MASLD and HFpEF: a 35% relative increase over a third of a percentage point

Design

systematic review and meta-analysis of 3 observational studies, PROSPERO registered

Population

899,629 adults, of whom 47,610 had MASLD

Primary outcome

prevalence of clinically diagnosed heart failure with preserved ejection fraction

Effect

2.2% versus 1.85%; pooled odds ratio 1.35 (95% CI 1.26-1.45), absolute increase 0.35 percentage points, I squared 0%

Three studies - two cohorts and one cross-sectional analysis, 899,629 people including 47,610 with MASLD - were pooled to estimate how often clinically diagnosed heart failure with preserved ejection fraction occurs in MASLD. Prevalence was 2.2% with MASLD against 1.85% without, giving a pooled odds ratio of 1.35 (95% CI 1.26 to 1.45, p<0.0001) with no heterogeneity at all.

The authors state plainly that the absolute risk increase is 0.35 percentage points and that the finding should be regarded as hypothesis-generating, which is the honest framing of three studies with a shared risk-factor problem: MASLD, obesity, diabetes and hypertension travel together, and HFpEF is caused by all of them.

What is usable is directional rather than numerical. Breathlessness and exercise intolerance in a patient with MASLD, particularly one with advanced fibrosis, should prompt a cardiac assessment rather than being attributed to deconditioning or weight - and that is a low-cost change in threshold. Instituting a screening protocol on the strength of a 0.35 percentage point difference is not supported, and the paper does not claim it is.

• Assess breathlessness in a MASLD patient cardiologically rather than attributing it to weight
• Treat shared risk factors - blood pressure, glycaemia, weight - which is the intervention either way
• Do not institute echocardiographic screening in MASLD on this evidence
• Note that advanced fibrosis is where the risk concentrates, so stage the liver disease
• Remember GLP-1 receptor agonists sit at the intersection of both conditions and are already indicated for many of these patients

Why it matters

It names a cardiac question that MASLD clinics rarely ask, while showing the effect is too small to justify a screening programme.

Don't overread it

Three observational studies with shared risk factors - this cannot show MASLD causes HFpEF.

The statistics, in plain English

This is the clearest recent illustration of relative and absolute risk diverging. A 35% relative increase sounds substantial; the underlying figures are 2.2% against 1.85%, so about 285 people with MASLD would need to be followed for one extra HFpEF diagnosis. Zero heterogeneity across only three studies is not reassurance, it is a consequence of having few studies. And with two cohorts and one cross-sectional study, residual confounding by obesity, diabetes and hypertension - all causes of HFpEF in their own right - cannot be excluded by any amount of adjustment.

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