Mitochondrial Creatine Kinase Attenuates Pathologic Remodeling in Heart Failure.

BACKGROUND: Abnormalities in cardiac energy metabolism occur in heart failure (HF) and contribute to contractile dysfunction, but their role, if any, in HF-related pathologic remodeling is much less established. CK (creatine kinase), the primary muscle energy reserve reaction which rapidly provides ATP at the myofibrils and regenerates mitochondrial ADP, is down-regulated in experimental and human HF. We tested the hypotheses that pathologic remodeling in human HF is related to impaired cardiac CK energy metabolism and that rescuing CK attenuates maladaptive hypertrophy in experimental HF. METHODS: First, in 27 HF patients and 14 healthy subjects, we measured cardiac energetics and left ventricular remodeling using noninvasive magnetic resonance 31P spectroscopy and magnetic resonance imaging, respectively. Second, we tested the impact of metabolic rescue with cardiac-specific overexpression of either Ckmyofib (myofibrillar CK) or Ckmito (mitochondrial CK) on HF-related maladaptive hypertrophy in mice. RESULTS: In people, pathologic left ventricular hypertrophy and dilatation correlate closely with reduced myocardial ATP levels and rates of ATP synthesis through CK. In mice, transverse aortic constriction-induced left ventricular hypertrophy and dilatation are attenuated by overexpression of CKmito, but not by overexpression of CKmyofib. CKmito overexpression also attenuates hypertrophy after chronic isoproterenol stimulation. CKmito lowers mitochondrial reactive oxygen species, tissue reactive oxygen species levels, and upregulates antioxidants and their promoters. When the CK capacity of CKmito-overexpressing mice is limited by creatine substrate depletion, the protection against pathologic remodeling is lost, suggesting the ADP regenerating capacity of the CKmito reaction rather than CK protein per se is critical in limiting adverse HF remodeling. CONCLUSIONS: In the failing human heart, pathologic hypertrophy and adverse remodeling are closely related to deficits in ATP levels and in the CK energy reserve reaction. CKmito, sitting at the intersection of cardiac energetics and redox balance, plays a crucial role in attenuating pathologic remodeling in HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00181259.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

AIMS: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Peroxisome Proliferator-Activated Receptor Gamma Regulates Interleukin-6-Induced Lipoprotein (a) Gene Expression in Human HepG2 Cells.

Lipoprotein(a) [Lp(a)] is a risk factor for coronary disease. Although levels are primarily genetically determined, data from patients with inflammatory diseases indicate that the inflammatory milieu is associated with increased Lp(a) levels. Lp(a) is synthesized in the liver and the LPA gene promoter contains an interleukin-6 (IL-6) responsive binding site, but the regulatory steps linking inflammation with hepatic Lp(a) synthesis are not well clarified. We explored the interplay between IL-6, peroxisome proliferator-activated receptor gamma (PPARγ), and Lp(a) synthesis in HepG2 cells. Through genetic mapping, a regulatory variant within the LPA promoter overlapping with a PPARγ binding site was identified. In in vitro experiments, IL-6-mediated LPA gene transcription was heightened with PPARγ knock-down and suppressed with pioglitazone, a PPARγ agonist. These results demonstrate an important role of PPARγ as a negative regulator of IL-6 induced hepatic Lp(a) production and may represent a new therapeutic target for patients with inflammatory conditions characterized by elevated Lp(a).

Deep learning-based atherosclerotic coronary plaque segmentation on coronary CT angiography.

OBJECTIVES: Volumetric evaluation of coronary artery disease (CAD) allows better prediction of cardiac events. However, CAD segmentation is labor intensive. Our objective was to create an open-source deep learning (DL) model to segment coronary plaques on coronary CT angiography (CCTA). METHODS: Three hundred eight individuals' 894 CCTA scans with 3035 manually segmented plaques by an expert reader (considered as ground truth) were used to train (186/308, 60%), validate (tune, 61/308, 20%), and test (61/308, 20%) a 3D U-net model. We also evaluated the model on an external test set of 50 individuals with vulnerable plaques acquired at a different site. Furthermore, we applied transfer learning on 77 individuals' data and re-evaluated the model's performance using intra-class correlation coefficient (ICC). RESULTS: On the test set, DL outperformed the currently used minimum cost approach method to quantify total: ICC: 0.88 [CI: 0.85-0.91] vs. 0.63 [CI: 0.42-0.76], noncalcified: 0.84 [CI: 0.80-0.88] vs. 0.45 [CI: 0.26-0.59], calcified: 0.99 [CI: 0.98-0.99] vs. 0.96 [CI: 0.94-0.97], and low attenuation noncalcified: 0.25 [CI: 0.13-0.37] vs. -0.01 [CI: -0.13 to 0.11] plaque volumes. On the external dataset, substantial improvement was observed in DL model performance after transfer learning, total: 0.62 [CI: 0.01-0.84] vs. 0.94 [CI: 0.87-0.97], noncalcified: 0.54 [CI: -0.04 to 0.80] vs. 0.93 [CI: 0.86-0.96], calcified: 0.91 [CI:0.85-0.95] vs. 0.95 [CI: 0.91-0.97], and low attenuation noncalcified 0.48 [CI: 0.18-0.69] vs. 0.86 [CI: 0.76-0.92]. CONCLUSIONS: Our open-source DL algorithm achieved excellent agreement with expert CAD segmentations. However, transfer learning may be required to achieve accurate segmentations in the case of different plaque characteristics or machinery. KEY POINTS: • Deep learning 3D U-net model for coronary segmentation achieves comparable results with expert readers' volumetric plaque quantification. • Transfer learning may be needed to achieve similar results for other scanner and plaque characteristics. • The developed deep learning algorithm is open-source and may be implemented in any CT analysis software.

Temporal assessment of lesion morphology on radiological images beyond lesion volumes-a proof-of-principle study.

OBJECTIVES: To develop a general framework to assess temporal changes in lesion morphology on radiological images beyond volumetric changes and to test whether cocaine abstinence changes coronary plaque structure on serial coronary CT angiography (CTA). METHODS: Chronic cocaine users with human immunodeficiency virus (HIV) infection were prospectively enrolled to undergo cash-based contingency management to achieve cocaine abstinence. Participants underwent coronary CTA at baseline and 6 and 12 months following recruitment. We segmented all coronary plaques and extracted 1103 radiomic features. We implemented weighted correlation network analysis to derive consensus eigen radiomic features (named as different colors) and used linear mixed models and mediation analysis to assess whether cocaine abstinence affects plaque morphology correcting for clinical variables and plaque volumes and whether serum biomarkers causally mediate these changes. Furthermore, we used Bayesian hidden Markov network changepoint analysis to assess the potential rewiring of the radiomic network. RESULTS: Sixty-nine PLWH (median age 55 IQR: 52-59 years, 19% female) completed the study, of whom 26 achieved total abstinence. Twenty consensus eigen radiomic features were derived. Cocaine abstinence significantly affected the pink and cyan eigen features (-0.04 CI: [-0.06; -0.02], p = 0.0009; 0.03 CI: [0.001; 0.04], p = 0.0017, respectively). These effects were mediated through changes in endothelin-1 levels. In abstinent individuals, we observed significant rewiring of the latent radiomic signature network. CONCLUSIONS: Using our proposed framework, we found 1 year of cocaine abstinence to significantly change specific latent coronary plaque morphological features and rewire the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics. KEY POINTS: • We propose a general methodology to decompose the latent morphology of lesions on radiological images using a radiomics-based systems biology approach. • As a proof-of-principle, we show that 1 year of cocaine abstinence results in significant changes in specific latent coronary plaque morphologic features and rewiring of the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics. • We found endothelin-1 levels to mediate these structural changes providing potential pathological pathways warranting further investigation.

Contribution of Risk Factors to the Development of Coronary Atherosclerosis as Confirmed via Coronary CT Angiography: A Longitudinal Radiomics-based Study.

Background Various cardiovascular risk factors are thought to modify atherosclerosis in a similar fashion (ie, by increasing the magnitude of coronary artery disease [CAD]). However, coronary CT angiography allows precision phenotyping of plaque characteristics through use of radiomics. Purpose To assess whether different cardiovascular risk factors have distinctive contributions to the changes in plaque morphologic features over time. Materials and Methods Individuals with or without HIV infection and cocaine use and without cardiovascular symptoms underwent coronary CT angiography between May 2004 and August 2015. In the current HIPAA-compliant study, the effects of cocaine use, HIV infection, and atherosclerotic cardiovascular disease (ASCVD) risk on the temporal changes (mean ± standard deviation, 4.0 years ± 2.3 between CT angiographic examinations) in CAD structure were analyzed by using radiomic analysis. The changes in radiomic features were analyzed by using linear mixed models, with correction for factors that may change plaque structure: high-sensitivity C-reactive protein level, statin use, positive family history of CAD, and total plaque volume to account for any potential intrinsic correlation between volume and morphologic features. Clusters among significant radiomic features were identified by using hierarchical clustering. Bonferroni-corrected P values less than .00004 (.05 divided by 1276) were considered to indicate significant differences. Results Of 1429 participants, 300 with CAD confirmed at coronary CT angiography were randomly selected (mean age, 48 years ± 7; 210 men, 226 people infected with HIV, 174 people who use cocaine) and 1276 radiomic features were quantified for each plaque. Cocaine use was significantly associated with 23.7% (303 of 1276) of the radiomic features, HIV infection was significantly associated with 1.3% (17 of 1276), and elevated ASCVD risk was significantly associated with 8.2% (104 of 1276) (P < .00004 for all). Parameters associated with elevated ASCVD risk or cocaine use and HIV infection did not overlap. There were 13 clusters among the 409 parameters, eight of which were affected only by cocaine use and three of which were affected only by ASCVD risk. Conclusion Radiomics-based precision phenotyping indicated that conventional risk factors, cocaine use, and HIV infection each had different effects on CT angiographic morphologic changes in coronary atherosclerosis over 4 years. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Schoepf and Emrich in this issue.

Cardiovascular risk factors and illicit drug use may have a more profound effect on coronary atherosclerosis progression in people living with HIV.

OBJECTIVES: To assess whether HIV infection directly or indirectly promotes coronary artery disease (CAD) volume progression in a longitudinal study of African Americans. METHODS: We randomly selected 300 individuals with subclinical CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV infected, 174 cocaine users) from 1429 cardiovascularly asymptomatic participants of a prospective epidemiological study between May 2004 and August 2015. Individuals underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years). We quantified noncalcified (NCP: -100-350HU), low-attenuation noncalcified (LA-NCP: -100-30HU), and calcified (CP: ≥ 351 HU) plaque volumes. Linear mixed models were used to assess the effects of HIV infection, atherosclerotic cardiovascular disease (ASCVD) risk, and years of cocaine use on plaque volumes. RESULTS: There was no significant difference in annual progression rates between HIV-infected and HIV-uninfected regarding NCP (8.7 [IQR: 3.0-19.4] mm3/year vs. 4.9 [IQR: 1.5-18.3] mm3/year, p = 0.14), LA-NCP (0.2 [IQR: 0.0-1.6] mm3/year vs. 0.2 [IQR: 0.0-0.9] mm3/year, p = 0.07) or CP volumes (0.3 [IQR: 0.0-3.4] mm3/year vs. 0.1 [IQR: 0.0-3.2] mm3/year, p = 0.30). Multivariately, HIV infection was not associated with NCP (-6.9mm3, CI: [-32.8-19.0], p = 0.60), LA-NCP (-0.1mm3, CI: [-2.6-2.4], p = 0.92), or CP volumes (-0.3mm3, CI: [-9.3-8.6], p = 0.96). However, each percentage of ASCVD and each year of cocaine use significantly increased total, NCP, and CP volumes among HIV-infected individuals, but not among HIV-uninfected. Importantly, none of the HIV-associated medications had any effect on plaque volumes (p > 0.05 for all). CONCLUSIONS: The more profound adverse effect of risk factors in HIV-infected individuals may explain the accelerated progression of CAD in these people, as HIV infection was not independently associated with any coronary plaque volume. KEY POINTS: • Human immunodeficiency virus-infected individuals may have similar subclinical coronary artery disease, as the infection is not independently associated with coronary plaque volumes. • However, cardiovascular risk factors and illicit drug use may have a more profound effect on atherosclerosis progression in those with human immunodeficiency virus infection, which may explain the accelerated progression of CAD in these people. • Nevertheless, through rigorous prevention and abstinence from illicit drugs, these individuals may experience similar cardiovascular outcomes as -uninfected individuals.

Long-term cocaine use is associated with increased coronary plaque burden - a pilot study.

Background: There is a lack of research regarding whether prolonged use of cocaine would lead to increase of coronary plaque burden. Objectives: To study the effects of cocaine use on the coronary artery plaque volume. We hypothesize the longer the cocaine use, the greater the plaque burden. Methods: We used coronary computed tomography angiography to evaluate plaque volumes. The study included chronic (N = 33 with 27 HIV+) and non-cocaine users (N = 15 with 12 HIV+). Chronic cocaine use was defined as use by any route for at least 6 months, administered at least 4 times/month. The Student's t-test was used to compare the plaque volumes between chronic and non-cocaine users. Multivariable regression analysis adjusted for age, sex, body mass index, HIV status, cigarette smoking, diabetes, and total cholesterol was performed to determine the relationship between years of cocaine use and plaque volumes. Results: The total plaque volumes between groups showed no difference (p = .065). However, the total left anterior descending artery (LAD) plaque volume in the chronic cocaine group was significantly higher than that in the non-cocaine group (p = .047). For each year increase in cocaine use, total plaque volume and total LAD plaque volume increased by 7.23 mm3 (p = .013) and 4.56 mm3 (p = .001), respectively. In the multivariable analyses, both total plaque volume and total LAD plaque volume were significantly associated with years of cocaine use (p = .039 and 0.013, respectively). Conclusion: Prolonged cocaine use accelerates the development of sub-clinical atherosclerosis.

MRI gadolinium dosing on basis of blood volume.

PURPOSE: Gadolinium-based contrast agents (GBCAs) for MRI are generally administrated in direct relationship to body weight. Instead, we propose a model for GBCA dosing on the basis of blood volume. The new method was tested by exploring the associations between MRI T1 mapping indices and weight in the MESA (Multi-Ethnic Study of Atherosclerosis. METHODS: Empirically derived methods based on sex and body habitus were used to calculate blood volumes. GBCA dose (in mL) in blood (in L) was calculated as the injected volume divided by the blood volume (i.e., DBV). Of the 1219 participants with cardiac MRI T1 mapping, 845 studies had standard dose of 0.15 mmol/kg (cohort 1) and 166 studies had 30 mL of GBCA regardless of weight (cohort 2). We also created a specific cohort with similar DBV (N = 357; cohort 3). RESULTS: Postcontrast blood relaxation rate R1blood and DBV were significantly correlated (R = 0.641; P < 0.001). R1blood was significantly associated with weight in cohort 1 and 2, but the correlation coefficient was positive for cohort 1 and negative for cohort 2, indicating GBCA overdosing in cohort 1 and underdosing in cohort 2 in heavy relative to lean subjects. R1blood was not associated with weight in cohort 3. Simulated results demonstrated that less contrast should be administrated for heavy subjects compared to the conventional weight-based dose. CONCLUSION: GBCA dosing on the basis of blood volume could improve the efficacy and safety of contrast-enhanced MRI studies. This method could be implemented to standardize dose and augment precision in study comparisons.

Cocaine use modifies the association between antiretroviral therapy and endothelial dysfunction among adults with HIV infection.

Cocaine is commonly used among HIV-infected people and may worsen HIV disease progression. In addition, existing evidence suggests a link between antiretroviral regimens and endothelial dysfunction. This study aimed to examine whether the associations of antiretroviral therapy (ART) regimens with endothelial dysfunction may be modified by cocaine use in adults with HIV infection. Between 2003 and 2014, 466 HIV-positive participants residing in Baltimore, Maryland, were enrolled in a study investigating comorbidities associated with HIV/ART. The associations between various risk factors and endothelial dysfunction indicators were examined by robust regression models fitted for the overall subjects and cocaine subgroups, separately. Duration of nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy was negatively associated with plasma vWF:Ag levels in cocaine non-users (ß = -.715, SE = .220, P < .05). However, cocaine users on longer-term NNRTI-based regimens had greater plasma endothelin-1 (ET-1) concentrations than their counterparts (ß = .003, SE = .001, P < .05). In addition, current cigarette smoking was significantly positively associated with ET-1 concentrations in both cocaine non-users (ß = .609, SE = .164, P < .05) and cocaine users (ß = .331, SE = .086, P < .05). In conclusion, cocaine use modified the potential effects of NNRTI-based therapy on biomarkers of endothelial dysfunction. These findings suggested that reduction in cocaine use may improve endothelial function in HIV-infected cocaine users.

The influence of febuxostat on coronary artery endothelial dysfunction in patients with coronary artery disease: A phase 4 randomized, placebo-controlled, double-blind, crossover trial.

BACKGROUND: The xanthine oxidase (XO) system is a significant source of vascular oxidative stress, which is believed to impair endothelial function, an important contributor to atherosclerotic disease. We tested whether febuxostat, a potent XO inhibitor, improves coronary endothelial function (CEF) in patients with stable coronary artery disease (CAD) in a single-center, randomized, placebo-controlled, double-blind crossover trial. METHODS: CEF was measured using noninvasive magnetic resonance imaging (MRI) assessment of changes in 30 patients with stable CAD and baseline impaired CEF. Patients received either febuxostat or placebo for 6 weeks and then were crossed over to the alternative for an additional 6 weeks. MRI-detected changes in coronary flow and in coronary cross-sectional area from rest to isometric handgrip exercise, a known endothelial-dependent stressor, were measured at the end of each 6 week period. RESULTS: Mean serum urate levels were lower at the end of the 6-week febuxostat period (2.9±0.8mg/dL) than at the end of the 6-week placebo period (5.9±0.04, P<.001). However, there were no significant differences in any of the CEF parameters measured at the end of the febuxostat and placebo periods. CONCLUSIONS: In summary, although XO inhibition with febuxostat was well tolerated and lowered serum urate, it did not improve the primary end point of the study, CEF measured using MRI after 6 weeks of treatment. In conclusion, these findings suggest that short-term inhibition of XO does not significantly improve impaired CEF in patients with stable CAD.

Gender differences in the associations between urinary bisphenol A and body composition among American children: The National Health and Nutrition Examination Survey, 2003-2006.

BACKGROUND: As an endocrine disruptor, bisphenol A (BPA) exposure has been implicated as a potential risk factor in childhood obesity, which is defined using percentiles of body mass index for age. We aimed to examine the associations between BPA exposure, reflected by urinary BPA concentration, and body composition in American children. METHODS: Data of 1860 children aged 8-19 years who participated in the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were analyzed in this study. Urinary BPA concentration (ng/mL) was used to indicate BPA status in the body. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Multivariate linear regression models were fitted using survey procedures to investigate the associations between urinary BPA level and body composition separately for boys and girls. RESULTS: After adjusting for demographic and lifestyle covariates, higher quartiled and log-transformed urinary BPA levels were significantly associated with elevated lean body mass index (LBMI) z-scores in boys (p < 0.05), and significantly associated with elevated fat mass index (FMI) z-scores in girls (p < 0.05). Lower urinary BPA concentration was associated with lower percentage of trunk fat in girls (compared to 1st quartile, 2nd-quartile: ß = 2.85, 95% CI, 0.92-4.78; 3rd-quartile: ß = 2.57, 95% CI, 0.28-4.85; 4th-quartile: ß = 2.79, 95% CI, 0.44-5.14; all p < 0.05). Such patterns were not observed in boys. CONCLUSIONS: Higher BPA levels may be associated with elevated LBM in boys, but not in girls, while higher BPA levels may be associated with elevated FM in girls, but not in boys.

Age and Gender Differences in the Association between Serum 25-Hydroxyvitamin D and Stroke in the General US Population: The National Health and Nutrition Examination Survey, 2001-2006.

BACKGROUND: Previous findings on the association between serum 25(OH)D level and stroke have been controversial. We aimed to examine whether these controversial findings could be possibly due to difference in study participant characteristics, especially age and gender differences in these studies, by analyzing the data from a representative sample of the general US population. METHODS: Data of 13,642 adults 20 years or older who participated in the 2001-2006 National Health and Nutrition Examination Survey were analyzed in this study. Serum 25(OH)D was used to reflect vitamin D status. Stroke history was self-reported using questionnaires. Unadjusted and adjusted logistic regression models were fitted using SAS survey procedures to investigate the associations between 25(OH)D level and stroke for the pooled sample and age-gender subgroups (men versus women, <50 years old versus ≥50 years old), respectively. RESULTS: After adjusting for demographic and lifestyle covariates, vitamin D deficiency (defined as serum 25(OH)D < 12 ng/mL) was significantly associated with increased risk of stroke (adjusted odds ratio [OR] = 1.62, 95% confidence interval [CI] = 1.11, 2.36), and higher vitamin D levels were significantly associated with reduced risk of stroke (adjusted OR = .70, 95% CI = .51, .96). The association between high levels of serum 25(OH)D and stroke was particularly evident among young females (age ≤20 years to <50 years) (adjusted OR = .26, 95% CI = .14, .49). CONCLUSIONS: The findings add to the evidence suggesting maintaining ideal 25(OH)D levels may reduce the risk of stroke among US adults, particularly in adult women younger than 50 years.

Circulating Prolactin and Risk of Type 2 Diabetes: A Prospective Study.

Prolactin plays an important role in maintaining a normal glucose homeostasis during pregnancy and beyond. Studies investigating the association between prolactin and type 2 diabetes beyond pregnancy are rare and none is prospective. We aimed to examine whether prolactin associates with type 2 diabetes prospectively in a Chinese population. In 2009, 2,377 participants aged 40 years or older were enrolled from Shanghai, China. Among 1,596 diabetes-free participants at baseline, 1,510 completed the follow-up investigation in 2013. Participants who had a fasting plasma glucose ≥126 mg/dL and/or a 2-hour plasma glucose ≥200 mg/dL during a 75-g oral glucose tolerance test had a definite diagnosis of type 2 diabetes or received antidiabetic therapies during follow-up were classified as having type 2 diabetes. During a mean follow-up of 3.7 years, 189 new cases of type 2 diabetes were documented. After multivariate adjustment, women in the highest quartile of prolactin showed the lowest risk for diabetes compared with those in the lowest quartile (hazard ratio = 0.48, 95% confidence interval: 0.26, 0.90). However, such significant associations were not observed in men. Prolactin may be a mediator in the pathogenesis of type 2 diabetes in women; however, more studies are needed to elucidate the underlying sex-specific mechanism.

Prevalence of Diabetes and Cardiometabolic Disorders in Spouses of Diabetic Individuals.

Pairs of spouses share common lifestyle factors. In a cross-sectional analysis, we investigated whether spouses of diabetic individuals had a higher prevalence of diabetes and cardiometabolic disorders in a community-based population of Chinese adults aged 40 years or older between 2011 and 2012. A total of 34,805 pairs of spouses were identified. All participants underwent a standard oral glucose tolerance test and provided detailed clinical, sociodemographic, and lifestyle information. Diabetes and multiple cardiometabolic disorders were defined according to standard criteria. Compared with participants whose spouses did not have diabetes, participants whose spouses had diabetes had higher odds of having diabetes (for men, odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.22, 1.45; for women, OR = 1.35, 95% CI: 1.24, 1.47), obesity (for men, OR = 1.34, 95% CI: 1.13, 1.59; for women, OR = 1.19, 95% CI: 1.05, 1.35), metabolic syndrome (for men, OR = 1.31, 95% CI: 1.21, 1.42; for women, OR = 1.12, 95% CI: 1.04, 1.20), and cardiovascular disease (for men, OR = 1.18, 95% CI: 1.03, 1.34; for women, OR = 1.18, 95% CI: 1.03, 1.35). The associations were independent of age, body mass index, education, family history of diabetes, cigarette smoking, alcohol drinking, physical activity, and diet. Spousal diabetes was simple and valuable information for identifying individuals at risk for diabetes and cardiometabolic disorders.

Cocaine Use May be Associated with Increased Depression in Persons Infected with HIV.

HIV infection, depression, and cocaine use are independently associated with increased inflammatory signal production. There is increasing evidence about the role of inflammation in depression. In HIV disease, cocaine use may increase disease progression as well as alter T cell functioning resulting in cytokine activation and thereby increasing susceptibility to depression. We examined the association between cocaine use and depression among 447 African American persons infected with HIV who were frequent cocaine users or non-users, enrolled in an observational study in Baltimore, Maryland, between August 2003 and December 2012. The overall prevalence of depression was 40.9 % (183 of 447) participants. Among persons who were depressed, the prevalence of cocaine use was 81.4 % (149 of 183), compared to 69.3 % among persons who were not depressed (183 of 264), P = 0.004. Cocaine use was associated with nearly twofold increased odds of depression, unadjusted odds ratio (OR) 1.94, (95 % CI 1.23, 3.06); P = 0.004, compared to never using cocaine, and OR 1.02, (95 % CI 1.10, 1.05); P = 0.04 in adjusted analysis. A dose-response relationship between increasing duration of cocaine use and depression was observed. Frequency and duration of cocaine use may be associated with depression. We speculate that depression among cocaine users with HIV may involve an inflammatory component that needs further examination.

Coronary Plaque Burden at Coronary CT Angiography in Asymptomatic Men and Women.

Purpose To assess the relationship between total, calcified, and noncalcified coronary plaque burdens throughout the entire coronary vasculature at coronary computed tomographic (CT) angiography in relationship to cardiovascular risk factors in asymptomatic individuals with low-to-moderate risk. Materials and Methods This HIPAA-compliant study had institutional review board approval, and written informed consent was obtained. Two hundred two subjects were recruited to an ongoing prospective study designed to evaluate the effect of HMG-CoA reductase inhibitors on atherosclerosis. Eligible subjects were asymptomatic individuals older than 55 years who were eligible for statin therapy. Coronary CT angiography was performed by using a 320-detector row scanner. Coronary wall thickness and plaque were evaluated in all epicardial coronary arteries greater than 2 mm in diameter. Images were analyzed by using dedicated software involving an adaptive lumen attenuation algorithm. Total plaque index (calcified plus noncalcified plaque) was defined as plaque volume divided by vessel length. Multivariable regression analysis was performed to determine the relationship between risk factors and plaque indexes. Results The mean age of the subjects was 65.5 years ± 6.9 (standard deviation) (36% women), and the median coronary artery calcium (CAC) score was 73 (interquartile range, 1-434). The total coronary plaque index was higher in men than in women (42.06 mm(2) ± 9.22 vs 34.33 mm(2) ± 8.35; P < .001). In multivariable analysis controlling for all risk factors, total plaque index remained higher in men than in women (by 5.01 mm(2); P = .03) and in those with higher simvastatin doses (by 0.44 mm(2)/10 mg simvastatin dose equivalent; P = .02). Noncalcified plaque index was positively correlated with systolic blood pressure (ß = 0.80 mm(2)/10 mm Hg; P = .03), diabetes (ß = 4.47 mm(2); P = .03), and low-density lipoprotein (LDL) cholesterol level (ß = 0.04 mm(2)/mg/dL; P = .02); the association with LDL cholesterol level remained significant (P = .02) after additional adjustment for the CAC score. Conclusion LDL cholesterol level, systolic blood pressure, and diabetes were associated with noncalcified plaque burden at coronary CT angiography in asymptomatic individuals with low-to-moderate risk. (©) RSNA, 2015 Online supplemental material is available for this article.

Awareness, treatment and control of cardiometabolic disorders in Chinese adults with diabetes: a national representative population study.

BACKGROUND: The diagnosis of diabetes has important clinic implications for the prevention and management of cardiometabolic disorders. We aimed to investigate the awareness, treatment and control of hypertension and dyslipidemia in previously-diagnosed and newly-diagnosed diabetes in Chinese adult population. METHODS: We conducted a cross-sectional survey in a nationally representative sample of 98658 Chinese adults aged 18 years or older in 2010, using a complex, multistage, probability sampling design. Glycemic status were defined according to the 2010 American Diabetes Association criteria. Hypertension was diagnosed by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Dyslipidemia was diagnosed by the 2004 National Cholesterol Education Program Adult Treatment Panel III. RESULTS: The weighted prevalence of hypertension and dyslipidemia gradually increased in adults with normal glucose regulation, prediabetes, newly-diagnosed diabetes and previously-diagnosed diabetes. Compared to newly-diagnosed diabetes patients, previously-diagnosed diabetes patients were more likely to be aware of hypertension (weighted percentage [95% confidence interval]: 55.2% [52.9%-57.5%] vs 37.6% [35.9%-39.3%]) and dyslipidemia (33.9% [31.8%-36.1%] vs 12.8% [11.7%-13.9%]), to receive blood pressure-lowing (43.7% [41.5%-46.0%] vs 27.5% [26.0%-29.0%]) and lipid-lowering (18.9% [17.2%-20.7%] vs 5.4% [4.6%-6.2%]) therapies, and to have controlled blood pressure (4.7% [3.5%-6.2%] vs 3.5% [2.6%-4.8%]) and lipid (15.9% [12.3%-20.3%] vs 9.5% [6.4%-13.8%]) levels. CONCLUSIONS: Detection and control of hypertension and dyslipidemia is far from optimal in Chinese adults, especially in newly-diagnosed diabetes. Improved screening for diabetes is required to promote a better prevention, treatment and control of hypertension and dyslipidemia in China.

Relationship between gestational fasting plasma glucose and neonatal birth weight, prenatal blood pressure and dystocia in pregnant Chinese women.

BACKGROUND: Little is known about the optimal cut-off point of fasting plasma glucose for the diagnosis of gestational diabetes mellitus for pregnant Chinese women. This study investigates the relationship between gestational fasting plasma glucose and several variables: neonatal birth weight, prenatal blood pressure and dystocia rate of pregnant women. In this study, we hoped to provide a useful tool to screen gestational diabetes mellitus in pregnant Chinese women. METHODS: For 1058 pregnant women enrolled in our hospital at pregnancy weeks 22-30, fasting plasma glucose, neonatal birth weight and prenatal blood pressure, as well as dystocia conditions, were examined. We analysed the correlations between the following: gestational fasting plasma glucose and neonatal birth weight; prenatal blood pressure and gestational fasting plasma glucose as well as dystocia rate and gestational fasting plasma glucose group. RESULTS: A modest correlation was observed between gestational fasting plasma glucose and neonatal birth weight (r = 0.093, p = 0.003). The macrosomia rate was smallest when the gestational fasting plasma glucose was in the range 3.51-5.5 mmol/L. Prenatal blood pressure increased linearly with increasing gestational fasting plasma glucose (p = 0.000). There was a significant difference between the dystocia rates in different fasting plasma glucose groups (chi-squared = 13.015, p = 0.043). The results showed that the dystocia rate significantly increased when gestational fasting plasma glucose was >4.9 mmol/L; p = 0.03, OR = 2.156 (95% CI, 1.077-4.318). CONCLUSION: We suggest that the optimal range of gestational fasting plasma glucose for pregnant Chinese women is in the range 3.5-4.9 mmol/L.