{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:12:04Z","timestamp":1787829124266,"version":"build-2784847793"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,9,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Dyslipidemia is common in heart failure with preserved ejection fraction. Sacubitril\/valsartan improves glycemic control and augments natriuretic peptide signaling, providing mechanisms by which sacubitril\/valsartan may affect serum lipids. However, empiric data on these effects are lacking.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We analyzed 4774 participants from PARAGON\u2010HF (Prospective Comparison of Angiotensin Receptor\u2013Neprilysin Inhibitor With Angiotensin\u2010Receptor Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction) with available screening lipids. During follow\u2010up visits, we analyzed the treatment effect on lipid levels and assessed for interaction by baseline lipid levels. At the 16\u2010week visit, we adjusted these treatment effects for the change in several biomarkers (including hemoglobin A\n              <jats:sub>1c<\/jats:sub>\n              and urinary cyclic guanosine monophosphate\/creatinine [a biomarker of natriuretic peptide activation]). The average age was 73\u00b18\u00a0years, 52% were women, 43% had diabetes mellitus, and 64% were on statin therapy. Compared with valsartan, sacubitril\/valsartan reduced triglycerides \u22125.0% (95% CI, \u22126.6% to \u22123.5%), increased high\u2010density lipoprotein cholesterol +2.6% (95% CI, +1.7% to +3.4%), and increased low\u2010density lipoprotein cholesterol +1.7% (95% CI, +0.4% to +3.0%). Sacubitril\/valsartan reduced triglycerides most among those with elevated baseline levels (triglycerides\u2265200\u00a0mg\/dL) (\n              <jats:italic>P<\/jats:italic>\n              \u2010interaction&lt;0.001), and at 16\u00a0weeks by \u221213.0% (95% CI, \u221218.1% to \u22127.6%), or \u221229.9 (95% CI, \u221244.3 to \u221215.5) mg\/dL, in this group. Adjusting for the change in urinary cyclic guanosine monophosphate\/creatinine significantly attenuated treatment effects on triglycerides and high\u2010density lipoprotein cholesterol, but not low\u2010density lipoprotein cholesterol, while adjusting for other biomarkers did not significantly alter the treatment effects.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Sacubitril\/valsartan significantly reduces triglycerides compared with valsartan, an effect that was nearly threefold stronger in those with elevated baseline triglycerides. Modest increases in high\u2010density lipoprotein cholesterol and low\u2010density lipoprotein cholesterol cholesterol were also observed with therapy. The underlying mechanism(s) of changes in high\u2010density lipoprotein cholesterol and triglycerides are related to sacubitril\/valsartan\u2019s effects on natriuretic peptide activity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT01920711.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.022069","type":"journal-article","created":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T14:00:32Z","timestamp":1621173632000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Effects of Sacubitril\/Valsartan on Serum Lipids in Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8418-7623","authenticated-orcid":false,"given":"Senthil","family":"Selvaraj","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Medicine Hospital of the University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Brigham and Women\u2019s Hospital Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[{"name":"Baylor Heart and Vascular InstituteBaylor University Medical Center Dallas TX"},{"name":"Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"INSERM Centre d'Investigation Clinic 1433 and Universite de LorraineCentre Hospitalier Regional et Universitaire Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1308-4963","authenticated-orcid":false,"given":"Inder S.","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkert","family":"Pieske","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology German Center for Cardiovascular Research partner site Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Novartis Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor C.","family":"Shi","sequence":"additional","affiliation":[{"name":"Novartis East Hanover NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin P.","family":"Lefkowitz","sequence":"additional","affiliation":[{"name":"Novartis East Hanover NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J. 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