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

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)840-847
Number of pages8
JournalDiabetes Care
Volume35
Issue number4
DOIs
StatePublished - Apr 2012
Externally publishedYes

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1-Alkyl-2-acetylglycerophosphocholine Esterase
Cardiovascular Diseases
Obesity
Population
Lipoproteins
Insulin Resistance
North American Indians
Case-Control Studies

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

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

In: Diabetes Care, Vol. 35, No. 4, 04.2012, p. 840-847.

Research output: Contribution to journalArticle

Kizer, Jorge ; Umans, Jason G. ; Zhu, Jianhui ; Devereux, Richard B. ; Wolfert, Robert L. ; Lee, Elisa T. ; Howard, Barbara V. / 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. In: Diabetes Care. 2012 ; Vol. 35, No. 4. pp. 840-847.
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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.",
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AU - Lee, Elisa T.

AU - Howard, Barbara V.

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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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