Previous studies demonstrated that men were more likely to have plaque rupture and are at greater risk for myocardial infarction and stroke than women. We evaluated differences in carotid plaque characteristics by MRI between men and women with mild-moderate atherosclerosis and elevated ApoB levels. One hundred eighty-two subjects (104 men and 78 women) with CAD or carotid stenosis (≥ 15% by ultrasound), ApoB ≥ 120 mg/dL and carotid MRI scan were included. Percent wall volume (%WV) was calculated as (wall volume/total vessel volume) × 100%. Three major plaque compositions, fibrous tissue (FT), calcification (CA) and lipid rich necrotic core (LRNC), were identified and quantified using published MRI criteria. Adventitial and plaque neovascularization as fractional plasma volume (Vp) and permeability as transfer constant (Ktrans) were analyzed using kinetic modeling. These characteristics were compared between men and women. Men, compared to women, were younger (54 ± 8 vs. 58 ± 8 years, p = 0.01), had higher rate of previous MI (46 vs. 26%, p = 0.005) but lower proportions of metabolic syndrome (37 vs. 59%, p = 0.003). After adjusting for between-gender differences, men were significantly more likely to have LRNC (OR 2.22, 95% CI 1.04–4.89, p = 0.04) and showed significantly larger %LRNC than women (diff = 4.3%, 95% CI 1.6–6.9%, p = 0.002), while %WV, FT, and CA were similar between men and women. There were no statistically significant differences in adventitial and plaque Vp or Ktrans. Men were significantly more likely to have LRNC and had larger LRNC than women. However, men and women showed relatively similar levels of adventitial and plaque neovascularization and permeability. Trial registration: NCT00715273 at ClinicalTrials.gov. Registered 15 July 2008, retrospectively registered.

Importance The Second Universal Definition of Myocardial Infarction (MI) divides MIs into different types. Type 1 MIs result spontaneously from instability of atherosclerotic plaque, whereas type 2 MIs occur in the setting of a mismatch between oxygen demand and supply, as with severe hypotension. Type 2 MIs are uncommon in the general population, but their frequency in human immunodeficiency virus (HIV)–infected individuals is unknown. Objectives To characterize MIs, including type; identify causes of type 2 MIs; and compare demographic and clinical characteristics among HIV-infected individuals with type 1 vs type 2 MIs. Design, Setting, and Participants This longitudinal study identified potential MIs among patients with HIV receiving clinical care at 6 US sites from January 1, 1996, to March 1, 2014, using diagnoses and cardiac biomarkers recorded in the centralized data repository. Sites assembled deidentified packets, including physician notes and electrocardiograms, procedures, and clinical laboratory tests. Two physician experts adjudicated each event, categorizing each definite or probable MI as type 1 or type 2 and identifying the causes of type 2 MI. Main Outcomes and Measures The number and proportion of type 1 vs type 2 MIs, demographic and clinical characteristics among those with type 1 vs type 2 MIs, and the causes of type 2 MIs. Results Among 571 patients (median age, 49 years [interquartile range, 43-55 years]; 430 men and 141 women) with definite or probable MIs, 288 MIs (50.4%) were type 2 and 283 (49.6%) were type 1. In analyses of type 1 MIs, 79 patients who underwent cardiac interventions, such as coronary artery bypass graft surgery, were also included, totaling 362 patients. Sepsis or bacteremia (100 [34.7%]) and recent use of cocaine or other illicit drugs (39 [13.5%]) were the most common causes of type 2 MIs. A higher proportion of patients with type 2 MIs were younger than 40 years (47 of 288 [16.3%] vs 32 of 362 [8.8%]) and had lower current CD4 cell counts (median, 230 vs 383 cells/µL), lipid levels (mean [SD] total cholesterol level, 167 [63] vs 190 [54] mg/dL, and mean (SD) Framingham risk scores (8% [7%] vs 10% [8%]) than those with type 1 MIs or who underwent cardiac interventions. Conclusions and Relevance Approximately half of all MIs among HIV-infected individuals were type 2 MIs caused by heterogeneous clinical conditions, including sepsis or bacteremia and recent use of cocaine or other illicit drugs. Demographic characteristics and cardiovascular risk factors among those with type 1 and type 2 MIs differed, suggesting the need to specifically consider type among HIV-infected individuals to further understand MI outcomes and to guide prevention and treatment.

manuscript submissions. The editors of Diabetes Care sincerely appreciate the efforts of all of our reviewers who volunteer their time and expertise to provide valuable feedback to ensure the consistently high quality of the research published in each issue. The names of every reviewer are too numerous to list here, but we would like to recognize the “top” reviewers— based on the number of reviews completed, timeliness, reliability, and quality—for their outstanding contributions and dedication to Diabetes Care.

Introduction: Postmortem coronary artery histopathology and post-surgical carotid endarterectomy studies demonstrate that women have less calcification and inflammatory cells, but more smooth muscle cells than men. Gender differences in atherosclerotic plaque composition are not well known. Yet, the age-adjusted incidence of stroke and myocardial infarction are higher in men than women. Hypothesis: We hypothesized that gender differences exist in carotid plaque composition (CPC), % lipid rich necrotic core (LRNC) and % wall volume (PWV), comparing living women and men. Methods: The CPC study is a prospective, randomized study evaluating the effect of 1) atorvastatin + placebo + placebo vs 2) atorvastatin + niacin ER + placebo 3) atorvastatin + niacin ER + colsevelam on CPC. Participants had coronary or carotid artery disease and ApoB levels ≥120 mg/dL. CPC was evaluated using MRI. Baseline PWV [(wall volume/total vessel volume) х 100%], a measure of plaque burden that adjusts for variation in artery size, and % LRNC volume (among slices with LRNC present) were evaluated. Statistical analysis used Wilcoxon rank sum test, chi-square, and multivariate linear regression. Results: There were 82 women and 118 men. Women vs. men were older, mean±SD age 58±8 vs. 55±8 yrs. (p=0.008), had higher HDL-C, 48±13 vs. 40±10 mg/dL (p<0.001), higher ApoA1 147±24 vs. 126±19 mg/dL (p<0.001), higher ApoE 5.5±3.4 vs. 4.5±1.6 mg/dL (p=0.04), lower % of prior myocardial infarction 22% vs. 52% (p=0.02) and higher % of metabolic syndrome 48% vs. 46% (p=0.01). There were no significant differences in ApoB levels, 123±32 vs. 120±29 (p=0.4). After adjusting for age, HDL-C (strongly correlated with ApoA1, r=0.89), ApoE, prevalence of myocardial infarction and metabolic syndrome, the men-women difference in PWV was small and statistically non-significant ([[Unable to Display Character: ∆]] 0.0%, 95% CI -2.5 to 2.6%, p=1.0). However, among participants with LRNC, men had more % LRNC than women ([[Unable to Display Character: ∆]] 5.9%, 95% CI 1.4 to 10.3%, p=0.01) after the same adjustments. Conclusions: Gender differences exist in CPC in that there is a higher volume of LRNC in men compared to women. Further studies are needed which delineate the mechanisms underlying the differences in prevalence of LRNC comparing men to women.

Introduction: Recent, age-adjusted stroke death rates declined greater in men than women. Whether this is related to gender differences in the atherosclerotic plaque response to therapy is not known. Postmortem coronary artery histopathology and post-surgical carotid endarterectomy studies demonstrate that women have less calcification and inflammatory cells, but more smooth muscle cells than men. Hypothesis: We hypothesized that gender differences exist in carotid plaque composition (CPC) in response to lipid lowering therapy (LLT) comparing living men and women. Methods: The CPC study is a prospective, randomized study evaluating the effect of LLT: 1) atorvastatin + placebo + placebo vs 2) atorvastatin + niacin ER + placebo 3) atorvastatin + niacin ER + colsevelam on CPC. Participants had coronary or carotid artery disease and ApoB levels ≥120 mg/dL. CPC was evaluated using MRI. The change over two years in % wall volume (PWV) [(wall volume/total vessel volume) х 100%], a measure of plaque burden that adjusts for variation in artery size, and % lipid rich necrotic core (LRNC) volume among slices with LRNC present were evaluated. Statistical analysis used Wilcoxon rank sum test, chi-square, and multivariate linear regression. Results: There were 40 women and 73 men in the study with both baseline and 2 year MRI scans. Women vs. men were older, mean±SD age 58±9 vs. 54±8 yrs. (p=0.009), had higher HDL-C, 49±14 vs. 40±11 mg/dL (p=0.002), and higher ApoA1 145±26 vs. 126±20 mg/dL (p<0.001). ApoB levels were not significantly different, 127±31 vs. 121±25 mg/dL (p=0.2). Adjusted for age, HDL-C (strongly correlated with ApoA1, r=0.89), ApoE, prevalence of MI and metabolic syndrome (statistically significant in the full baseline cohort), there were no statistically significant gender differences at 2 years with LLT in change in PWV, [[Unable to Display Character: ∆]] -0.1 (95% CI: -0.7, 0.6%) (p=0.8) or %LRNC among participants with LRNC, [[Unable to Display Character: ∆]] 0.5 (95% CI: -2.5, 3.5%) (p=0.7). Conclusions: We did not detect statistically significant gender differences in change in PWV and %LRNC in response to LLT. Although the results are consistent with no gender differences they remain inconclusive due to the small sample size. Further gender studies in the biology and treatment of arterial atherosclerosis are needed.

Background: 37% of Americans are affected by metabolic syndrome (MS), but the effect of Omega-3 fatty acids (O3FA) in MS is largely unexplored. By new guidelines, those with MS may not meet criteria for statin treatment but are still at increased risk of CVD. O3FA supplementation reduced CV events in 2 large trials (Gissi-Prevenzione and JELIS). In a prior abstract we reported the impact of O3FA on lipid levels and inflammatory markers in 101 subjects with MS. Apo B, Apo A1, and triglycerides were significantly reduced, but there was no change in CRP or serum amyloid A. Here we report results on CIMT. Methods: 101 subjects with MS, mean age 55.1 years, 53% women, were randomized to placebo or O3FA (1.8 grams of EPA +DHA) daily vs. matching placebo for 2 years. Common carotid (CCIMT) and internal carotid IMT (ICIMT) were measured at baseline and at 2 years. Results: 80 subjects completed the CIMT protocol. There were no significant differences in any baseline clinical characteristics between groups (supplement (S) vs. placebo (P)), or between baseline mean CCIMT or ICIMT. After two years, there were non-significant increases in the IMT in both S and P but no between group differences (see table and figure). The results were similar whether comparing the average of the maximum of both sides or comparing the sides with the greatest IMT at baseline. Removing the significant outlier in the S group, did not change the results (see figure). Conclusion: In this modest sized sample group, despite favorable effects on lipid levels, treatment with O3FA did not stop progression of carotid IMT although the increase in CIMT in both groups was small and insignificant.

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.

Objective— The American College of Cardiology and American Heart Association have issued guidelines indicating that the contribution of apolipoprotein B-100 (ApoB) to cardiovascular risk assessment remains uncertain. The present analysis evaluates whether lipoprotein particle measures convey risk of coronary heart disease (CHD) in 4679 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Approach and Results— Cox regression analysis was performed to determine associations between lipids or lipoproteins and primary CHD events. After adjustment for nonlipid variables, lipoprotein particle levels in fourth quartiles were found to convey significantly greater risk of incident CHD when compared to first quartile levels (hazard ratio [HR]; 95% confidence interval [CI]): ApoB (HR, 1.84; 95% CI, 1.25–2.69), ApoB/ApoA-I (HR, 1.91; 95% CI, 1.32–2.76), total low-density lipoprotein-particles (LDL-P; HR, 1.77; 95% CI, 1.21–2.58), and the LDL-P/HDL-P (high-density lipoprotein-P) ratio (HR, 2.28; 95% CI, 1.54–3.37). Associations between lipoprotein particle measures and CHD were attenuated after adjustment for standard lipid panel variables. Using the American Heart Association/American College of Cardiology risk calculator as a baseline model for CHD risk assessment, significant net reclassification improvement scores were found for ApoB/ApoA-I (0.18; P =0.007) and LDL-P/high-density lipoprotein-P (0.15; P <0.001). C -statistics revealed no significant increase in CHD event discrimination for any lipoprotein measure. Conclusions— Lipoprotein particle measures ApoB/ApoA-I and LDL-P/high-density lipoprotein-P marginally improved net reclassification improvement scores, but null findings for corresponding c -statistic are not supportive of lipoprotein testing. The attenuated associations of lipoprotein particle measures with CHD after the adjustment for lipids indicate that their measurement does not detect risk that is unaccounted for by the standard lipid panel. However, the possibility that lipoprotein measures may identify CHD risk in a subpopulation of individuals with normal cholesterol, but elevated lipoprotein particle numbers cannot be ruled out.

ObjectivePrevious studies describing menses duration and heaviness of flow during the menopausal transition (MT) have been short in duration and limited to white women. We estimated the frequency of and risk factors for prolonged bleeding, spotting and heavy bleeding during the MT in an ethnically diverse population.DesignProspective community-based cohort study.SettingUSA: southeastern Michigan, northern California and Los Angeles, California.PopulationA total of 1320 midlife women who participated in the Study of Women's Health Across the Nation (SWAN) Menstrual Calendar Substudy. Participants included African-American, white, Chinese, and Japanese women.MethodsWomen completed daily menstrual calendars from 1996 to 2006, and provided information on hormone therapy, smoking and physical activity. Annual measures included height and weight. Kaplan-Meier survival analysis and multivariable regression were used to analyse the data.Main outcome measuresMenses of 10+days, spotting of 6+days, heavy bleeding of 3+days.ResultsAt least three occurrences of menses 10+days was reported by 77.7% (95% confidence interval [95% CI] 56.7-93.2), of 6+days of spotting by 66.8% (95% CI 55.2-78.0) and of 3+days of heavy bleeding by 34.5% (95% CI 30.2-39.2) of women. Menses of 10+days, 6+days of spotting, and 3+days of heavy bleeding were associated with MT stage, uterine fibroids, hormone use and ethnicity. Body mass index was associated with 3+days of heavy bleeding.ConclusionsThese data provide clinicians and women with important information about the expected frequency of prolonged and heavy bleeding and spotting during the menopausal transition that may facilitate clinical decision making.

syndrome (MetS) group to normal control group. Fig 1. The black-blood DCE MR images of one slice of a representative case. The white arrow points the carotid artery, and the white circle shows the selected reference region in sternocleidomastoid muscle. The intensity versus time curves for the vessel wall and reference region were shown in the bottom image. The fitting results were: K=0.058min, vp=0.1822. Detecting early arterial wall changes in premenopausal women with Metabolic syndrome by using black-blood DCE-MRI Huijun Chen, Pathmaja Paramsothy, Alice Dowdy, Arthi Thirumalai, Sarah Prager, Xihai Zhao, Xue-Qiao Zhao, Edward Gill, and William Kerwin Tsinghua University, Beijing, Beijing, China, University of Washington, Seattle, WA, United States

Omega-3 fatty acid (O3FA) supplementation reduced cardiovascular disease (CVD) events in two large trials (ie, the Gissi-Prevenzionne and JELIS). The benefit may be attributable to a reduction in ventricular arrhythmias, atherosclerosis, inflammation, or by modulating dyslipidemia. We evaluated the effects of O3FA supplementation on subjects with metabolic syndrome (MetS) who typically have high triglycerides (TGs), low high-density lipoprotein (HDL), and an increased risk of CVD.

Effective January 2010, prior reports of the types listed below were renamed " consensus reports. " EXPERT COMMITTEE REPORTS

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.

JOHN L. KITZMILLER, MD, MS JENNIFER M. BLOCK, BS RN, CDE FLORENCE M. BROWN, MD PATRICK M. CATALANO, MD DEBORAH L. CONWAY, MD DONALD R. COUSTAN, MD ERICA P. GUNDERSON, RD, PHD WILLIAM H. HERMAN, MD, MPH LISA D. HOFFMAN, MSW, LCSW MARIBETH INTURRISI, RN MS CNS, CDE LOIS B. JOVANOVIC, MD SIRI I. KJOS, MD ROBERT H. KNOPP, MD MARTIN N. MONTORO, MD EDWARD S. OGATA, MD PATHMAJA PARAMSOTHY, MD, MS DIANE M. READER, RD, CDE BARAK M. ROSENN, MD ALYCE M. THOMAS, RD M. SUE KIRKMAN, MD