High blood pressure may pose greatest risk of death in MASLD
New study also warns of 2 other risk factors for fatty liver disease patients
High blood pressure is a leading cardiometabolic risk factor — a condition linked to problems such as heart disease, stroke, and diabetes — associated with death in people with metabolic dysfunction-associated steatotic liver disease (MASLD), a type of fatty liver disease, a new study reports.
Low levels of high-density lipoprotein (HDL), sometimes called good cholesterol, were also linked with a significantly higher risk of death, as was prediabetes or diabetes. But the highest risk of death, by nearly 40% among MASLD patient, was seen for individuals with elevated blood pressure levels, according to the researchers.
The research team, based at the University of Southern California (USC)’s Keck School of Medicine, highlighted that each of these factors posed distinctive risks. These new insights may help clinicians establish treatment priorities in individuals with several risk factors, the scientists noted.
“MASLD is a complicated disease, and this study sheds new light on where doctors may want to focus their efforts when treating patients,” Norah A. Terrault, MD, the study’s senior author and a liver disease specialist at Keck Medicine, said in a university press release. “Knowing which aspects of MASLD might lead to poorer outcomes can help us offer patients the best possible care.”
Matthew Dukewich, MD, the study’s first author and a USC transplant hepatology fellow, noted that the finding that high blood pressure, or hypertension, was associated with a higher chance of death than diabetes surprised the team.
“Until now, it was commonly thought that diabetes was the most pressing health problem for MASLD patients,” Dukewich said, calling this “a key insight.”
The study, “Differential Effects of Cardiometabolic Risk Factors on All-Cause Mortality in US Adults with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD),” was published in the journal Clinical Gastroenterology and Hepatology.
In fatty liver disease, fat deposits build up in the liver. MASLD is the most common type of fatty liver disease, in which fat buildup is related to cardiometabolic risk factors such as being overweight or obese, hypertension, type 2 diabetes, high blood sugar (glucose) levels, low blood HDL levels, and high triglyceride levels, a type of fat.
Being overweight or obese is defined using high body mass index (BMI), a ratio of height to weight, or waist circumference.
Trying to ID, prioritize factors behind risk of death in MASLD
Until now, according to the researchers, each of these factors’ contribution to overall disease risks remained unclear.
“Characterizing the contribution of individual [risk factors] to clinical outcomes may guide prioritization of interventions,” the team wrote, noting that their study focused on adults and all-cause mortality.
To learn more about the risk of death among U.S. patients, the team examined data from the National Health and Nutrition Examination Survey (NHANES) — covering 134,515 individuals — and linked mortality data.
Among these individuals, 21,872 were adults who met criteria for MASLD. Their mean age was 51, and slightly more than half (54%) were men. The most common risk factor was overweight or obesity, found in 99.3% of the patients.
In an initial analysis, the researchers determined that each additional risk factor corresponded with a 15% greater chance of death from any cause.
When examining each factor individually and accounting for potential influencing factors, the team found that hypertension was significantly associated with the highest risk of death, by 39%.
Importantly, hypertension was “associated with [a] greater risk than lipid-related [fats-related] risk factors,” the team wrote.
Glucose intolerance, a sign of prediabetes or type 2 diabetes, was significantly linked to a 26% higher risk, and low HDL to a 15% higher risk. High triglycerides did not significantly correlate with differences in mortality risk, the data showed.
High blood pressure surprisingly found to be higher risk factor than diabetes
To assess obesity-related risks, the team divided participants into categories based on BMI. Compared with people with a BMI between 25 and 30 — typically considered overweight but not obese — obese participants with BMIs greater than 40 had a significantly higher risk of death.
Risk of death was also significantly higher in individuals with a BMI below 25, which corresponds to normal or low weights. However, the researchers noted, relatively few patients met this criterion, limiting potential conclusions.
These results support the team’s hypothesis that different categories of BMI may have different associated risks. The findings also highlight “that the longitudinal shifting between these risk categories may translate into changes in mortality and would have significant implications for real-world patient counseling and treatment,” the team wrote.
Still, the team noted that, although BMI is easily measurable, it is an imperfect way of measuring body fat and estimating related risks. The variability in findings across different BMIs “supports the need for improved methods of characterizing the risk of excess adiposity [body fat] in those with MASLD,” the researchers wrote.
Also importantly, the scientists noted, being overweight or obese and having glucose intolerance or hypertension corresponded to a significantly higher risk than being overweight or obese alone. However, low HDL levels did not significantly increase the risk beyond obesity alone.
“These findings suggest that not only does the number of [cardiometabolic risk factors] matter to clinically-relevant outcomes, but the individual [risk factors] exert independent, distinct risks,” the researchers wrote.
The more we can understand about the drivers of the disease, the more we can identify those most in need of interventions and prioritize our resources for enhanced outcomes.
The data suggest a hierarchy of the most serious risk factors in MASLD. Hypertension corresponds with the greatest risk of death, followed by glucose intolerance and low HDL. High triglycerides are the lowest concern on this ranking.
More research is needed, the team noted, especially given “reporting limitations of race/ethnicity in NHANES,” the database used.
If other trials do bear out these findings, clinicians may want to prioritize treating hypertension in people with MASLD, the researchers noted.
Terrault summed it up: “The more we can understand about the drivers of the disease, the more we can identify those most in need of interventions and prioritize our resources for enhanced outcomes.”
