The Association of Mitral Annular Calcification With Cardiovascular and Noncardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis.

Mitral annular calcification (MAC) may be a potential marker of biologic aging. However, the association of MAC with noncardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and noncardiovascular mortality, is not well-studied in a multiracial cohort. We used data from 6,814 participants (mean age: 62.2 ± 10.2 years, 52.9% women) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with noncontrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed the cross-sectional association of MAC with BMD and walking pace. Furthermore, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. In addition, we assessed the association of MAC with cardiovascular and noncardiovascular mortality using competing risks regression. The prevalence of MAC was 9.5% and was higher in women (10.7%) than in men (8.0%). MAC was associated with low BMD (coefficient -0.04, 95% confidence interval [CI] -0.06 to -0.02), with significant interaction by gender (p-interaction = 0.035). MAC was, however, not associated with impaired walking pace (odds ratio 1.09, 95% CI 0.89 to 1.33). Compared with participants without MAC, those with MAC had an increased risk of incident renal failure, albeit nonsignificant (hazard ratio [HR] 1.18, 95% CI 0.95 to 1.45), and a significantly higher hazards of dementia (HR 1.36, 95% CI 1.10 to 1.70). IN addition, participants with MAC had a substantially higher risk of all-cause (HR 1.47, 95% CI 1.29 to 1.69), cardiovascular (subdistribution HR 1.39, 95% CI 1.04 to 1.87), and noncardiovascular mortality (subdistribution HR 1.35, 95% CI 1.14 to 1.60) than those without MAC. MAC ≥100 versus <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and noncardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia and all-cause, cardiovascular, and noncardiovascular mortality in this multiracial cohort. Thus, MAC may be a marker not only for atherosclerotic burden but also for other metabolic and inflammatory factors that increase the risk of noncardiovascular outcomes and death from other causes.

Computational Evaluation of Bioactive Compounds from Colocasia affinis Schott as a Novel EGFR Inhibitor for Cancer Treatment.

INTRODUCTION: Epidermal growth factor receptor (EGFR) is a transmembrane protein that belongs to the ErbB/HER-family of tyrosine kinase receptors. Somatic mutations and overexpression of EGFR have been reported to play a vital role in cancer cell development and progression, including cell proliferation, differentiation, angiogenesis, apoptosis, and metastatic spread. Hence, EGFR is an important therapeutic target for the treatment of various types of epithelial cancers. Somatic mutations have led to resistance to clinically approved synthetic EGFR inhibitors. Furthermore, synthetic EGFR inhibitors have been associated with several side effects. Thus, there is a need to develop novel EGFR inhibitors with an acceptable biosafety profile and high efficacy. METHODS: Herein, we employed structural bioinformatics and theoretical chemistry techniques via molecular docking, molecular mechanics generalized Born surface area (MM-GBSA) calculation, density functional theory analysis (DFT), and pharmacokinetic study to identify novel EGFR inhibitors. RESULTS: The stringent molecular docking and MM-GBSA calculations identified MET 793, LYS 745, PHE 723, ASP 855, ARG 411, and THR 854 as principal amino acid residues for EGFR-ligands interactions. Furthermore, Colocasia affinis Schott compounds exhibited higher binding energy and more stable interactions than the reference compound (gefitinib). DFT analysis also ascertains better bioactivity and chemical reactivity of C. affinis Schott with favorable intramolecular charge transfer between electron-donor and electron acceptor groups. The pharmacokinetic profile of C. affinis Schott bioactive compounds satisfies Lipinski's rule of five assessment. CONCLUSION: Collectively, C. affinis Schott compounds demonstrated higher inhibitory potentials against EGFR and better pharmacological properties when compared with gefitinib. C. affinis Schott compounds are therefore suggested as promising therapeutic EGFR inhibitors for cancer treatment.

Life's Simple 7 and Nonalcoholic Fatty Liver Disease: The Multiethnic Study of Atherosclerosis.

BACKGROUND: The American Heart Association (AHA) has defined Life's Simple 7 (LS7) as a measure of overall cardiovascular health . Nonalcoholic fatty liver disease (NAFLD) has been involved as a risk factor for cardiovascular disease. We evaluated the association between LS7 and NAFLD. METHODS: We evaluated participants form the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Cardiovascular health score was calculated from the Life's Simple 7 metrics. A score of 0-8 was considered inadequate, 9-10 average, and 11-14 optimal. NAFLD was defined using noncontrast cardiac computed tomography (CT) and a liver/spleen attenuation ratio (L/S) < 1. Multivariable regression were performed to evaluate the association. RESULTS: Our cross-sectional analysis of 3901 participants showed 19% (n = 747) had optimal cardiovascular health, 33% (n = 1270) had average, and 48% (n = 1884) had inadequate. White participants were most likely to have an optimal score (51%, n = 378), whereas African American participants had the lowest proportion with optimal scores (16%, n = 120; P < 0.001). The overall prevalence of NAFLD was 18% with a distribution of 7%, 14%, and 25% in the optimal, average, and inadequate score categories, respectively (P < 0.001). Adjusted for risk factors, average and optimal health categories had lower odds of NAFLD compared to those with inadequate scores: odds ratio for average, 0.44 (95% confidence interval 0.36-0.54); optimal, odds ratio 0.19 (95% confidence interval 0.14-0.26). This association was similar across gender, race and age groups. CONCLUSION: A more favorable cardiovascular health score was associated with a lower prevalence of NAFLD. This study may suggest a potential of Life's Simple 7 in the prevention of liver disease.

Alcohol type and ideal cardiovascular health among adults of the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Light to moderate alcohol consumption is associated with favorable cardiovascular health (CVH). However, the association between alcohol type and ideal CVH has not been well-established. We examined the relationship between alcohol type and ideal CVH as measured by the American Heart Association's seven CVH metrics. METHODS: We analyzed data from 6,389 men and women aged 45-84 years from a multi-ethnic cohort free of cardiovascular disease. Alcohol type (wine, beer and liquor) was categorized as never, former, 0 but drink other alcohol types, >0 but <1 drink/day, 1-2 drinks/day and >2 drinks/day. A CVH score ranging from 0 to 14 points was created from the seven CVH metrics (Inadequate score, 0-8; average, 9-10; optimal, 11-14). We used multinomial logistic regression to examine the association between alcohol type and CVH, adjusting for age, sex, race/ethnicity, education, income, health insurance, field site and total calorie intake. RESULTS: The mean (SD) age of participants was 62 (10) years and 53 % were women. Participants who consumed 1-2 drinks/day of wine had higher odds of optimal CVH scores compared to those who never drank wine [adjusted prevalence odds ratio (POR) 1.64 (1.12-2.40)]. In comparison to participants who never drank beer, those who consumed >2 drinks/day of beer had lower odds of optimal CVH scores [0.31 (0.14-0.69)]. Additionally, those who consumed >2 drinks/day of liquor had lower odds of optimal scores compared to those who never drank liquor [0.32 (0.16-0.65)]. CONCLUSION: Moderate consumption of wine was associated with favorable CVH. However, heavy consumption of beer or liquor was associated with poorer CVH.

Femoral Artery Chronic Total Occlusion Revascularization (FACTOR) Score and Algorithm: Feasibility and Validation in a Single-Center Study of Femoropopliteal Occlusions.

OBJECTIVES: To develop and validate a hybrid algorithm to approach complex superficial femoral artery (SFA) chronic total occlusions (CTOs) in a step-wise fashion. BACKGROUND: SFA-CTO represents one of the most challenging subsets of lower-extremity peripheral arterial disease. Depending on lesion characteristics, successful percutaneous crossing of the occluded segment may prove to be very difficult. METHODS: We retrospectively evaluated all consecutive patients with SFA-CTO at our institution. The included patients had baseline Rutherford category (2-4) symptoms and were graded using the femoral artery chronic total occlusion revascularization (FACTOR) score. Multiple modalities (wire-based strategies, CTO devices, re-entry devices) were used to cross the occlusions based on the proposed FACTOR algorithm. Primary endpoint was technical success, defined as successful CTO crossing. RESULTS: A total of 150 patients (mean age, 71 years) with SFA-CTO were retrospectively reviewed to evaluate the feasibility and utility of the FACTOR score and algorithm in a single center across multiple experienced operators. Following the FACTOR algorithm, overall procedural success was achieved in 143 out of 150 patients (95%). Successful antegrade CTO crossing occurred in 59%; success rates increased to 85% when additional retrograde popliteal, tibiopedal, and direct SFA accesses were used. In multivariate analysis, retrograde wire crossing, stent placement, and atherectomy were independent predictors of successful revascularization. CONCLUSIONS: The results of our study show that utilization of the FACTOR score and algorithm can result in high rates of successful SFA-CTO revascularization.

Non-Alcoholic Fatty Liver Disease Modifies Serum Gamma-Glutamyl Transferase in Cigarette Smokers.

BACKGROUND: Serum gamma-glutamyl transferase (GGT) is a marker of oxidative stress, associated with increased cardiovascular (CV) risk. The impact of smoking on oxidative stress may be aggravated in individuals with non-alcoholic fatty liver disease (NAFLD). We aimed to ascertain the association of smoking on GGT levels in the presence or absence of NAFLD. METHODS: We evaluated 6,354 healthy subjects (43 ± 10 years, 79% males) without clinical cardiovascular disease (CVD) undergoing an employer-sponsored physical between December 2008 and December 2010. NAFLD was diagnosed by ultrasound and participants were categorized as current or non-smokers by self report. A multivariate linear regression of the cross-sectional association between smoking and GGT was conducted based on NAFLD status. RESULTS: The prevalence of NAFLD was 36% (n = 2,299) and 564 (9%) were current smokers. Smokers had significantly higher GGT levels in the presence of NAFLD (P < 0.001). After multivariable adjustment, current smoking was associated with 4.65 IU/L higher GGT level, P < 0.001, compared to non-smokers. When stratified by NAFLD, the magnitude of this association was higher in subjects with NAFLD (ß-coefficient: 11.12; 95% confidence interval (CI): 5.76 - 16.48; P < 0.001); however, no such relationship was observed in those without NAFLD (ß: -0.02; 95% CI: -3.59, 3.56; P = 0.992). Overall the interaction of NAFLD and smoking with GGT levels as markers of oxidative stress was statistically significant. CONCLUSIONS: Smoking is independently associated with significantly increased oxidative stress as measured by GGT level. This association demonstrates effect modification by NAFLD status, suggesting that smoking may intensify CV risk in individuals with NAFLD.

Benefits and Risks of Continuing Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Antagonists, and Mineralocorticoid Receptor Antagonists during Hospitalizations for Acute Heart Failure.

BACKGROUND: The renin-angiotensin-aldosterone axis plays a pivotal role in the pathophysiology of acute and chronic heart failure (HF) and represents an important target for guideline-directed medical therapy. SUMMARY: The use of appropriate directed medical therapies for inhibition of the renin-angiotensin-aldosterone axis in chronic HF has been the subject of several landmark clinical trials, with high levels of adherence exhibited in the outpatient setting. However, less clarity exists with respect to the initiation, continuation, and cessation of renin-angiotensin-aldosterone system inhibitors (RAASi) in the setting of acute HF and exacerbation of HF necessitating hospitalization. In this review, we summarize relevant aspects of the physiology of the renin-angiotensin-aldosterone axis in acute HF and during decongestion. We also summarize the available evidence for the risks and benefits of initiating and continuing RAASi in acute HF. Key Message: We offer a decision-making pathway for the use of RAASi in the setting of acute HF that would help guide the cardiologist and nephrologist caring for patients with acute HF and cardiorenal syndrome.

Outcomes of Transpedal Arterial Access Hemostasis Using a Radial Hemostatic Band.

BACKGROUND: There is increasing burden of peripheral arterial disease (PAD) in the United States. Despite advancements in endovascular therapy, there have been significant limitations in invasive interventions aimed at revascularization. The transpedal tibial artery retrograde approach has been described as an alternative access for patients with complex disease requiring dual access or failed revascularization via conventional common femoral artery access. In this study, we examined the safety and efficacy of a radial hemostatic band to achieve hemostasis post procedure without compromising the integrity of the accessed tibial artery. METHODS: This study included 20 patients with PAD requiring endovascular revascularization on whom the RadAR band device (Advanced Vascular Dynamics) was applied for postprocedure hemostasis following transpedal access between December 2011 and May 2014. All patients underwent routine postprocedure ankle-brachial indices (ABIs) following hemostasis to determine outcomes of the overall ABI and that of the accessed pedal artery. RESULTS: Mean patient age was 77 years and mean patient weight was 80.9 kg. Mean follow-up was 11 months post procedure. Lesions were located as follows: 3 popliteal, 13 superficial femoral, 3 posterior tibial, and 1 anterior tibial. Nine procedures were performed on the left leg and 11 on the right leg. All patients received heparin as anticoagulation, with a targeted activated clotting time between 250-300 seconds. Access was made into the posterior tibial in 15 patients and in the anterior tibial in 5 patients. RadAR band was deployed in a fashion similar to its deployment on the radial artery. Hemostasis was achieved in all 20 cases without complication. Postprocedure ABI and pedal-brachial index (PBI) improved significantly compared with the preprocedure values. There was an average improvement of approximately 50% in ABIs, improving from 0.59 to 0.88. The PBI also improved from 0.59 before the procedure to 0.87 post procedure. There was, however, no significant difference in ABI or PBI in anterior vs posterior tibial artery access patients. CONCLUSION: Transpedal tibial arterial access is an effective technique for revascularization in the lower extremity, and postprocedure access-vessel hemostasis and patency are reliably and safely achieved using a hemostatic band device.

Nonalcoholic Fatty Liver Disease Is Associated With Arterial Distensibility and Carotid Intima-Media Thickness: (from the Multi-Ethnic Study of Atherosclerosis).

Nonalcoholic fatty liver disease (NAFLD) is considered a potential independent risk factor for cardiovascular disease (CVD). The Multi-Ethnic Study of Atherosclerosis cohort enrolled 6,814 adults without previous CVD. We excluded 2,692 participants who had missing variables, were heavy drinkers, or history of steroid use and/or chronic liver disease. NAFLD was defined using noncontrast cardiac CT and a liver/spleen Hounsfield Unit attenuation ratio <1. Ultrasound-measured carotid arterial compliance and stiffness, was expressed as distensibility coefficient and Young's modulus. Common and internal carotid intima-media thickness (CIMT) and coronary artery calcium (CAC) >0 were used as markers of subclinical CVD. A multivariate robust linear regression and logistic regression analysis were done to evaluate the association of NAFLD and this subclinical CVD markers. Our analysis of 4,123 participants showed 55% were female with a mean age of 63 (±10) years, 39% white, 10% Chinese, 28% black, and 23% were Hispanic. The prevalence of NAFLD was 17% (n = 729). Patients with NAFLD had higher distensibility coefficient and higher CIMT. Multivariate linear regression analysis showed the presence of NAFLD was associated with both the common carotid and internal carotid IMT and logCAC. Logistic analysis showed an independent association with CAC > 0 (odds ratio [OR] 1.44 95% confidence interval [CI] 1.18, 1.75) and CIMT > 1 mm (OR 1.30 95% 1.08, 1.56). When stratified by race the association with CIMT > 1 mm was significant in whites (OR 1.37 95% 1.00, 1.90) and Hispanic (OR 1.53 95% 1.08, 2. 17) and CAC > 0 was significant in Hispanics (OR 1.52 95% 1.06, 2.19). In conclusion, NAFLD is modestly associated with carotid IMT and coronary artery calcification in a multiethnic population.

The relationship of erectile dysfunction and subclinical cardiovascular disease: A systematic review and meta-analysis.

Erectile dysfunction (ED) is associated with cardiovascular disease (CVD) and CVD mortality. However, the relationship between ED and subclinical CVD is less clear. We synthesized the available data on the association of ED and measures of subclinical CVD. We searched multiple databases for published literature on studies examining the association of ED and measures of subclinical CVD across four domains: endothelial dysfunction measured by flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), coronary artery calcification (CAC), and other measures of vascular function such as the ankle-brachial index, toe-brachial index, and pulse wave velocity. We conducted random effects meta-analysis and meta-regression on studies that examined an ED relationship with FMD (15 studies; 2025 participants) and cIMT (12 studies; 1264 participants). ED was associated with a 2.64 percentage-point reduction in FMD compared to those without ED (95% CI: -3.12, -2.15). Persons with ED also had a 0.09-mm (95% CI: 0.06, 0.12) higher cIMT than those without ED. In subgroup meta-analyses, the mean age of the study population, study quality, ED assessment questionnaire (IIEF-5 or IIEF-15), or the publication date did not significantly affect the relationship between ED and cIMT or between ED and FMD. The results for the association of ED and CAC were inconclusive. In conclusion, this study confirms an association between ED and subclinical CVD and may shed additional light on the shared mechanisms between ED and CVD, underscoring the importance of aggressive CVD risk assessment and management in persons with ED.

Life's Simple 7 and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The American Heart Association introduced the Life's Simple 7 (LS7) metrics to assess and promote cardiovascular health. We sought to examine the association between the LS7 metrics and incident heart failure (HF) in a multiethnic cohort. METHODS AND RESULTS: We analyzed data from 6506 participants of the Multi-Ethnic Study of Atherosclerosis free of cardiovascular disease at baseline. The LS7 metrics (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose) were graded on a scale of 0 to 2, with 2 indicating "ideal" status, 1 "intermediate" status, and 0 "poor" status. Points were summed, thus the LS7 score ranged from 0 to 14. Cox proportional hazard ratios and incidence rates of HF per 1000 person-years were calculated. During a median follow-up of 12.2 years, 262 (4%) participants developed HF. Incidence of HF decreased as the number of ideal LS7 metrics increased; 5.9 per 1000 person-years for participants with 0 to 1 ideal metrics and 0.6 per 1000 person-years for those with 6 to 7 ideal metrics. Compared with inadequate scores (0-8 points), hazard ratios for HF were 0.57 (0.43-0.76) and 0.31 (0.19-0.49) for average (9-10 points) and optimal (11-14 points) scores, respectively. A similar pattern was observed when the results were stratified by 4 racial/ethnic groups: white, Chinese American, black, and Hispanic. CONCLUSIONS: A lower risk of HF with more favorable LS7 status regardless of race/ethnicity suggests that efforts to achieve ideal cardiovascular health may reduce the burden of HF, a major source of morbidity and mortality.

Elevated gamma-glutamyl transferase is associated with subclinical inflammation independent of cardiometabolic risk factors in an asymptomatic population: a cross-sectional study.

BACKGROUND: Serum Gamma-Glutamyl Transferase (GGT), a marker of oxidative stress, has been suggested to be independently associated with cardiovascular disease (CVD) events. We examined the association of serum GGT levels with the burden of subclinical inflammation across a spectrum of metabolic conditions. METHODS: We evaluated 5,446 asymptomatic subjects (43 ± 10 years, 78 % males) who had an employer-sponsored physical between 2008 and 2010. Highly sensitivity C-reactive protein (hsCRP) was measured as a marker of underlying systemic inflammation. A linear regression of GGT quartiles with log transformed hsCRP and a multivariate logistic regression of GGT quartiles with elevated hsCRP (≥3 mg/L) were performed. RESULTS: Median GGT was 31 IU/l (IQR: 22-45 IU/l), 1025 (19 %) had hsCRP ≥ 3 mg/L. The median hsCRP increased with GGT quartiles (Q1: 0.9 mg/L, Q2: 1.1 mg/L, Q3: 1.4 mg/L, Q4: 1.6 mg/L, p < 0.001). Linear regression models showed GGT in the fourth quartile was associated with 0.45 mg/L (95 % CI 0.35, 0.54, p < 0.001) increase in log transformed hsCRP adjusting for risk factors. The Odds Ratio (OR) for an elevated hsCRP (≥3 mg/L) also increased with higher GGT quartiles; GGT Q2 1.44 (95 % CI 1.12, 1.85), GGT Q3 1.89 (95 % CI 1.45, 2.46), GGT Q4 2.22 (95 % CI 1.67, 2.95), compared to GGT Q1. The strength of association increased in the presence of and combination of metabolic conditions. CONCLUSION: In our cohort of asymptomatic individuals a higher serum GGT level was independently associated with increased burden of subclinical inflammation across metabolic states. These findings may explain GGT association with increased CVD risk.

Obesity Modifies the Effect of Fitness on Heart Rate Indices during Exercise Stress Testing in Asymptomatic Individuals.

OBJECTIVE: To assess the impact of aerobic fitness on exercise heart rate (HR) indices in an asymptomatic cohort across different body mass index (BMI) categories. METHODS: We performed a cross-sectional analysis of 506 working-class Brazilian subjects, free of known clinical cardiovascular disease(e.g. ischemic heart disease and stroke) who underwent an exercise stress test. RESULTS: There was a significant trend towards decreased HR at peak exercise, HR recovery and chronotropic index (CI) measures as BMI increased, but resting HR increased significantly across BMI categories. In multivariate analysis, the change in CI per unit change in metabolic equivalents of task was greater among the obese subjects than the normal-weight (2.7 vs. ­0.07; p interaction = 0.029)and overweight (2.7 vs. 0.7; p interaction = 0.044) subjects. A similar pattern was seen with peak HR and HR recovery, although the formal tests of interaction did not achieve statistical significance. CONCLUSION: Our findings strongly suggest that fitness is associated with a favorable HR profile and is modified by BMI. Intervention programs should place emphasis on fitness and not only on weight loss.

Blood pressure is associated with the presence and severity of nonalcoholic fatty liver disease across the spectrum of cardiometabolic risk.

OBJECTIVES: To determine the relationship between clinically relevant blood pressure (BP) groups and nonalcoholic fatty liver disease (NAFLD) presence and severity especially in the milieu of other metabolic risk factors. PATIENTS AND METHODS: From a Brazilian cohort of 5362 healthy middle-aged men and women who presented for yearly physical examination and testing, the cross-sectional relationship between BP categories and NAFLD was assessed. BP groups were categorized as normal, prehypertension (PHT), and hypertension (HTN) according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification. NAFLD was ultrasound diagnosed, excluding persons with alcohol consumption more than 20 g/day. NAFLD severity was estimated using the Fibrosis-4 (FIB-4) risk score. RESULTS: The prevalence of NAFLD was 36.2%. Participants with NAFLD were older (mean 46 vs. 42 years, P < 0.001) and had elevated BMI (mean 29.0 vs. 24.7 kg/m, P < 0.001). The prevalence of NAFLD among persons with normal BP, PHT, and HTN was 16.5, 37.5, and 59.3%, respectively. In multivariate analyses, PHT and HTN were associated with elevated odds of NAFLD (PHT-adjusted odds ratio 1.3, 95% confidence interval 1.1, 1.6; HTN-adjusted odds ratio 1.8, 95% confidence interval 1.4-2.3) compared with normal BP. Among nonobese hypertensive patients, BP control (BP < 140/90 mmHg) was independently associated with 40% lower odds of prevalent NAFLD. Compared with hypertensive patients, both normotensive individuals and prehypertensive patients were more likely to have a low fibrosis risk (FIB-4 ≥ 1.3). CONCLUSION: Prevalent NAFLD may be seen early in the development of hypertension, even in the absence of other metabolic risk factors. Controlling BP among nonobese hypertensive patients may be beneficial in preventing or limiting NAFLD.

Relation of physical activity to prevalence of nonalcoholic Fatty liver disease independent of cardiometabolic risk.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance and has been linked with increased cardiovascular risk. Although physical activity (PA) and lifestyle modification are often recommended in patients at cardiovascular risk, the benefit across the cardiometabolic risk spectrum is unclear. We aimed to evaluate the relation of PA and NAFLD independent of metabolic syndrome (MS) or obesity. We evaluated 5,743 healthy Brazilian subjects (43 ± 10 years, 79% men) without clinical coronary heart disease from December 2008 to December 2010. NAFLD was diagnosed using ultrasounds, and self-reported PA was assessed using the International Physical Activity Questionnaire scale. In a multivariate logistic regression adjusted for cardiometabolic risk factors, we evaluated for an independent association of NAFLD and PA. In the total study population, NAFLD prevalence was 36% (n = 2,075), obesity 23% (1,300), and MS 20% (1,152). NAFLD was more prevalent in subjects with MS (74%) than those without (26%) and in those obese (73%) than in those nonobese (25%). Overall, 1,305 (23%) subjects reported low activity, 1,990 (35%) moderate activity, and 2,448 (42%) high activity. NAFLD prevalence was lower at higher levels of reported PA (low 45%, moderate 38%, and high 30%, p <0.001). After adjusting for risk factors, subjects with high activity had lower odds of having NAFLD. The favorable association was independent of obesity or MS. In conclusion, PA presents a dose-response association with NAFLD independent of the MS or obesity. Our results are compatible with the idea that benefits of PA are relevant to everyone regardless of cardiometabolic risk.

Systematic review on noninvasive assessment of subclinical cardiovascular disease in obstructive sleep apnea: new kid on the block!

Patients with obstructive sleep apnea (OSA) have a high burden of cardiovascular disease (CVD) but a causal relationship between OSA and atherosclerotic CVD remains unclear. We systematically reviewed the literature analyzing the relationship. A review of the Medline database for studies noninvasively evaluating subclinical CVD in OSA was conducted. A total of fifty-two studies were included in this review. Across the studies the prevalence of atherosclerosis, as assessed by coronary artery calcification, carotid intima-media thickness, brachial artery flow-mediated dilation and pulse wave velocity was higher in patients with OSA and correlated with increasing severity and duration of OSA. This study shows OSA is an independent predictor of subclinical CVD as CVD is more likely to occur in patients with long standing and severe OSA. Further research is however necessary to identify specific OSA populations that would benefit from aggressive screening.

Subclinical cardiovascular disease in plaque psoriasis: association or causal link?

BACKGROUND: Psoriasis patients have a high prevalence of cardiovascular events and are thought to have a relative risk increase of 25% as compared to the general population. However, a causal relationship between psoriasis and cardiovascular disease has not been established. We sought to perform a systematic review of existing data regarding the presence of endothelial dysfunction and subclinical atherosclerosis in patients with plaque psoriasis. METHODS: A systematic literature search was performed, using Medline database and Ovid SP for relevant literature up to November 2012. Twelve studies met inclusion criteria from an initial search result of 529 articles. RESULTS: Among the twelve studies meeting inclusion criteria, two (17%) reported increased mean coronary artery calcification (CAC) in psoriatic patients. Six studies (50%) showed carotid intima-media thickness [CIMT] increase in psoriasis. Five studies (42%) examined flow mediated dilation [FMD], of which three showed decreased FMD in psoriasis patients. One study (8%) each demonstrated a decreased coronary flow reserve and increased arterial stiffness as assessed by pulse wave velocity. CONCLUSIONS: Patients with psoriasis have an increased burden of subclinical atherosclerosis and endothelial dysfunction. Patients with greater severity and/or disease duration should be targeted for primary screening for cardiovascular disease risk reduction.

Statin use is not associated with presence of and severity of nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: There is concern that statin use may exacerbate nonalcoholic fatty liver disease (NAFLD). We aimed to assess the association of statin use with NALFD and severity of liver fibrosis among NAFLD individuals. METHODS: We evaluated 6,385 cross-sectional healthy Brazilian subjects (43 ± 10 years, 79% males) without clinical coronary heart disease between November 2008 and July 2010. NAFLD was diagnosed by ultrasound. Severity of liver fibrosis was predicted by fatty liver index and FIB-4. RESULTS: NAFLD prevalence was 36% (n = 2310). Overall 552 (9%) individuals were using statins of whom 49% had NAFLD. Statin users were more likely to be men, older age, and have higher burden of risk factors (p <0.05). In age gender adjusted analysis the odds ratio for NAFLD with statin use was 0.87 (0.61-1.25, p = 0.46) in the presence of metabolic syndrome and 1.08 (0.88-1.32, p = 0.56) in its absence. On further adjustment for metabolic risk factors, LDL and smoking the results remained unchanged (OR: 0.89, 95% CI: 0.65-1.32, p = 0.56 and 0.90 (0.69-1.18, p = 0.46). There was no significant association between statin use and fatty liver index in a subanalysis of NAFLD individuals (71 ± 18 vs. 69 ± 23, p = 0.18). Although FIB-4 was mildly elevated with statin use (1.20 ± 0.51 vs. 1.02 ± 0.46, p <0.001), a multivariate analysis adjusted for age, gender and risk factors revealed statin use was not associated with severe fibrosis (FIB >1.45) (OR 0.88, 95% CI: 0.60-1.29, p = 0.50). CONCLUSIONS: The results of this study favor statin use in subjects with NAFLD as its use is not associated with the presence of NAFLD or increased fibrosis.

A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care?

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an emerging disease and a leading cause of chronic liver disease. The prevalence in the general population is approximately 15-30% and it increases to 70-90% in obese or diabetic populations. NAFLD has been linked to increased cardiovascular disease (CVD) risk. It is therefore critical to evaluate the relationship between markers of subclinical CVD and NAFLD. METHOD: An extensive search of databases; including the National Library of Medicine and other relevant databases for research articles meeting inclusion criteria: observational or cohort, studies in adult populations and clearly defined NAFLD and markers of subclinical CVD. RESULTS: Twenty-seven studies were included in the review; 16 (59%) presented the association of NAFLD and carotid intima-media thickness (CIMT), 7 (26%) the association with coronary calcification and 7 (26%) the effect on endothelial dysfunction and 6 (22%) influence on arterial stiffness. CIMT studies showed significant increases among NAFLD patients compared to controls. These were independent of traditional risk factors and metabolic syndrome. The association was similar in coronary calcification studies. The presence of NAFLD is associated with the severity of the calcification. Endothelial dysfunction and arterial stiffness showed significant independent associations with NAFLD. Two studies argued the associations were not significant; however, these studies were limited to diabetic populations. CONCLUSION: There is evidence to support the association of NAFLD with subclinical atherosclerosis independent of traditional risk factors and metabolic syndrome. However, there is need for future longitudinal studies to review this association to ascertain causality and include other ethnic populations.