Impact Cardiovascular Disease Risk Research Articles

Protein Consumption and Risk of CVD Among U.S. Adults: The Multi-Ethnic Study of Atherosclerosis (MESA).

Although some randomized trials have reported beneficial effects of protein intake on cardiometabolic risk factors, evidence from prospective studies have not supported a strong link between protein intake and cardiovascular disease (CVD) risk. It is also unclear whether diversity in protein intake plays a role in CVD risk. We investigated prospective associations of (1) protein intake, overall and by food source and (2) diversity of protein sources with risk of CVD, coronary heart disease (CHD), and stroke. In a multi-ethnic cohort of 5879 U.S. adults (45-84 years), who were free of CVD at baseline, protein intake was assessed at baseline (2000-2002) using a validated 120-item food frequency questionnaire. Two different aspects of protein diversity were assessed including count (number of protein food consumed at least once/week) and dissimilarity (diversity of the attributes of the protein sources consumed). Relationships with incident CVD outcomes through 2019 were assessed using Cox proportional hazards models adjusting for sociodemographic, lifestyle, and comorbidity factors. During 83,430 person-years, 1045 CVD cases were identified, including 668 CHD and 332 stroke cases. In multivariable models, we found no significant associations between protein intake, overall and by food source, with incident CVD, CHD, or stroke. Protein count, but not protein dissimilarity, was weakly associated with CVD risk. We found no significant associations between diversity of consumption of animal or plant food source and CVD outcomes. Our findings suggest protein consumption may not significantly impact CVD risk in middle-aged adults.

Chronic Illness Perceptions and Cardiovascular Disease Risk Behaviors in Black and Latinx Sexual Minority Men with HIV: A Cross-Sectional Analysis.

Ethnic and racial sexual minority men with HIV have a disproportionately higher risk of HIV-related cardiovascular disease (CVD). There is a lack of tailored and culturally salient behavioral interventions to address HIV-related chronic illness in ethnic and racial sexual minority men, and literature on their understanding and awareness of modifiable behavioral risks is limited. The purpose of this study was to assess illness perceptions about HIV and HTN, and describe physical activity, tobacco, and e-cigarette use in Black and Latinx sexual minority men living with HIV. We used the validated Illness Perception Questionnaire-Revised (IPQ-R) to assess perceptions about two interrelated chronic diseases, HIV and CVD. To assess CVD behavioral risk, we assessed physical activity using the International Physical Activity Questionnaire. Tobacco and e-cigarette use were assessed using items from the Behavioral Risk Factor Surveillance System. Sleep difficulties were the most prevalent symptom attributed to HIV, and were statistically associated with fatigue, upset stomach, and loss of strength. Anxiety was reported to be caused by HIV (57%) and HTN (39%). Half of the participants engaged in vigorous activity for 128 min (SD = 135) daily, and 63% engaged in moderate activity for 94 min (SD = 88) daily. Over a third reported current tobacco use and 20% reported current e-cigarette use. This study provides formative data to better understand how Black and Latinx sexual minority men with HIV perceive intersecting chronic illnesses and their engagement in modifiable CVD risk behaviors. Sleep, mental health disparities, and financial hardships were commonly reported. More research is needed to address intersecting chronic illnesses and mental health conditions that are influenced by social positioning over the life course, and impact CVD risk factors. This study was not registered.

Income variability and incident cardiovascular disease in diabetes: a population-based cohort study.

Longitudinal change in income is crucial in explaining cardiovascular health inequalities. However, there is limited evidence for cardiovascular disease (CVD) risk associated with income dynamics over time among individuals with type 2 diabetes (T2D). Using a nationally representative sample from the Korean National Health Insurance Service database, 1 528 108 adults aged 30-64 with T2D and no history of CVD were included from 2009 to 2012 (mean follow-up of 7.3 years). Using monthly health insurance premium information, income levels were assessed annually for the baseline year and the four preceding years. Income variability was defined as the intraindividual standard deviation of the percent change in income over 5 years. The primary outcome was a composite event of incident fatal and nonfatal CVD (myocardial infarction, heart failure, and stroke) using insurance claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated after adjusting for potential confounders. High-income variability was associated with increased CVD risk (HRhighest vs. lowest quartile 1.25, 95% CI 1.22-1.27; Ptrend < .001). Individuals who experienced an income decline (4 years ago vs. baseline) had increased CVD risk, which was particularly notable when the income decreased to the lowest level (i.e. Medical Aid beneficiaries), regardless of their initial income status. Sustained low income (i.e. lowest income quartile) over 5 years was associated with increased CVD risk (HRn = 5 years vs. n = 0 years 1.38, 95% CI 1.35-1.41; Ptrend < .0001), whereas sustained high income (i.e. highest income quartile) was associated with decreased CVD risk (HRn = 5 years vs. n = 0 years 0.71, 95% CI 0.70-0.72; Ptrend < .0001). Sensitivity analyses, exploring potential mediators, such as lifestyle-related factors and obesity, supported the main results. Higher income variability, income declines, and sustained low income were associated with increased CVD risk. Our findings highlight the need to better understand the mechanisms by which income dynamics impact CVD risk among individuals with T2D.

Evaluation of brewers’ spent grain on cardiovascular disease risk factors in adults: Lessons learned from a pilot study

The beer industry generates large amounts of leftover barley called brewers’ spent grain (BSG). Fiber-rich grains like barley are associated with ameliorating cardiovascular disease (CVD) risk factors. This randomized pilot study investigated the influence of daily BSG consumption for 8 weeks on lipid profiles, inflammation, and metabolic functions in healthy adults. Subjects (n = 37, 26 ± 4 y; BMI 23 ± 3 kg/m2) received muffins containing 8.3 g BSG or 0 g BSG daily for 8 weeks. Body composition, blood pressure, and fasting blood were collected at baseline and week 8. Gastrointestinal symptoms and Bristol stool scale ratings remained stable throughout the study in both groups. Dietary fiber intake increased in the BSG group (5 g/day; 26%; p = 0.003); however, there were no significant between-group effects on blood lipids, glucose, insulin sensitivity, C-reactive protein, body composition, or blood pressure. Consuming 8.3 g BSG for 8 weeks is well tolerated and improves dietary fiber intake but does not significantly impact CVD risk factors in this sample of healthy adults. Subject health status, sample size, and BSG flour substitution rate may support the lack of effect in the current study. Larger controlled trials are needed to understand the potential of BSG as a value-added ingredient and its impact on human health.

The Risk of Cardiovascular Disease Among Immigrants in Canada.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. The global surge in migration to high-income countries, especially Canada, highlights the importance of studies evaluating the risk factors and the disparities in the rate of incidence of CVD among immigrants. Canada is home to a diverse group of immigrants, each presenting with a risk profile that is unique to their ethnicity and country of birth. A variety of cardiac risk factors, such as dietary habits, physical activity, smoking, cultural traditions as well as preponderance to certain diseases like type II diabetes mellitus, hypertension, and high lipid levels act in concert and impact CVD risk and overall incidence. This narrative review focuses on CVD risks and how it is related to the immigration status among various ethnic groups in Canada.

The significant places of African American adults and their perceived influence on cardiovascular disease risk behaviors

BackgroundAA living in rural areas of the southeastern U.S. experience a disproportionate burden of cardiovascular disease (CVD) morbidity and mortality. Neighborhood environmental factors contribute to this disparity and may decrease the effectiveness of lifestyle interventions aimed at preventing CVD. Furthermore, the influence of neighborhood factors on AA CVD risk behaviors (i.e. physical activity) may be obscured by the use of researcher-defined neighborhoods and researcher-defined healthy and unhealthy places. The objective of this study was to elucidate the effects of neighborhood environments on AA CVD risk behaviors among AA adults who recently completed a lifestyle intervention. We specifically sought to identify AA adults’ self-perceived places of significance and their perceptions of how these places impact CVD risk behaviors including diet, physical activity and smoking.MethodsWe conducted semi-structured interviews with AA adults (N = 26) living in two rural North Carolina counties (Edgecombe and Nash, North Carolina, USA). Participants were recruited from a community-based behavioral CVD risk reduction intervention. All had at least one risk factor for CVD. Participants identified significant places including where they spent the most time, meaningful places, and healthy and unhealthy places on local maps. Using these maps as a reference, participants described the impact of each location on their CVD risk behaviors. Data were transcribed verbatim and coded using NVivo 12.ResultsThe average age of participants was 63 (SD = 10) and 92% were female. Places participants defined as meaningful and places where they spent the most time included churches and relatives’ homes. Healthy places included gyms and parks. Unhealthy places included fast food restaurants and relatives’ homes where unhealthy food was served. Place influenced CVD risk behaviors in multiple ways including through degree of perceived control over the environment, emotional attachment and loneliness, caretaking responsibilities, social pressures and social support.ConclusionsAs we seek to improve cardiovascular interventions for rural AA in the American South, it will be important to further assess the effect of significant places beyond place of residence. Strategies which leverage or modify behavioral influences within person-defined significant places may improve the reach and effectiveness of behavioral lifestyle interventions.

Impact of low-fat and full-fat dairy foods on fasting lipid profile and blood pressure: exploratory endpoints of a randomized controlled trial

Dietary guidelines traditionally recommend low-fat dairy because dairy's high saturated fat content is thought to promote cardiovascular disease (CVD). However, emerging evidence indicates that dairy fat may not negatively impact CVD risk factors when consumed in foods with a complex matrix. The aim was to compare the effects of diets limited in dairy or rich in either low-fat or full-fat dairy on CVD risk factors. In this randomized controlled trial, 72 participants with metabolic syndrome completed a 4-wk run-in period, limiting their dairy intake to ≤3 servings/wk of nonfat milk. Participants were then randomly assigned to 1 of 3 diets, either continuing the limited-dairy diet or switching to a diet containing 3.3 servings/d of either low-fat or full-fat milk, yogurt, and cheese for 12 wk. Exploratory outcome measures included changes in the fasting lipid profile and blood pressure. In the per-protocol analysis (n=66), there was no intervention effect on fasting serum total, LDL, and HDL cholesterol; triglycerides; free fatty acids; or cholesterol content in 38 isolated plasma lipoprotein fractions (P>0.1 for all variables in repeated-measures ANOVA). There was also no intervention effect on diastolic blood pressure, but a significant intervention effect for systolic blood pressure (P=0.048), with a trend for a decrease in the low-fat dairy diet (-1.6±8.6 mm Hg) compared with the limited-dairy diet (+2.5±8.2 mm Hg) in post hoc testing. Intent-to-treat results were consistent for all endpoints, with the exception that systolic blood pressure became nonsignificant (P=0.08). In men and women with metabolic syndrome, a diet rich in full-fat dairy had no effects on fasting lipid profile or blood pressure compared with diets limited in dairy or rich in low-fat dairy. Therefore, dairy fat, when consumed as part of complex whole foods, does not adversely impact these classic CVD risk factors. This trial was registered at clinicaltrials.gov as NCT02663544.

Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study.

BackgroundAlcohol consumption and smoking, 2 major risk factors for cardiovascular disease (CVD), often occur together. The objective of this study is to use a wide range of CVD risk factors and outcomes to evaluate potential total and direct causal roles of alcohol and tobacco use on CVD risk factors and events.Methods and findingsUsing large publicly available genome-wide association studies (GWASs) (results from more than 1.2 million combined study participants) of predominantly European ancestry, we conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess the independent impact of alcohol consumption and smoking on a wide range of CVD risk factors and outcomes. Multiple sensitivity analyses, including complementary Mendelian randomization (MR) methods, and secondary alcohol consumption and smoking datasets were used. SVMR showed genetic predisposition for alcohol consumption to be associated with CVD risk factors, including high-density lipoprotein cholesterol (HDL-C) (beta 0.40, 95% confidence interval (CI), 0.04–0.47, P value = 1.72 × 10−28), triglycerides (TRG) (beta −0.23, 95% CI, −0.30, −0.15, P value = 4.69 × 10−10), automated systolic blood pressure (BP) measurement (beta 0.11, 95% CI, 0.03–0.18, P value = 4.72 × 10−3), and automated diastolic BP measurement (beta 0.09, 95% CI, 0.03–0.16, P value = 5.24 × 10−3). Conversely, genetically predicted smoking was associated with increased TRG (beta 0.097, 95% CI, 0.014–0.027, P value = 6.59 × 10−12). Alcohol consumption was also associated with increased myocardial infarction (MI) and coronary heart disease (CHD) risks (MI odds ratio (OR) = 1.24, 95% CI, 1.03–1.50, P value = 0.02; CHD OR = 1.21, 95% CI, 1.01–1.45, P value = 0.04); however, its impact was attenuated in MVMR adjusting for smoking. Conversely, alcohol maintained an association with coronary atherosclerosis (OR 1.02, 95% CI, 1.01–1.03, P value = 5.56 × 10−4). In comparison, after adjusting for alcohol consumption, smoking retained its association with several CVD outcomes including MI (OR = 1.84, 95% CI, 1.43, 2.37, P value = 2.0 × 10−6), CHD (OR = 1.64, 95% CI, 1.28–2.09, P value = 8.07 × 10−5), heart failure (HF) (OR = 1.61, 95% CI, 1.32–1.95, P value = 1.9 × 10−6), and large artery atherosclerosis (OR = 2.4, 95% CI, 1.41–4.07, P value = 0.003). Notably, using the FinnGen cohort data, we were able to replicate the association between smoking and several CVD outcomes including MI (OR = 1.77, 95% CI, 1.10–2.84, P value = 0.02), HF (OR = 1.67, 95% CI, 1.14–2.46, P value = 0.008), and peripheral artery disease (PAD) (OR = 2.35, 95% CI, 1.38–4.01, P value = 0.002). The main limitations of this study include possible bias from unmeasured confounders, inability of summary-level MR to investigate a potentially nonlinear relationship between alcohol consumption and CVD risk, and the generalizability of the UK Biobank (UKB) to other populations.ConclusionsEvaluating the widest range of CVD risk factors and outcomes of any alcohol consumption or smoking MR study to date, we failed to find a cardioprotective impact of genetically predicted alcohol consumption on CVD outcomes. However, alcohol was associated with and increased HDL-C, decreased TRG, and increased BP, which may indicate pathways through impact CVD risk, warranting further study. We found smoking to be a risk factor for many CVDs even after adjusting for alcohol. While future studies incorporating alcohol consumption patterns are necessary, our data suggest causal inference between alcohol, smoking, and CVD risk, further supporting that lifestyle modifications might be able to reduce overall CVD risk.

Whole Milk and Full-Fat Dairy Products and Hypertensive Risks

Lifestyle modifications in the form of diet and exercise are generally the first-line approach to reduce hypertensive risk and overall cardiovascular disease (CVD) risk. Accumulating research evidence has revealed that consumption of non- and low-fat dairy products incorporated into the routine diet is an effective means to reduce elevated blood pressure and improve vascular functions. However, the idea of incorporating whole-fat or full-fat dairy products in the normal routine diet as a strategy to reduce CVD risk has been met with controversy. The aim of this review was to evaluate both sides of the argument surrounding saturated fat intake and CVD risk from the standpoint of dairy intake. Throughout the review, we examined observational studies on relationships between CVD risk and dairy consumption, dietary intervention studies using non-fat and whole-fat dairy, and mechanistic studies investigating physiological mechanisms of saturated fat intake that may help to explain increases in cardiovascular disease risk. Currently available data have demonstrated that whole-fat dairy is unlikely to augment hypertensive risk when added to the normal routine diet but may negatively impact CVD risk. In conclusion, whole-fat dairy may not be a recommended alternative to non- or low-fat dairy products as a mean to reduce hypertensive or overall CVD risk.

Review article: the impact of liver-directed therapies on the atherogenic risk profile in non-alcoholic steatohepatitis.

SummaryBackgroundPatients with non‐alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, are at higher risk of cardiovascular disease (CVD) and associated mortality. Therefore, it is important to understand how new therapies for non‐alcoholic steatohepatitis (NASH) may impact CVD risk factors in these patients.AimsTo summarise the effects of drug therapies on lipid and lipoprotein levels in patients with NASH and provide insight into the potential mechanisms for the observed changes.MethodsPubMed searches of the literature were performed and results were compiled.ResultsRecent clinical trials have highlighted the safety and efficacy of drug candidates for the treatment of NASH. Several agents have shown improvements in the histological features of NASH and liver function. Pioglitazone, a drug that is currently available for type 2 diabetes and may be useful for NASH, exhibits beneficial effects on lipids. However, agents such as farnesoid X receptor agonists, which are in development for NASH, may adversely affect circulating lipids and lipoproteins.ConclusionsNASH is a multi‐system disease with a disproportionate CVD burden. Current and future drugs for NASH have had variable impact on the atherogenic risk profile. Potential co‐administration of a statin may help mitigate the negative impact of some of these therapies on lipid and lipoprotein levels.

Public health guidelines should recommend reducing saturated fat consumption as much as possible: Debate Consensus

There is ongoing debate as to whether public health guidelines should advocate reducing SFA consumption as much as possible to reduce the risk of chronic diseases, especially cardiovascular disease (CVD). In considering both sides of this question, we identified a number of points of agreement, most notably that the overall dietary patterns in which SFAs are consumed are of greater significance for cardiometabolic and general health than SFA intake alone. Nevertheless, there remained significant disagreements, centered largely on the interpretation of evidence bearing on 4 major questions: 1) does reducing dietary SFAs lower the incidence of CVD, 2) is the LDL-cholesterol reduction with lower SFA intake predictive of reduced CVD risk, 3) do dietary SFAs affect factors other than LDL cholesterol that may impact CVD risk, and 4) is there a sufficient rationale for setting a target for maximally reducing dietary SFAs? Finally, we identified specific research needs for addressing knowledge gaps that have contributed to the controversies.

Impact of Low-Fat and Full-Fat Dairy Intake on Cardiovascular Disease Risk Factors: A Randomized Controlled Trial

Abstract Objectives Dairy fat has been hypothesized to promote cardiovascular disease (CVD) due to its high saturated fat content, contributing to recommendations to consume low-fat dairy foods. However, emerging evidence indicates that dairy fat does not negatively impact CVD risk, particularly when consumed in foods with a complex matrix. Though, few trials have directly compared the effect of low-fat versus full-fat dairy foods. Therefore, we aimed to test the effects of diets rich in low-fat or full-fat dairy on CVD risk factors, compared to a limited dairy diet. We hypothesized that diets rich in dairy would not impact CVD risk factors. Methods Seventy-two participants with the metabolic syndrome completed a 4-week wash-in period; limiting their dairy intake to ≤ 3 servings of skim milk per week. Participants were then randomized to either continue the limited dairy diet or switch to a diet containing 3.3 servings per day of either low-fat or full-fat milk, yogurt, and cheese for 12-weeks. The plasma lipid profile and blood pressure were assessed before and after the intervention period. Results In the per protocol analysis (n = 66), there was no intervention effect on fasting plasma total-, low-density lipoprotein-, and high-density lipoprotein-cholesterol, triglycerides, free fatty acids, or cholesterol content in 38 isolated lipoprotein fractions (p &amp;gt; 0.1 for all variables). There was also no intervention effect on diastolic blood pressure. There was a significant difference among the diet interventions for systolic blood pressure (P = 0.045), with a trend for a decrease in the low-fat dairy diet compared to the limited dairy diet in post hoc testing after adjustment for multiple testing. Conclusions In individuals with the metabolic syndrome, consuming 3.3 servings of dairy per day, regardless of fat content, did not affect blood lipids and modestly improved blood pressure compared to a diet virtually free of dairy. This provides further evidence that dairy fat, when consumed as part of complex whole foods, does not significantly impact CVD risk factors. Funding Sources This work was supported by the National Dairy Council, Dairy Farmers of Canada, the Dutch Dairy Association, Dairy Australia, and the French Dairy Interbranch Organization.

Using Telehealth to Disseminate Primary, Secondary, and Tertiary CVD Interventions to Rural Populations.

This study aims to review the evidence on telehealth interventions in rural communities that use primary, secondary, or tertiary strategies for the prevention and management of cardiovascular disease (CVD). Studies focused on the reduction of CVD risk factors and mitigation of disease progression among rural populations using telehealth are limited in number but appear to be increasing in the last 5years. These studies suggest primary-, secondary-, and tertiary-level interventions can impact CVD risk and management. The current review found more studies addressing primary CVD intervention strategies, although the evidence for efficacy at all intervention levels is in the early stages. Leveraging prevention strategies via telehealth may be an effective vehicle to facilitate improved CVD outcomes among populations traditionally marginalized by geographic location.

An Overview of Genomic Biomarker Use in Cardiovascular Disease Clinical Trials.

Clinical trial designs targeting patient subgroups with certain genetic characteristics may enhance the efficiency of developing drugs for cardiovascular disease (CVD). To evaluate the extent to which genetic knowledge translates to the CVD pipeline, we analyzed how genomic biomarkers are utilized in trials. Phase II and III trial protocols for investigational new drugs for CVD and risk factors were evaluated for prospective and exploratory genomic biomarker use; drug targets were evaluated for the presence of evidence that genetic variations can impact CVD risk or drug response. We identified 134 programs (73 unique drug targets) and 147 clinical trials. Less than 1% (n=1/147) trials used a genomic biomarker prospectively for in-trial enrichment despite 32% (n=23/73) of the drug targets having evidence of genetic variations. Additionally, 46% (n=68/147) of the trials specified exploratory biomarker use. The results highlight an opportunity for more targeted CVD drug development by leveraging genomic biomarker knowledge.

Abstract MP29: Body Fat and Cardiovascular Disease Risk in Postmenopausal Women With Normal Body Mass Index: the Women’s Health Initiative

Introduction: Excess body weight characterized by higher BMI is associated with increased risk of cardiovascular disease (CVD). In individuals with normal BMI, the extent to which body fat distribution may impact CVD risk is unclear, particularly in postmenopausal women who often experience fat redistribution. Hypothesis: We hypothesized a detrimental impact of trunk fat and a favorable impact of leg fat on risk of CVD risk among postmenopausal women with normal BMI. Methods: We analyzed data from 2683 normal-weight (BMI: 18.5-24.9 kg/m 2 ) women in the Women’s Health Initiative study without known CVD at baseline (1993-1998). Body composition including whole body and regional fat mass (FM) were determined by dual-energy X-ray absorptiometry. Incident CVD events including coronary heart disease (coronary death, nonfatal myocardial infarction, or coronary revascularization) and stroke were ascertained through February 2017. Results: There were 291 incident cases of CVD during a median 17.9 years of follow-up. After multivariable adjustment, whole body FM or FM percentage was not significantly associated with CVD risk. Higher trunk FM percentage was associated with increased risk of CVD (HR comparing extreme quartiles = 1.91, 95% CI: 1.33-2.74, P -trend &lt;0.001), while higher leg FM percentage was associated with lower risk of CVD (HR = 0.62, 95% CI: 0.43-0.89, P -trend = 0.008) ( Figure ). These associations were slightly attenuated but remained significant after further adjustment for waist circumference or waist-to-hip ratio. Higher trunk fat combined with lower leg fat was associated with particularly higher risk of CVD (HR comparing extreme groups = 3.33, 95% CI: 1.46-7.62). Similar significant associations of trunk fat and leg fat were observed for coronary heart disease but not for stroke. Conclusions: Among postmenopausal women with normal BMI, higher trunk fat was associated with increased risk of CVD, while higher leg fat was associated with decreased risk of CVD, independently of central adiposity measures.

Cardiovascular Risk Reduction Associated with Pharmacological Weight Loss: A Meta-Analysis.

Obesity is a growing pandemic that is associated with multiple cardiovascular disease (CVD) risk factors such as hypertension, diabetes, dyslipidemia and obstructive sleep apnea. With the increase in obesity rates where nearly two thirds of Americans are either obese or overweight, there has been an increase in the use of pharmacological therapy weight loss. While these therapies have shown benefit in weight reduction, the clinical impact these pharmacological agents on overall CVD outcomes has yet to be determined. We aimed to assess the effect of pharmacological agents used for weight reduction on CVD risk and all-cause mortality. We conducted a meta-analysis of peer-reviewed literature that evaluated the impact of anti-obesity drugs on cardiovascular outcomes. Key words used included: "orlistat", "lorcaserin", "phentermine/topiramate" or "naltrexone/bupropion" and "cardiovascular outcomes" among others. We reviewed 791 articles, only 47 studies were randomized controlled trials and only 7 studies fulfilled all the inclusion criteria including, quantitative data on cardiovascular risk factors such as, Hemoglobin A1C (A1C), changes in body mass index (BMI), blood pressure and CVD morbidity and mortality. Data was retrieved from these studies and evaluated with comprehensive meta-analysis software® to assess pooled effects for medical management versus placebo. There were 7 studies included in the final analysis, with a total of 18,598 subjects, of which 8,685 were in the intervention (INT) group and 9,913 in the control (CTRL) group. For all cause mortality, there were 45 events in the INT and 55 in the CTRL groups, suggesting no significant difference between the two groups (OR: 0.843, 95%CI: 0.571-1.244, Z: -0.860, P: 0.390). For CVD mortality, there were 17 events in the INT and 36 events in the CTRL groups suggesting a significant mortality benefit in the INT group (OR:0.496, 95% CI: 0.282-0.873, Z: -2.433, P: 0.015). There was a significant absolute reduction in A1C in the INT group (Hg: -0.238, 95%CI: -0.291 to -0.186, Z: -8.937, P< 0.001). The percentage weight reduction was significantly higher for the INT group compared to the CTRL group (Hg: -0.431, 95%CI: -0.477 to -0.385, Z: -18.472, P< 0.001) and the blood pressure reduction was higher for the INT group compared to the CTRL group. (Hg: -0.052, 95%CI: -0.101- -0.003, Z: -2.086, P: 0.037). The heterogeneity observed for our meta analysis is Q: 1.884, df: 6, P: 0.930. Our study demonstrated the favorable and significant effect of pharmacological weight reduction strategies on weight loss, blood pressure reduction, glycemic control (A1C reduction), and CVD mortality.While weight loss without pharmacological means has been shown to reduce CVD risk, the mechanism by which weight loss medications impact CVD risk reduction could be a direct effect of these agents or merely an effect of weight reduction itself. Weight loss has been noted to modify risk factors via improving insulin sensitivity, reducing inflammation, decreasing blood pressure and modifying the lipid profile, In addition, the mechanism of action of the medications are not directly anti-inflammatory, and do not directly modify insulin sensitivity, blood pressure or the lipid profile. Thus, it is most likely that the benefit on cardiovascular disease from these therapies is via weight reduction and not direct medication effect.Given the limited efficacy of the lifestyle modification on sustained weight loss and the surgical risk and limited availability of bariatric surgical options. Our data suggests pharmacological weight loss therapy may be a valuable treatment option to reduce CVD risk in obese patients. Further research is needed to clarify the effects these therapies on overall mortality and evaluate the mechanisms by which these medications reduce CVD risk factors and mortality.

Long‐Acting Beta‐Agonist Use is Associated with Lower Carotid Artery Stiffness and Greater Carotid Artery Compliance in Individuals with Chronic Obstructive Pulmonary Disease

BackgroundCardiovascular disease (CVD) is the most prevalent comorbidity in individuals with chronic obstructive pulmonary disease (COPD). Elevated large elastic artery stiffness (i.e. carotid and aorta) is a robust predictor of CVD events and mortality and is associated with airway obstruction in COPD patients, suggesting that large artery stiffness may contribute, at least in part, to the high CVD risk in COPD. Previous studies demonstrate that in COPD patients, bronchodilator therapy improves respiratory symptoms, lowers the risk of exacerbations and reduces aortic stiffness, as measured by carotid‐femoral pulse wave velocity (CFPWV), in COPD patients with a very high CFPWV (≥ 11 m/s). However, the long‐term benefits of bronchodilator therapy on cardiovascular risk remain controversial. We hypothesized that individuals with COPD who reported using a long‐acting beta‐agonist (LABA) or an inhaled corticosteroid (ICS) would have lower carotid artery stiffness/greater compliance compared with COPD patients not on LABAs or ICSs.MethodsSixty‐three adults with COPD (age 70 ± 7 yrs; 23M/40F; GOLD stage 1–4; 6% stage 1, 47% stage 2, 24% stage 3, 23% stage 4) completed measurements of common carotid artery stiffness and compliance (carotid artery ultrasound and tonometry) and were retrospectively stratified by self‐report of LABA and ICS use.ResultsThirty‐two (49%) participants reported using a LABA/ICS combination bronchodilator. Seven (11%) of patients reported using a LABA alone and 7 (11%) of patients reported using an ICS alone. COPD patients using a LABA/ICS combination bronchodilator had significantly lower carotid β‐stiffness (8.7 ± 0.5 vs. 10.9 ± 0.9 U, P=0.04) and greater carotid compliance (0.11 ± 0.01 vs. 0.08 ± 0.01 mm/mmHg, P=0.01) compared with patients not using a LABA/ICS. This difference remained significant after adjusting for age, gender, BMI, oxygen use and smoking pack‐years (carotid β‐stiffness P=0.04; carotid compliance P=0.05). BP, heart rate and oxygen saturation did not differ between COPD patients using vs. not using a LABA/ICS. Furthermore, patients that reported using a LABA alone, and not in combination with an ICS, had significantly lower carotid β‐stiffness (6.9 ± 0.6 vs. 10.1 ± 0.6 U, P&lt;0.01), but not greater carotid compliance (0.11 ± 0.01 vs. 0.09 ± 0.01 mm/mmHg, P=0.2) compared with those not using a LABA. In contrast, there was no difference in carotid β‐stiffness (9.0 ± 1.2 vs. 9.9 ± 0.6 U, P=0.60) or carotid compliance (0.10 ± 0.01 vs. 0.10 ± 0.01 mm/mmHg, P=0.93) between COPD patients that reported using vs. not using an ICS.ConclusionThese data indicate that COPD patients who are taking a LABA, either in combination with an ICS or alone, have lower carotid artery stiffness than those not taking a LABA. This finding raises the possibility that LABAs may be beneficial in reducing the CVD risk observed in COPD, however randomized, controlled clinical trials are needed to test whether LABAs impact CVD risk.Support or Funding InformationNIH K23 HL095658, R01 HL089897, NIH/NCATS CTSI UL1 TR001082This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases.

The human gastrointestinal tract is home to trillions of bacteria, which vastly outnumber host cells in the body. Although generally overlooked in the field of endocrinology, gut microbial symbionts organize to form a key endocrine organ that converts nutritional cues from the environment into hormone-like signals that impact both normal physiology and chronic disease in the human host. Recent evidence suggests that several gut microbial-derived products are sensed by dedicated host receptor systems to alter cardiovascular disease (CVD) progression. In fact, gut microbial metabolism of dietary components results in the production of proatherogenic circulating factors that act through a meta-organismal endocrine axis to impact CVD risk. Whether pharmacological interventions at the level of the gut microbial endocrine organ will reduce CVD risk is a key new question in the field of cardiovascular medicine. Here we discuss the opportunities and challenges that lie ahead in targeting meta-organismal endocrinology for CVD prevention.

GW25-e1704 Fructose Diet Elevates Circulating PCSK9 and LDL-cholesterol Levels and Reduces Liver LDL Receptor Protein Abundance in Hamsters through a Novel Mechanism

The liver secreted serum protein PCSK9 binds to hepatic LDL receptor (LDLR) and triggers its intracellular degradation. Thus, circulating PCSK9 concentrations influence plasma LDL-c levels and impact cardiovascular disease risk. High fructose diet (HFD) induces dyslipidemia and insulin resistance in animals and humans; however, whether PCSK9 has a causal role in the development of dyslipidmia by high fructose consumption remains elusive. In this study, we showed that serum levels of LDL-c were elevated in hamsters fed HFD as compared to animals fed a normal diet (ND). The increase in circulating LDL-c was accompanied by a 50% reduction of liver LDLR protein abundance in HFD group without changes in LDLR mRNA levels. Examinations of serum PCSK9 levels and liver PCSK9 expressions revealed that hepatic PCSK9 mRNA and protein were reduced by HFD, but serum PCSK9 levels in HFD group were 2.2-fold higher than ND group. PCSK9 in hamster serum was detected as two forms of ~60 kDa and ~53 kDa, the latter being the dominant one. It was previously reported that proprotein convertases furin and PC5A cleave human PCSK9 at Arg 218 -Gln 219 to produce PCSK9-ΔN218 (53 kDa) that circulates in blood along with the intact form. To assess the activity of the equivalent hamster 53 kDa PCSK9-ΔN224 in degrading hepatic LDLR, we conducted in vitro experiments in Huh7 cells by exogenous overexpression of hamster PCSK9 alone or with furin/PC5A. Western blotting of culture medium from transfected Huh7 cells with anti-hamster PCSK9 antibody demonstrated that coexpression of hamster PCSK9 with either furin or PC5A increased the 53 kDa form to 82% and 70% of total PCSK9 species respectively, compared to 18% of the PCSK9 species in the absence of furin or PC5A coexpression. Importantly, the corresponding LDLR protein abundances were reduced by similar extents in Huh7 cells expressing hamster PCSK9 without or with furin/PC5A coexpression. Comparable results were obtained by treating naive Huh7 cells with culture medium of HEK293 cells expressing hamster PCSK9 alone or with furin/PC5A. Altogether, these new findings suggest that HFD may reduce serum LDL-c uptake by LDLR in hamster liver through a novel mechanism that elevates circulating PCSK9 concentration without increasing its hepatic synthesis.

State of the science on cardiometabolic risk after spinal cord injury: recap of the 2013 Asia pre-conference on cardiometabolic disease.

Cardiovascular disease (CVD) is a leading cause of death in persons with spinal cord injury (SCI) who survive at least 1 year post injury. Persons with SCI who are younger than 45 years of age are four times more likely to die of cardiac causes than their age-matched counterparts without SCI. There is evidence that people with SCI are at increased risk for CVD compared to the general population, however prospective trials documenting true incidence have not confirmed this. These figures are not surprising, due to the effect of paralysis on body composition, challenges to physical activity, and the body’s response to physical activity after SCI. Individuals with SCI may also be less likely, depending on level of injury, to experience angina or other cardiac-related symptoms as a warning sign of cardiac compromise due to sympathetic nervous system disruption. Because measures of risk, and subsequent preventive practices, are based on and designed for the general population and because persons with SCI experience CVD earlier and with fewer cardiac symptoms than the general population, there is a need to better characterize the risks in this population.6 One of the significant risks of CVD in persons with SCI is their tendency to develop cardiometabolic syndrome, defined as a cluster of risk factors that includes obesity, insulin resistance, diabetes mellitus, dyslipidemia, and subclinical atherosclerosis. Cardiometabolic risk (CMR) has been a principal research focus of the Rehabilitation Research and Training Center (RRTC) on Secondary Conditions in the Rehabilitation of Individuals with Spinal Cord Injury. Research conducted during a previous cycle of SCI-RRTC (2003-2009) funding demonstrated that 76.9% of subjects exhibited risk clustering, with elevated low-density lipoprotein cholesterol (LDL-C) occurring in 64% of subjects and depressed high-density lipoprotein cholesterol (HDL-C) occurring in 53% of subjects (42% and 11%, respectively, for males and females). Further, overweight/obesity was the most prevalent CMR (74%) among 121 community-dwelling persons with chronic SCI. Body mass index (BMI) provides a proxy measure of body fat, as the ratio of weight (kg) and height (m2). Although BMI may be adequate for providing a gross estimate of obesity in the general population, it is problematic after SCI due to the significant changes in body composition that are nearly universal and are characterized by a loss of lean and increase in fat mass. As a result, the BMI scale significantly underestimates obesity in individuals after SCI and therefore may not signal actual risk. Similarly, although optimization of the lipid profile is integral to general population CVD prevention, the way in which lipid patterns may differ after SCI and how those differences impact CVD risk in persons with SCI have not received much attention.