Traditional Risk Factors Are More Relevant than HIV-Specific Ones for Carotid Intima-Media Thickness (cIMT) in a Brazilian Cohort of HIV-Infected Patients

BackgroundCombination antiretroviral therapy (cART) had a dramatic impact on the mortality profile in human immunodeficiency virus (HIV) infected individuals and increased their life-expectancy. Conditions associated with the aging process have been diagnosed more frequently among HIV-infected patients, particularly, cardiovascular diseases.MethodsPatients followed in the Instituto de Pesquisa Clínica Evandro Chagas (IPEC) prospective cohort in Rio de Janeiro were submitted to the general procedures from the Brazilian Longitudinal Study of Adult Health, comprising several anthropometric, laboratory and imaging data. Carotid intima-media thickness (cIMT) was measured by ultrasonography, following the Mannheim protocol. Linear regression and proportional odds models were used to compare groups and covariables in respect to cIMT. The best model was chosen with the adaptive lasso procedure.ResultsA valid cIMT exam was available for 591 patients. Median cIMT was significantly larger for men than women (0.56mm vs. 0.53mm; p = 0.002; overall = 0.54mm). In univariable linear regression analysis, both traditional risk factors for cardiovascular diseases (CVD) and HIV-specific characteristics were significantly associated with cIMT values, but the best multivariable model chosen included only traditional characteristics. Hypertension presented the strongest association with higher cIMT terciles (OR = 2.51; 95%CI = 1.69–3.73), followed by current smoking (OR = 1,82; 95%CI = 1.19–2.79), family history of acute myocardial infarction or stroke (OR = 1.60; 95%CI = 1.10–2.32) and age (OR per year = 1.12; 95%CI = 1.10–1.14).ConclusionsOur results show that traditional cardiovascular disease (CVD) risk factors are the major players in determining increased cIMT among HIV infected patients in Brazil. This finding reinforces the need for thorough assessment of those risk factors in these patients to guarantee the incidence of CVD events remain under control.     

The Development of the Pediatric NAFLD Fibrosis Score (PNFS) to Predict the Presence of Advanced Fibrosis in Children with Nonalcoholic Fatty Liver Disease

Background

Noninvasive hepatic fibrosis scores that predict the presence of advanced fibrosis have been developed and validated in adult patients with NAFLD. The aims of our study were to assess the utility of commonly used adult fibrosis scores in pediatric NAFLD and to develop a pediatric specific fibrosis score that can predict advanced fibrosis.

Methods

Consecutive children with biopsy-proven NAFLD were included. Fibrosis was determined by an experienced pathologist (F0–4). Advanced fibrosis was defined as fibrosis stage ≥3. The following adult fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio index (APRI), NAFLD fibrosis score (NFS), and FIB-4 Index. Multivariable logistic regression analysis was performed to build a new pediatric model for predicting advanced fibrosis.

Results

Our cohort consisted of 242 children with a mean age of 12.4±3.1 years and 63% were female. 36 (15%) subjects had advanced fibrosis. APRI and FIB-4 were higher in patients with advanced fibrosis compared to those with fibrosis stage 0–2; however, AST/ALT ratio and NFS were not different between the two groups. We used our data to develop a new model to predict advanced fibrosis which included: ALT, alkaline phosphatase, platelet counts and GGT. The multivariable logistic regression model (z) was defined as follows: z = 1.1+(0.34*sqrt(ALT))+(0.002*alkaline phosphatase) – (1.1*log(platelets) – (0.02*GGT). This value was then converted into a probability distribution (p) with a value between 0 to 100 by the following formula: p = 100×exp(z)/[1+exp(z)]. The AUCROC for this model was 0.74 (95% CI: 0.66, 0.82). This was found to be significantly better than APRI, NAFLD Fibrosis Score and FIB-4 Index.

Conclusion

Noninvasive hepatic fibrosis scores developed in adults had poor performance in diagnosing advanced fibrosis in children with NAFLD. We developed a new pediatric NAFLD fibrosis score with improved performance characteristics.     

Non-Alcoholic Fatty Liver Disease as a Predictor of Atrial Fibrillation in Middle-Aged Population (OPERA Study)

Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are widespread diseases and have multiple common risk factors and comorbidities. No studies of association between ultrasonography-diagnosed NAFLD and AF exist in other than diabetic population. The goal of this prospective study was to study the value of NAFLD as a predictor of atrial fibrillation. This study had 958 subjects from the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort, and the mean follow-up time was 16.3 years. NAFLD was diagnosed if the subject had fatty liver in ultrasonography and no excess alcohol intake. AF was followed in the National Registers. In this study 249 subjects (26.0%) had NAFLD and 37 (14.9%) of these had AF whereas only 56 (7.9%) of those without NAFLD experienced AF during the follow-up time (p = 0.001). In the multiple Cox regression analysis including potential confounders (age, sex, study group, diabetes, body mass index (BMI), waist circumference, alcohol consumption, smoking, serum alanine aminotransferase concentration (ALT), systolic blood pressure, quick index, left ventricular mass index, left atrial diameter, coronary artery disease (CAD), atrial natriuretic peptide (ANP) and high sensitive C-reactive protein (hs-CRP)), NAFLD remained as an independent predictor of AF (Adjusted OR, 1.88 (95% Confidence interval (CI) 1.03–3.45)). In conclusion, our data shows that NAFLD is independently associated with the risk of AF.     

Association of Cardiovascular Risk Factors with Carotid Intima Media Thickness in Patients with Rheumatoid Arthritis with Low Disease Activity Compared to Controls: A Cross-Sectional Study

ObjectivesRheumatoid arthritis (RA) has been identified as an independent cardiovascular risk factor. The importance of risk factors such as hypertension and hyperlipidemia in the generation of atherosclerosis in RA patients is unclear. This study analyzed clinical parameters associated with carotid intima media thickness (cIMT) in patients with RA.MethodsSubjects with RA and healthy controls without RA, both without known cardiovascular disease, were included. Participants underwent a standard physical examination and laboratory measurements including a lipid profile. cIMT was measured semi-automatically by ultrasound.ResultsIn total 243 RA patients and 117 controls were included. The median RA disease duration was 7 years (IQR 2–14 years). The median DAS28 was 2.4 (IQR 1.6–3.2) and 114 (50.4%) of the RA patients were in remission. The presence of RA and cIMT were not associated (univariate analysis). Multivariable regression analysis showed that cIMT in RA patients was associated with age (B = 0.006, P<0.001) and systolic blood pressure (B = 0.003, P = 0.003). In controls, cIMT was associated with age (B = 0.006, P<0.001) and smoking (B = 0.097, P = 0.001).ConclusioncIMT values were similar between RA patients and controls. Hypertension was strongly associated with cIMT in RA patients. After adjustment, no association between cIMT and specific RA disease characteristics was found in this well treated RA cohort.     

HDL Size is More Accurate than HDL Cholesterol to Predict Carotid Subclinical Atherosclerosis in Individuals Classified as Low Cardiovascular Risk

Background

Misclassification of patients as low cardiovascular risk (LCR) remains a major concern and challenges the efficacy of traditional risk markers. Due to its strong association with cholesterol acceptor capacity, high-density lipoprotein (HDL) size has been appointed as a potential risk marker. Hence, we investigate whether HDL size improves the predictive value of HDL-cholesterol in the identification of carotid atherosclerotic burden in individuals stratified to be at LCR.

Methods and Findings

284 individuals (40–75 years) classified as LCR by the current US guidelines were selected in a three-step procedure from primary care centers of the cities of Campinas and Americana, SP, Brazil. Apolipoprotein B-containing lipoproteins were precipitated by polyethylene glycol and HDL size was measured by dynamic light scattering (DLS) technique. Participants were classified in tertiles of HDL size (<7.57; 7.57–8.22; >8.22 nm). Carotid intima-media thickness (cIMT) <0.90 mm (80^th percentile) was determined by high resolution ultrasonography and multivariate ordinal regression models were used to assess the association between cIMT across HDL size and levels of lipid parameters. HDL-cholesterol was not associated with cIMT. In contrast, HDL size >8.22 nm was independently associated with low cIMT in either unadjusted and adjusted models for age, gender and Homeostasis Model Assessment 2 index for insulin sensitivity, ethnicity and body mass index (Odds ratio 0.23; 95% confidence interval 0.07–0.74, p = 0.013).

Conclusion

The mean HDL size estimated with DLS constitutes a better predictor for subclinical carotid atherosclerosis than the conventional measurements of plasma HDL-cholesterol in individuals classified as LCR.     

Association of Non-alcoholic Fatty Liver Disease with Chronic Kidney Disease: A Systematic Review and Meta-analysis

Background

Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.

Methods and Findings

English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69–2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65–1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58–4.05) and incidence (HR 2.12, 95% CI 1.42–3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14–8.61) and incidence (HR 3.29, 95% CI 2.30–4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies.

Conclusion

The presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors'' Summary     

High Dietary Sodium Intake Assessed by Estimated 24-h Urinary Sodium Excretion Is Associated with NAFLD and Hepatic Fibrosis

Background

Although high sodium intake is associated with obesity and hypertension, few studies have investigated the relationship between sodium intake and non-alcoholic fatty liver disease (NAFLD). We evaluated the association between sodium intake assessed by estimated 24-h urinary sodium excretion and NAFLD in healthy Koreans.

Methods

We analyzed data from 27,433 participants in the Korea National Health and Nutrition Examination Surveys (2008–2010). The total amount of sodium excretion in 24-h urine was estimated using Tanaka’s equations from spot urine specimens. Subjects were defined as having NAFLD when they had high scores in previously validated NAFLD prediction models such as the hepatic steatosis index (HSI) and fatty liver index (FLI). BARD scores and FIB-4 were used to define advanced fibrosis in subjects with NAFLD.

Results

The participants were classified into three groups according to estimated 24-h urinary excretion tertiles. The prevalence of NAFLD as assessed by both FLI and HSI was significantly higher in the highest estimated 24-h urinary sodium excretion tertile group. Even after adjustment for confounding factors including body fat and hypertension, the association between higher estimated 24-h urinary sodium excretion and NAFLD remained significant (Odds ratios (OR) 1.39, 95% confidence interval (CI) 1.26–1.55, in HSI; OR 1.75, CI 1.39–2.20, in FLI, both P < 0.001). Further, subjects with hepatic fibrosis as assessed by BARD score and FIB-4 in NAFLD patients had higher estimated 24-h urinary sodium values.

Conclusions

High sodium intake was independently associated with an increased risk of NAFLD and advanced liver fibrosis.     

Cost-Effectiveness Analysis: Risk Stratification of Nonalcoholic Fatty Liver Disease (NAFLD) by the Primary Care Physician Using the NAFLD Fibrosis Score

Background

The complications of Nonalcoholic Fatty Liver Disease (NAFLD) are dependent on the presence of advanced fibrosis. Given the high prevalence of NAFLD in the US, the optimal evaluation of NAFLD likely involves triage by a primary care physician (PCP) with advanced disease managed by gastroenterologists.

Methods

We compared the cost-effectiveness of fibrosis risk-assessment strategies in a cohort of 10,000 simulated American patients with NAFLD performed in either PCP or referral clinics using a decision analytical microsimulation state-transition model. The strategies included use of vibration-controlled transient elastography (VCTE), the NAFLD fibrosis score (NFS), combination testing with NFS and VCTE, and liver biopsy (usual care by a specialist only). NFS and VCTE performance was obtained from a prospective cohort of 164 patients with NAFLD. Outcomes included cost per quality adjusted life year (QALY) and correct classification of fibrosis.

Results

Risk-stratification by the PCP using the NFS alone costs $5,985 per QALY while usual care costs $7,229/QALY. In the microsimulation, at a willingness-to-pay threshold of $100,000, the NFS alone in PCP clinic was the most cost-effective strategy in 94.2% of samples, followed by combination NFS/VCTE in the PCP clinic (5.6%) and usual care in 0.2%. The NFS based strategies yield the best biopsy-correct classification ratios (3.5) while the NFS/VCTE and usual care strategies yield more correct-classifications of advanced fibrosis at the cost of 3 and 37 additional biopsies per classification.

Conclusion

Risk-stratification of patients with NAFLD primary care clinic is a cost-effective strategy that should be formally explored in clinical practice.     

The Impact of PNPLA3 rs738409 Genetic Polymorphism and Weight Gain ≥10 kg after Age 20 on Non-Alcoholic Fatty Liver Disease in Non-Obese Japanese Individuals

Non-alcoholic fatty liver disease (NAFLD) in non-obese individuals is inadequately elucidated. We aim to investigate the impact of known genetic polymorphisms on NAFLD and the interaction between genetic risks and weight gain on NAFLD in obese and non-obese Japanese individuals. A total of 1164 participants who received health checkups were included. Participants with excessive alcohol consumption, with viral hepatitis or other inappropriate cases were excluded. Fatty liver was diagnosed by ultrasonography. Participants with a body mass index (BMI) of <18.5 kg/m², 18.5–22.9 kg/m², 23.0–24.9 kg/m² and ≥25 kg/m² were classified underweight, normal weight, overweight and obese, respectively. Self-administered questionnaire for lifestyle was assessed and a total of 8 previously reported genetic polymorphisms were chosen and examined. In all, 824 subjects were enrolled. The overall prevalence of NAFLD was 33.0%: 0% in underweight, 15.3% in normal weight, 41.1% in overweight and 71.7% in obese individuals. The prevalence of NAFLD is more affected by the G allele of patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 in normal weight (odds ratio (OR) 3.52; 95%-CI: 1.42–8.71; P = 0.0063) and in overweight individuals (OR 2.60; 95%-CI: 1.14–5.91; P = 0.0225) than in obese individuals (not significant). Moreover, the G allele of PNPLA3 rs738409 and weight gain ≥10 kg after age 20 had a joint effect on the risk of NAFLD in the normal weight (OR 12.00; 95% CI: 3.71–38.79; P = 3.3×10⁻⁵) and the overweight individuals (OR 13.40; 95% CI: 2.92–61.36; P = 0.0008). The G allele of PNPLA3 rs738409 is a prominent risk factor for NAFLD and the interaction between the PNPLA3 rs738409 and weight gain ≥10 kg after age 20 plays a crucial role in the pathogenesis of NAFLD, especially in non-obese Japanese individuals.     

Serum γ-glutamyl Transferase Levels,Insulin Resistance and Liver Fibrosis in Patients with Chronic Liver Diseases

Background and Aims

Serum levels of γ-glutamyl-transpeptidase(γ-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis.

Methods

843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum γ-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of γ-GT.

Results

By multivariate logistic regression analysis, abnormal γ-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120–6.564,p = 0.02), G1CHC (OR3.461,CI2.138–5.603,p<0.001) and CHB (OR2.778,CI1.042–7.414,p = 0.04), together with IR and liver necroinflammation, and with a negative predictive value>80%. Interestingly, among patients with high or normal γ-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal γ-GT values only (OR4.150,CI1.079–15.970,p = 0.03 for NAFLD; OR2.250,CI1.211–4.181,p = 0.01 for G1CHC; OR3.096,CI2.050–34.220,p = 0.01 for CHB).

Conclusions

In patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal γ-GT values, without differences according to liver disease etiology, and suggesting a role of γ-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and pharmacologic management of patients with CLD.     

Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

Background/Aims

We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes.

Methods

Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defined as a focal thickening >1.3 mm.

Results

Prevalence of high OSA risk was similar in patients refusing or accepting PG (76% vs 68%, p = 0.17). Among those accepting PG, overall OSA prevalence was significantly higher in patients with F2-F4 fibrosis compared to those without (72% vs 44%; p = 0.04). Significant fibrosis was independently associated with mean nocturnal oxygen saturation (SaO₂)<95% (OR 3.21, 95%C.I. 1.02–7.34; p = 0.04). Prevalence of OSA tended to be higher in patients with, than in those without, carotid plaques (64% vs 40%; p = 0.08). Carotid plaques were independently associated with %time at SaO2<90% >1 (OR 6.30, 95%C.I. 1.02–12.3; p = 0.01).

Conclusions

In NAFLD patients with chronically elevated ALT at low prevalence of morbid obesity, OSA was highly prevalent and indexes of SaO₂ resulted independently associated with severity of liver fibrosis and carotid atherosclerosis. These data suggest to consider sleep disordered breathing as a potential additional therapeutic target in severe NAFLD patients.     

Cardiovascular Risk Factor Profiles for Peripheral Artery Disease and Carotid Atherosclerosis among Chinese Older People: A Population-Based Study

Objectives

Epidemiological data concerning atherosclerotic disease among older people in rural China are sparse. We seek to determine prevalence and cardiovascular risk factor profiles for peripheral artery disease (PAD) and carotid atherosclerosis (CAS) among Chinese older people living in a rural community.

Methods

This cross-sectional study included 1499 participants (age ≥60 years, 59.0% women) of the Confucius Hometown Aging Project in Shandong, China. From June 2010–July 2011, data were collected through interviews, clinical examinations, and laboratory tests. PAD was defined as an ankle-brachial index ≤0.9. Carotid intima-media thickness (cIMT) and carotid artery stenosis were assessed by ultrasonography. We defined moderate stenosis as carotid stenosis ≥50%, and severe stenosis as carotid stenosis ≥70%. cIMT≥1.81 mm was considered as an increased cIMT (a measure of CAS). Data were analyzed with multiple logistic models.

Results

The prevalence was 5.7% for PAD, 8.9% for moderate stenosis, 1.8% for severe stenosis, and 11.2% for increased cIMT. After controlling for multiple potential confounders, diabetes, an increased low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, and hypertension were significantly or marginally associated with PAD. Ever smoking, hypertension, and an increased LDL-C/HDL-C ratio were significantly associated with an increased likelihood of increased cIMT. An increasing number of those cardiovascular risk factors were significantly associated with an increasing odds ratio of PAD and increased cIMT, respectively (p for linear trend <0.001).

Conclusion

Among Chinese older people living in a rural community, PAD, carotid artery stenosis, and an increased cIMT are relatively uncommon. Cardiovascular risk factor profiles for PAD and CAS are slightly different, with hypertension and an increased LDL-C/HDL-C ratio being associated with an increased likelihood of both PAD and increased cIMT.     

Risk of Obstructive Sleep Apnea with Daytime Sleepiness Is Associated with Liver Damage in Non-Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease

Background

A high prevalence of obstructive sleep apnea syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), but few studies have evaluated OSAS in non-morbidly obese NAFLD patients.

Aims

To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage.

Methods

We considered 159 consecutive patients with histological NAFLD and body mass index (BMI) <35 Kg/m², and 80 controls without ultrasonographic steatosis matched for age, sex, and BMI. OSAS risk was determined by positivity for Berlin questionnaire (BQ), and daytime sleepiness by the Sleepness Epworth Scale (ESS). Liver damage was evaluated according to the NAFLD activity score.

Results

In NAFLD patients, BQ alone was positive in 39 (25%), ESS in 8 (5%), and both in 13 (8%, OSAS with sleepines); p = ns vs. controls without steatosis. In NAFLD patients at risk for OSAS with (but not in those without) sleepiness, we observed a higher prevalence of nonalcoholic steatohepatitis (NASH; 11/13, 85% vs. 72/146, 49%; p = 0.018), and of clinically significant fibrosis (stage>1; 9/13, 69% vs. 39/146, 27%; p = 0.003). At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7–51, p = 0.005 and OR 14.0, 95% c.i. 3.5–70, p = 0.0002, respectively).

Conclusions

A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.     

Gender Differences in the Association of Smoking and Drinking with the Development of Cognitive Impairment

Modifiable lifestyle-related factors such as smoking and alcohol drinking are associated with cognitive impairment in the elderly population but the relationships have shown various results. To evaluate the relationship of alcohol drinking and smoking in the early 60 s with the risk of developing incident cognitive impairment. In 1999, we evaluated cognitive function, smoking, and drinking status in 3,174 inhabitants aged 60–64 years in a rural area of Korea, with a follow-up assessment of cognitive function 7 years later. A total of 1,810 individuals who did not show cognitive impairment at baseline were included. A stratified analysis was applied to evaluate how smoking and alcohol drinking affected the risk of developing cognitive impairment based on gender. Current smokers showed a higher risk for developing cognitive impairment than did never smokers (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.09–2.15). The OR for female current smokers compared with never smokers was 1.62 (95% CI, 1.05–2.52), and smokers with higher pack-years were more likely to develop cognitive impairment than never smokers, showing a dose–response relationship (P for trend = 0.004). Frequent alcohol consumption increased the risk of developing cognitive impairment (OR, 1.68; 95% CI, 1.01–2.78), and a dose–response relationship was observed among male subjects (P for trend = 0.044). Infrequent drinking in females decreased the odds of developing cognitive impairment (OR, 0.67; 95% CI, 0.42–1.00), whereas frequent drinking tended to increase the odds, although this trend was not significant, suggesting a U-shaped relationship. Although the sample was small for some analyses, especially in female, our data suggest that smoking and drinking in the early 60 s are associated with a risk of developing cognitive impairment, and this relationship is characterized by gender differences.     

Epidemiology of Severe Acute Respiratory Illness (SARI) among Adults and Children Aged ≥5 Years in a High HIV-Prevalence Setting, 2009–2012

ObjectiveThere are few published studies describing severe acute respiratory illness (SARI) epidemiology amongst older children and adults from high HIV-prevalence settings. We aimed to describe SARI epidemiology amongst individuals aged ≥5 years in South Africa.MethodsWe conducted prospective surveillance for individuals with SARI from 2009–2012. Using polymerase chain reaction, respiratory samples were tested for ten viruses, and blood for pneumococcal DNA. Cumulative annual SARI incidence was estimated at one site with population denominators.FindingsWe enrolled 7193 individuals, 9% (621/7067) tested positive for influenza and 9% (600/6519) for pneumococcus. HIV-prevalence was 74% (4663/6334). Among HIV-infected individuals with available data, 41% of 2629 were receiving antiretroviral therapy (ART). The annual SARI hospitalisation incidence ranged from 325-617/100,000 population. HIV-infected individuals experienced a 13–19 times greater SARI incidence than HIV-uninfected individuals (p<0.001). On multivariable analysis, compared to HIV-uninfected individuals, HIV-infected individuals were more likely to be receiving tuberculosis treatment (odds ratio (OR):1.7; 95%CI:1.1–2.7), have pneumococcal infection (OR 2.4; 95%CI:1.7–3.3) be hospitalised for >7 days rather than <2 days (OR1.7; 95%CI:1.2–2.2) and had a higher case-fatality ratio (8% vs 5%;OR1.7; 95%CI:1.2–2.3), but were less likely to be infected with influenza (OR 0.6; 95%CI:0.5–0.8). On multivariable analysis, independent risk indicators associated with death included HIV infection (OR 1.8;95%CI:1.3–2.4), increasing age-group, receiving mechanical ventilation (OR 6.5; 95%CI:1.3–32.0) and supplemental-oxygen therapy (OR 2.6; 95%CI:2.1–3.2).ConclusionThe burden of hospitalized SARI amongst individuals aged ≥5 years is high in South Africa. HIV-infected individuals are the most important risk group for SARI hospitalization and mortality in this setting.     

Waterpipe Tobacco Smoking and Gastric Cancer Risk among Vietnamese Men

BackgroundThe association of waterpipe tobacco (WPT) smoking with gastric cancer (GC) risk was suggested.MethodsA hospital-based case-control study was conducted to examine the association of WPT with GC risk among Vietnamese men, in Hanoi city, during the period of 2003–2011. Newly-diagnosed GC cases (n = 454) and control patients (n = 628) were matched by age (+/- 5 years) and the year of hospitalization. Information on smoking and alcohol drinking habits and diet including salty food intake and fruits/vegetables consumption were obtained by the interview. Maximum likelihood estimates of odds ratios (ORs) and corresponding 95% confidence intervals (Cis) were obtained using conditional logistic regression models.ResultsThe group with the highest consumption of citrus fruits showed a significantly low GC risk (OR = 0.6, 95%CI = 0.4–0.8, P for trend = 0.002). However, there was no association of raw vegetable consumption with GC risk. Referring to never smokers, GC risk was significantly higher in current WPT smokers (OR = 1.8, 95%CI = 1.3–2.4), and it was more evident in exclusively WPT smokers (OR = 2.7, 95%CI = 1.2–6.5). GC risk tended to be higher with daily frequency and longer duration of WPT smoking but these trends were not statistically significant (P for trend: 0.144 and 0.154, respectively). GC risk of those who started smoking WPT before the age of 25 was also significantly high (OR = 3.7, 95%CI = 1.2–11.3). Neither cigarette smoking nor alcohol drinking was related to GC risk.ConclusionThe present findings revealed that WPT smoking was positively associated with GC risk in Vietnamese men.     

Fatty liver: Role of inflammation and fatty acid nutrition

Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver damage, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. NAFLD is strongly associated with insulin resistance and is defined by accumulation of liver fat >5% per liver weight in the presence of <10 g of daily alcohol consumption. The exact prevalence of NAFLD is uncertain because of the absence of simple noninvasive diagnostic tests to facilitate an estimate of prevalence but in subgroups of people such as those with type 2 diabetes, the prevalence may be as high as 70%. NASH is an important subgroup within the spectrum of NAFLD that progresses over time with worsening fibrosis and cirrhosis, and NASH is associated with increased risk for cardiovascular disease. It is, therefore, important to understand the pathogenesis of NASH specifically, to develop strategies for interventions to treat this condition. The purpose of this review is to discuss the roles of inflammation, fatty acids and fatty acids in nutrition, in the pathogenesis and potential treatment of NAFLD.     

Increased Risk of Sudden Cardiac Arrest in Obstructive Pulmonary Disease: A Case-Control Study

Background

We aimed to determine whether (1) patients with obstructive pulmonary disease (OPD) have an increased risk of sudden cardiac arrest (SCA) due to ventricular tachycardia or fibrillation (VT/VF), and (2) the SCA risk is mediated by cardiovascular risk-profile and/or respiratory drug use.

Methods

A community-based case-control study was performed, with 1310 cases of SCA of the ARREST study and 5793 age, sex and SCA-date matched non-SCA controls from the PHARMO database. Only incident SCA cases, age older than 40 years, that resulted from unequivocal cardiac causes with electrocardiographic documentation of VT/VF were included. Conditional logistic regression analysis was used to assess the association between SCA and OPD. Pre-specified subgroup analyses were performed regarding age, sex, cardiovascular risk-profile, disease severity, and current use of respiratory drugs.

Results

A higher risk of SCA was observed in patients with OPD (n = 190 cases [15%], 622 controls [11%]) than in those without OPD (OR adjusted for cardiovascular risk-profile 1.4 [1.2–1.6]). In OPD patients with a high cardiovascular risk-profile (OR 3.5 [2.7–4.4]) a higher risk of SCA was observed than in those with a low cardiovascular risk-profile (OR 1.3 [0.9–1.9]) The observed SCA risk was highest among OPD patients who received short-acting β2-adrenoreceptor agonists (SABA) or anticholinergics (AC) at the time of SCA (SABA OR: 3.9 [1.7–8.8], AC OR: 2.7 [1.5–4.8] compared to those without OPD).

Conclusions

OPD is associated with an increased observed risk of SCA. The most increased risk was observed in patients with a high cardiovascular risk-profile, and in those who received SABA and, possibly, those who received AC at the time of SCA.     

Regular Exercise Is Associated with a Reduction in the Risk of NAFLD and Decreased Liver Enzymes in Individuals with NAFLD Independent of Obesity in Korean Adults

Background

We evaluated the association of regular physical exercise with the presence of non-alcoholic fatty liver disease (NAFLD) and liver enzymes in relation to obesity and insulin resistance.

Methodology/Principal Findings

A cross-sectional analysis was conducted in 72,359 healthy Korean adults without diabetes who participated in a comprehensive health check-up. Subjects who have been exercising regularly (more than 3 times per week, at least for 30 minutes each time and for consecutive 3 month) were categorized into exercise group. All subjects were categorized into deciles based on their body mass index (BMI) and we estimated the odds ratios (ORs) for having NAFLD according to exercise regularity in each decile. The diagnosis of NAFLD was based on ultrasonography findings. Individuals with NAFLD (n = 19,921) were analyzed separately to evaluate ORs for having elevated liver enzymes based on regularity of exercise. The risk for NAFLD was significantly reduced in exercise group with age- and sex-adjusted ORs of 0.53–0.72 for all BMI deciles except at BMI categories of <19.6 and 20.7–21.6 kg/m². While no difference was seen in BMI between subjects in exercise and non-exercise group across the BMI deciles, the values of body fat percentage and metabolic risk factors differed. Among NAFLD patients, subjects in exercise group had a lower risk for having elevated liver enzymes with multivariable adjusted OR of 0.85 (95% CI 0.74–0.99, for AST) and 0.74 (95% CI 0.67–0.81, for ALT) than did subjects in non-exercise group.

Conclusions/Significance

Regular exercise was associated with a reduced risk for having NAFLD and decreased liver enzymes in patients with NAFLD, and this relationship was also independent of obesity.     

Use of Non-Invasive Parameters of Non-Alcoholic Steatohepatitis and Liver Fibrosis in Daily Practice - An Exploratory Case-Control Study

Background

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of a metabolic syndrome. To date, liver biopsy has been the gold standard used to differentiate between simple steatosis and steatohepatitis/fibrosis. Our aim was to compare the relevance of serum non-invasive parameters and scoring systems in the staging of liver fibrosis and non-alcoholic steatohepatitis (NASH) in patients with NAFLD.

Methods and Findings

A total of 112 consecutive patients diagnosed with NAFLD were included. A liver biopsy was performed on 56 patients. The Kleiner score was used for the staging and grading of the histology. Non-invasive parameters for fibrosis (hyaluronic acid; AST/ALT; fibrosis scoring indexes OELF, ELF, BARD score, APRI, NAFLD fibrosis score); and inflammation (M30 and M65 cytokeratin-18 fragments) were measured and calculated. The same analyses were performed in 56 patients diagnosed with NAFLD, who were not indicated for liver biopsy. Based on the liver histology, NASH was diagnosed in 38 patients; simple steatosis in 18 patients. A cut-off value of 750 U/L of serum M65 discriminated patients with and without NASH with a 80% sensitivity and 82% specificity (95% CI:57–95). Fibrosis stage F0–F2 was present in 39 patients; F3–F4 in 17 patients. Serum concentrations of hyaluronic acid were higher in patients with advanced fibrosis (p<0.01); a cut-off value of 25 µg/l discriminated patients with F3–F4 with a 90% sensitivity and 84% specificity from those with F0–F2 (95% CI:59–99). When applying the non-invasive criteria to those patients without a liver biopsy, NASH could only be diagnosed in 16%; however, advanced fibrosis could be diagnosed in 35% of them.

Conclusions

In patients with NAFLD, non-invasive serum parameters with a high accuracy can differentiate those patients with NASH and/or advanced fibrosis from those with simple steatosis. A substantial portion of those patients not indicated for liver biopsy might have undiagnosed advanced fibrosis.