Monocyte miRNAs Are Associated With Type 2 Diabetes.

miRNAs are small noncoding RNAs that may contribute to common diseases through epigenetic regulation of gene expression. Little is known regarding the role of miRNAs in type 2 diabetes (T2D). We performed miRNA sequencing and transcriptomic profiling of peripheral monocytes from the longitudinal Multi-Ethnic Study of Atherosclerosis (MESA) (N = 1,154). We examined associations between miRNAs and prevalent impaired fasting glucose and T2D and evaluated the T2D-associated miRNA effect on incident T2D. Of 774 detected miRNAs, 6 (miR-22-3p, miR-33a-5p, miR-181c-5p, miR-92b-3p, miR-222-3p, and miR-944) were associated with prevalent T2D. For five of the six miRNAs (all but miR-222-3p), our findings suggest a dose-response relationship with impaired fasting glucose and T2D. Two of the six miRNAs were associated with incident T2D (miR-92b-3p: hazard ratio [HR] 1.64, P = 1.30E-03; miR-222-3p: HR 1.97, P = 9.10E-03) in the highest versus lowest tertile of expression. Most of the T2D-associated miRNAs were also associated with HDL cholesterol concentrations. The genes targeted by these miRNAs belong to key nodes of a cholesterol metabolism transcriptomic network. Higher levels of miRNA expression expected to increase intracellular cholesterol accumulation in monocytes are linked to an increase in T2D risk.

Associations between self-reported periodontal disease, assessed using a very short questionnaire, cardiovascular disease events and all-cause mortality in a contemporary multi-ethnic population: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Periodontal disease (PD) is believed to be associated with cardiovascular disease (CVD) events. Nevertheless, the additive prognostic value of PD for the prediction of CVD events beyond traditional risk factors is unclear, particularly when self-reported using a short questionnaire. METHODS: In the community-based, multicenter, prospective, Multi-Ethnic Study of Atherosclerosis (MESA), PD was assessed at baseline using a two-item questionnaire. We used Cox proportional hazards regression models to evaluate the independent associations between self-reported PD and coronary heart disease (CHD), CVD events, and all-cause death. In addition, the area under the receiver-operator characteristic curve (AUC) was calculated for each of the study endpoints, for models including traditional CVD risk factors alone and models including traditional CVD risk factors plus information on PD. Subgroup analyses were performed stratifying by age and tobacco use. RESULTS: Among the 6640 MESA participants, high education level, high income, and access to healthcare were more frequent among individuals who self-reported PD. In multivariable analyses, null associations were observed between self-reported PD and incident CVD events, CHD events, and all-cause mortality; and self-reported PD did not improve risk prediction beyond traditional CVD risk factors in terms of AUC, for any of the three study endpoints. Subgroup analyses were consistent with the overall results. CONCLUSIONS: Our findings suggest that the prevalence of self-reported PD may be strongly influenced by educational status and other socioeconomic features. In this context, self-reported PD does not improve CVD risk assessment when evaluated using a brief questionnaire. Future studies should prioritize objective, dental health-expert assessments of PD.

Thoracic aortic calcium, cardiovascular disease events, and all-cause mortality in asymptomatic individuals with zero coronary calcium: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: TAC is associated with incident CVD and all-cause mortality. Nevertheless, the independent 10-year prognostic value of TAC in individuals with CAC = 0 beyond traditional risk factors is not well established. METHODS: 3415 MESA participants with baseline CAC = 0 were followed for CHD, CVD events and all-cause mortality. TAC was measured in the ascending and descending aorta in all participants and quantified using Agatston's score. Multivariable Cox proportional hazards regression models were used to study the associations between TAC and incident CHD, CVD events and all-cause mortality. Likelihood ratio tests were used to compare prediction models including traditional risk factors plus TAC versus risk factors alone. RESULTS: 406 participants (11.9%) had TAC>0 at baseline. Over a median follow-up of 11.3 years, unadjusted event rates per 1000 person-years were higher in TAC>0 than in TAC = 0 participants: CHD 2.18 vs. 2.03; CVD 6.85 vs. 3.42; all-cause mortality 12.84 vs. 4.96. However, in multivariable Cox regression analyses adjusting for CVD risk factors, neither TAC>0, TAC>100 nor log(TAC+1) were independently associated with any of the study outcomes, nor improved their prediction compared to traditional risk factors alone (p value of likelihood ratio tests >0.05). CONCLUSIONS: In a multi-ethnic, modern US population of asymptomatic individuals with CAC = 0 at baseline, the prevalence of TAC>0 was low, and TAC did not improve 10-year estimation of prognosis beyond traditional risk factors. In the presence of CAC = 0, measurement of TAC is unlikely to provide sufficient additional prognostic information to further improve risk assessment.

Regional left ventricular myocardial dysfunction as a predictor of incident cardiovascular events MESA (multi-ethnic study of atherosclerosis).

OBJECTIVES: We sought to examine the prognostic value of subclinical left ventricular (LV) regional myocardial dysfunction (RMD) measured by magnetic resonance imaging (MRI) among asymptomatic individuals. BACKGROUND: LV RMD, defined as segmental impairment in systolic wall thickening, predicts adverse events in patients with established cardiovascular disease. MRI is highly accurate for detecting subtle RMD, of which the prognostic significance in a large multiethnic asymptomatic population is not known. METHODS: We used MRI to evaluate baseline regional LV myocardial function and prospectively followed a multiethnic (African American, Caucasian, Chinese, and Hispanic) population-based sample of 4,510 men and women without cardiovascular disease for a mean of 4.6 years. Regional myocardial dysfunction was defined as the presence of impaired systolic wall thickening (<10th percentile of segment-specific population distribution) in ≥2 contiguous LV segments within any given coronary artery territory. RESULTS: Baseline prevalence of RMD was 25.6%. Heart failure developed in 34 (1.0%) and 30 (2.6%) participants without and with RMD, respectively (p < 0.001). After adjustment for demographics and traditional risk factors, RMD remained independently associated with incident heart failure (hazard ratio [HR]: 2.62; 95% confidence interval [CI]: 1.56 to 4.39; p < 0.001). The relationship persisted after further adjustment for biomarkers of reported association with cardiovascular disease and indexes of global LV systolic dysfunction and hypertrophy (HR: 1.80; 95% CI: 1.02 to 3.20; p = 0.044). Similarly, RMD independently conferred an increased risk for hard coronary events (myocardial infarction or death from coronary heart disease; HR: 1.75; 95% CI: 1.06 to 2.89; p = 0.029), the composite of hard coronary events and stroke (HR: 1.72; 95% CI: 1.16 to 2.56; p = 0.005), and all atherosclerotic cardiovascular events (HR: 1.50; 95% CI: 1.09 to 2.07; p = 0.012). CONCLUSIONS: Among an asymptomatic multiethnic American cohort, RMD is an independent predictor beyond traditional risk factors and global LV assessment for incident heart failure and atherosclerotic cardiovascular events. The clinical utility of early recognition of this subclinical phenotype deserves further investigation. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Accurate myocardial T1 measurements: toward quantification of myocardial blood flow with arterial spin labeling.

In this study, we investigated a method for accurately measuring myocardial T(1) for the quantification of myocardial blood flow (MBF) with arterial spin labeling (ASL). A single-shot gradient-echo (GE)-based ASL sequence with an adiabatic hyperbolic secant inversion recovery pulse was modified to acquire a pair of myocardial T(1)'s within a breath-hold. A multivariable regression algorithm that accounted for the magnetization saturation effects was developed to calculate T(1). The MBF was then determined with a well-developed model. The accuracy of our T(1) calculation was first evaluated in a phantom, and then in six dogs for the MBF calculation, with (N = 4) and without (N = 2) coronary artery stenosis. In the phantom study, the accuracy of T(1) measured with a slice-selective inversion prepared pulse was within 2.5% of error. In healthy dogs, the MBF increased 2-5 times during vasodilation. In contrast, regional differences of MBF were well visualized in the stenotic dogs during vasodilation (perfusion reserve of 2.75 +/- 0.83 in normal myocardium, and 1.46 +/- 0.75 in the stenotic area). A correlation analysis revealed a close agreement in MBF between the ASL and microsphere (MS) in both healthy and stenotic dogs. In summary, the modified ASL technique and T(1) regression algorithm proposed here provide an accurate measurement of myocardial T(1) and demonstrate potential for reliably assessing MBF at steady state.