Dataset Information

Secretory leukocyte protease inhibitor and risk of heart failure in the Multi-Ethnic Study of Atherosclerosis.

ABSTRACT: Circulating protease inhibitors are important regulators of inflammation that are implicated in the pathophysiology of heart failure (HF). Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor which protects pulmonary tissues against inflammatory damage; however, its role in HF is not well understood. We sought to evaluate associations of circulating SLPI and genetically-mediated serum SLPI with incident HF and its subtypes in a multi-ethnic cohort of adults using clinical and genetic epidemiological approaches. Among 2,297 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), each doubling of serum SLPI was independently associated with incident HF (HR 1.77; 95% CI 1.02-3.02; P = 0.04), particularly incident HF with preserved ejection fraction (HFpEF; HR 2.44; 95% CI 1.23-4.84; P = 0.01) but not HF with reduced ejection fraction (HFrEF; HR 0.95; 95% CI 0.36-2.46; P = 0.91). Previously reported circulating SLPI protein quantitative trait loci (pQTLs) were not associated with serum SLPI levels or incident HF among MESA participants. In conclusion, baseline serum SLPI levels, but not genetically-determined serum SLPI, were significantly associated with incident HF and HFpEF over long-term follow-up in a multi-ethnic cohort. Serum circulating SLPI may be a correlate of inflammation that sheds insight on the pathobiology of HFpEF.

SUBMITTER: Sawicki KT

PROVIDER: S-EPMC9837113 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Secretory leukocyte protease inhibitor and risk of heart failure in the Multi-Ethnic Study of Atherosclerosis.

Sawicki Konrad Teodor KT Nannini Drew R DR Bielinski Suzette J SJ Larson Nicholas B NB Lloyd-Jones Donald M DM Psaty Bruce B Taylor Kent D KD Shah Sanjiv J SJ Rasmussen-Torvik Laura J LJ Wilkins John T JT McNally Elizabeth M EM Patel Ravi B RB

Scientific reports 20230112 1

Circulating protease inhibitors are important regulators of inflammation that are implicated in the pathophysiology of heart failure (HF). Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor which protects pulmonary tissues against inflammatory damage; however, its role in HF is not well understood. We sought to evaluate associations of circulating SLPI and genetically-mediated serum SLPI with incident HF and its subtypes in a multi-ethnic cohort of adults using clinical ...[more]

PMID: 36635319

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Project description:BackgroundAlthough diabetes increases heart failure (HF) risk, it is unclear how various dysglycemia markers (hemoglobin A1C [HbA1C], fasting plasma glucose [FPG], homeostasis model assessment of insulin resistance, and fasting insulin) are associated with HF subtypes (HF with preserved ejection fraction [HFpEF] and HF with reduced ejection fraction [HFrEF]). We assessed the relation of markers of dysglycemia and risks of HFpEF and HFrEF.Methods and resultsWe included 6688 adults without prevalent cardiovascular disease who attended the first MESA visit (2000-2002) and were followed for incident hospitalized HF (HFpEF or HFrEF). Association of glycemic markers and status (normoglycemia, prediabetes, diabetes) with HFpEF and HFrEF were evaluated using adjusted Cox models. Over a median follow-up of 14.9 years, there were 356 HF events (145 HFpEF, 173 HFrEF, and 38 indeterminate HF events). Diabetes status conferred higher risks of HFpEF (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.57-2.68) and HFrEF (HR 2.02, 95% CI 1.38-2.97) compared with normoglycemia. Higher levels of FPG (≥126 mg/dL) and HbA1C (≥6.5%) were associated with similarly higher risks of HFpEF (HR for FPG 1.96, 95% CI 1.21-3.17; HR for HbA1C 2.00, 95% CI 1.20-3.31) and HFrEF (HR for FPG 1.84, 95% CI 1.18-2.88; HR for HbA1C 1.99, 95% CI 1.28-3.09) compared with reference values. Prediabetic range HbA1C (5.7%-6.4%) or FPG (100%-125 mg/dL), homeostasis model assessment of insulin resistance, and fasting insulin were not significantly associated with HFpEF or HFrEF.ConclusionsAmong community-dwelling individuals, HbA1C and FPG in the diabetes range were each associated with higher risks of HFpEF and HFrEF, with similar magnitudes of their associations.Lay abstractHeart failure (HF) has 2 major subtypes (the heart's inability to pump or to fill up). Diabetes is known to increase HF risk, but its effects and that of markers of high glucose levels (fasting blood glucose and hemoglobin A1C) on the occurrence of HF subtypes remains unknown. Among 6688 adults without known cardiovascular disease followed for nearly 15 years, diabetes conferred significantly higher risks of both HF types, compared with those with normal blood glucose levels. Higher levels of fasting blood glucose and hemoglobin A1C were similarly associated with higher risks of both types of HF.

Project description:BackgroundCurrent prevalence estimates of heart failure (HF) are primarily based on self-report or HF hospitalizations. There is an unmet need to define the prevalence and pathogenesis of early symptomatic HF, which may be undiagnosed and precedes HF hospitalization.MethodsThe MESA (Multi-Ethnic Study of Atherosclerosis) Early HF study was conducted during MESA exam 6 to determine the prevalence of early HF and investigate the transition from risk factors to early HF in a diverse population-based cohort of older adults. Between 2016 and 2018, 3285 MESA participants from 6 field centers underwent comprehensive speckle-tracking echocardiography with passive leg raise maneuver, Kansas City Cardiomyopathy Questionnaire, 6-minute walk test, arterial stiffness assessment, and proteomics (including NT-proBNP [N-terminal pro-B-type natriuretic peptide]).ResultsMedian age was 73 (25th-75th percentile 67-81) years, 53.2% were female, 25.6% were Black, 12.8% were Chinese, and 40.0% were White. The prevalence of HF risk factors was high: hypertension, 61.9%; former or current smoking, 53.7%; obesity 34.8%; diabetes; 24.7%; and chronic kidney disease; 22%. Overt cardiovascular disease, which ranged from 2.1% (HF) to 13.6% (atrial fibrillation), was less common. Of the 3285 participants, 96% underwent proteomics, 94% Kansas City Cardiomyopathy Questionnaire, 93% speckle-tracking echocardiography with passive leg raise, 82% arterial stiffness exam, and 77% 6-minute walk test. Feasibility of resting speckle-tracking echocardiography (87%-99% across cardiac chambers) and passive leg raise Doppler/speckle-tracking echocardiography (>84%) measurements was high. A total of 120 unique echocardiographic indices were measured.ConclusionsThe MESA Early HF study is a key resource for cardiovascular researchers who are interested in improving the epidemiological and phenotypic characterization of early HF.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT00005487.

Dataset Information

Secretory leukocyte protease inhibitor and risk of heart failure in the Multi-Ethnic Study of Atherosclerosis.

Publications

Secretory leukocyte protease inhibitor and risk of heart failure in the Multi-Ethnic Study of Atherosclerosis.

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