Age modification of the association of lipoprotein, lipid, and lipoprotein ratio with carotid intima-media thickness (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Multiple studies have demonstrated an age-related attenuation in risk associations of lipoproteins and lipoprotein ratios with cardiovascular disease events. We recently reported a similar age-related attenuation in risk associations of lipoproteins and lipoprotein ratios with coronary artery calcium. We assessed risk associations of lipoproteins and lipoprotein ratios with carotid intima-media thickness (CIMT), which has not been reported previously. We performed multivariable linear regression using data from the Multi-Ethnic Study of Atherosclerosis (MESA). MESA participants were community-dwelling adults 45 to 84 years of age without clinically apparent cardiovascular disease at baseline, and 4,961 met inclusion criteria for these analyses. In fully adjusted models, differences in CIMT were similar across the MESA age spectrum, with differences in internal CIMT per SD increase in low-density lipoprotein of 0.037 mm (95% confidence interval 0.018 to 0.055) for those 45 to 54 years old and 0.087 mm (95% confidence interval 0.027 to 0.146) for those 75 to 84 years old (p for interaction = 0.2). Similarly, the difference in internal CIMT per SD increase in the total/high-density lipoprotein cholesterol ratio was 0.029 mm (95% confidence interval 0.009 to 0.049) for those 45 to 54 years old and 0.101 mm (95% confidence interval 0.033, 0.169) for those 75 to 84 years old (p for interaction = 0.03). In general, risk associations of lipoproteins and lipoprotein ratios were associated with similar differences in CIMT across all age categories. In conclusion, abnormal lipoproteins and lipoprotein ratios in middle-aged and older patients are powerful risk factors for early atherosclerosis as manifested by an increased CIMT.

Paramsothy P ，Katz R ，Owens DS ，Burke GL ，Probstfield JL ，O'Brien KD ... -  《-》

Age-modification of lipoprotein, lipid, and lipoprotein ratio-associated risk for coronary artery calcium (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Although abnormal lipoproteins and lipoprotein ratios are powerful risk factors for clinical cardiovascular events, these associations are stronger in younger than in older subjects. Whether age modifies the relation of lipoproteins and lipoprotein ratios to the relative risk of subclinical cardiovascular disease (CVD), as assessed by coronary artery calcium (CAC) scores, has not been examined in a contemporary, multiethnic cohort. We performed multivariate relative risk regression analyses to determine the relative risks for associations of lipoproteins and lipoprotein ratios with prevalent CAC in participants in Multi-Ethnic Study of Atherosclerosis (MESA). The participants were community-dwelling adults aged 45 to 84 years without clinically apparent CVD at baseline. We excluded those taking lipid-lowering therapy (15%) and stratified the results by decades of age. A total of 5,092 participants met the inclusion criteria. In the fully adjusted models, per SD of low-density lipoprotein, the age-stratified, adjusted relative risk for CAC was 1.17 (95% confidence interval [CI] 1.07 to 1.28) for those aged 45 to 84 years but was 1.05 (95% CI 1.01 to 1.10) for those aged 75 to 84 years (p-interaction = 0.12). The relative risk per SD of total/high-density lipoprotein cholesterol ratio was 1.20 (95% CI 1.12 to 1.29) for those aged 45 to 54 years but only 1.04 (95% CI 1.00 to 1.09) for those aged 75 to 84 years (p-interaction <0.001). The lipoproteins levels and lipoprotein ratios were associated with increased relative risks for CAC across all age categories. However, these associations were markedly attenuated by age. In conclusion, abnormal lipoprotein levels in middle age are a powerful risk factor for early atherosclerosis, as manifested by prevalent CAC.

Paramsothy P ，Katz R ，Owens DS ，Burke GL ，Probstfield JL ，O'Brien KD ... -  《-》

Association of combinations of lipid parameters with carotid intima-media thickness and coronary artery calcium in the MESA (Multi-Ethnic Study of Atherosclerosis).

The purpose of this study was to determine the association of combinations of lipid parameters with subclinical atherosclerosis. Carotid intima-media thickness (CIMT) and coronary artery calcium (CAC) are significantly associated with incident cardiovascular disease (CVD). The association between common dyslipidemias (combined hyperlipidemia, [simple] hypercholesterolemia, dyslipidemia of metabolic syndrome, isolated low high-density lipoprotein cholesterol, and isolated hypertriglyceridemia) compared with normolipemia, and CIMT and CAC has not been previously examined. The MESA (Multi-Ethnic Study of Atherosclerosis) participants were White, Chinese, African-American, or Hispanic adults without clinical CVD. Subjects with diabetes mellitus or who were receiving lipid-lowering therapy were excluded. Every participant was classified into only 1 of 6 groups defined by specific low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride cut points. Multivariate linear and relative risk regressions evaluated the cross-sectional associations with CIMT and CAC after adjusting for CVD risk factors. Interactions with race, sex, and high-sensitivity C-reactive protein were evaluated for CIMT and CAC outcomes. Among 4,792 participants, only those with combined hyperlipidemia and hypercholesterolemia demonstrated both increased common CIMT (combined hyperlipidemia 0.048 mm thicker, 95% confidence interval [CI]: 0.016 to 0.080 mm; hypercholesterolemia 0.048 mm thicker, 95% CI: 0.029 to 0.067 mm) and internal CIMT (combined hyperlipidemia 0.120 mm thicker, 95% CI: 0.032 to 0.208 mm; and hypercholesterolemia 0.161 mm thicker, 95% CI: 0.098 to 0.223 mm) as well as increased risk for prevalent CAC (combined hyperlipidemia relative risk: 1.22, 95% CI: 1.08 to 1.38; hypercholesterolemia relative risk: 1.22, 95% CI: 1.11 to 1.34) compared with normolipemia. The interactions between lipid parameters and race, sex, or high-sensitivity C-reactive protein were not significant for any outcomes. Combined hyperlipidemia and simple hypercholesterolemia were associated with increased CIMT and prevalent CAC in a relatively healthy multiethnic population.

Paramsothy P ，Knopp RH ，Bertoni AG ，Blumenthal RS ，Wasserman BA ，Tsai MY ，Rue T ，Wong ND ，Heckbert SR ... -  《-》

High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (multi-ethnic study of atherosclerosis).

The purpose of this study was to evaluate independent associations of high-density lipoprotein cholesterol (HDL-C) and particle (HDL-P) concentrations with carotid intima-media thickness (cIMT) and incident coronary heart disease (CHD). HDL-C is inversely related to CHD, and also to triglycerides, low-density lipoprotein particles (LDL-P), and related metabolic risk. HDL-P associations with CHD may be partially independent of these factors. In a multiethnic study of 5,598 men and women ages 45 to 84 years old, without baseline CHD, excluding subjects on lipid-lowering medications, triglycerides >400 mg/dl, or missing values, we evaluated associations of HDL-C and nuclear magnetic resonance spectroscopy-measured HDL-P with cIMT and incident CHD (myocardial infarction, CHD death, and angina, n = 227 events; mean 6.0 years follow-up). All models were adjusted for age, sex, ethnicity, hypertension, and smoking. HDL-C and HDL-P correlated with each other (ρ = 0.69) and LDL-P (ρ = -0.38, -0.25, respectively, p < 0.05 for all). For (1 SD) higher HDL-C (15 mg/dl) or HDL-P (6.64 μmol/l), cIMT differences were - 26.1 (95% confidence interval [CI]: -34.7 to -17.4) μm and -30.1 (95% CI: -38.8 to - 21.4) μm, and CHD hazard ratios were 0.74 (95% CI: 0.63 to 0.88) and 0.70 (95% CI: 0.59 to 0.82), respectively. Adjusted for each other and LDL-P, HDL-C was no longer associated with cIMT (2.3; 95% CI: - 9.5 to 14.2 μm) or CHD (0.97; 95% CI: 0.77 to 1.22), but HDL-P remained independently associated with cIMT (-22.2; 95% CI: - 33.8 to -10.6 μm) and CHD (0.75; 95% CI: 0.61 to 0.93). Interactions by sex, ethnicity, diabetes, and high-sensitivity C-reactive protein were not significant. Adjusting for each other and LDL-P substantially attenuated associations of HDL-C, but not HDL-P, with cIMT and CHD. Potential confounding by related lipids or lipoproteins should be carefully considered when evaluating HDL-related risk.

Mackey RH ，Greenland P ，Goff DC Jr ，Lloyd-Jones D ，Sibley CT ，Mora S ... -  《-》

Association of carotid intima-media thickness with progression of urine albumin-creatinine ratios in The Multi-Ethnic Study of Atherosclerosis (MESA).

The association between measures of subclinical cardiovascular disease and progression of urine albumin-creatinine ratios (UACRs) over time is uncertain. Prospective cohort study. The Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of adults aged 45-84 years without baseline clinical cardiovascular disease. Examinations were completed approximately every 1.5 years, and UACR was measured during the first 3 examinations. Analysis was limited to 4,878 participants without baseline micro- or macroalbuminuria. 1-standard deviation (SD) unit difference in baseline maximum common and internal carotid intima-media thickness (CIMT) measured using ultrasonography. Baseline UACR was categorized as normal or high-normal. UACR progression was categorized as no progression (consistent UACR category across all 3 examinations or regression to a lower category) and definite progression (higher UACR category at examination 2 compared with baseline, then stabilizing or progressing at examination 3). UACR changes not consistent with definite or no UACR progression were classified as intermediate UACR progression. Change in log UACR also was examined. In the 4,878 participants, median baseline UACR was 4.6 mg/g (range, 0.4-24.6 mg/g). Definite and intermediate UACR progression was noted in 279 and 807, respectively. Every 1-SD unit difference in common CIMT was associated with a 22% increased adjusted odds of definite compared with no UACR progression (95% CI, 1.07-1.41). No significant association was noted between 1-SD unit difference in maximum internal CIMT and definite UACR progression after adjusting for covariates (OR, 1.08; 95% CI, 0.96-1.21). In the mixed-effects model, changes in log UACR were 0.029 (95% CI, 0.012-0.046) and 0.019 mg/g (95% CI, 0.001-0.037) per 1-SD difference in maximum common and internal CIMT after adjustment for covariates, respectively. UACR was measured in a single spot urine specimen at each exam. Higher common CIMT is associated with UACR progression.

Yu Z ，Schneck M ，Jacobs DR Jr ，Liu K ，Allison M ，O'Leary D ，Durazo R ，Darwin C ，Kramer H ... -  《-》