Background Neighborhood characteristics serve as risk factors for metabolic syndrome (MetS). However, the intermediary factors linking this relationship remain understudied. Thus, we investigated the sex‐specific mediating role of C‐reactive protein, physical activity (PA), and perceived stress in the associations of perceived neighborhood social environment (PNSE) with MetS severity among Black adults. Methods and Results This cross‐sectional study included 3185 adults (64% women) from exam 1 (2000–2004) of the Jackson Heart Study. MetS severity Z scores were calculated based on the Adult Treatment Panel III criteria formula. PNSE included neighborhood violence, problems, and social cohesion. Men and women were analyzed separately. A bootstrap resampling technique with 95% bias‐corrected CI (95% BC CI) was used to evaluate whether C‐reactive protein, PA, and perceived stress mediated the association between each PNSE and MetS severity, adjusting for covariates. All PNSE factors were directly related to MetS severity in women but not in men. In women, neighborhood problems were indirectly associated with MetS severity mediated through PA (β=0.02 [95% BC CI, 0.00–0.05]). In men, neighborhood violence, problems, and social cohesion were indirectly associated with MetS severity mediated through PA (β=0.05 [95% BC CI, 0.01–0.10]; β=0.03 [95% BC CI, 0.00–0.06]; and β=−0.04 [95% BC CI, −0.09 to −0.01], respectively). Neither C‐reactive protein nor perceived stress mediated such associations in either women or men. Conclusions All PNSEs (violence, problems, and social cohesion) were directly related to MetS severity in women only. PA mediated the relationship between each PNSE and MetS in a sex‐specific manner. Efforts focusing on local conditions are needed to better understand why such disparities exist for at‐risk minoritized groups.

In the primary prevention of atherosclerotic cardiovascular disease (ASCVD), a significant portion of high-risk patients have diabetes. Two decades ago, patients with or without cardiovascular disease were identified as having coronary heart disease (CHD) risk equivalents because prospective studies showed that they were at risk for future CHD events equivalent to that of patients with established CHD. Thus, for patients with CHD, cholesterol guidelines recommended that patients with diabetes should be treated routinely with statins. However, recently, the treatment of diabetes has been greatly improved, and the risk for ASCVD has decreased. For this reason, it may be appropriate to re-evaluate the recommendations for routine use of statins in patients with diabetes. One of the major advances in the risk assessment for ASCVD is the introduction of coronary artery calcium measurement. This report will examine the role of coronary artery calcium scanning for the decision to initiate statin therapy in the primary prevention for patients with diabetes.

By current guidelines, statin treatment decisions depend on multiple risk factor algorithms (e.g., pooled cohort equations [PCEs]). By available PCEs most older middle-aged women are statin eligible. But several studies cast doubt on reliability of available PCEs for ASCVD risk assessment. An alternative method for risk assessment is a coronary artery calcium (CAC) score. Many older women have zero CAC, which equates to low risk for ASCVD; these women can delay statin therapy for several years before re-scanning. When CAC is 1-99 Agatston units, risk is only borderline high and statin delay also is an option until re-scanning. When CAC is > 100 Agatston units, risk is high enough to warrant a statin. In most women, CAC is the best guide to treatment decisions. In high-risk women (e.g., diabetes and severe hypercholesterolemia), generally are indicated, but CAC can assist in risk assessment, but other risk factors also can aid in treatment decisions.

Introduction: Metabolic syndrome (MetS) can lead to harmful effects on cardiovascular health. Assessing whether links between perceived neighborhood social environment (PNSE) and MetS are mediated by physical activity (PA) levels will inform interventions to reduce population-level mortality attributed to MetS. Hypothesis: PNSE will be both directly and indirectly related to MetS severity via PA. Methods: This study utilized baseline data from the Jackson Heart Study, a prospective, community-based cohort of African American adults in Jackson, MS (total sample=3082; mean age 53.3 years; 64% female). PNSE variables included neighborhood violence, problems (higher value=more violence or problems), and social cohesion (higher value=more cohesion). MetS severity Z-score was the outcome (higher score indicates worse MetS). Validated self-reported total PA, based on active living, sports, and home/yard indices, was tested as the mediator. Linear regressions with bootstrap-generated 95% bias-corrected confidence intervals ( BC CIs ) were estimated to test for significant unstandardized indirect effects, controlling for covariates (age, education, smoking status, alcohol consumption, and diet). All analyses were stratified by sex. Results: In women, neighborhood violence, problems, and social cohesion were indirectly related to MetS via PA (B for indirect effects=.04, 95% BC CI =.01, .08; .03, 95% BC CI =.01, .06; and -.03, 95% BC CI =-.07, -.01, respectively). That is, higher violence and problems were related to lower PA (B=-1.06, 95%CI=-1.76, -.36; B=-.79, 95%CI=-1.26, -.32, respectively), while higher social cohesion was associated with higher PA (B=.86, 95%CI=.15, 1.58). In turn, higher PA was associated with lower MetS. All PNSE factors were directly related to MetS (p<.05). In men, neighborhood violence, problems, and social cohesion were indirectly related to MetS via PA (B for indirect effects=.06, 95% BC CI =.02, .12; .04, 95% BC CI =.01, .08; and -.06, 95% BC CI =-.11, -.02, respectively). Again, higher violence and problems were related to lower PA (B=-1.65, 95%CI=-2.58, -.71; B=-1.02, 95%CI=-1.64, -.40, respectively), while higher social cohesion was associated with higher PA (B=1.58, 95%CI=.64, 2.52). In turn, higher PA was associated with lower MetS. No PNSEs were directly related to MetS. Conclusions: Consistent with what we expected, higher perceived neighborhood violence and problems were positively related to MetS, and vice versa for social cohesion. These associations may be explained in part by PA levels. The data showed that indirect effects by PA were more pronounced in men than women. Future interventions to reduce MetS attributed to neighborhood issues should consider PA promotion tailored to women and men in conjunction with community efforts to reduce neighborhood violence and problems and encourage cohesive neighborhoods.

Background: Pooled cohort equations (PCEs) estimate 10-year risk for atherosclerotic cardiovascular disease (ASCVD) in US adults. One use is to guide statin eligibility. However, PCEs risk estimate is inaccurate in some US subpopulations. Objective: Recent cholesterol guidelines proposed addition of risk enhancing factors to improve risk assessment for selection of statin therapy. This study examines frequencies of several risk enhancing biomarkers in NHANES subjects at intermediate risk (7.5 -<20% 10-year risk for ASCVD) and considers how they may be used to better assess risk for individuals. Methods: Prevalence of the following biomarkers were determined; elevations in apolipoprotein B-containing lipoproteins, i.e., LDL cholesterol (LDL-C) (160-189 mg/dL), non-HDL-cholesterol (non-HDL-C) (190-219 mg/dL), or total apolipoprotein B (apoB) (>= 130 mg/dL), serum triglyceride (>= 175 mg/dL), hemoglobin A1c (5.7-6.4%), high sensitivity C-reactive protein (2-10 mg/L), and waist circumference >= 102 cm, and abnormal estimated glomerular filtration rate (15 - <= 60 mg/min/1.73 m(2)). Results: 25% of NHANES population had intermediate risk. In this subpopulation, 85% had >= 1 biomarkers-similarly in women and men-with a third having >= 3 abnormal markers. Frequencies were not age-related, except in those 40-49 years, in whom >= 40% had >= 3 abnormal biomarkers. It made little difference whether LDL-C, non-HDL-C or apoB was used as the atherogenic lipoprotein. Conclusion: Three or more enhancing risk factors in intermediate risk subjects can complement PCE-estimated 10-year risk and guide the patient-provider discussion toward use of lipid-lowering medication. Future research is needed to integrate risk estimates by PCE and multiple risk enhancers. (C) 2021 National Lipid Association. Published by Elsevier Inc.

Statins are among the most widely prescribed drugs. They reduce risk for atherosclerotic cardiovascular disease by lowering serum apolipoprotein B-containing lipoproteins, particularly low-density lipoprotein (LDL) cholesterol (LDL-C).1 Statins inhibit cholesterol synthesis in the liver, which increases expression of LDL receptors and lowers serum LDL-C.2 The latter slows progression of atherosclerotic lesions, reduces coronary plaque rupture, and decreases likelihood of acute cardiovascular syndromes (ie, myocardial infarction and stroke).

To standardize a method for 1H MRS intramuscular absolute quantification of carnosine in the thigh, using a surface coil and water as internal reference. Carnosine spectra were acquired in phantoms (5, 10, and 15 mM) as well as in the right gastrocnemius medialis (GM) and right vastus lateralis (VLM) muscles of young team sports athletes, using volume (VC) and surface (SC) coils on a 3 T scanner, with the same receiver gain. Water spectra were used as internal reference for the absolute quantification of carnosine. Phantom’s experiments showed a maximum error of 7%, highlighting the validity of the measurements in the study setup. The carnosine concentrations (mmol/kg ww, mean ± SD) measured in the GM were 6.8 ± 2.2 with the VC (CcarVC) and 10.2 ± 3.0 with the SC (CcarSC) (P = 0.013; n = 9). Therefore, a correction was applied to these measurements (CcarVC = 0.6582*CcarSC), to make coils performance comparable (6.8 ± 2.2 for VC and 6.7 ± 2.0 for SC, P = 0.97). After that, only the SC was used to quantify carnosine in the VLM, where a concentration of 5.4 ± 1.5 (n = 30) was found, with significant differences between men (6.2 ± 1.3; n = 15) and women (4.6 ± 1.2; n = 15). The error in quantitation was 5.3–5.5% with both coils. The method using the SC and water as internal reference can be used to quantify carnosine in voluminous muscles and regions of the body in humans, where the VC is not suitable, such as the VLM.

BACKGROUND: Chronic kidney disease (CKD) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). American cardiovascular societies consider CKD a risk-enhancing factor that supports statin therapy in intermediate-risk patients aged 40-75 years. In contrast, European cardiovascular societies recommend statins for all middle-aged adults with CKD. The Kidney Disease: Improving Global Outcomes lipid management guideline for CKD recommends statin therapy for all patients with CKD > 50 years. Clinical implications for these differences have not been examined. OBJECTIVE: This study examines CKD prevalence and statin eligibility in non-ASCVD adults, representative of the US population, at 3 levels of 10-year risk of ASCVD estimated by pooled cohort equations. METHODS: National Health and Nutrition Examination Surveys 1999-2016 weighted data were evaluated for CKD defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2. Overall prevalence of low, intermediate, and high 10-year risk for ASCVD was determined. RESULTS: A total of 92.5% of all participants had estimated glomerular filtration rate >= 60 mL/ min/1.73 m2; 7.5% (confidence interval 6.9%, 8.1%) had CKD. Among participants with CKD, 46.3% had 10-year risk for ASCVD < 7.5% (low risk); 31.7% had intermediate risk (7.5-< 20%), and 22.0% had high risk (> 20%). In participants with CKD, 62.5% were women. A total of 19.6% of all participants with CKD had diabetes. A total of 46.3% of participants with CKD at intermediate or high risk reported taking cholesterol-lowering drugs. CONCLUSION: A total of 46.3% of patients with CKD aged 40?75 years had 10-year risk < 7.5% (low risk) and hence were statin eligible by European and Kidney Disease: Improving Global Outcomes (> 50 years) guidelines. US cardiovascular guidelines limit statin eligibility to intermediateand high-risk CKD. Statin eligibility in lower-risk patients may be best determined by measuring coronary artery calcium. (c) 2020 National Lipid Association. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND: Statins effectively reduce risk for atherosclerotic cardiovascular disease (ASCVD) when 10-year risk is >_ 7.5%. In many patients at intermediate risk (7.5-<20% risk), there is uncertainty about reliability of risk assessment by current pooled cohort equations (PCE). A decision to initiate statin therapy is favored by several risk enhancing factors not employed in PCEs. OBJECTIVE: This study examines the scope of the metabolic syndrome, a risk enhancing factor, and its principal sequala, diabetes, in 26,796 US adults age 40-75 years from the NHANES survey data, 1999-2016. METHODS: The prevalence of metabolic syndrome without diabetes (MetS+) and of diabetes (DM+) were determined for 10-year risk categories estimated to be low (<7.5%), intermediate (7.5% -< 20%) and high (>_20%). Data were weighted to account for complex study design. RESULTS: 90.4% of the population was free of ASCVD. In subjects projected to be at low risk by PCEs, MetS+ was present in 15.0% and 17.6% of women and men, respectively. MetS + increased to 30.6% of women and 29.6% of men at intermediate risk, and to 21.5% of women and 32.2% of men at high risk. In addition, DM+ was present in 6.1%/5.3% (F/M) of low risk individuals, 20.1%/14.8% (F/ M) of intermediate risk subjects, and 44.3%/39.4% (F/M) of high-risk persons. Prevalence of both MetS+ and DM + rose progressively with age in women and men. CONCLUSIONS: MetS+ and DM + are common multiplex risk factors that predispose to higher lifetime risk and support statin therapy in patients at intermediate and high risk. 2021 National Lipid Association. All rights reserved. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Serum concentrations of cholesterol are positively correlated with exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) in humans. The associated change in cholesterol is small across a broad range of exposure to PFOA and PFOS. Animal studies generally have not indicated a mechanism that would account for the association in humans. The extent to which the relationship is causal is an open question. Nonetheless, the association is of particular importance because increased serum cholesterol has been considered as an endpoint to derive a point of departure in at least one recent risk assessment. To gain insight into potential mechanisms for the association, both causal and non-causal, an expert workshop was held Oct 31 and Nov 1, 2019 to discuss relevant data and propose new studies. In this report, we summarize the relevant background data, the discussion among the attendees, and their recommendations for further research.

BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-C) includes atherogenic cholesterol and low-density lipoproteins (LDL) and triglyceride-rich lipoproteins. Patients with diabetes frequently have elevations in non-HDL-C. OBJECTIVE: This study examines temporal trends in the levels of non-HDL-C in free-living subjects with diabetes but a negative history of atherosclerotic cardiovascular disease. METHODS: National Health and Nutrition Examination Surveys conducted between 1999 and 2016 had data from 3,219 adults (aged 40-75 years) with diabetes. Temporal trends in changes in the distribution of total cholesterol, non-HDL-C, LDL cholesterol (LDL-C), and HDL-C were evaluated. Data were weighted to account for complex survey design. RESULTS: Significant decreases were observed in non-HDL-C (20.1%; P < .0001) and total cholesterol (16.1%; P < .0001) levels between 1999 and 2016. No significant changes were noted in HDL-C levels. LDL-C was reduced by 29.6% in a subset of subjects. The reduction in non-HDL-C and LDL-C occurred simultaneously, with an increase of 4.4% of subjects per year taking cholesterol-lowering drugs and statins. In contrast, the fraction of subjects taking antihypertensives or hypoglycemia agents rose at a rate of 2.2% per year. There was also a significant trend for increases in weight gain (P <= .013). CONCLUSIONS: In subjects with diabetes, non-HDL-C levels have declined over time in parallel with reported increases in cholesterol-lowering drugs. Nonetheless, treatment targets for lipids in subjects with diabetes lag behind current recommendations. Reported intakes for antihypertensive agents and hypoglycemia agents were relatively high throughout the period of study, with little change over time. However, there was a trend for weight increase in diabetic subjects, which may offset some of the benefits of pharmacotherapy. (C) 2020 National Lipid Association. Published by Elsevier Inc.

Optimal medical management of patients with peripheral arterial disease (PAD) includes statin therapy, which has been shown to decrease the risk of major cardiovascular events. However, the relationship between low-density lipoprotein (LDL) lowering, PAD progression and limb outcomes remains controversial. Although prevention of coronary and cerebrovascular events is a priority, limb outcomes are still important determinants of quality of life and healthcare spending. This review will highlight differences between coronary artery disease (CAD) and PAD, and in particular, the more prevalent role of lipids and LDL cholesterol in CAD versus calcification in PAD. This difference may contribute to the differential impact of LDL cholesterol levels on coronary events and outcomes versus limb outcomes. Beyond LDL lowering, immune modulators have emerged as another agent to treat atherosclerosis in CAD, however similar data in PAD are lacking. Small studies have suggested that other lipids besides LDL cholesterol, such as triglycerides or small dense LDL, may have a greater impact on limb outcomes in patients with PAD. Although statin therapy is central in the management of patients with PAD, current understanding of the distinctions between PAD and CAD suggest that there may be other non-LDL targets for risk reduction that require further study.

•Chronic kidney disease (CKD) is an independent cardiovascular disease (CVD) risk factor, and 7.5% of USA population has CKD.•A total of 46.3% of participants with CKD have low 10-year CVD risk; 31.7% have intermediate risk.•A total of 45.8% report cholesterol-lowering treatment.•Guidelines for statin eligibility vary widely.

Evidence suggests that substantial testosterone therapy is occurring without checking levels of testosterone, presumably based on the presence of symptoms alone. We sought to explore the relationship between total testosterone level and non-specific symptoms, metabolic abnormalities, and sexual dysfunction associated with hypogonadism. This cross-sectional study included 2994 generally healthy men aged 50–79 years examined at a preventive medicine clinic in Dallas, TX from January 2012 to March 2016. Symptoms of hypogonadism were assessed. Screening morning total testosterone levels were measured and categorized into low (<250 ng/dL), low normal (250–399 ng/dL), and normal (≥400 ng/dL). Multiple logistic regression models were used to test the associations between total testosterone and signs and symptoms of hypogonadism. When considering symptoms and signs of hypogonadism, only decreased libido (OR 1.31, 95% CI 1.00 to 1.70), fasting glucose ≥100 mg/dL (OR 1.47, CI 1.15 to 1.88), and hemoglobin A1c over 6% (OR 1.47, 95% CI 1.06 to 2.03) were associated with increased odds of low testosterone after adjustment for age, body mass index, and cardiorespiratory fitness. Testosterone levels were not associated with fatigue, depression, or erectile dysfunction in our study (p>0.6). In this preventive medicine cohort, symptoms commonly attributed to testosterone deficiency were not associated with low total testosterone levels.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) are targets for prevention of atherosclerotic cardiovascular disease (ASCVD). The American Heart Association and American College of Cardiology recently modified recommendations for clinical management of cholesterol in secondary and primary prevention. Accordingly, the present article examines the need for cholesterol-lowering drugs in the U.S. population with ASCVD. OBJECTIVE: This study examines trends in non-HDL-C and LDL-C levels in a free living population of ASCVD subjects between 1999 and 2016. METHODS: National Health and Nutrition Examination Surveys database included 4920 adults with ASCVD aged 40 to 85 years. Complete data were available for 4226. Trend analysis of changes in lipids is shown in box plots. RESULTS: Mean age was 67 years with 57% males. Over 17 years, LDL-C decreased significantly by 24% and non-HDL-C by 21%. Over the period of study, reported intake of cholesterol-lowering drugs rose from 37% in 1999-2000 to 69% in 2015 to 2016. Over this same period, serum triglycerides decreased by 29% (P <.001) and HDL-C rose by 6%. CONCLUSIONS: The changes in LDL-C and non-HDL-C in patients with ASCVD over a 17-year period probably are related to increased treatment with statins. However, the changes are too small to be explained by widespread use of high-intensity statins, which is the current recommendation for patients with ASCVD. These findings pose a challenge for professional education to support implementation of current guidelines for cholesterol-lowering therapies. (C) 2019 National Lipid Association. Published by Elsevier Inc.

Survivors of childhood brain tumors may be at risk for early onset of metabolic syndrome, possibly secondary to surgery and/or radiation exposure. This study examines effects of radiation exposure to hypothalamus-pituitary-adrenal axis (HPA) on metabolic risk among survivors of childhood brain tumors. One hundred forty-two met inclusion criteria; 60 had tumor surgery plus radiation exposure (>1 Gray (Gy)) to HPA. The second subgroup of 82 subjects had surgery only and were not exposed to radiation. Both subgroups had survived for approximately 5 years at the time of study. All had clinical evaluation, vital signs, anthropometry, measurement of body composition by dual X-ray absorptiometry and fasting laboratory assays (metabolic panel, insulin, C-peptide, insulin-like growth factor-1, leptin and adiponectin). Body composition data for both subgroups was compared with the National Health and Nutrition Survey (NHANES) subgroup of similar age, gender and body mass index. Cranial surgery was associated with obesity of similar severity in both subgroups. However, survivors exposed to radiation to the HPA also had increased visceral fat mass and high prevalence of growth hormone deficiency and metabolic syndrome. Fat mass alone did not explain the prevalence of the metabolic syndrome in radiation exposure subgroup. Other factors such as growth hormone deficiency may have contributed to metabolic risk. We conclude that prevalence of metabolic syndrome among subjects exposed to hypothalamic radiation was higher than expected from hypothalamic obesity alone. Radiation exposure may exert untoward endocrinopathies due to HPA exposure that worsens metabolic risk. Early screening for metabolic syndrome in this population is indicated.

Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort.

BackgroundThe metabolic syndrome is a constellation of risk factors including dyslipidemia, dysglycemia, hypertension, a pro-inflammatory state, and a prothrombotic state. All of these factors are accentuated by obesity. However, obesity can be defined by body mass index (BMI), percent body fat, or by body fat distribution. The latter consists of upper body fat (subcutaneous and visceral fat) and lower body fat (gluteofemoral fat). Waist circumference is a common surrogate marker for upper body fat. MethodsData from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2006 was examined for associations of metabolic risk factors with percent body fat, waist circumference, and BMI. ResultsAssociations between absolute measures of waist circumference and risk factors were similiar for men and women. The similarities of associations between waist circumference and risk factors suggests that greater visceral fat in men does not accentuate the influence of upper body fat on risk factors. ConclusionsDifferent waist concumference values should not be used to define abdominal obesity in men and women.