Lipoprotein-associated phospholipase A(2) and future risk of subclinical disease and cardiovascular events in individuals with type 2 diabetes: the Cardiovascular Health Study.

AIMS/HYPOTHESIS: Type 2 diabetes is an established risk factor for cardiovascular disease (CVD). This increased risk may be due in part to the increased levels of inflammatory factors associated with diabetes. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a risk marker for CVD and has pro-inflammatory effects in atherosclerotic plaques. We therefore sought to determine whether Lp-PLA(2) levels partially explain the greater prevalence of subclinical CVD and greater incidence of CVD outcomes associated with type 2 diabetes in the Cardiovascular Health Study. METHODS: We conducted a cross-sectional and prospective study of 4,062 men and women without previous CVD from the Cardiovascular Health Study (1989 to 2007). Lp-PLA(2) mass and activity were measured in baseline plasma. Subclinical disease was determined at baseline and incident CVD was ascertained annually. We used logistic regression for cross-sectional analyses and Cox proportional hazards models for incident analyses. RESULTS: At baseline, Lp-PLA(2) mass did not differ significantly by type 2 diabetes status; however, Lp-PLA(2) activity was significantly higher among type 2 diabetic individuals. Baseline subclinical disease was significantly associated with baseline diabetes and this association was similar in models unadjusted or adjusted for Lp-PLA(2) (OR 1.68 [95% CI 1.31-2.15] vs OR 1.67 [95% CI 1.30-2.13]). Baseline type 2 diabetes was also significantly associated with incident CVD events, including fatal CHD, fatal myocardial infarction (MI) and non-fatal MI in multivariable analyses. There were no differences in these estimates after further adjustment for Lp-PLA(2) activity. CONCLUSIONS/INTERPRETATION: In this older cohort, differences in Lp-PLA(2) activity did not explain any of the excess risk for subclinical disease or CVD outcomes related to diabetes.

Tissue factor pathway inhibitor, vascular risk factors and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is an endothelial membrane-associated anticoagulant protein. Higher circulating levels might reflect endothelial damage. OBJECTIVE: We hypothesized an association of higher total TFPI with subclinical atherosclerosis. PATIENTS/METHODS: Total TFPI was measured in 1000 participants of the Multi-Ethnic Study of Atherosclerosis, a cohort of 6814 men and women without clinical vascular disease, aged 45-84, from four ethnic groups. Subclinical atherosclerosis measures were coronary artery calcium (CAC), carotid intima-media thickness (IMT) and ankle-brachial index (ABI). RESULTS: TFPI was higher with age, male gender, higher LDL-cholesterol, smoking and diabetes, but not ethnicity. Adjusting for risk factors, TFPI in the 4th quartile versus 1st quartile was associated with a 1.2-fold increased risk of detectable CAC (95% CI 1.0-1.4), a 2.1-fold increased risk of CAC >400 Agatston units (95% CI 1.1-4.0) and a 1.6-fold (95% CI 1.1-2.5) increased risk of internal carotid IMT above the 80th percentile, but not with external carotid IMT or low ABI. Findings were consistent across ethnic groups. CONCLUSIONS: In this diverse population, higher total TFPI was associated with prevalent CAC (limited to levels >400 units), and elevated internal carotid IMT, independent of other factors. Higher TFPI may indicate endothelial dysfunction. Further study is needed of TFPI and progression of atherosclerosis.

The incidence of gastric carcinoma in Asian migrants to the United States and their descendants.

OBJECTIVES: We examined the incidence of gastric carcinoma in Chinese, Japanese, and Filipino residents of the United States to obtain additional information about the etiology of this disease. METHODS: The age, race, and birthplace of residents of Hawaii, San Francisco/Oakland, and northwestern Washington who were diagnosed with gastric carcinoma during the period 1973-1986 were obtained from population-based registries, and a special tabulation from the 1980 Census was used to estimate the number of person-years at risk for each category of resident. RESULTS: The incidence of gastric carcinoma in Japanese-Americans was three to six times higher than that of US-born whites, with the highest rates occurring in those persons born in Japan. The rate in US-born Chinese and Chinese men who immigrated to the US was similar to that of whites, whereas the rate in Chinese female migrants was twice that of white American women. Filipino men, regardless of birthplace, were only at 60% the risk of US-born white men, while their female counterparts had a rate very similar to that of US-born white women. The high incidence observed among Japanese-Americans and Chinese female immigrants was largely restricted to sites other than the gastric cardia. CONCLUSIONS: Our findings suggest that dietary and other lifestyle differences between the different generations of Japanese-Americans, and between Japanese residents of the US and Japan may provide clues regarding the etiologies of stomach cancers that arise beyond the gastric cardia.