Moderate Cardiovascular Disease Research Articles

Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas for Sight-Threatening Diabetic Retinopathy

To investigate whether the choice of glucose-lowering agent for type 2 diabetes (T2D) impacts a patient's risk of developing sight-threatening diabetic retinopathy complications. Retrospective observational database study emulating an idealized target trial. Adult (≥21 years) enrollees in United States commercial, Medicare Advantage, and Medicare fee-for-service plans from January 1, 2014, to December 31, 2021, with T2D and moderate cardiovascular disease (CVD) risk who had no baseline history of advanced diabetic retinal complications, initiating treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sulfonylureas. We used inverse propensity scoring weights in time-to-event Cox proportional hazards models. Treatment for either diabetic macular edema or proliferative diabetic retinopathy. The final study population included 371 698 patients, of whom 42 265 initiated GLP-1 RA, 53 476 initiated SGLT2i, 78 444 initiated DPP-4i, and 197 513 initiated sulfonylurea agents. The probability of treatment for sight-threatening retinopathy within 2 and 5 years was 0.3% and 0.7% for patients initiating SGLT2i (median follow-up 830 [interquartile range (IQR), 343-1401] days), 0.4% and 1.0% for GLP-1 RA (669 [IQR, 256-1167] days), 0.4% and 0.9% for DPP-4i (1263 [IQR, 688-1938] days), and 0.5% and 1.2% for sulfonylurea (1223 [IQR, 662-1879] days). Sodium-glucose cotransporter 2 inhibitors use was associated with a lower risk of treatment for sight-threatening retinopathy compared with all other medication classes, including GLP-1 RA (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.97), DPP-4i (HR, 0.79; 95% CI, 0.64-0.97), and sulfonylurea (HR, 0.61; 95% CI, 0.50-0.74). Glucagon-like peptide-1 receptor agonists use was associated with a similar risk of sight-threatening retinopathy as DPP-4i (HR, 1.07; 95% CI, 0.85-1.35) and sulfonylurea (HR, 0.83; 95% CI, 0.67-1.03). Sodium-glucose cotransporter 2 inhibitors use was associated with a lower risk of sight-threatening diabetic retinopathy among adults with T2D and moderate CVD risk compared with other glucose-lowering therapies. Glucagon-like peptide-1 receptor agonists do not confer increased retinal risk, relative to DPP-4i and sulfonylurea medications. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Reduced cerebral vascular fractal dimension among asymptomatic individuals as a potential biomarker for cerebral small vessel disease

Cerebral small vessel disease is a neurological disease frequently found in the elderly and detected on neuroimaging, often as an incidental finding. White matter hyperintensity is one of the most commonly reported neuroimaging markers of CSVD and is linked with an increased risk of future stroke and vascular dementia. Recent attention has focused on the search of CSVD biomarkers. The objective of this study is to explore the potential of fractal dimension as a vascular neuroimaging marker in asymptomatic CSVD with low WMH burden. Df is an index that measures the complexity of a self-similar and irregular structure such as circle of Willis and its tributaries. This exploratory cross-sectional study involved 22 neurologically asymptomatic adult subjects (42 ± 12 years old; 68% female) with low to moderate 10-year cardiovascular disease risk prediction score (QRISK2 score) who underwent magnetic resonance imaging/angiography (MRI/MRA) brain scan. Based on the MRI findings, subjects were divided into two groups: subjects with low WMH burden and no WMH burden, (WMH+; n = 8) and (WMH−; n = 14) respectively. Maximum intensity projection image was constructed from the 3D time-of-flight (TOF) MRA. The complexity of the CoW and its tributaries observed in the MIP image was characterised using Df. The Df of the CoW and its tributaries, i.e., Df (w) was significantly lower in the WMH+ group (1.5172 ± 0.0248) as compared to WMH− (1.5653 ± 0.0304, p = 0.001). There was a significant inverse relationship between the QRISK2 risk score and Df (w), (rs = − .656, p = 0.001). Df (w) is a promising, non-invasive vascular neuroimaging marker for asymptomatic CSVD with WMH. Further study with multi-centre and long-term follow-up is warranted to explore its potential as a biomarker in CSVD and correlation with clinical sequalae of CSVD.

Perceived cardiovascular disease risk and tailored communication strategies among rural and urban community dwellers in Rwanda: a qualitative study

BackgroundIn Rwanda, cardiovascular diseases (CVDs) are the third leading cause of death, and hence constitute an important public health issue. Worldwide, most CVDs are due to lifestyle and preventable risk factors. Prevention interventions are based on risk factors for CVD risk, yet the outcome of such interventions might be limited by the lack of awareness or misconception of CVD risk. This study aimed to explore how rural and urban population groups in Rwanda perceive CVD risk and tailor communication strategies for estimated total cardiovascular risk.MethodsAn exploratory qualitative study design was applied using focus group discussions to collect data from rural and urban community dwellers. In total, 65 community members took part in this study. Thematic analysis with Atlas ti 7.5.18 was used and the main findings for each theme were reported as a narrative summary.ResultsParticipants thought that CVD risk is due to either financial stress, psychosocial stress, substance abuse, noise pollution, unhealthy diets, diabetes or overworking. Participants did not understand CVD risk presented in a quantitative format, but preferred qualitative formats or colours to represent low, moderate and high CVD risk through in-person communication. Participants preferred to be screened for CVD risk by community health workers using mobile health technology.ConclusionRural and urban community members in Rwanda are aware of what could potentially put them at CVD risk in their respective local communities. Community health workers are preferred by local communities for CVD risk screening. Quantitative formats to present the total CVD risk appear inappropriate to the Rwandan population and qualitative formats are therefore advisable. Thus, operational research on the use of qualitative formats to communicate CVD risk is recommended to improve decision-making on CVD risk communication in the context of Rwanda.

Effect of continuous positive airway pressure treatment on ambulatory blood pressures in high-risk sleep apnea patients: a randomized controlled trial.

The long-term effect of continuous positive airway pressure (CPAP) on 24-hour blood pressure (BP) in patients at high risk with obstructive sleep apnea (OSA) is uncertain. We aimed to determine the effect of CPAP treatment on ambulatory BP in individuals with moderate or severe OSA and cardiovascular disease or multiple cardiovascular disease risk factors without severe sleepiness. In this randomized, controlled, parallel group study, 169 participants were randomly assigned to CPAP treatment or the control group. The primary outcome was the change in mean 24-hour systolic BP between groups from baseline to the average of 6- and 12-month measurements using mixed-effect linear regression models. The 24-hour systolic BP did not significantly differ by group, although there was a trend of decrease in the CPAP group (treatment effect -2.7 mm Hg [95% confidence interval -5.9 to 0.6]; P = .105) compared with control. CPAP had the greatest effect on nighttime systolic BP (treatment effect -5.9 mm Hg [95% confidence interval -9.9 to -1.9]; P = .004). Similar improvements in other nocturnal BP indices were observed. In patients at high risk with moderate-severe OSA without severe sleepiness, CPAP resulted in modest BP improvements over 6 to 12 months of follow-up, with possibly larger effects for nocturnal BP. Use of office blood pressure may underestimate the effect of CPAP on BP profile in patients with OSA. Registry: ClinicalTrials.gov; Title: Sleep Apnea Intervention for Cardiovascular Disease Reduction; Identifier: NCT01261390; URL: https://clinicaltrials.gov/ct2/show/NCT01261390. Zhao YY, Wang R, Gleason KJ, et al. Effect of continuous positive airway pressure treatment on ambulatory blood pressures in high-risk sleep apnea patients: a randomized controlled trial. J Clin Sleep Med. 2022;18(8):1899-1907.

Phytosterol Therapy Effectively Reduces LDL-C in Middle-Aged, Borderline Risk South Asians

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> Piper Biosciences. <h3>Background/Synopsis</h3> The effectiveness of a plant sterol gummy supplement was studied in a South-Asian (SA) patient population with low to moderate cardiovascular disease (CVD) risk as defined by an Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score of < 7.5%, and a low density lipoprotein (LDL)-C level of 120-189 mg/dl. Statin therapy is often not recommended to patients with ASCVD score < 7.5% even in the presence of risk accelerators such as SA ethnicity, to which the 2018 National Lipid Association (NLA) guidelines call attention. <h3>Objective/Purpose</h3> Phytosterols are known to lower LDL-C and are included in NLA and other global guidelines. This study aimed to establish their impact on LDL-C levels in 'borderline' risk SAs. <h3>Methods</h3> 50 SAs were recruited during the COVID 19 pandemic, mainly from a preventive cardiology clinic dedicated to reducing SA heart disease risk. Eligible subjects had a 10-year CV risk score (ASCVD) <7.5% and LDL-C level of 120-193mg/dl at study enrollment. Subjects intolerant of or refusing statins were also recruited. The study was administered with a fully decentralized design, leveraging mailed supplements, televisits, remote lab collection, and SMS-based communications. Upon completing baseline labs and surveys, subjects were provided a 90-day supply of 1400mg phytosterol gummy supplements in individual packets (Piper Biosciences, Los Altos, CA) to be ingested twice daily. Subjects were instructed to continue current lifestyle habits and report major dietary pattern deviations. The primary endpoint was LDL-C reduction at 3 months. Pre- and post-study surveys were administered to assess diet and lifestyle. <h3>Results</h3> 33 of the 50 subjects successfully completed the protocol. A significant overall reduction in LDL-C of 5.8% was observed (p=0.03) (Table 1, Figure 1). Subgroup A (n=27) completed the protocol with no significant dietary variation, demonstrating a significant LDL-C reduction of 6.5% (p=0.002), as well as a total cholesterol (TC) reduction of 4.4% (p=0.01). There was no significant change in other metrics, including BMI, fasting glucose, or HbA1C. Patients who completed the protocol but reported worsening dietary habits (Subgroup B, n=6) showed an average increase in LDL-C of 6% (p=0.2) and in TC of 8% (p=0.002). Survey responses indicate that 94% of subjects would be interested in long-term supplementation if recommended by physician and 80% would prefer taking it proactively to manage cholesterol levels. <h3>Conclusions</h3> Plant sterols are an effective and sustainable means to lower LDL-C in middle-aged SAs, whose CV risk is often underestimated. To our knowledge this study represents the first demonstration of phytosterol effectiveness in the highest coronary disease risk population globally.

Salusin-β in patients with subclinical hypothyroidism and low to moderate cardiovascular disease risk

Abstract :BACKGROUND AND OBJECTIVES: Because Subclinical hypothyroidism may be a risk factor for cardiovascular disease, we aimed to measure the level of salusin-β which is a new biomarker for predicting atherosclerotic cardiovascular diseases (CVD) in those patients.PATIENTS AND METHODS: 57 subclinical hypothyroid patients were compared with a control group of 60 euthyroid subjects whose age and sex were matched to the patient group. Both groups have low to moderate 10-year risk of fatal CVD. We studied the serum level of salusin-β in the selected group of SC hypothyroid patients to find out if it can be used as an indicator of the cardiovascular adverse effects in them. We also studied the association between salusin-β levels and TSH level, thyroid Ab, and individual’s risk of CVD.RESULTS: Salusin-β was higher in the SC hypothyroidism group with a significant difference (p = 0.001). TSH, FT4, diastolic BP and triglycerides showed a significant difference between the two groups. Systolic BP, total cholesterol, smoking, and SCORE showed no significant difference between the two groups. There was a highly +ve correlation with TSH level in the SC hypothyroid group.Conclusion:The elevated salusin-𝛽 level supports the opinion that SC hypothyroidism has a cardiovascular risk and can support treatment of these cases whose TSH < 10 mIU/l.KEYWORDS: salusin-β, Subclinical hypothyroidism, cardiovascular disease risk.

Assessment of Coronary Artery Disease With Computed Tomography Angiography and Inflammatory and Immune Activation Biomarkers Among Adults With HIV Eligible for Primary Cardiovascular Prevention

Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in PWH with low to moderate traditional CVD risk. To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation. This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020. HIV disease. The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP). The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median [IQR] IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01). In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.

Postprandial Fatty Acid Profile, but Not Cardiometabolic Risk Markers, Is Modulated by Dairy Fat Manipulation in Adults with Moderate Cardiovascular Disease Risk: The Randomized Controlled REplacement of SaturatEd fat in dairy on Total cholesterol (RESET) Study.

ABSTRACTBackgroundChronic consumption of dairy products with an SFA-reduced, MUFA-enriched content was shown to impact favorably on brachial artery flow-mediated dilatation (FMD). However, their acute effect on postprandial cardiometabolic risk biomarkers requires investigation.ObjectiveThe effects of sequential high-fat mixed meals rich in fatty acid (FA)–modified or conventional (control) dairy products on postprandial FMD (primary outcome) and systemic cardiometabolic biomarkers in adults with moderate cardiovascular risk (≥50% above the population mean) were compared.MethodsIn a randomized crossover trial, 52 participants [mean ± SEM age: 53 ± 2 y; BMI (kg/m2) 25.9 ± 0.5] consumed a high-dairy-fat breakfast (0 min; ∼50 g total fat: modified: 25 g SFAs, 20 g MUFAs; control: 32 g SFAs, 12 g MUFAs) and lunch (330 min; ∼30 g total fat; modified: 15 g SFAs, 12 g MUFAs; control: 19 g SFAs, 7 g MUFAs). Blood samples were obtained before and until 480 min after breakfast, with FMD assessed at 0, 180, 300, and 420 min. Data were analyzed by linear mixed models.ResultsPostprandial changes in cardiometabolic biomarkers were comparable between the different dairy meals, with the exception of a tendency for a 4% higher AUC for the %FMD response following the modified-dairy-fat meals (P = 0.075). Plasma total lipid FA analysis revealed that incremental AUC responses were 53% lower for total SFAs, 214% and 258% higher for total cis-MUFAs (predominantly cis-9 18:1), and trans-18:1, respectively, following the modified relative to the control dairy meals (all P < 0.0001).ConclusionsIn adults at moderate cardiovascular risk, acute consumption of sequential high-fat meals containing FA-modified dairy products had little impact on postprandial endothelial function or systemic cardiometabolic biomarkers, but a differential effect on the plasma total lipid FA profile, relative to conventional dairy fat meals.This trial was registered at clinicaltrials.gov as NCT02089035.

Effect of Rosuvastatin Therapy on Biomarkers of Inflammation and Immune Activation in People With Human Immunodeficiency Virus at Intermediate Cardiovascular Risk.

Statins may help prevent cardiovascular disease (CVD) in people with human immunodeficiency virus (PWH) with chronic inflammation owing to their pleotropic lipid-lowering and anti-inflammatory properties. The impact of 48 weeks of rosuvastatin therapy on inflammation and immune activation in a double-blind, placebo-controlled trial in PWH at moderate cardiovascular disease risk was assessed. Rosuvastatin did not alter plasma levels of interleukin 6, soluble tumor necrosis factor receptor type 2, CXCL10, soluble CD14, or soluble vascular cellular adhesion molecule 1 (P ≥ .1 for all). Proportions of CD16+ monocyte subsets were increased in PWH receiving rosuvastatin. The potential benefits of statin use in PWH with normal lipid levels requires further clinical outcome research.

Determinants of Metabolic Syndrome and 5-Year Cardiovascular Risk Estimates among HIV-Positive Individuals from an Indian Tertiary Care Hospital.

Longer survival due to use of antiretroviral therapy (ART) has made human immunodeficiency virus- (HIV-) infected individuals prone to chronic diseases such as diabetes, hypertension, and cardiovascular diseases (CVD). Metabolic syndrome (MS), a constellation of risk factors which increase chances of the cardiovascular disease and diabetes, can increase the morbidity and mortality among this population. Hence, the present study was conducted with the objectives of estimating the prevalence and determinants of MS among ART naïve and ART-treated patients and assess their 5-year CVD risk using the reduced version of Data Collection on Adverse Effects of Anti-HIV Drugs (D : A : D) risk prediction model (D : A : D(R)). This hospital-based cross-sectional study included 182 adults aged ≥ 18 years. MS was defined using the National Cholesterol Education Program-Adult Treatment Panel-3 (NCEP ATP-3) criteria. Univariate and multivariate logistic regressions were done to identify the factors associated with MS. Prevalence of MS was 40.1% (95% confidence interval (CI) = 33.0%–47.2%). About 24.7% of the participants had at least a single criterion for MS. Age >45 years (adjusted odds ratio (AOR) = 2.3; 95% CI = 1.1–4.9, p < 0.018) and body mass index (BMI) > 23 kg/m2 (AOR = 6.4; 95% CI = 3.1–13.1, p < 0.001) were positively associated with MS, whereas daily consumption of high sugar items was inversely associated (AOR = 0.2; 95% CI = 0.1–0.5, p < 0.001). More than 50% of the participants were found to have moderate or high 5-year CVD risk. Observed prevalence of MS among HIV patients was higher than other studies done in India. Considering a sizeable number of participants to be having moderate to high CVD risk, culturally appropriate lifestyle interventions need to be planned.

A Meaningful Increase in C-Reactive Protein is Associated with Adverse Events in Head and Neck Cancer Radiation Therapy Patients

Serum C-Reactive Protein (CRP) is an acute-phase biomarker that rises during periods of elevated generalized body inflammation and has been correlated with fatigue. As fatigue impacts the care of the irradiated head and neck cancer (HNC) patient, it has been routinely evaluated during (chemo)radiation (C/RT) to guide decisions regarding placement of therapeutic enteral tube support for nutrition. We sought to understand if CRP also correlated with serious adverse events (SAE) during CRT. 230 subjects with weekly CRP data during C/RT were identified between 1/1/17 and 1/7/20. Subjects were considered eligible for inclusion in the study analysis if weekly peak CRP ³ 3.0 mg/dL throughout definitive treatment, as £ 3.0 mg/dL may be considered normal in individuals, especially those individuals who have moderate cardiovascular disease. Subjects with biopsy proven metastatic disease, history of renal or liver transplant, history of multiple myeloma, indeterminate time of SAE, or CRP < 3.0 mg/dL were excluded from analysis. Subjects who met inclusion/exclusion criteria were then binarized into “a SAE event” or “non-event” for analysis: SAE was defined as a clinical or diagnostic EHR-documentation of an adverse events within +/- 7 days of peak CRP throughout the course of RT. Based on the predefined inclusion/exclusion criteria, 54 patients were eligible for inclusion in the final analysis, of which 40 (74.1%) were male and 14 (25.9%) were female. The association of a SAE occurring with an increase in CRP was statistically significant (beta = 0.62, p = <0.01 adjusted = 0.37). SAE occurred in 69.7% (n = 23) of those with peak CRP ³ 5.5 mg/dL, and 19% in those with peak CRP <5.5 mg/dL (p = 0.0006, RR = 0.27), thus those with SAE had a higher peak CRP (median = 9.9, IQR = 6.9-12.7) than those with non-events (median = 5.0, IQR = 3.7 – 6.5, Cohens d = 1.61). There were no statistically significant differences among SAE and non-events when consideration was given to gender (male vs. female, p = 0.35), primary site of tumor (oral/nasal vs. pharynx/larynx; p = 0.50), or laterality of disease (unilateral vs. bilateral; p = 0.37). Of those events found to be pulmonary in nature (pneumonia or pulmonary embolism, n = 15, 55.5%), 93% (n = 14) were found in individuals with a peak CRP ³ 5.5 mg/dL. Elevated CRP in HNC patients undergoing active C/RT is associated with an increased incidence of SAEs. A CRP ³ 5.5 mg/dL is highly suggestive of a coinciding adverse event. Use of serial CRP evaluation in conjunction with routine clinical assessment may provide valuable insight into evolving SAE in the HNC C/RT patient warranting increased clinical evaluation. Further validation of these observations is warranted.

Physical Function Impairment and Frailty in Middle-Aged People Living With Human Immunodeficiency Virus in the REPRIEVE Trial Ancillary Study PREPARE.

People with human immunodeficiency virus (PWH) are at risk for accelerated development of physical function impairment and frailty; both associated with increased risk of falls, hospitalizations, and death. Identifying factors associated with physical function impairment and frailty can help target interventions. The REPRIEVE trial enrolled participants 40-75 years of age, receiving stable antiretroviral therapy with CD4+ T-cell count >100 cells/mm3, and with low to moderate cardiovascular disease risk. We conducted a cross-sectional analysis of those concurrently enrolled in the ancillary study PREPARE at enrollment. Among the 266 participants, the median age was 51 years; 81% were male, and 45% were black, and 28% had hypertension. Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was 25 to <30 in 38% and ≥30 in 30%, 33% had a high waist circumference, 89% were physically inactive, 37% (95% confidence interval, 31%, 43%) had physical function impairment (Short Physical Performance Battery score ≤10), and 6% (4%, 9%) were frail and 42% prefrail. In the adjusted analyses, older age, black race, greater BMI, and physical inactivity were associated with physical function impairment; depression and hypertension were associated with frailty or prefrailty. Physical function impairment was common among middle-aged PWH; greater BMI and physical inactivity are important modifiable factors that may prevent further decline in physical function with aging. NCT02344290.

Impact of the Apolipoprotein E (epsilon) Genotype on Cardiometabolic Risk Markers and Responsiveness to Acute and Chronic Dietary Fat Manipulation

Apolipoprotein (APO) E (ε) genotype is considered to play an important role in lipid responses to dietary fat manipulation but the impact on novel cardiometabolic risk markers is unclear. To address this knowledge gap, we investigated the relationship between the APOE genotype and cardiometabolic risk markers in response to acute and chronic dietary fat intakes. Associations with fasting (baseline) outcome measures (n = 218) were determined using data from the chronic DIVAS (n = 191/195 adults at moderate cardiovascular disease risk) and acute DIVAS-2 (n = 27/32 postmenopausal women) studies examining the effects of diets/meals varying in saturated, polyunsaturated and monounsaturated (MUFA) fatty acid composition. Participants were retrospectively genotyped for APOE (rs429358, rs7412). For baseline cardiometabolic outcomes, E4 carriers had higher fasting total and low-density lipoprotein-cholesterol (LDL-C), total cholesterol: high-density lipoprotein-cholesterol (HDL-C) and LDL-C: HDL-C ratios, but lower C-reactive protein (CRP) than E3/E3 and E2 carriers (p ≤ 0.003). Digital volume pulse stiffness index was higher in E2 carriers than the E3/E3 group (p = 0.011). Following chronic dietary fat intake, the significant diet × genotype interaction was found for fasting triacylglycerol (p = 0.010), with indication of a differential responsiveness to MUFA intake between the E3/E3 and E4 carriers (p = 0.006). Test fat × genotype interactions were observed for the incremental area under the curve for the postprandial apolipoprotein B (apoB; p = 0.022) and digital volume pulse reflection index (DVP-RI; p = 0.030) responses after the MUFA-rich meals, with a reduction in E4 carriers and increase in the E3/E3 group for the apoB response, but an increase in E4 carriers and decrease in the E3/E3 group for the DVP-RI response. In conclusion, baseline associations between the APOE genotype and fasting lipids and CRP confirm previous findings, although a novel interaction with digital volume pulse arterial stiffness was observed in the fasted state and differential postprandial apoB and DVP-RI responses after the MUFA-rich meals. The reported differential impact of the APOE genotype on cardiometabolic markers in the acute and chronic state requires confirmation.

Wine and Health-New Evidence.

Health benefits of moderate wine consumption have been studied during the past decades, first in observational studies and more recently, in experimental settings and randomized controlled studies. Suggested biological pathways include antioxidant, lipid regulating, and anti-inflammatory effects. Both the alcoholic and polyphenolic components of wine are believed to contribute to these beneficial effects. Although several of these studies demonstrated protective associations between moderate drinking and cardiovascular disease, atherosclerosis, hypertension, certain types of cancer, type 2 diabetes, neurological disorders, and the metabolic syndrome, no conclusive recommendations exist regarding moderate wine consumption. Yet, it is suggested that the physician and patient should discuss alcohol use. In the CASCADE (CArdiovaSCulAr Diabetes & Ethanol) trial, 224 abstainers with type 2 diabetes were randomized to consume red wine, white wine or mineral water for two years. Here, we summarize our previous findings, offer new evidence concerning the differential effects of wine consumption among men and women, and further suggest that initiating moderate alcohol consumption among well-controlled persons with type 2 diabetes is apparently safe, in regard to changes in heart rate variability and carotid plaque formation.

Cardiovascular health profile among Québec male and female police officers

To document the cardiovascular health profile of Québec police officers (PO). Participants answered an online questionnaire evaluating the presence of cardiovascular disease (CVD) risk factors and symptoms. Two thousand, ninety-nine (2,099) male (age: 40.8 ± 9.2 years) and 756 female (age: 37.9 ± 7.9 years) PO participated in this study. The prevalence of obesity (body mass index ≥30 kg/m2) and diagnosed hypertension was respectively 21.1, and 14.3% in male and 7.3 and 4.1% in female PO. According to 2013 American College of Sports Medicine guidelines, 27.0 and 48.0% of male and 12.1 and 56.7% of female PO were categorized as being at moderate and high CVD risk, respectively. These findings suggest that Québec police departments should help PO to adopt and maintain a healthy lifestyle to decrease CVD risk.

Trends in the epidemiology of chronic kidney disease in Russian Federation according to the Federal Diabetes Register (2013–2016)

BACKGROUND: Chronic kidney disease (CKD) is one of the most severe complications of diabetes mellitus (DM), this determines the importance of the study of epidemiological characteristics of the disease.&#x0D; AIMS: To assess the epidemiological characteristics of CKD in adult DM patients with type 1 (T1), 2 (T2) in Russian Federation in 201316.&#x0D; METHODS: We have used the database of the Russian Federal Diabetes register, 81st regions included in online register. Indicators were estimated per 10,000 adult DM patients (18years).&#x0D; RESULTS: In 2016, the CKD frequency registration was T1 23%, T2 6.9% with marked interregional differences 1.5-49.9%, 0.623.5%, respectively. The CKD prevalence in dynamics 20132016 was 2171.42303.0 in T1 and 512.687.2 in T2. The incidence of new CKD cases increased 2 times in T1 (215.5 vs 104.2), and 3.7 times in T2 (190.4 vs 51.8). The analysis of distribution by CKD stages by KDIGO indicates the increase in the proportion of patients with low and moderate cardiovascular risk and end stage renal disease (ESRD) (with the initial stages of CKD, C1/2 A1) - 12.046.8% in T1; 10.050.4% in T2. The proportion of patients with a very high risk (stages C4/5 C3aA3 and C3bA2-3) progressively decreases: 13.46.7% in T1, 11.34.4% in T2. We observed relation between the CKD prevalence and DM duration. CKD develops in 5.1% patients if T15 years and in 48.0% if T130years; in T2 3.5% and 20.3%, respectively. The average age of CKD onset in T1 increased for 4,3yr (36,140,2), in T2 for 2,4yr (64,466,8), DM duration until CKD development increased in T1 11.814.2yr, in T2 7.68.2yr.&#x0D; CONCLUSIONS: There is a significant improvement in the quality of CKD diagnostics at the earlier stages, older age and a longer DM duration before CKD onset in both types while we observed the increasing trends in CKD prevalence in Russian Federation in the dynamics of 2013-2016. Advances in the management of patients with DM in recent years do not reduce the risk of CKD, but give us a delay in its development. The marked interregional differences frequency of registration of CKD might indicate some remaining problems in verification in a number of regions where the standard for mandatory assessment of albuminuria and glomerular filtration rate not implemented.

A data-driven approach for addressing the lack of flow waveform data in studies of cerebral arterial flow in older adults**The authors gratefully acknowledge support from the National Institute of Neurological Disorders and Stroke (NINDS) through 1R01NS097457-01.

Objective: Blood flow waveforms—essential data for hemodynamic modeling—are often in practice unavailable to researchers. The objectives of this work were to assess the variability among the waveforms for a clinically relevant older population, and develop data-based methods for addressing the missing waveform data for hemodynamic studies. Approach: We analyzed 272 flow waveforms from the internal carotid arteries of older patients (73 ± 13 yr) with moderate cardiovascular disease, and used these data to develop methods to guide new approaches for hemodynamic studies. Main results: Profound variations in waveform parameters were found within the aged population that were not seen in published data for young subjects. Common features in the aged population relative to the young included a larger systole-to-diastole flow rate ratio, increased flow during late systole, and absence of a dicrotic notch. Eight waveforms were identified that collectively represent the range of waveforms in the older population. A relationship between waveform shape and flow rate was obtained that, in conjunction with equations relating flow rate to diameter, can be used to provide individualized waveforms for patient-specific geometries. The dependence of flow rate on diameter was statistically different between male and female patients. Significance: It was shown that a single archetypal waveform cannot well-represent the diverse waveforms found within an aged population, although this approach is frequently used in studies of flow in the cerebral vasculature. Motivated by these results, we provided a set of eight waveforms that can be used to assess the hemodynamic uncertainty associated with the lack of patient-specific waveform data. We also provided a methodology for generating individualized waveforms when patient gender, age, and cardiovascular disease state are known. These data-driven approaches can be used to devise more relevant in vitro or in silico intra-cranial hemodynamic studies for older patients.

Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk

BackgroundConsumption of ≤10% total energy from fat as saturated fatty acids (SFA) is recommended for cardiovascular disease risk reduction in the UK; however there is no clear guidance on the optimum replacement nutrient. Lipid-associated single-nucleotide polymorphisms (SNPs) have been shown to modify the lipid responses to dietary fat interventions. Hence, we performed a retrospective analysis in 120 participants from the Dietary Intervention and VAScular function (DIVAS) study to investigate whether lipoprotein lipase (LPL) and apolipoprotein E (APOE) SNPs modify the fasting lipid response to replacement of SFA with monounsaturated (MUFA) or n-6 polyunsaturated (PUFA) fatty acids.MethodsThe DIVAS study was a randomized, single-blinded, parallel dietary intervention study performed in adults with a moderate cardiovascular risk who received one of three isoenergetic diets rich in SFA, MUFA or n-6 PUFA for 16 weeks.ResultsAfter the 16-week intervention, a significant diet-gene interaction was observed for changes in fasting total cholesterol (P = 0.001). For the APOE SNP rs1064725, only TT homozygotes showed a significant reduction in total cholesterol after the MUFA diet (n = 33; −0.71 ± 1.88 mmol/l) compared to the SFA (n = 38; 0.34 ± 0.55 mmol/l) or n-6 PUFA diets (n = 37; −0.08 ± 0.73 mmol/l) (P = 0.004). None of the interactions were statistically significant for the other SNPs.ConclusionsIn summary, our findings have demonstrated a greater sensitivity of the APOE SNP rs1064725 to dietary fat composition, with a total cholesterol lowering effect observed following substitution of SFA with MUFA but not n-6 PUFA. Further large intervention studies incorporating prospective genotyping are required to confirm or refute our findings.Trial registrationThe trial was registered at www.clinicaltrials.gov as NCT01478958.

Projections of non-communicable disease and health care costs among HIV-positive persons in Italy and the U.S.A.: A modelling study.

BackgroundCountry-specific forecasts of the growing non-communicable disease (NCD) burden in ageing HIV-positive patients will be key to guide future HIV policies. We provided the first national forecasts for Italy and the Unites States of America (USA) and quantified direct cost of caring for these increasingly complex patients.Methods and SettingWe adapted an individual-based model of ageing HIV-positive patients to Italy and the USA, which followed patients on HIV-treatment as they aged and developed NCDs (chronic kidney disease, diabetes, dyslipidaemia, hypertension, non-AIDS malignancies, myocardial infarctions and strokes). The models were parameterised using data on 7,469 HIV-positive patients from the Italian Cohort Naïve to Antiretrovirals Foundation Study and 3,748 commercially-insured patients in the USA and extrapolated to national level using national surveillance data.ResultsThe model predicted that mean age of HIV-positive patients will increase from 46 to 59 in Italy and from 49 to 58 in the USA in 2015–2035. The proportion of patients in Italy and the USA diagnosed with ≥1 NCD is estimated to increase from 64% and 71% in 2015 to 89% and 89% by 2035, respectively, driven by moderate cardiovascular disease (CVD) (hypertension and dyslipidaemia), diabetes and malignancies in both countries. NCD treatment costs as a proportion of total direct HIV costs will increase from 11% to 23% in Italy and from 40% to 56% in the USA in 2015–2035.ConclusionsHIV patient profile in Italy and the USA is shifting to older patients diagnosed with multiple co-morbidity. This will increase NCD treatment costs and require multi-disciplinary patient management.

Effect of Continuous Positive Airway Pressure Treatment on Health-Related Quality of Life and Sleepiness in High Cardiovascular Risk Individuals With Sleep Apnea: Best Apnea Interventions for Research (BestAIR) Trial.

The long-term effect of continuous positive airway pressure (CPAP) on health-related quality of life (HRQOL) in patients with high cardiovascular disease risk and obstructive sleep apnea (OSA) without severe sleepiness is uncertain. We aimed to determine the effect of CPAP treatment on HRQOL in individuals with moderate or severe OSA and cardiovascular disease (CVD) or multiple CVD risk factors without severe sleepiness. In this randomized, controlled, parallel group study, 169 participants were assigned to treatment with CPAP or the control group (conservative medical therapy [CMT] or CMT with sham CPAP). Analyses were based on an intention-to-treat approach. Linear mixed effect models were fitted to compare the changes in the Medical Outcomes Study Short Form-36 (SF-36) and in subjective sleepiness (Epworth Sleepiness Scale [ESS]) between groups from baseline to the average of 6- and 12-month measurements. CPAP improved several domains of HRQOL including bodily pain (treatment effect 9.7 [95% confidence interval, CI 3.9 to 15.4]; p = .001), vitality (5.7 [95% CI 1.5 to 9.9]; p = .008), general health (8.2 [95% CI 3.7 to 12.7]; p < .001), physical functioning (5.5 [95% CI 1.1 to 10.0]; p = .016), and the physical health summary score (3.3 [95% CI 1.4 to 5.3]; p = .001). CPAP also resulted in less daytime sleepiness (mean change in ESS -1.0 point [95% CI -2.0 to -0.0]; p = .040). In patients with moderate-severe OSA at high risk of cardiovascular events and without severe sleepiness, CPAP improved daytime sleepiness and multiple domains of HRQOL over 6 to 12 months of follow-up, with the largest improvement observed for bodily pain.