatty liver disease and cardiovascular risk together, rather than through separate approaches.

This shared approach has practical consequences. Cholesterol-lowering statin medications, long avoided out of concern for the liver, are safe in people with fatty liver disease and should be prescribed when cardiovascular risk warrants it. The 2024 European guidelines are clear on this point. Certain diabetes and obesity treatments, particularly those in the semaglutide family, act simultaneously on weight, blood sugar, cardiovascular risk, and liver fat. Finally, lifestyle measures (weight loss, physical activity, a Mediterranean-style diet, quitting smoking) have demonstrated effects on both fronts at once.

The liver, a sentinel organ for metabolism

In a sense, detected fatty liver disease can be seen as a warning signal broader than the liver alone. It's an invitation to get a full metabolic workup (blood sugar, blood pressure, cholesterol, waist circumference), rather than focusing solely on liver health.

Fat often builds up in the liver before blood sugar or blood pressure cross diagnostic thresholds. The liver can thus reveal a metabolic disorder years before diabetes appears. For people in whom fatty liver disease has been found, several of the hub's tools can help complete the picture: What is my cardiovascular risk? for overall 10-year risk, Do I have high blood pressure? for blood pressure, and Am I at risk of diabetes? for blood sugar. If you already have diabetes, SCORE2-Diabetes is better suited. Sleep apnea, common on this same terrain, is also worth checking for with the STOP-BANG test.

What to remember

Fatty liver disease and cardiovascular risk share common roots far more than they share a direct cause-and-effect relationship. In practice, this means that acting on one generally benefits the other.

For most affected people, the main benefit of screening for fatty liver disease is therefore revealing a previously unrecognized cardiovascular risk, and acting on it in time.

To estimate your own risk level, take the “Do I have fatty liver disease?” test.