Lipoprotein-associated phospholipase A 2 mass and activity and risk of cardiovascular disease in a population with high prevalences of obesity and diabetes: The strong heart study

Jorge R. Kizer; Jason G. Umans; Jianhui Zhu; Richard B. Devereux; Robert L. Wolfert; Elisa T. Lee; Barbara V. Howard

doi:10.2337/dc11-1639

Lipoprotein-associated phospholipase A ₂ mass and activity and risk of cardiovascular disease in a population with high prevalences of obesity and diabetes: The strong heart study

Jorge R. Kizer, Jason G. Umans, Jianhui Zhu, Richard B. Devereux, Robert L. Wolfert, Elisa T. Lee, Barbara V. Howard

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

OBJECTIVE - To investigate the association of lipoprotein-associated phospholipase A ₂ (LpPLA ₂) mass and activity with incident cardiovascular disease (CVD) in a population with high prevalences of insulin resistance and diabetes, conditions for which epidemiological data remain sparse. RESEARCH DESIGN AND METHODS - We conducted a nested, case-control study (n = 1,008) within a population-based cohort of American Indians. Case subjects were defined by incidence of first-ever CVD up to 10 years later. Control subjects comprised participants free of CVD events during the follow-up period who were frequency matched to case subjects by age, sex, and diabetes status. LpPLA ₂ mass and activity were measured using commercially available assays. RESULTS - LpPLA ₂ mass and activity were moderately correlated with each other (r = 0.30), but only LpPLA ₂ activity exhibited moderate correlations with lipid fractions. After extensive adjustment for covariates, both LpPLA ₂ measures were significantly associated with incident CVD, but the relationship was inverse for LpPLA ₂ mass (highest versus lowest tertile, relative risk [RR] 0.55 [95% CI 0.39-0.79]) and positive for LpPLA ₂ activity (highest versus lowest tertile, 1.65 [1.12-2.42]). These associations were similar when participants with and without diabetes were examined separately. CONCLUSIONS - In this population-based cohort enriched with dysmetabolic phenotypes, LpPLA ₂ mass and activity showed divergent associations with CVD. The inverse relationship for LpPLA ₂ mass is contrary to observations from predominantly nondiabetic populations and will require independent replication. Whether this finding relates to redistribution of LpPLA ₂ to lipoprotein classes where it is less atherogenic or reflects incomplete measurement of LpPLA ₂ mass associated with altered lipoprotein composition in insulin resistance warrants further investigation.

Original language	English (US)
Pages (from-to)	840-847
Number of pages	8
Journal	Diabetes care
Volume	35
Issue number	4
DOIs	https://doi.org/10.2337/dc11-1639
State	Published - Apr 2012
Externally published	Yes

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Advanced and Specialized Nursing

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10.2337/dc11-1639

Cite this

@article{492ece58ee604c43a2906237b47f7242,

title = "Lipoprotein-associated phospholipase A 2 mass and activity and risk of cardiovascular disease in a population with high prevalences of obesity and diabetes: The strong heart study",

abstract = "OBJECTIVE - To investigate the association of lipoprotein-associated phospholipase A 2 (LpPLA 2) mass and activity with incident cardiovascular disease (CVD) in a population with high prevalences of insulin resistance and diabetes, conditions for which epidemiological data remain sparse. RESEARCH DESIGN AND METHODS - We conducted a nested, case-control study (n = 1,008) within a population-based cohort of American Indians. Case subjects were defined by incidence of first-ever CVD up to 10 years later. Control subjects comprised participants free of CVD events during the follow-up period who were frequency matched to case subjects by age, sex, and diabetes status. LpPLA 2 mass and activity were measured using commercially available assays. RESULTS - LpPLA 2 mass and activity were moderately correlated with each other (r = 0.30), but only LpPLA 2 activity exhibited moderate correlations with lipid fractions. After extensive adjustment for covariates, both LpPLA 2 measures were significantly associated with incident CVD, but the relationship was inverse for LpPLA 2 mass (highest versus lowest tertile, relative risk [RR] 0.55 [95% CI 0.39-0.79]) and positive for LpPLA 2 activity (highest versus lowest tertile, 1.65 [1.12-2.42]). These associations were similar when participants with and without diabetes were examined separately. CONCLUSIONS - In this population-based cohort enriched with dysmetabolic phenotypes, LpPLA 2 mass and activity showed divergent associations with CVD. The inverse relationship for LpPLA 2 mass is contrary to observations from predominantly nondiabetic populations and will require independent replication. Whether this finding relates to redistribution of LpPLA 2 to lipoprotein classes where it is less atherogenic or reflects incomplete measurement of LpPLA 2 mass associated with altered lipoprotein composition in insulin resistance warrants further investigation.",

author = "Kizer, {Jorge R.} and Umans, {Jason G.} and Jianhui Zhu and Devereux, {Richard B.} and Wolfert, {Robert L.} and Lee, {Elisa T.} and Howard, {Barbara V.}",

year = "2012",

month = apr,

doi = "10.2337/dc11-1639",

language = "English (US)",

volume = "35",

pages = "840--847",

journal = "Diabetes care",

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number = "4",

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TY - JOUR

T1 - Lipoprotein-associated phospholipase A 2 mass and activity and risk of cardiovascular disease in a population with high prevalences of obesity and diabetes

T2 - The strong heart study

AU - Kizer, Jorge R.

AU - Umans, Jason G.

AU - Zhu, Jianhui

AU - Devereux, Richard B.

AU - Wolfert, Robert L.

AU - Lee, Elisa T.

AU - Howard, Barbara V.

PY - 2012/4

Y1 - 2012/4

N2 - OBJECTIVE - To investigate the association of lipoprotein-associated phospholipase A 2 (LpPLA 2) mass and activity with incident cardiovascular disease (CVD) in a population with high prevalences of insulin resistance and diabetes, conditions for which epidemiological data remain sparse. RESEARCH DESIGN AND METHODS - We conducted a nested, case-control study (n = 1,008) within a population-based cohort of American Indians. Case subjects were defined by incidence of first-ever CVD up to 10 years later. Control subjects comprised participants free of CVD events during the follow-up period who were frequency matched to case subjects by age, sex, and diabetes status. LpPLA 2 mass and activity were measured using commercially available assays. RESULTS - LpPLA 2 mass and activity were moderately correlated with each other (r = 0.30), but only LpPLA 2 activity exhibited moderate correlations with lipid fractions. After extensive adjustment for covariates, both LpPLA 2 measures were significantly associated with incident CVD, but the relationship was inverse for LpPLA 2 mass (highest versus lowest tertile, relative risk [RR] 0.55 [95% CI 0.39-0.79]) and positive for LpPLA 2 activity (highest versus lowest tertile, 1.65 [1.12-2.42]). These associations were similar when participants with and without diabetes were examined separately. CONCLUSIONS - In this population-based cohort enriched with dysmetabolic phenotypes, LpPLA 2 mass and activity showed divergent associations with CVD. The inverse relationship for LpPLA 2 mass is contrary to observations from predominantly nondiabetic populations and will require independent replication. Whether this finding relates to redistribution of LpPLA 2 to lipoprotein classes where it is less atherogenic or reflects incomplete measurement of LpPLA 2 mass associated with altered lipoprotein composition in insulin resistance warrants further investigation.

AB - OBJECTIVE - To investigate the association of lipoprotein-associated phospholipase A 2 (LpPLA 2) mass and activity with incident cardiovascular disease (CVD) in a population with high prevalences of insulin resistance and diabetes, conditions for which epidemiological data remain sparse. RESEARCH DESIGN AND METHODS - We conducted a nested, case-control study (n = 1,008) within a population-based cohort of American Indians. Case subjects were defined by incidence of first-ever CVD up to 10 years later. Control subjects comprised participants free of CVD events during the follow-up period who were frequency matched to case subjects by age, sex, and diabetes status. LpPLA 2 mass and activity were measured using commercially available assays. RESULTS - LpPLA 2 mass and activity were moderately correlated with each other (r = 0.30), but only LpPLA 2 activity exhibited moderate correlations with lipid fractions. After extensive adjustment for covariates, both LpPLA 2 measures were significantly associated with incident CVD, but the relationship was inverse for LpPLA 2 mass (highest versus lowest tertile, relative risk [RR] 0.55 [95% CI 0.39-0.79]) and positive for LpPLA 2 activity (highest versus lowest tertile, 1.65 [1.12-2.42]). These associations were similar when participants with and without diabetes were examined separately. CONCLUSIONS - In this population-based cohort enriched with dysmetabolic phenotypes, LpPLA 2 mass and activity showed divergent associations with CVD. The inverse relationship for LpPLA 2 mass is contrary to observations from predominantly nondiabetic populations and will require independent replication. Whether this finding relates to redistribution of LpPLA 2 to lipoprotein classes where it is less atherogenic or reflects incomplete measurement of LpPLA 2 mass associated with altered lipoprotein composition in insulin resistance warrants further investigation.

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