HDL (High-Density Lipoprotein) Subspecies, Prevalent Covert Brain Infarcts, and Incident Overt Ischemic Stroke: Cardiovascular Health Study.

Background: Whether HDL (high-density lipoprotein) is associated with risk of vascular brain injury is unclear. HDL is comprised of many apo (apolipoprotein) species, creating distinct subtypes of HDL.

Methods: We utilized sandwich ELISA to determine HDL subspecies from plasma collected in 1998/1999 from 2001 CHS (Cardiovascular Health Study) participants (mean age, 80 years).

Associations of HDL Subspecies Defined by ApoC3 with Non-Alcoholic Fatty Liver Disease: The Multi-Ethnic Study of Atherosclerosis.

Previously, we reported that inverse associations of high-density lipoprotein (HDL) with cardiovascular disease and diabetes were only observed for HDL that lacked the pro-inflammatory protein apolipoprotein C3 (apoC3). To provide further insight into the cardiometabolic properties of HDL subspecies defined by the presence or absence of apoC3, we aimed to examine these subspecies with liver fat content and non-alcoholic fatty liver disease (NAFLD). We investigated cross-sectional associations between ELISA-measured plasma levels of apoA1 in HDL that contained or lacked apoC3 and computed tomography-determined liver fat content and NAFLD (<51 HU) at baseline (2000-2002) among 5007 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) without heavy alcohol consumption (>14 drinks/week in men and >7 drinks/week in women).

Apolipoprotein C-III and its defined lipoprotein subspecies in relation to incident diabetes: the Multi-Ethnic Study of Atherosclerosis.

Aims/hypothesis: Apolipoprotein C-III (apoC-III) is a small proinflammatory protein that may play a key role in diabetes pathophysiology. However, prior observational studies have been limited to predominantly white populations, and the biological links between apoC-III and diabetes, particularly the role of apoC-III on specific lipoprotein particles, are not yet well understood. We therefore investigated associations of total apoC-III and apoC-III-defined lipoprotein subspecies with incident diabetes and glucose metabolism measures in a multi-ethnic cohort.

High-Density Lipoprotein Subspecies Defined by Apolipoprotein C-III and Subclinical Atherosclerosis Measures: MESA (The Multi-Ethnic Study of Atherosclerosis).

Background: Apolipoprotein C-III (apoC-III), a small proinflammatory protein present on 6% to 7% of high-density lipoprotein (HDL) particles, defines a subspecies of HDL adversely associated with coronary heart disease in primarily white cohorts. In a multi-ethnic population free of clinical cardiovascular disease, we evaluated the relationship between apoC-III-defined HDL subspecies and subclinical markers of atherosclerotic pathology.

Methods And Results: We investigated cross-sectional associations between apolipoprotein A-I concentrations of apoC-III-defined HDL subspecies, measured via ELISA and imaging measures of subclinical atherosclerosis, among 4659 participants in the MESA (The Multi-Ethnic Study of Atherosclerosis) at baseline (2000-2002).

High density lipoprotein with apolipoprotein C-III is associated with carotid intima-media thickness among generally healthy individuals.

Background And Aims: About 6-7% of high density lipoprotein (HDL) has a protein called apolipoprotein (apo) C-III that regulates lipoprotein metabolism and can provoke an inflammatory response. HDL without apoC-III is inversely associated with coronary heart disease (CHD), whereas HDL with apoC-III is directly associated with CHD. We investigated how the presence of apoC-III affects the association between HDL and early stages of atherosclerosis measured as carotid intima-media thickness (cIMT).

High-Density Lipoprotein Subspecies Defined by Presence of Apolipoprotein C-III and Incident Coronary Heart Disease in Four Cohorts.

Background: The causal role of high-density lipoprotein (HDL) cholesterol in cardioprotection has been questioned by genetic and randomized studies. Novel measures that relate to HDL function may contribute new information to the prediction of cardiovascular risk. Apolipoprotein C-III (apoC-III) is a key regulator of lipoprotein metabolism.

Apolipoprotein C-III and High-Density Lipoprotein Subspecies Defined by Apolipoprotein C-III in Relation to Diabetes Risk.

Apolipoprotein C-III (apoC-III) is a potentially novel biomarker that may play an important role in the pathogenesis of diabetes, particularly when present on the surface of high-density lipoprotein (HDL). In a case-cohort study carried out among 434 incident diabetes cases occurring before 2007 and 3,101 noncases in the Danish Diet, Cancer, and Health Study, we examined associations of baseline (1993-1997) plasma concentrations of apoC-III and subspecies of HDL defined by the presence or absence of apoC-III with risk of diabetes using Cox regression. ApoC-III was strongly associated with risk of diabetes (for top quintile vs.

Fetuin-A and Risk of Diabetes Independent of Liver Fat Content: The Multi-Ethnic Study of Atherosclerosis.

Fetuin-A is a hepatic secretory protein and a novel risk factor for diabetes. However, it remains unclear whether the association between high levels of fetuin-A and diabetes can be attributed to nonalcoholic fatty liver disease. We conducted a case-cohort study among 1,957 subcohort members and 455 incident diabetes cases in the Multi-Ethnic Study of Atherosclerosis, a multicenter US study of Caucasian, African-American, Hispanic, and Chinese-American adults aged 45-84 years.

Fetuin-A, glycemic status, and risk of cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis.

Aims: Fetuin-A is a hepatic secretory protein that both promotes insulin resistance and inhibits arterial calcification. Previous studies have suggested that the association of fetuin-A with incident cardiovascular disease (CVD) might be modified by glycemic status.

Methods And Results: We conducted a case-cohort study of fetuin-A and incident non-fatal CVD nested in the Multi-Ethnic Study of Atherosclerosis with follow-up from 2000 to 2007.

Breast cancer risk by extent and type of atypical hyperplasia: An update from the Nurses' Health Studies.

Background: Women with atypical hyperplasia (AH) on a benign breast biopsy specimen are at increased risk for the development of breast cancer. However, the relation between the type and extent of AH (atypical ductal hyperplasia [ADH] vs atypical lobular hyperplasia [ALH]) and the magnitude of the breast cancer risk is not well defined.

Methods: A nested case-control study of benign breast disease and breast cancer risk was conducted.

New and emerging biomarkers in cardiovascular disease.

Cardiovascular disease (CVD) is the most common cause of death and disability worldwide. Therefore, great importance has been placed on the discovery of novel risk factors and metabolic pathways relevant in the prevention and management of CVD. Such research is ongoing and may continue to lead to better risk stratification of individuals and/or the development of new intervention targets and treatment options.

Plasma matrix metalloproteinase 2 levels and breast cancer risk.

Matrix metalloproteinase 2 (MMP2) is an enzyme with important functions in breast cancer invasion and metastasis. However, it is unclear whether circulating MMP2 levels may predict breast cancer risk. We conducted a prospective nested case-control analysis in the Nurses' Health Study among 1136 cases who were diagnosed with invasive breast cancer between 1992 and 2004 and 1136 matched controls.

Plasma matrix metalloproteinase 1, 3, and 7 levels and breast cancer risk in the Nurses' Health study.

Purpose: Matrix metalloproteinases (MMPs), in particular MMP1, 3, and 7, are believed to be critical to breast cancer invasion and metastasis and also may have important functions earlier in breast carcinogenesis. However, the relationship between circulating levels of MMP1, 3, and 7 and breast cancer risk is uncertain.

Methods: We examined associations between plasma MMP1, 3, and 7 and breast cancer risk in a prospective case-control study nested within the Nurses' Health Study.

Radial scars and subsequent breast cancer risk: results from the Nurses' Health Studies.

Radial scars (RS) are benign proliferative lesions associated with an increased risk of subsequent breast cancer. However, it remains unclear whether RS are an independent risk factor for breast cancer or whether their association with breast cancer is due to their common occurrence with other proliferative lesions known to increase breast cancer risk. We performed an updated analysis of the association between RS and subsequent breast cancer risk in a nested case-control study among 460 cases and 1,792 controls with benign breast disease (BBD) in the Nurses' Health Studies.

Columnar cell lesions and subsequent breast cancer risk: a nested case-control study.

Introduction: Histologic and genetic evidence suggests that at least some columnar cell lesions (CCL) of the breast represent precursor lesions in the low-grade breast neoplasia pathway. However, the risk of subsequent breast cancer associated with the presence of CCL in a benign breast biopsy is poorly understood.

Methods: The authors examined the association between the presence of CCL and subsequent breast cancer risk in a nested case-control study of benign breast disease (BBD) and breast cancer within the Nurses' Health Studies (394 cases, 1,606 controls).