Coronary Atherosclerosis Across the Glycemic Spectrum Among Asymptomatic Adults: The Miami Heart Study at Baptist Health South Florida.

BACKGROUND: The contemporary burden and characteristics of coronary atherosclerosis, assessed using coronary computed tomography angiography (CCTA), is unknown among asymptomatic adults with diabetes and prediabetes in the United States. The pooled cohort equations and coronary artery calcium (CAC) score stratify atherosclerotic cardiovascular disease risk, but their association with CCTA findings across glycemic categories is not well established. METHODS: Asymptomatic adults without atherosclerotic cardiovascular disease enrolled in the Miami Heart Study were included. Participants underwent CAC and CCTA testing and were classified into glycemic categories. Prevalence of coronary atherosclerosis (any plaque, noncalcified plaque, plaque with ≥1 high-risk feature, maximal stenosis ≥50%) assessed by CCTA was described across glycemic categories and further stratified by pooled cohort equations-estimated atherosclerotic cardiovascular disease risk and CAC score. Adjusted logistic regression was used to evaluate the associations between glycemic categories and coronary outcomes. RESULTS: Among 2352 participants (49.5% women), the prevalence of euglycemia, prediabetes, and diabetes was 63%, 30%, and 7%, respectively. Coronary plaque was more commonly present across worsening glycemic categories (euglycemia, 43%; prediabetes, 58%; diabetes, 69%), and similar pattern was observed for other coronary outcomes. In adjusted analyses, compared with euglycemia, prediabetes and diabetes were each associated with higher odds of any coronary plaque (OR, 1.30 [95% CI, 1.05-1.60] and 1.75 [1.17-2.61], respectively), noncalcified plaque (OR, 1.47 [1.19-1.81] and 1.99 [1.38-2.87], respectively), and plaque with ≥1 high-risk feature (OR, 1.65 [1.14-2.39] and 2.53 [1.48-4.33], respectively). Diabetes was associated with stenosis ≥50% (OR, 3.01 [1.79-5.08]; reference=euglycemia). Among participants with diabetes and estimated atherosclerotic cardiovascular disease risk <5%, 46% had coronary plaque and 10% had stenosis ≥50%. Among participants with diabetes and CAC=0, 30% had coronary plaque and 3% had stenosis ≥50%. CONCLUSIONS: Among asymptomatic adults, worse glycemic status is associated with higher prevalence and extent of coronary atherosclerosis, high-risk plaque, and stenosis. In diabetes, CAC was more closely associated with CCTA findings and informative in a larger population than the pooled cohort equations.

Atherosclerotic plaque in individuals without known cardiovascular disease but with established obstructive sleep apnea and at high risk of obstructive sleep apnea.

Objectives: In a large U.S. cohort free of CVD evaluated by coronary computed CT angiography, we aimed to assess the association between established / high risk of Obstructive Sleep Apnea (OSA) and coronary plaque. Background: There are limited data available depicting the association between established / high risk of OSA and the presence of coronary plaque in a population-based sample free from CVD. Methods: Cross-sectional data from 2359 participants enrolled in the Miami Heart Study (MiHeart) who underwent coronary CT angiography was used for this study. The Berlin questionnaire was used to stratify patients as having high or low risk of OSA. Multiple multivariable logistic regression analyses were conducted to investigate the association between the risk of developing OSA with the presence, volume, and composition of plaque. Results: According to the Berlin questionnaire, 1559 participants were (66.1%) at low risk of OSA and 800 patients (33.9%) with established / high risk of OSA. Plaque characterization on CCTA revealed a greater incidence of any possible plaque composition in the established / high risk of OSA category (59.6% vs. 43.5%) compared to the low risk of OSA cohort. In logistic regression models, after adjusting for demographics and cardiovascular risk factors, a significant association could still be noted between established / high risk of OSA and any coronary plaque on CCTA (OR=1.31, CI 1.05, 1.63, p = 0.016). Subgroup analysis in the Hispanic population also portrayed a significant association between established / high risk of OSA and the presence of coronary plaque on CCTA (OR = 1.55 CI 1.13, 2.12, p = 0.007). Conclusion: After accounting for CVD risk factors, individuals at established / high risk of OSA have a higher likelihood of the presence of coronary plaque. Future studies should focus on OSA presence or risk, OSA severity, and the longitudinal consequences of coronary atherosclerosis.

The association of sex-specific hormones with coronary artery plaque characteristics from Miami Heart (MiHeart) study.

Objective: The association of sex-specific hormones with coronary computed tomography angiography(CCTA)-based plaque characteristics in women without cardiovascular disease is not well understood. We investigated the association of sex-specific hormones with coronary artery plaque characteristics in a contemporary multiracial cohort with no clinical coronary artery disease (CAD). Methods: In this cross-sectional analysis, we utilized data from 2,325 individuals with no clinical CAD from the Miami Heart (MiHeart) study. Multivariable logistic regression models were used to investigate the association of sex hormones: sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), free and total testosterone, estradiol, with plaque characteristics among women and men. Results: Of the 1,155 women, 34.2% had any plaque and 3.4% had any high-risk plaque features (HRP) while among men (n = 1170), 63.1% had any plaque and 10.4% had HRP. Among women, estradiol and SHBG were associated with lower odds of any plaque after adjusting for age and race-ethnicity (estradiol OR per SD increase: 0.87, 95%CI: 0.76-0.98; SHBG OR per SD increase: 0.82, 95%CI: 0.72-0.93) but the significance did not persist after adjustment of cardiovascular risk factors. High free testosterone was associated with higher odds of HRP (aOR:3.48, 95%CI:1.07-11.26) but null associations for the other sex hormones with HRP, in the context of limited sample size. Among men, there were no significant associations between sex-specific hormones and plaque or HRP. Conclusion: Among young to middle-aged women with no clinical CAD, increasing estradiol and SHBG were associated with lower odds of any plaque and higher free testosterone was associated with HRP. Larger cohorts may be needed to validate this.

REsCue trial: Randomized controlled clinical trial with extended-release calcifediol in symptomatic COVID-19 outpatients.

OBJECTIVES: This double-blind randomized controlled trial investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in patients with mild to moderate COVID-19. METHODS: COVID-19 outpatients received oral ERC (300 mcg on days 1-3 and 60 mcg on days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily. Primary end points were raising 25D to ≥50 ng/mL and decreasing resolution time for five aggregated symptoms (three respiratory). RESULTS: In all, 171 patients were randomized, 160 treated and 134 (65 ERC, 69 placebo) retained. The average age was 43 y (range 18-71), 59% were women. The mean baseline 25D was 37 ± 1 (SE) ng/mL. In the full analysis set (FAS), 81% of patients in the ERC group achieved 25D levels of ≥50 ng/mL versus 15% in the placebo group (P < 0.0001). In the per-protocol (PP) population, mean 25D increased with ERC to 82 ± 4 (SE) ng/mL (P < 0.0001) by day 7; the placebo group trended lower. Symptom resolution time was unchanged in the FAS by ERC (hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.695-1.390; P = 0.922). In the PP population, respiratory symptoms resolved 4 d faster when 25D was elevated above baseline level at both days 7 and 14 (median 6.5 versus 10.5 d; HR, 1.372; 95% CI, 0.945-1.991; P = 0.0962; Wilcoxon P = 0.0386). Symptoms resolved in both treatment groups to a similar extent by study end. Safety concerns including hypercalcemia were absent with ERC treatment. CONCLUSION: ERC safely raised serum 25D to ≥50 ng/mL in outpatients with COVID-19, possibly accelerating resolution of respiratory symptoms and mitigating the risk for pneumonia. These findings warrant further study.

Coronary Atherosclerosis in an Asymptomatic U.S. Population: Miami Heart Study at Baptist Health South Florida.

BACKGROUND: The burden of total coronary plaque, plaque subtypes, and high-risk plaque features was unknown in asymptomatic individuals from the general U.S. primary prevention population. OBJECTIVES: In a large, asymptomatic U.S. cohort evaluated using coronary computed tomography angiography (CCTA), we aimed to assess the burden of total coronary plaque, plaque subtypes, and high-risk plaque features; the interplay between CCTA findings and coronary artery calcium (CAC) scores; and identify independent predictors of coronary plaque. METHODS: Cross-sectional analysis in the MiHeart (Miami Heart Study), a cohort of 2,359 asymptomatic individuals from the Greater Miami Area (mean age 53 years, 50% women, 47% Hispanic/Latino, 43% non-Hispanic White). We estimated the burden of CAC (=0, >0 to <100, ≥100), CCTA-based plaque features (any plaque, stenosis ≥50%, ≥70%, high-risk features), and their interplay. RESULTS: Overall, 58% participants had CAC = 0, 28% CAC >0 to <100, and 13% CAC ≥100. A total of 49% participants had plaque on the CCTA, including 16% among those with CAC = 0. Overall, 6% participants had coronary stenosis ≥50% (12% among those with coronary plaque), 1.8% had stenosis ≥70% (3.7% among those with plaque), and 7% had at least 1 coronary plaque with ≥1 high-risk feature (13.8% among those with plaque). Only 0.8% participants with CAC = 0 had stenosis ≥50%, 0.1% stenosis ≥70%, and 2.3% plaque with high-risk features. In logistic regression models, independent predictors of coronary plaque and high-risk plaque were older age, male sex, tobacco use, diabetes, overweight, and obesity. Male sex, overweight, and obesity were independent predictors of plaque if CAC = 0. CONCLUSIONS: The Miami Heart Study confirms substantial prevalence of coronary plaque in asymptomatic individuals. Overall, 49% of participants had coronary plaque, 6% had stenosis ≥50%, and 7% had plaques with at least 1 high-risk feature. These proportions were 16%, 0.8%, and 2.3%, respectively, among those with CAC = 0. Longitudinal follow-up will shed further light on the prognostic implications of these findings in asymptomatic individuals.

The Miami Heart Study (MiHeart) at Baptist Health South Florida, A prospective study of subclinical cardiovascular disease and emerging cardiovascular risk factors in asymptomatic young and middle-aged adults: The Miami Heart Study: Rationale and Design.

OBJECTIVE: The Miami Heart Study (MiHeart) at Baptist Health South Florida is an ongoing, community-based, prospective cohort study aimed at characterizing the prevalence, characteristics, and prognostic value of diverse markers of early subclinical coronary atherosclerosis and of various potential demographic, psychosocial, and metabolic risk factors. We present the study objectives, detailed research methods, and preliminary baseline results of MiHeart. METHODS: MiHeart enrolled 2,459 middle-aged male and female participants from the general population of the Greater Miami Area. Enrollment occurred between May 2015 and September 2018 and was restricted to participants aged 40-65 years free of clinical cardiovascular disease (CVD). The baseline examination included assessment of demographics, lifestyles, medical history, and a detailed evaluation of psychosocial characteristics; a comprehensive physical exam; measurement of multiple blood biomarkers including measures of inflammation, advanced lipid testing, and genomics; assessment of subclinical coronary atherosclerotic plaque and vascular function using coronary computed tomography angiography, the coronary artery calcium score, carotid intima-media thickness, pulse wave velocity, and peripheral arterial tonometry; and other tests including 12-lead electrocardiography and assessment of pulmonary function. Blood samples were biobanked to facilitate future ancillary research. RESULTS: MiHeart enrolled 1,261 men (51.3%) and 1,198 women (48.7%). Mean age was 53 years, 85.6% participants were White and 47.4% were of Hispanic/Latino ethnicity. The study included 7% individuals with diabetes, 33% with hypertension, and 15% used statin therapy at baseline. Overweight or obese participants comprised 72% of the population and 3% were smokers. Median 10-year estimated atherosclerotic CVD risk using the Pooled Cohort Equations was 4%. CONCLUSION: MiHeart will provide important, novel insights into the pathophysiology of early subclinical atherosclerosis and further our understanding of its role in the genesis of clinical CVD. The study findings will have important implications, further refining current cardiovascular prevention paradigms and risk assessment and management approaches moving forward.

Rationale and design of a randomized study to assess the efficacy and safety of evolocumab in patients with diabetes and dyslipidemia: The BERSON clinical trial.

Type 2 diabetes mellitus (T2DM) is a major independent risk factor for cardiovascular disease, and diabetic dyslipidemia is a major contributor to cardiovascular risk in these patients. Here we report the rationale and design of a phase 3, double-blind study specifically designed to evaluate the lipid-lowering efficacy of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab in patients with T2DM and hyperlipidemia or mixed dyslipidemia who are on background statin therapy. In the BERSON (evolocumaB Efficacy for LDL-C Reduction in subjectS with T2DM On background statiN) trial, patients with T2DM, a screening low-density lipoprotein cholesterol (LDL-C) level of ≥ 2.6 mmol/L (≥100 mg/dL) or ≥ 3.4 mmol/L (≥130 mg/dL), and with or without statin treatment at screening, respectively, were enrolled and started on atorvastatin 20 mg/day for a lipid stabilization period of at least 4 weeks. Then, patients were randomly assigned in a 2:2:1:1 ratio to receive atorvastatin 20 mg once daily plus either evolocumab 140 mg every 2 weeks (Q2W), evolocumab 420 mg every month (QM), placebo Q2W, or placebo QM. The co-primary outcome measures were the percentage change from baseline in LDL-C at week 12 and the percentage change from baseline in LDL-C at the mean of weeks 10 and 12. The BERSON trial has completed enrollment. The study completed in the first half of 2018, and will provide information on the efficacy and safety of evolocumab in patients with T2DM and dyslipidemia.

Implications of Coronary Artery Calcium Testing for Treatment Decisions Among Statin Candidates According to the ACC/AHA Cholesterol Management Guidelines: A Cost-Effectiveness Analysis.

This review evaluates the cost-effectiveness of using coronary artery calcium (CAC) to guide long-term statin therapy compared with treating all patients eligible for statins according to 2013 American College of Cardiology/American Heart Association cholesterol management guidelines for atherosclerotic cardiovascular disease. The authors used a microsimulation model to compare costs and effectiveness from a societal perspective over a lifetime horizon. Both strategies resulted in similar costs and quality-adjusted life years (QALYs). CAC resulted in increased costs (+$81) and near-equal QALY (+0.01) for an incremental cost-effectiveness ratio of $8,100/QALY compared with the treat-all strategy. For 10,000 patients, the treat-all strategy would theoretically avert 21 atherosclerotic cardiovascular disease events, but would add 47,294 person-years of statins. With CAC costs <$100, and higher cost and/or disutility associated with statin therapy, CAC strategy was favored. These findings suggest the economic value of both approaches were similar. Clinicians should account for individual preferences in context of shared decision making when choosing the most appropriate strategy to guide statin decisions.

Rationale and design of the Baptist Employee Healthy Heart Study: a randomized trial assessing the efficacy of the addition of an interactive, personalized, web-based, lifestyle intervention tool to an existing health information web platform in a high-risk employee population.

BACKGROUND: Metabolic syndrome (MetS) and diabetes confer a high risk for developing subsequent cardiovascular disease (CVD). Persons with MetS constitute 24-34 % of the employee population at Baptist Health South Florida (BHSF), a self-insured healthcare organization. The Baptist Employee Healthy Heart Study (BEHHS) aims to assess the addition of a personalized, interactive, web-based, nutrition-management and lifestyle-management program to the existing health-expertise web platform available to BHSF employees in reducing and/or stabilizing CVD and lifestyle risk factors and markers of subclinical CVD. METHODS/DESIGN: Subjects with MetS or Type II Diabetes will be recruited from an employee population at BHSF and randomized to either an intervention or a control arm. The intervention arm will be given access to a web-based personalized diet-modification and weight-modification program. The control arm will be reminded to use the standard informational health website available and accessible to all BHSF employees. Subjects will undergo coronary calcium testing, carotid intima-media thickness scans, peripheral arterial tonometry, and advanced lipid panel testing at visit 1, in addition to lifestyle and medical history questionnaires. All tests will be repeated at visits 2 and 4 with the exception of the coronary calcium test, which will only be performed at baseline and visit 4. Visit 3 will capture vitals, anthropometrics, and responses to the questionnaires only. CONCLUSION: Results of this study will provide information on the effectiveness of personalized, web-based, lifestyle-management tools in reducing healthcare costs, promoting healthy choices, and reducing cardiovascular risk in an employee population. It will also provide information about the natural history of carotid atherosclerosis and endothelial dysfunction in asymptomatic but high-risk populations. TRIAL REGISTRATION: ClinicalTrials.gov registry, NCT01912209 . Registered on 3 July 2013.

Omega-3 Fatty Acid Formulations in Cardiovascular Disease: Dietary Supplements are Not Substitutes for Prescription Products.

Omega-3 fatty acid products are available as prescription formulations (icosapent ethyl, omega-3-acid ethyl esters, omega-3-acid ethyl esters A, omega-3-carboxylic acids) and dietary supplements (predominantly fish oils). Most dietary supplements and all but one prescription formulation contain mixtures of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Products containing both EPA and DHA may raise low-density lipoprotein cholesterol (LDL-C). In clinical trials, the EPA-only prescription product, icosapent ethyl, did not raise LDL-C compared with placebo. To correct a common misconception, it is important to note that omega-3 fatty acid dietary supplements are not US FDA-approved over-the-counter drugs and are not required to demonstrate safety and efficacy prior to marketing. Conversely, prescription products are supported by extensive clinical safety and efficacy investigations required for FDA approval and have active and ongoing safety monitoring programs. While omega-3 fatty acid dietary supplements may have a place in the supplementation of diet, they generally contain lower levels of EPA and DHA than prescription products and are not approved or intended to treat disease. Perhaps due to the lack of regulation of dietary supplements, EPA and DHA levels may vary widely within and between brands, and products may also contain unwanted cholesterol or fats or potentially harmful components, including toxins and oxidized fatty acids. Accordingly, omega-3 fatty acid dietary supplements should not be substituted for prescription products. Similarly, prescription products containing DHA and EPA should not be substituted for the EPA-only prescription product, as DHA may raise LDL-C and thereby complicate the management of patients with dyslipidemia.

Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial.

IMPORTANCE: In phase 2 studies, evolocumab, a fully human monoclonal antibody to PCSK9, reduced LDL-C levels in patients receiving statin therapy. OBJECTIVE: To evaluate the efficacy and tolerability of evolocumab when used in combination with a moderate- vs high-intensity statin. DESIGN, SETTING, AND PATIENTS: Phase 3, 12-week, randomized, double-blind, placebo- and ezetimibe-controlled study conducted between January and December of 2013 in patients with primary hypercholesterolemia and mixed dyslipidemia at 198 sites in 17 countries. INTERVENTIONS: Patients (n = 2067) were randomized to 1 of 24 treatment groups in 2 steps. Patients were initially randomized to a daily, moderate-intensity (atorvastatin [10 mg], simvastatin [40 mg], or rosuvastatin [5 mg]) or high-intensity (atorvastatin [80 mg], rosuvastatin [40 mg]) statin. After a 4-week lipid-stabilization period, patients (n = 1899) were randomized to compare evolocumab (140 mg every 2 weeks or 420 mg monthly) with placebo (every 2 weeks or monthly) or ezetimibe (10 mg or placebo daily; atorvastatin patients only) when added to statin therapies. MAIN OUTCOMES AND MEASURES: Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) level at the mean of weeks 10 and 12 and at week 12. RESULTS: Evolocumab reduced LDL-C levels by 66% (95% CI, 58% to 73%) to 75% (95% CI, 65% to 84%) (every 2 weeks) and by 63% (95% CI, 54% to 71%) to 75% (95% CI, 67% to 83%) (monthly) vs placebo at the mean of weeks 10 and 12 in the moderate- and high-intensity statin-treated groups; the LDL-C reductions at week 12 were comparable. For moderate-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 115 to 124 mg/dL to an on-treatment mean of 39 to 49 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 123 to 126 mg/dL to an on-treatment mean of 43 to 48 mg/dL. For high-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 35 to 38 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 33 to 35 mg/dL. Adverse events were reported in 36%, 40%, and 39% of evolocumab-, ezetimibe-, and placebo-treated patients, respectively. The most common adverse events in evolocumab-treated patients were back pain, arthralgia, headache, muscle spasms, and pain in extremity (all <2%). CONCLUSIONS AND RELEVANCE: In this 12-week trial conducted among patients with primary hypercholesterolemia and mixed dyslipidemia, evolocumab added to moderate- or high-intensity statin therapy resulted in additional LDL-C lowering. Further studies are needed to evaluate the longer-term clinical outcomes and safety of this approach for LDL-C lowering. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01763866.

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.

Rationale and design of LAPLACE-2: a phase 3, randomized, double-blind, placebo- and ezetimibe-controlled trial evaluating the efficacy and safety of evolocumab in subjects with hypercholesterolemia on background statin therapy.

Low-density lipoprotein cholesterol (LDL-C) levels are significantly associated with atherosclerotic cardiovascular disease (ASCVD) risk, and studies using interventions that lower LDL-C levels have been shown to reduce the risk of ASCVD events and mortality. Statin treatment is the current first-line therapy for lowering LDL-C and reducing ASCVD risk. However, many patients are still unable to reach recommended LDL-C goals on maximally tolerated statin therapy. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9, including evolocumab (previously AMG 145), dramatically lowered LDL-C in phase 2 clinical trials when administered alone or in combination with a statin. The aim of this phase 3 study is to evaluate the efficacy of 12 weeks of subcutaneous evolocumab (vs placebo) administered every 2 weeks or every month in combination with a statin in patients with hypercholesterolemia and mixed dyslipidemia. This study will also provide comparative efficacy, safety, and tolerability data between evolocumab and ezetimibe when added to background atorvastatin therapy.

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.

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.