Among individuals with heart failure (HF), one in six patients have no recorded risk factors (RFs) or RFs without trials. Researchers offer a systematic map of primary prophylactic opportunities across a broad range of RFs for HF, showing a high burden of co-occurrence as well as the necessity for trials tackling multiple RFs.

• In this systematic review of trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF, researchers analyzed 170,885 individuals aged ≥30 years with incident HF from 1997 to 2017.

• Only 10/92 factors were found to have high quality observational evidence for a link with incident HF.

• Experts succeeded at mapping 91/92 risk factors to electronic health records using 5,961 terms, and 88/91 factors were represented by at least one patient.

• In the 5 years before HF diagnosis, 44.3% were found to have ≥4 RFs.

• Hypertension (48.5%), stable angina (34.9%), unstable angina (16.8%), myocardial infarction (15.8%), and diabetes (15.1%) were the most common randomized controlled trial (RCT)-HF RFs.

• RCT-CVD (cardiovascular disease) RFs included smoking (46.4%) and obesity (29.9%); and RCT-0 RFs comprised atrial arrhythmias (17.2%), cancer (16.5%), heavy alcohol consumption(14.9%).

• Variation in mortality, at 1 year, was evident across all 91 factors (lowest: pregnancy-related hormonal disorder 4.2%; highest: pheochromocytoma 73.7%).

• Of new HF cases, 28.5% were found to have no RCT-HF RFs and 38.6% exhibited no RCT-CVD RFs.

• Among new HF cases, 28.5% had no RCT-HF RFs and 38.6% had no RCT-CVD RFs.

• 15.6% carried either no RF or only RCT-0 RFs.