Major Cardiovascular Disease Risk Research Articles

Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars)

BackgroundWe aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting.MethodsThe PolyPars Study is a two-arm...

Prospective cohort of parameters of glycemic and lipid metabolism after abdominoplasty in normal weight and formerly obese patiens

BackgroundObesity poses a major risk for cardiovascular diseases, while it is almost a consensus that intra-abdominal adiposity has a more deleterious effect for metabolic syndrome. In this sense, it is speculated that lipectomy or liposuction would be metabolically harmful, as it changes the abdominal-superficial adipose tissue ratio. However, the literature has shown conflicting evidence. MethodsIn order to evaluate the possibility of metabolism alteration resulting from body coutouring surgery, a prospective cohort was implemented with 35 patients who underwent abdominoplasty, including some with a history of massive weight loss. Fasting blood glucose, fasting plasma insulin, triglycerides, total cholesterol and fractions were requested preoperatively and in the third postoperative month. The groups were also compared with each other. ResultsNo statistically significant variation between the exams collected in the preoperative period and those collected after abdominoplasty was found. There was a statistically significant difference in LDL (low-density lipoprotein; p = 0.033) and non-HDL (non-high-density lipoprotein) cholesterol (p = 0.020) between the two control tests of the groups surveyed. There were also differences in comorbidities (p = 0.006) and complications (p <0.001) between the groups. ConclusionsAbdominoplasty was not able of changing tests that assess glycemic and lipid metabolism three months after the operation. Our attention was drawn to the fact that patients who had massive weight loss had better control of LDL cholesterol (p = 0.033) and non-HDL cholesterol (p = 0.020), despite having higher weight and body mass index (p <0.001).

Liver disease is a significant risk factor for cardiovascular outcomes – A UK Biobank study

Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events. Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c). A total of 33,616 participants (mean age 65 years, mean BMI 26kg/m2, mean haemoglobin A1c 35mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p= 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p= 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p= 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001). Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat. Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.

Systolic Blood Pressure Control Targets to Prevent Major Cardiovascular Events and Mortality in Patients With Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.

Previous meta-analyses using traditional pairwise comparisons did not support intensive systolic blood pressure (SBP) control in patients with diabetes and included trials published before 2015. We aimed to identify the optimal SBP control targets in patients with type 2 diabetes using a systematic review and network meta-analysis of accumulating evidence. We systematically searched PubMed, Embase, and Cochrane Library from inception to August 29, 2022 for randomized controlled trials comparing different blood pressure targets, antihypertensive agents against placebo, or dual antihypertensive agents against single agent in patients with type 2 diabetes. Network meta-analysis was used to obtain pooled results of direct and indirect comparisons of each 5 mm Hg SBP category in association with clinical outcomes adjusted for baseline risk and intervention duration (PROSPERO [International Prospective Register of Systematic Reviews], CRD 42022316697). We identified 30 trials including 59 934 patients with type 2 diabetes. The mean achieved SBP levels ranged from 117 mm Hg to 144 mm Hg among treatment groups. A total of 7799 major cardiovascular diseases events and 4130 deaths were reported. The lowest risk of major cardiovascular diseases was found in patients with achieved SBP level of 120 to 124 mm Hg. The hazard ratio and 95% CI were 0.73 (0.52-1.02) compared with 130 to 134 mm Hg, 0.60 (0.41-0.85) compared with 140 to 144 mm Hg, and 0.41 (0.26-0.63) compared with ≥150 mm Hg. Similar results were found for cardiovascular diseases components including stroke, myocardial infarction, heart failure, and cardiovascular mortality. All-cause mortality was reduced at an achieved SBP <140 mm Hg but further reduction did not show additional benefits. Our findings support an intensive blood pressure-lowering strategy to prevent major cardiovascular diseases in patients with type 2 diabetes.

Risk of Major Cardiovascular Disease after Exposure to Contrast Media: A Nationwide Population-Based Cohort Study on Dialysis Patients.

Contrast associated kidney injury is caused by side effects of iodinated contrast media (ICM), including inflammation. Chronic inflammation among dialysis patient contributes to atherosclerosis, which leads to simultaneous conditions of the kidney, brain, and vasculature. Data to investigate the pathologic effects of ICM on cardiovascular complications in dialysis patients are lacking. Dialysis patients who had been exposed to ICM from computed tomography (ICM-CT) were allocated as the ICM-CT cohort (N = 3751), whereas dialysis patients without ICM exposure were randomly allocated as the non-ICM cohort (N = 17,196). Furthermore, 540 pairs were selected for analyses through propensity score-matching in terms of age, sex, comorbidities, dialysis vintage, and index date. During a median follow-up of 10.3 years, ICM-CT cohort had significantly higher risks in the following, compared with non-ICM cohort: all-cause mortality (adjusted hazard ratio [aHR], 1.36; 95% confidence interval [CI], 1.26-1.47), cardiovascular events (aHR,1.67; 95% CI, 1.39-2.01), acute coronary syndrome (adjusted HR: 2.92; 95% CI, 1.72-4.94), sudden cardiac arrest (aHR, 1.69; 95% CI, 0.90-3.18), heart failure (aHR, 1.71; 95% CI,1.28-2.27), and stroke (aHR, 1.84; 95% CI,1.45-2.35). The proinflammatory ICM is significantly associated with an increased risk of major cardiovascular events in patients on dialysis.

S-14-3: WHICH IS THE OPTIMAL BP TARGET TO ACHIEVE? SHOULD GUIDELINES BE UPDATED?

Hypertension Guidelines disagree on the definition of the more appropriate blood pressure (BP) target to achieve. A shared feature of Guidelines was the definition of precise (albeit differing across Guidelines) BP targets in different patient categories (Table). Does the evidence support the definition of precise BP targets overall and in different patient categories? Evidence from observational studies. A direct relation between BP and risk of cardiovascular disease emerged from observational studies including a large meta-analysis (Lancet 2002). Most studies showed that after correction for several confounders (cancer; heart failure etc) the lowest cardiovascular risk occurred at low values of achieved BP (&lt;120/80 or even &lt; 100/60 mmHg). Evidence from intervention studies. Meta-analyses of randomized studies between different drugs or BP targets showed two main findings: (a) The larger the BP difference between randomized groups in the achieved BP the greater the benefit (particularly on stroke and heart failure) in the group with the lower achieved BP. (b) When comparing a more intensive with a less intensive BP target (i.e. 120 vs 140 mmHg) the risk of major cardiovascular disease was lower with the more intensive strategy. In a meta-analysis a more intensive strategy reduced stroke by 20%; myocardial infarction by 15%; heart failure by 25%; cardiovascular death by 18% and all-cause death by 11% (Hypertension 2016) when compared to a less intensive strategy. BP targets considerably differed across the studies. Evidence regarding tolerability of treatment. Some Guidelines suggest that a more intensive BP target could be achieved at condition that the treatment is well tolerated. However the concept of good treatment tolerability holds at any level of achieved BP (not only below 140/90 mmHg) irrespective of the BP target. There is no evidence supporting safety thresholds not to be exceeded when the treatment is well tolerated. Conclusion: The lowest well tolerated BP is a reasonable and evidence-based BP target irrespective of the cardiovascular risk status of the patient. Table: BP targets according to major hypertension Guidelines.

Cardiovascular benefits and risks associated with calcium, vitamin D, and antiresorptive therapy in the management of skeletal fragility.

Osteoporosis affects one in every five women over the age of 50 worldwide. With a rapidly ageing population, the prevalence of fragility fractures, considered a largely preventable consequence of osteoporosis, is expected to increase. Age is also a major risk for cardiovascular disease and mortality, thus highlighting the importance of cardiovascular profiling of osteoporosis interventions. Although calcium and vitamin D are essential for a healthy bone metabolism, excessive supplementation may be associated with increased risk. Conversely, early pre-clinical data have suggested a possible cardiovascular benefit from bisphosphonate therapy. This review evaluates the evidence behind the cardiovascular benefits and risks that may be associated with osteoporosis therapy.

Should we rethink the blood pressure targets in hypertension guidelines?

Hypertension Guidelines disagree on the definition of the more appropriate blood pressure (BP) target to achieve. A shared feature of Guidelines was the definition of precise, albeit differing across Guidelines, BP targets in different patient categories (i.e., 140 mmHg, 130 mmHg, etc.). The definition of rigid and precise BP targets overall and in different risk categories is not fully supported by evidence. Observational studies: A direct relation between BP and risk of cardiovascular disease emerged from observational studies, including a large meta-analysis (Lancet 2002:1903). The majority of the studies showed that after correction for several confounders (cancer, heart failure, etc.), the lowest cardiovascular risk occurred at low values of achieved BP (<120/80 mmHg, or even <100/60 mmHg). Intervention studies: Meta-analyses of randomized studies between different drugs or BP targets showed two main findings: (a) the larger the BP difference between randomized groups in the achieved BP, the greater the benefit (particularly on stroke and heart failure) in the group with the lower achieved BP; (b) when comparing a more intensive with a less intensive BP target (i.e., 120 vs 140 mmHg), the risk of major cardiovascular disease was lower in association with the more intensive strategy. In a meta-analysis, a more intensive strategy reduced stroke by 20%, myocardial infarction by 15%, heart failure by 25%, cardiovascular death by 18% and all-cause death by 11% (Hypertension 2016:642) when compared to a less intensive strategy. Notably, BP targets considerably differed across the studies. Evidence regarding tolerability of treatment: According to Guidelines, a more intensive BP target may be allowed at condition that the treatment is well tolerated. However, the concept of ‘good tolerability of treatment’ holds at any level of achieved BP, irrespective of the BP target. No evidence supports the concept of ‘safety thresholds’ in patients who tolerate treatment very well. Conclusion: The ‘lowest well tolerated BP’ looks like a simple, evidence-based and reasonable BP target regardless of the cardiovascular risk status of the patient.

Impact of reproductive factors on major cardiovascular disease risk in women: a Mendelian randomization study

Abstract Background Cardiovascular disease is a major cause of morbidity and mortality in women. Multiple observational studies have explored the role of female reproductive history on the risk of cardiovascular disease and suggested that factors such as high parity and early menarche are associated with higher rates of cardiovascular disease later in life. However, effect estimates derived from observational studies are liable to influence by residual confounding and bias in study design. We utilise Mendelian randomisation to explore causal pathways underlying this association by leveraging genetic variability in reproductive factors using instrumental variable analysis. Methods Uncorrelated single nucleotide polymorphisms (r2&amp;lt;0.001) were extracted from summary statistics of published sex-specific genome wide association studies (GWAS) for the exposures of age at first birth (n=131,987, unit = years), number of live births (n=193,953, coded into three categories of &amp;lt;2, 2 or &amp;gt;2 live births), age at menarche (n=329,345, unit = years) and age at menopause (n=106,048, unit = years). Genetic association estimates for the outcomes of coronary artery disease, ischaemic stroke, stroke of any type, heart failure and atrial fibrillation were extracted from GWAS analyses on respectively 122,733 cases, 34,217 cases, 40,585 cases, 47,309 cases and 60,620 cases. All GWAS studies were on populations of predominantly European ancestry. Inverse-variance weighted MR was utilised for primary analyses; sensitivity analyses using MR-Egger and weighted median MR were carried out. Results Earlier age at first birth was associated with increased risk of coronary artery disease (OR per 1-year lower age = 1.49, 95% CI 1.28–1.74, p&amp;lt;0.001). Lower age at menarche was also associated with increased risk of coronary artery disease (OR per 1-year lower age = 1.10, 95% CI 1.06–1.14, p&amp;lt;0.001) and increased risk of heart failure (OR 1.12, 95% CI 1.07–1.17, p&amp;lt;0.001). Finally, higher number of live births was associated with increased risk of atrial fibrillation (OR per increase in category of &amp;lt;2, 2 or &amp;gt;2 live births = 2.91, 95% CI 1.16–7.29, p=0.023), increased risk of heart failure (OR 1.90, 95% CI 1.28–2.82, p=0.001), increased risk of ischaemic stroke (OR 2.07, 95% CI 1.22–3.52, p=0.007) and of stroke of any type (OR 1.86, 95% CI 1.03–3.37, p=0.039). Conclusion The results of this study support the emerging evidence of female-specific risk factors for cardiovascular disease, by demonstrating that that earlier age at first birth, higher number of live births, and earlier menarche are all associated with increased cardiovascular morbidity in women. The results notably highlight parity as a major sex-specific risk factor of likely causal relevance. These findings support the inclusion of reproductive history in the routine evaluation of cardiovascular risk in females and identify key markers of risk that may be used to target primary prevention measures. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council GEPSI 946647 for EAWSBritish Heart Foundation RG/16/3/32175 for FSN

Dietary Patterns and Blood Biochemical and Metabolic Parameters in an Italian Population: A Cross-Sectional Study

Diet has long been identified as a major determinant of cardiovascular and other chronic diseases. In this study, we assess the relation between adherence to different dietary patterns and biochemical and metabolic parameters as well as the 10-year risk of major cardiovascular diseases (CVDs) in a community of blood donors in Northern Italy. We assess their adherence to four dietary patterns, namely, the Dietary Approach to Stop Hypertension (DASH) diet, the Mediterranean diet through the Greek and Italian Mediterranean Indices (GMI and IMI) and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, using a validated semi-quantitative food frequency questionnaire (FFQ). We then assess their association with blood parameters and the 10-year risk of major CVD using a spline regression model. We found an inverse association between the DASH and MIND diets and total and LDL cholesterol, and triglyceride and HDL cholesterol values for the Mediterranean diets (IMI and GMI). Additionally, according to our sex-stratified analyses, men who have greater adherence to dietary patterns have a decreased risk of major CVD for all patterns. The results suggest that greater adherence to dietary patterns positively influences blood biochemical and metabolic parameters, thus reducing the risk of developing cardiovascular disease and delaying the use of drug treatments.

171-OR: Effect of Interventions on Blood Pressure for Black Persons with Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Controlled Trials

Background: Uncontrolled blood pressure (BP) is a major cardiovascular disease (CVD) risk factor, and CVD is the leading cause of death among non-Hispanic Black persons with type 2 diabetes (T2D) . While many interventions have been designed to improve BP control in this population, disparities persist. A meta-analysis of randomized controlled trials was conducted to evaluate the effectiveness of T2D interventions at improving BP. Methods: An electronic search of Medline, PubMed, Scopus, CINAHL, and PsychINFO was conducted from 1985 to 2019. Keywords included those related to diabetes, study design and race/ethnicity. We included non-pharmacologic trials with ≥12.5% Black persons (using the 2020 US Census as a standard) . Interventions were aimed at improving outcomes including HbA1c, BP, weight and lipids. For this analysis, we focused on the outcomes mean systolic (SBP) and diastolic blood pressure (DBP) differences between control and experimental groups. A random effects meta-analysis was performed to calculate the pooled effect size to provide summary estimates. Results: Sixteen trials (n=2314) reported SBP and DBP outcomes; two additional trials (total n=2919) reported only SBP outcomes. The participants were 59% Black and 71% female with a mean age of 55.9 years. Average baseline BP was similar for the control and intervention groups (134/78 and 134/77, respectively) . Interventions included self-management education, telehealth support, lifestyle programs, and pharmacist-led support. Compared to control, these interventions demonstrated no difference in SBP (0.01, 95% CI -0.to 0.mmHg, p=0.55, I2=0%) or DBP (-0.05, 95% CI -0.15 to 0.mmHg, p=0.20, I2=22%) . Conclusion: In this meta-analysis of trials aimed to improve outcomes in Black patients with T2D, there was no improvement in BP control. Given the high risk of CVD in this population, more effective interventions are needed to improve BP control in Black persons with T2D. Disclosure C.Jiang: None. F.Osman: None. A.Deckard: None. W.Wan: n/a. J.Alexander: None. R.Shetty: None. E.M.Staab: None. N.Laiteerapong: None.

Hyperhomocysteinemia Increases Risk of Metabolic Syndrome and Cardiovascular Death in an Elderly Chinese Community Population of a 7-Year Follow-Up Study.

BackgroundHyperhomocysteinemia (HHcy) and abdominal obesity are risk factors for metabolic syndrome (MetS) and death from cardiovascular disease (CVD). Recent studies have shown a correlation between HHcy and abdominal obesity, suggesting that they may have a combined effect on the risk of MetS and CVD mortality. However, this suspicion remains to be confirmed, particularly in the elderly population. We explored their combined effects on the risk of MetS and CVD mortality among the community population aged 65 and above in China.Methods and ResultsThis prospective study enrolled 3,675 Chinese community residents aged 65 and above in May 2013 with 7-year follow-up of all-cause and CVD mortality. HHcy was defined as the blood homocysteine (Hcy) level >15 μmol/L and abdominal obesity as waist circumference (WC) ≥90 cm for men and ≥80 cm for women (HWC). All participants were grouped into four categories by WC and the blood level of Hcy: NWC (normal WC) /HHcy(–), NWC/HHcy(+), HWC/HHcy(–), and HWC/HHcy(+). The relationship of combined HHcy and abdominal obesity with MetS and metabolic profile was evaluated by logistic regression analysis and the association of combined HHcy and abdominal obesity with CVD and all-cause mortality evaluated by Cox regression analysis. The prevalence of HHcy, abdominal obesity and MetS in elderly Chinese community residents was 40.1, 59.3, and 41.4%, respectively. Using group without HHcy and abdominal obesity [NWC/HHcy(–)] as reference, the participants of other three groups had significantly higher risk of MetS and its component abnormalities, with HWC/HHcy(+) group having the highest risk (OR = 13.52; 95% CI = 8.61–14.55). After a median of 6.94 (±1.48) years follow-up, 454 deaths occurred with 135 CVD deaths. Compared with NWC/HHcy(–) group, the risk of 7-year follow-up CVD mortality (HR = 1.75; 95% CI = 1.02–3.03) and all-cause mortality (HR = 1.23; 95% CI = 1.04–2.18) of HWC/HHcy(+) group increased considerably after adjustment for major MetS and CVD risk factors.ConclusionsThere is high prevalence of HHcy, abdominal obesity, and MetS in the elderly Chinese community population. HHcy increases risk of MetS, CVD, and all-cause mortality, especially in the populations with abdominal obesity.

Role of Sodium-Glucose Cotransporter-2 Inhibitors in Readmissions for Congestive Heart Failure

<p style="text-align: justify;"><strong>Background: </strong>Patients with type II diabetes are at major risk for cardiovascular disease. Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) have demonstrated benefit for these patients. The purpose of this study is to determine whether SGLT-2 inhibitors significantly reduce heart failure readmission rates and improve outcomes in patients with congestive heart failure (CHF). <strong>Methods:</strong> Patient data was pulled on CHF patients with an active prescription for an SGLT-2 inhibitor, and it was analyzed using Fischer&rsquo;s Exact tests and two-tailed t-tests. The primary outcome was a 6-month hospital readmission rate due to CHF while taking SGLT-2 inhibitors. Secondary outcomes included 6-month all-cause hospital readmissions, renal function as measured by an estimated glomerular filtration rate change between admissions, mortality rates, and ejection fraction. <strong>Results: </strong>Of the 138 patients that met inclusion criteria for the first admission, the 6-month all-cause readmission rate for CHF patients still taking SGLT-2 inhibitors at readmission was 21 percent vs 16 percent (<em>p</em>=0.6) for the control group not taking SGLT-2 inhibitors. The 6-month CHF readmission rate in patients taking SGLT-2 inhibitors was 7.2 percent, and a CHF specific readmission rate was not collected for the control group. In patients with an eGFR less than 90, the average eGFR for the SGLT-2 group declined slightly but was not significant between patients at first admission and those with readmission (<em>p</em>=0.21). <strong>Conclusion:</strong> The use of SGLT-2 inhibitors in patients with CHF did not change the overall hospital readmission rate; however, larger randomized controlled trials are needed for further evaluation of the potential benefit. <p style="text-align: justify;"><strong>Key words: </strong>Cardiovascular Outcomes, Chronic Heart Failure, Heart Failure Hospitalization, SGLT2 Inhibition, Type II Diabetes.

Association between dairy product intake and high blood pressure in Chilean adults.

Hypertension is a major risk for cardiovascular disease. Several studies have connected dairy consumption with lower blood pressure (BP). However, these have not considered the Latin American population. The aim of this study was to examine the relationship between consumption of full-fat or low fat/fat free dairy products and high blood pressure in Chilean adults. Cross-sectional study containing data from 3,807 adults between 20 and 98 years old from the National Health Survey (NHS) of Chile 2016-2017. Information on lifestyle, food frequency, and socio-demographics was collected using standardized questionnaires. Trained fieldworkers took anthropometric and blood pressure measurements. The frequency of consumption data included seven ad-hoc questions on habitual eating and frequency options, based on the Mediterranean diet (fish products, fruit and vegetable, and dairy products) and its protective effect on cardiovascular diseases. The selection of foods was supported by expert opinion. Of the 3,807 adults, 37% were male and 63% were female. Sex, education level, frequency of dairy products and fish, smoking, and sport or physical activity had a direct relationship with consumption of dairy products (P < 0.05). Consumption of low fat/fat free dairy products was protectively associated with high blood pressure in the unadjusted model (OR: 0.76, CI 95% 0.64-0.91). However, after adjustment for confounding variables (education level modifies the effect 10.2%), this association was attenuated (OR: 0.88; CI 95% 0.71-1.08). We found limited evidence that the type of dairy products consumed is associated with high blood pressure in the Chilean population.

Abstract 18: Excess Dietary Salt-induced Blood Pressure Elevation Is Associated With Impaired Bile Acid Signaling And Human Monocyte Activation

Excess dietary sodium (Na + ) is a major risk for hypertension and cardiovascular disease. We previously found that excess dietary salt induces gut microbial dysbiosis and leads to activation of antigen presenting cells and hypertension, but the mechanisms are not known. The gut microbiome metabolizes bile acids, and these have been implicated in activation of antigen presenting cells. We hypothesized that high dietary Na + -induced inflammation leading to hypertension is associated with impaired bile acids signaling. We measured plasma bile acids via a metabolomics analysis in 75 volunteers. Blood pressure was also monitored. Based on the recommendations by the American Heart Association, we classified daily Na + intake &lt;2.3g as normal salt (NS, n=23), and high salt (HS, n=52) for subjects consuming ≥ 2.3g Na + . Spearman correlation was used to assess the relationship between Na + intake and blood pressure. We found that elevated diastolic (r=0.331, p=0.003), systolic (r=0.383, p&lt;0.001) and mean arterial pressure (r=0.278, p=0.014) were associated with increased Na + intake. Five taurine and glycine-conjugated secondary bile acids including taurodeoxycholate (1.320 ± 0.238 vs. 2.820 ± 0.669; p=0.010); glycodeoxycholate (1.197± 0.154 vs. 1.998± 0.432; p= 0.033); glycodeoxycholate sulfate (1.037± 0.132 vs. 1.521± 0.192; p= 0.044); glycolithocholate (0.829± 0.094 vs. 1.622± 0.363; p= 0.006) and glycolithocholate sulfate (1.083± 0.127 vs. 1.598± 0.205; p= 0.030) were lower in the HS when compared to the NS group. Interestingly, using RNA sequencing in human monocytes, we found that the NR1H4 gene which encodes the farnesoid X receptor, a nuclear receptor activated by bile acids, was significantly downregulated by high salt treatment, and this was associated with a pro-inflammatory phenotype (9.80± 1.65 vs. 11.82± 1.64; adjusted p-value=0.043). Our findings suggest that high salt impairs bile acids signaling leading to inflammation and salt-induced hypertension.

Abstract P205: Use Of A Noninvasive, Closed-loop, Allostatic, Neurotechnology Reduced Blood Pressure And Improved Sleep In Heterogeneous Cohort

Introduction: Elevated blood pressure is a major modifiable risk for cardiovascular disease. Disturbed central control of cardiovascular regulation due to trauma, stress, anxiety or other causes can lead to rise in blood pressure. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®) is a noninvasive, closed-loop, allostatic, acoustic stimulation neurotechnology using software algorithms to identify specific brain frequencies, and translate them in real time into audible tones, to support self-optimization of brain rhythms. Objective: To evaluate the benefits of adding this nontraditional therapy on BP and symptoms of insomnia in subjects with normal or controlled BP, who are enrolled in an IRB-approved open label feasibility study evaluating HIRREM for diverse neuropsychological disorders. Methods: 236 participants (105 female), mean (SD) age 43.1 (16.5), received 15.7 (4.8) HIRREM sessions over 22.6 (18.2) days, (9.3 (3.4) days with sessions). Brachial BP and insomnia score (ISI) were collected before, and 14.0 (14.0) days after HIRREM completion. Paired t-tests were performed. Results: Before HIRREM, participants were divided in the following groups based on ACC/AHA 2017 BP guidelines, normal n=78, elevated n=36, stage 1 n=50, stage 2 n=57, stage 3 n=14 and crisis n=2. There were no changes in medications throughout the study duration. The use of HIRREM was associated with significant reduction in systolic BP (from 126.1 (19.0) to 123.5 (17.0) mmHg, p=0.007), and diastolic BP (from 75.3 (10.6) to 73.0 (9.0) mmHg, p&lt;0.001), with no change in heart rate. Many participants moved to lower BP stage after V2 with the number of participants within normal BP at V2 increasing from 78 to 88. ISI score decreased from 13.2 (7.2) to 6.7 (5.6), p&lt;0.0001. This change met the clinically meaningful drop in ISI of 6 points or more. Conclusion: These data provide evidence of significant benefits of adding a closed-loop therapy for blood pressure reduction and improving sleep. Further studies are indicated to better define the role of this promising intervention to improve sleep, depression, anxiety, and cardiovascular outcomes.

Chronic stress induced perivascular adipose tissue impairment of aortic function and the therapeutic effect of exercise.

What is the central question of this study? Thoracic perivascular adipose tissue (tPVAT) is known to, in part, regulate aortic function: what are the effects of unpredictable chronic mild stress (UCMS) on the tPVAT regulation of aortic function and what is the role of exercise training in alleviating the potential negative actions of UCMS on tPVAT? What is the main finding and its importance? UCMS causes tPVAT to disrupt endothelium-dependent dilatation, increases inflammatory cytokine production and diminishes tPVAT-adiponectin. Exercise training proved efficacious in preventing tPVAT-mediated disruption of aortic function. The data support a tPVAT mechanism through which chronic stress negatively impacts vascular health, which adds to our knowledge of how psychological disorders might increase the risk of cardiovascular disease. Chronic stress is a major risk for cardiovascular disease. Perivascular adipose tissue (PVAT) has been shown to regulate vascular function; however, the impact of chronic stress and the comorbidity of metabolic syndrome (MetS) on thoracic (t)PVAT is unknown. Additionally, aerobic exercise training (AET) is known to combat the pathology of MetS and chronic stress, but the role of tPVAT in these actions is also unknown. Therefore, the purpose of this study was to examine the effects of unpredictable chronic mild stress (UCMS) on the tPVAT regulation of aortic function and the preventative effect of AET. Lean (LZR) and obese (OZR) Zucker rats (16-17weeks old) were exposed to 8weeks of UCMS with and without treadmill exercise (AET). In LZR, UCMS impaired aortic endothelium-dependent dilatation (EDD) (assessed ex vivo by wire myography) and aortic stiffness (assessed by elastic modulus) with no change in OZR subject to UCMS. However, both LZR and OZR UCMS tPVAT impaired EDD compared to respective controls. LZR and OZR subject to UCMS had higher oxidative stress production, diminished adiponectin and impaired aortic nitric oxide levels. Divergently, UCMS induced greater inflammatory cytokine production in LZR UCMS tPVAT, but not in OZR UCMS tPVAT. AET prevented the tPVAT impairment of aortic relaxation with UCMS in LZR and OZR. Additionally, AET reduced aortic stiffness in both LZR and OZR. These beneficial effects on tPVAT regulation of the aorta are likely due to AET preservation of adiponectin, reduced oxidative stress and inflammation, and enhanced nitric oxide. UCMS impaired tPVAT-regulated aortic function in LZR, and augmented MetS-induced EDD in OZR. Conversely, AET in combination with UCMS largely preserved aortic function and the tPVAT environment, in both groups.

Cell Signaling in Diabetic Dyslipidemia

Diabetes accompanies several metabolic complications and poor production and clearance of lipoprotein is one of them. Type 2 diabetes mellitus is linked with atherosclerosis, though exact mechanism is still unclear. There are different complications of type 2 diabetes mellitus. Dyslipidemia is one of them. It has been documented that deranged lipid profile is caused by insulin resistance. Dyslipidemia arises due to low level of high density lipoproteins and high level of triglycerides. Diabetic dyslipidimia occurs due to imbalance in reverse cholesterol transport mechanism which is a major risk for cardiovascular diseases. Reverse cholesterol transport is regulated by cell surface receptors scavenger receptor B1 and ATP binding cassette protein-1. These are HDL binding receptors and help to maintain balance of HDL. Genetic and epigenetic factors influence the regulation of cell surface receptors. It plays a significant role in lipid homeostasis. HDL receptors are encoded by SCARB1 and ABCA1 genes. Peroxisome proliferator activated receptor alpha (PPARα) is a down-stream transcriptional activator of SCARB1, ABCA1 and ApoA1 genes.

Premetabolic Syndrome is a Major Cardiovascular Disease Risk in Indian Population

The metabolic syndrome (MS) is characterized by several cardiovascular (CV) risk factors and is associated with an increased incidence of diabetes, CV events and mortality. The prevalence of MS is increasing in epidemic proportions worldwide, but presently it is most common in India. MS is characterized by the presence of abdominal obesity, high fasting glucose, atherogenic dyslipidemia and high blood pressure.[1] MS is related to other comorbidities including, prothrombotic state, proinflammatory state, non-alcoholic steatohepatitis and reproductive disorders. MS is also associated with increased risk of type 2 diabetes, CV disease and all-cause mortality. Furthermore, there is evidence that MS is an effective clinical tool to identify individual’s predisposition to high risk of CV disease and type 2 diabetes. Prevalence of MS is increasing in epidemic proportions in both developed countries and developing countries. The worldwide prevalence of MS in the adult population is estimated between 20% and 25%. According to data from the National Health and Nutrition Examination Survey (NHANES) 2009–2010, about one-fifth of the adult population of the United States had high cardiometabolic risk, with the prevalence of MS (adjusted for age) being estimated at 22.9%.[2] In Indian population, the prevalence of MS is more than 40% above the age of 40 years.[3]

CircPAN3 ameliorates myocardial ischaemia/reperfusion injury by targeting miR-421/Pink1 axis-mediated autophagy suppression

AbstractCardiovascular diseases are considered the leading cause of death worldwide. Myocardial ischaemia/reperfusion (I/R) injury is recognized as a critical risk factor for cardiovascular diseases. Although increasing advances have been made recently in understanding the mechanisms of I/R injury, they remain largely unknown. In this study, we found that the expression of circPAN3 (circular RNA PAN3) was decreased in a mouse model of myocardial I/R. Overexpression of circPAN3 significantly inhibited autophagy and alleviated cell apoptosis of cardiomyocytes, which was further verified in vivo by decreased autophagic vacuoles and reduced myocardial infarct sizes. Moreover, miR-421 (microRNA-421) was identified as a downstream target involved in circPAN3-mediated myocardial I/R injury. Additionally, miR-421 could negatively regulate Pink1 (phosphatase and tensin homologue-induced putative kinase 1) via a direct binding relationship. Furthermore, the mitigating effects of circPAN3 overexpression on myocardial I/R injury by suppressing autophagy and apoptosis were abolished by knockdown of Pink1. Our findings reveal a novel role for circPAN3 in modulating autophagy and apoptosis in myocardial I/R injury and the circPAN3–miR-421–Pink1 axis as a regulatory network, which might provide potential therapeutic targets for cardiovascular diseases.Cardiovascular diseases are the leading cause of death worldwide. Myocardial ischaemia/reperfusion (I/R) injury is a major risk for cardiovascular disease. Herein, the authors demonstrate that circPAN3 ameliorates myocardial I/R injury by absorbing miR-421 to regulate Pink1-mediated autophagy, which may provide potential therapeutic targets in I/R injury.