Greater Risk Of Cardiovascular Disease Research Articles

Association between the triglyceride-glucose index and albuminuria in hypertensive individuals

ABSTRACT Background Previous studies have demonstrated that the triglyceride-glucose (TyG) index is significantly associated with vascular damage. Albuminuria is a marker of hypertension-mediated organ damage (HMOD) and has been linked to a greater risk of cardiovascular disease (CVD). However, the association between the TyG index and albuminuria in patients with hypertension is not clear. This population research focused on subjects with hypertension to investigate the association between an elevated TyG index and albuminuria. Methods From September 2019 to November 2019, 789 hypertensive participants were involved in our research. Logistic regression models were performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for albuminuria according to the quartiles of the TyG index. Results Multivariate logistic regression analysis revealed that the TyG index was significantly associated with albuminuria. Using the lowest TyG index quartile as the reference, the fully adjusted ORs (95% CIs) for albuminuria for TyG index quartile II, quartile III, and quartile IV were 1.90 (1.17–3.12), 1.81 (1.07–3.07), and 3.46 (2.06–5.91), respectively. The results in the subgroup analysis were similar to the main analyses except for the smokers. Restricted cubic spline curves based on logistic regression models evaluated the linear association between the TyG index and albuminuria (P for nonlinear = 0.831). Conclusion The TyG index was positively associated with albuminuria among hypertensive participants.

Skeletal and nonskeletal consequences of hypoparathyroidism.

Hypoparathyroidism, despite the conventional therapy with calcium and active vitamin D, can lead to skeletal and nonskeletal abnormalities. Chronic hypoparathyroidism is associated with a significant reduction in bone remodeling, increases in areal and volumetric bone density, and improvement in trabecular microarchitecture and in trabecular bone score. Regardless of these advantages in bone mass and microarchitecture, recent data suggest an increased vertebral fracture risk in patients with nonsurgical hypoparathyroidism. Moreover, chronic hypoparathyroidism can lead to abnormalities in multiple organ systems, including the neurological, cardiovascular, renal, neuropsychiatric, ocular, and immune systems. Nephrocalcinosis, nephrolithiasis, and renal insufficiency, as well as decreased quality of life and cataracts, are common in patients with hypoparathyroidism. An increased incidence of hospitalization due to infections and a greater risk of cardiovascular diseases are observed in patients with hypoparathyroidism, particularly in those with nonsurgical disease. All these abnormalities may be because of the disease itself or complications of therapy. We herein reviewed the skeletal and nonskeletal consequences of hypoparathyroidism in patients conventionally managed with calcium and active vitamin D.

A Common Variant in GRK5 Reveals a PAR1-Specific Mechanism for Its Regulation of Platelet Function

Two separate genome wide association studies (GWAS), recently conducted by our group and another group, have identified the variant rs10886430 in the G protein-coupled receptor kinase 5 (GRK5) gene with a minor allele frequency of ~14% in Caucasians. Both studies show that the variant resides in a megakaryocyte-specific enhancer that alters the binding of the transcription factors GATA1 and MEIS1. In contrast to the major allele (A), the minor allele (G) is associated with decreased GRK5 mRNA expression, increased platelet reactivity, and greater risk of cardiovascular disease. However, the effect of the variant on protein expression has not been investigated by either group. In addition, there is an inconsistency between the findings of each of the studies regarding the specific role of GRK5 in thrombin receptor PAR1- and PAR4-mediated platelet activation. Further studies are needed to clarify whether, and how, GRK5 regulates platelet activity via PAR1, PAR4, or both. Here we introduce the A>G mutation into a megakaryoblastic cell line, Meg-01, by CRISPR-Cas9 genome editing. GRK5 protein expression is decreased by 80% in A>G mutant Meg-01 cells compared to WT control cells. To determine whether GRK5 regulates PAR1, PAR4, or both, we have isolated human platelets and specifically blocked GRK5 activity with compound CCG273261 to compare platelet responses to PAR1- and PAR4-specific agonists. Our data show that pharmacological inhibition of GRK5 increases markers of platelet activation such as integrin activation and P-selectin surface exposure in response to PAR1 receptor agonist peptide. Platelet activation in response to PAR4 receptor agonist peptide is normal. Furthermore, this inhibition increases Ca2+ mobilization in response to PAR1 receptor agonist, but not to PAR4 receptor agonist. Consistent with the results of our functional assays, mass spectrometry analysis revealed an interaction between GRK5 and PAR1 but did not detect an interaction with PAR4. Collectively, our data show that 1) this GRK5 intronic variant regulates GRK5 expression at both transcriptional and translational levels, 2) GRK5 preferentially regulates PAR-1 over PAR4-mediated signaling, and 3) GRK5 has a binding interaction with PAR1 (Fig 1). Our findings will enable us to develop superior therapeutics for cardiovascular risk groups especially those individuals who carry the intronic variant in GRK5 and as a result are more likely to experience thrombotic events. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effect of lower extremity amputation on cardiovascular hemodynamic environment: An in vitro study

Lower extremity amputation (LEA) was associated with a greater risk of cardiovascular disease, but its hemodynamic mechanisms have not been fully studied. Therefore, to clarify the interrelationship between them, and figure out the potential pathogenesis, the exploration of the hemodynamic environment change of patients after LEA was premeditatedly executed. A near-physiological mock circulatory system (MCS) was employed in the present work to replicate the cardiovascular circulation after LEA in a short time and the unsteady-state numerical simulation was utilized as an auxiliary method to observe the changes of the hemodynamic environment inside the blood vessel. Higher severity of LEA leads to higher peripheral vascular impedance, higher blood pressure, and more obvious redistribution of blood perfusion volume. In addition, higher severity of LEA leads to lower wall shear stress (WSS), higher oscillatory shear index (OSI), and higher relative residence time (RRT) appeared in the infrarenal abdominal aorta and the iliac artery, while these changes are closely related to the higher probability of cardiovascular diseases. Results showed that different degrees of LEA (varying heights, unilateral/bilateral) have diverse effects on the patient's hemodynamic environment. This study explained the potential pathogenesis of cardiovascular diseases after LEA from a hemodynamic perspective and provided a certain reference value for the improvement of the cardiovascular hemodynamic environment and the prevention of cardiovascular diseases in lower extremity amputees.

Abnormal Magnetic Resonance Image Signature in Virologically Stable HIV Individuals.

With implementation of combination antiretroviral therapy (cART), changes to brain integrity in people with HIV (PWH) are subtle compared to those observed in the pre-cART era. T1-weighted/T2-weighted (T1w/T2w) ratio has been proposed as a measure of cortical myelin. This study examines T1w/T2w values between virologically controlled PWH and persons without HIV (PWoH). Virologically well-controlled PWH (n = 164) and PWoH (n = 120) were compared on global and regional T1w/T2w values. T1w/T2w values were associated with HIV disease variables (nadir and current CD4 T-cell count, and CNS penetration effectiveness of cART regimen) in PWH, and as a function of age for both PWoH and PWH. PWH had reduced global and regional T1w/T2w values compared to PWoH in the posterior cingulate cortex, caudal anterior cingulate cortex, and insula. T1w/T2w values did not correlate with HIV variables except for a negative relationship with CNS penetration effectiveness. Greater cardiovascular disease risk and older age were associated with lower T1w/T2w values only for PWH. T1w/T2w values obtained from commonly acquired MRI protocols differentiates virologically well-controlled PWH from PWoH. Changes in T1w/T2w ratio do not correlate with typical HIV measures. Future studies are needed to determine the biological mechanisms underlying this measure.

Influence of hypertension duration and blood pressure levels on cardiovascular disease and all-cause mortality: A large prospective cohort study.

A longer duration of hypertension (HTN) has been suggested to be associated with a greater risk of cardiovascular disease (CVD). Whether such an association is similar for mortality risk, and whether HTN duration is associated with CVD/mortality beyond blood pressure (BP) control levels are yet to be assessed. We aimed to examine the associations of HTN duration and the combination of HTN duration and systolic blood pressure (SBP)/diastolic blood pressure (DBP) with risks of CVD and all-cause mortality. We used data on ∼450,000 UK residents. Participants were categorized by HTN status and HTN duration. The primary outcome was a composite of non-fatal myocardial infarction, non-fatal stroke and CVD death. We also explored the results for the above-mentioned CVD outcomes separately. All-cause mortality was also used as a secondary outcome. The age at HTN diagnosis was obtained by self-report. HTN duration was calculated as baseline age minus age at diagnosis. Among all participants, compared with non-hypertensive participants, those with a longer HTN duration had increased risks of CVD and all-cause mortality. These associations persisted among hypertensive patients. Specifically, compared with patients with HTN durations of < 5 y, patients with a HTN duration of 5 to < 10 y, 10 to < 15 y, and ≥ 15 y had adjusted HRs (95% CI) of 1.09 (1.03, 1.17), 1.21 (1.13, 1.31), and 1.38 (1.29, 1.48) for composite CVD (P-trend < 0.001); and 1.03 (0.97, 1.08), 1.09 (1.02, 1.16), and 1.17 (1.11, 1.24) for all-cause mortality (P-trend < 0.001). When compared with hypertensive patients with BP < 140/90 mmHg and a HTN duration of < 5 y, adjusted HRs of CVD and all-cause mortality were 1.35 (1.15, 1.57) and 1.26 (1.11, 1.42) for those with BP < 140/90 mmHg and a duration of ≥ 15 y, and 1.43 (1.26, 1.60) and 1.13 (1.03, 1.25) for those with BP ≥ 140/90 mmHg and durations of ≥ 15 y, respectively. A longer HTN duration was associated with increased risks of CVD and overall death in a linear fashion, and these associations were independent of BP control levels.

Web-based training intervention to increase physical activity level and improve health for adults with intellectual disability.

Individuals with intellectual disability (ID) are less physically active, have a higher body mass index (BMI) and are at greater risk for cardiovascular diseases (CVDs) than people without ID. The purpose of the study was to explore the effectiveness of a web-based training programme, consisting of 150min of activity per week, on the health of people with ID. Participants with ID living in supported accommodation (n=28, 48% female, age=36.4±9.56years) participated in a web-based training programme, consisting of a combination of exercises (endurance, strength balance and flexibility) of moderate intensity, 50min, three times per week for 12weeks. The body composition and waist circumference (WC) were measured, and questionnaires were used to assess enjoyment, quality of life (QoL) and physical activity (PA) level. Descriptive statistics and pairwise comparison pre and post intervention were carried out. A total of 22 out of 28 participants completed the 12-week training intervention with 83% mean attendance of training sessions. The intensity of the PA level increased and a decrease in fat mass of 1.9±2.4kg, P<0.001 and WC of 3±5cm, P=0.009 were observed. Enjoyment of training sessions was 3.9 out of 5, and no differences in QoL were found. A web-based training programme is an effective tool for improving health parameters of people with ID and offers a new way for caregivers to enhance the PA for the target group.

Association of Prenatal Exposure to Persistent Organic Pollutants and Childhood Lipid Levels: The Rhea Birth Cohort (Greece)

BACKGROUND AND AIM: Lipid disorders in childhood are associated with an earlier onset and greater risk of cardiovascular disease in adulthood. Prenatal exposure to persistent organic pollutants (POPs) has been linked to cardiometabolic risk factors in childhood, but there are limited studies evaluating the persistence of these associations into early adolescence. We assessed the impact of in-utero exposure to POPs on lipid profiles during childhood in the RHEA birth cohort in Greece. METHODS: Maternal serum concentrations of several polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethene (DDE), and hexachlorobenzene (HCB) were measured in first trimester. We measured triglycerides (TG), total cholesterol (TC), HDL- and LDL-cholesterol at 4, 6, and 11 years. Generalized estimating equations and multivariate regression models assessed the associations with repeated and single time-point measures, respectively. We also tested effect modification by sex. RESULTS: We did not find any strong evidence of lipid levels at age-four being associated to prenatal POPs exposure. DDE exposure in the third tertile (&amp;#x3e;2846 ng/mL) was associated with higher TC (β= 8.01 mg/dL, 95% CI:1.66, 14.36), HDL (β= 3.25 mg/dL, 95% CI: 0.04, 6.46) and LDL (β= 6.29 mg/dL, 95% CI: 0.78, 11.79). HCB in the second tertile (69 – 102.5 ng/mL) was associated with lower TC (β= -7.27mg/dL, 95% CI: -13.36, -1.19) and HDL (β= -3.34 mg/dL, 95% CI: -6.40, -0.27). We observed strong negative associations between all POPs and age-six TG levels. Similarly, HCB and PCB118 were associated with lower TC and LDL levels at 11 years. In GEE models of repeated outcome measures DDE was associated with higher TC and HDL levels. No clear differences by sex were observed. CONCLUSIONS: Our data indicate that in utero exposures to POPs may be associated with changes in child circulating lipids. These findings require further exploration in other settings and larger cohorts. KEYWORDS: prenatal, POPs, lipids, children

Time course of the triglyceride glucose index accumulation with the risk of cardiovascular disease and all-cause mortality

BackgroundFuture risk of cardiovascular disease (CVD) and mortality is associated with cumulative amount TyG index (cumTyG) exposure, while whether time course of TyG accumulation modulates the risk remains unclear. This study sought to examine the associations of cumTyG index accumulation time course with the risk of CVD and all-cause mortality.MethodsWe enrolled 51,734 participants free of CVD and underwent three examinations at year 2006, 2008, and 2010. CumTyG from baseline to the third examination was calculated. Time course of cumTyG accumulation was calculated as the slope of TyG versus time from 2006 to 2010, or as splinting the overall TyG index accumulation into early (cumTyG06 − 08) and late accumulation (cumTyG08 − 10). Participants were categorized by the combination of cumTyG < or ≥ median (34.44 × years) and a negative or positive TyG slope.ResultsDuring a median follow-up of 9.04 years, we identified 3,602 incident CVD cases and 3,165 deaths. The risk of CVD and all-cause mortality increased with decreased TyG slope, the corresponding adjusted hazard ratio (aHR) with 95% confidence interval (CI) was 1.11 (1.04–1.19) and 1.18 (1.10–1.26) for patients with a negative TyG slope, respectively. Consistently, a later accumulation of TyG index was not associated with the risk of CVD and all-cause mortality after adjustment for an early accumulation. When considering the combination of cumTyG index and time course, participants with a cumTyG ≥ median and a negative TyG slope had elevated risk of CVD (aHR, 1.37; 95% CI, 1.24–1.51) and all-cause mortality (aHR, 1.28; 95% CI, 1.15–1.43). Additionally, the association was more prominent in young adults.ConclusionEarly TyG index accumulation resulted in a greater risk of CVD and all-cause mortality than later TyG later accumulation with the same overall cumulative exposure, emphasizing the importance of optimal TyG index control earlier in life.

Associations of birth weight and later life lifestyle factors with risk of cardiovascular disease in the USA: A prospective cohort study.

SummaryBackgroundLow birth weight has been associated with a greater risk of cardiovascular disease (CVD). However, the interaction between low birth weight and adult lifestyle factors on the risk of CVD remains unclear.MethodsWe included 20,169 men from the Health Professionals Follow-up Study (HPFS, 1986–2016), 52,380 women from the Nurses’ Health Study (NHS, 1980–2018), and 85,350 women from the Nurses’ Health Study II (NHS II, 1991–2017) in the USA who reported birth weight and updated data on adult body weight, smoking status, physical activity, and diet every 2–4 years. Incident cases of CVD, defined as a combined endpoint of fatal and nonfatal coronary heart disease (CHD) and stroke, were self-reported and confirmed by physicians through reviewing medical records.FindingsDuring 4,370,051 person-years of follow-up, 16,244 incident CVD cases were documented, including 12,126 CHD and 4118 stroke cases. Cox proportional hazards regression models revealed an increased risk of CHD during adulthood across categories of decreasing birth weight in all cohorts (all P for linear trend <0.001). Additionally, we found an additive interaction between decreasing birth weight and unhealthy lifestyles on the risk of CHD among women, with a pooled relative excess risk due to interaction of 0.06 (95% CI: 0.04–0.08). The attributable proportions of the joint effect were 23.0% (95% CI: 11.0–36.0%) for decreasing birth weight alone, 67.0% (95% CI: 58.0–75.0%) for unhealthy lifestyle alone, and 11.0% (95% CI: 5.0–17.0%) for their additive interaction. Lower birth weight was associated with a greater stroke risk only among women, which was independent of later-life lifestyle factors.InterpretationLower birth weight may interact synergistically with unhealthy lifestyle factors in adulthood to further increase the risk of CHD among women.FundingThe National Institutes of Health grants.

Impact of Androgen Deprivation Therapy on Cardiovascular Outcomes in Prostate Cancer

Purpose: Substantial evidence indicates that men with prostate cancer are at an increased risk for cardiovascular disease, and medical and surgical androgen deprivation therapy is associated with further increased cardiovascular risk. There are conflicting reports of differences in cardiovascular safety between gonadotropin-releasing hormone (GnRH) agonists and antagonists. The purpose of this narrative review is to compare data on the cardiovascular risks and safety outcomes associated with different hormonal treatment options in prostate cancer patients and to provide guidance on how to manage the increased risk associated with the condition. Methods: A PubMed search was conducted for papers published in the last 15 years using the following MeSH terms: “prostate neoplasms,” “gonadotropin-releasing hormone,” “androgen agonist,” “androgen antagonists,” “cardiovascular disease,” “epidemiology.” Results: Evidence regarding the risk of cardiovascular events during treatment with GnRH agonists and antagonists is conflicting. Some retrospective studies have shown that agonists are associated with a greater risk of cardiovascular disease and cardiovascular mortality and morbidity, and a similar risk with agonists and combined androgen blockade. Some studies have reported that antagonists are associated with a decreased risk of cardiovascular mortality and morbidity compared with agonists. With respect to coronary heart disease, ischemic heart disease, myocardial infarction, stroke, or sudden cardiac death, current evidence has failed to demonstrate a significant difference between antagonists and agonists. Cardiovascular risks in patients should be mitigated by regular monitoring of blood pressure, blood glucose, and lipids, as well as counseling patients to abstain from alcohol and improve their diet and exercise. Statins, metformin, and aspirin should also be considered. Conclusions: The evidence for the increased cardiovascular risk of GnRH agonists over antagonists for androgen deprivation therapy is unclear. Differences in methodology, population sizes, risk stratification, and outcomes between studies make direct comparisons problematic. The single prospective, randomized prostate cancer trial with a primary cardiovascular end point in men with pre-existing cardiovascular disease comparing GnRH agonist to antagonist was stopped early due to an interim futility analysis. The results are inconclusive.

The G-Protein-Coupled Estrogen Receptor Agonist Prevents Cardiac Lipid Accumulation by Stimulating Cardiac Peroxisome Proliferator-Activated Receptor α: A Preclinical Study in Ovariectomized-Diabetic Rat Model.

Type 2 diabetes mellitus (T2DM) is associated with cardiometabolic changes, and menopause exacerbates these conditions, leading to a greater risk of cardiovascular diseases (CVDs). The G protein-coupled estrogen receptor (GPER), which mediates the rapid effects of estrogen, has beneficial cardiac effects in both T2DM and menopause, but its mechanism of action is not well understood. This study aimed to determine whether G1 as a selective GPER-agonist has beneficial effects on cardiac lipid metabolism in ovariectomized rats with T2DM. Female Wistar rats were divided into 5 groups (n = 7 in each group): Sham-control (Sh-Ctl), T2DM, ovariectomized-T2DM (OVX-T2DM), OVX-T2DM-G1 (GPER-agonist), and OVX-T2DM-vehicle (OVX-T2DM-Veh). After stabilization of T2DM, G1 (200 μg/Kg) was administrated for 6 weeks. Then, the levels of free fatty acids (FFAs), CD36, peroxisome proliferator-activated receptor α (PPARα), and lipid accumulation in the cardiac tissue were determined. Compared with the Sh-Ctl group, cardiac FFAs (P < 0.001), CD36 (P < 0.05), and lipid accumulation (P < 0.001) increased, and cardiac PPARα (P < 0.01) decreased in T2DM animals; ovariectomy intensified these changes. Also, cardiac FFAs, PPARα, and lipid accumulation (P < 0.05) significantly decreased in the OVX-T2DM-G1 group compared to the OVX-T2DM-Veh group. However, cardiac CD36 levels did not change. G1 as a selective GPER-agonist affects lipid metabolism in T2DM animals. It also plays a vital role in improving cardiac metabolism during postmenopausal diabetic conditions.

HIV and Global Cardiovascular Health.

Because of effective combination antiretroviral therapy, people living with HIV (PLWH) are living longer but developing chronic age-related conditions including cardiovascular disease (CVD), the leading cause of death globally. This review aims to discuss the epidemiology, mechanisms, and clinical considerations of CVD in PLWH from a global perspective. PLWH are at greater risk for CVD at chronologically younger ages than those without HIV. Potential underlying mechanisms for CVD in PLWH include systemic inflammation, comorbidities, immune-mediated, or treatment-related mechanisms. There is also risk factor variation based on geographical location, including non-traditional CVD risk factors. CVD is prevalent in PLWH and increasing on a global scale. Further understanding the unique epidemiology, risk factors, and treatment of CVD in this population will improve the care of PLWH.

Oxidative stress contributes to reductions in microvascular endothelial- and nitric oxide-dependent dilation in women with a history of gestational diabetes.

Women with a history of gestational diabetes mellitus (GDM) are twice as likely to develop cardiovascular disease (CVD) and ∼7 times as likely to develop type 2 diabetes as their age-matched counterparts. However, the mechanism(s) mediating these associations remain unclear. We hypothesized that endothelium- and (nitric oxide) NO-dependent dilation would be attenuated through oxidant stress mechanisms in the microvasculature of women with a history of GDM compared with control women with a history of uncomplicated pregnancy (HC). Ten HC (35 ± 4 yr) and 10 GDM (34 ± 4 yr) underwent a standard local heating protocol (42°C; 0.1°C·s-1). Two intradermal microdialysis fibers were placed in the ventral forearm for local delivery of lactated Ringer's (control) or 5 mM l-ascorbate. After full expression of the local heating response, 15 mM NG-nitro-l-arginine methyl ester (NO synthase inhibition) was perfused. Red cell flux was measured continuously by laser-Doppler flowmetry, and cutaneous vascular conductance (CVC = flux/MAP) was standardized to maximum (% CVCmax; 28 mM SNP + 43°C). Urine albumin:creatinine ratio (ACR) was measured. GDM had attenuated endothelium-dependent (GDM: 67 ± 7 vs. HC: 90 ± 4% CVCmax; P < 0.001) and NO-dependent (GDM: 54 ± 7 vs. HC: 71 ± 3% CVCmax; P = 0.001) dilation at the control site and tended to have higher urine ACR (P = 0.06). Both endothelium-dependent (R2 = 0.53, P = 0.02) and NO-dependent (R2 = 0.56, P = 0.01) dilation were related to urine ACR in GDM. l-ascorbate perfusion improved endothelium-dependent (82 ± 5% CVCmax; P = 0.03 vs. control) and NO-dependent (68 ± 5% CVCmax; P = 0.02 vs. control) dilation in GDM but had no effect in HC (P > 0.05). Otherwise healthy women with a history of GDM have attenuated microvascular endothelial function and this dysfunction is mediated, in part, by oxidative stress.NEW & NOTEWORTHY Women who have gestational diabetes during pregnancy are at greater risk for cardiovascular disease and type 2 diabetes in the decade following pregnancy. However, the mechanisms mediating this increased risk are unclear. Herein, we demonstrate that microvascular dysfunction, mediated by increase in oxidative stress, persists after pregnancy in women who had gestational diabetes, despite the remission of glucose tolerance.

Accuracy Difference of Noninvasive Blood Pressure Measurements by Sex and Height

Women are at higher risk of cardiovascular events than men with similar blood pressure (BP). Whether this discrepancy in risk is associated with the accuracy of brachial cuff BP measurements is unknown. To examine the difference in brachial cuff BP accuracy in men and women compared with invasively measured aortic BP and to evaluate whether noninvasive central BP estimation varies with sex. This cross-sectional study enrolled 500 participants without severe aortic stenosis or atrial fibrillation from January 1 to December 31, 2019, who were undergoing nonurgent coronary angiography at a tertiary care academic hospital. Simultaneous measurements of invasive aortic BP and noninvasive BP. Sex differences in accuracy were determined by calculating the mean difference between the noninvasive measurements (brachial and noninvasive central BP) and the invasive aortic BP (reference). Linear regression and mediation analyses were performed to identify mediators between sex and brachial cuff accuracy. This study included 500 participants (145 female [29%] and 355 male [71%]; 471 [94%] White; mean [SD] age, 66 [10] years). Baseline characteristics were similar for both sexes apart from body habitus. Despite similar brachial cuff systolic BP (SBP) (mean [SD], 124.5 [17.7] mm Hg in women vs 124.4 [16.4] in men; P = .97), invasive aortic SBP was higher in women (mean [SD], 130.9 [21.7] in women vs 124.7 [20.1] mm Hg in men; P < .001). The brachial cuff was relatively accurate compared with invasive aortic SBP estimation in men (mean [SD] difference, -0.3 [11.7] mm Hg) but not in women (mean [SD] difference, -6.5 [12.1] mm Hg). Noninvasive central SBP (calibrated for mean and diastolic BP) was more accurate in women (mean [SD] difference, 0.6 [15.3] mm Hg) than in men (mean [SD] difference, 8.3 [14.2] mm Hg). This association of sex with accuracy was mostly mediated by height (3.4 mm Hg; 95% CI, 1.1-5.6 mm Hg; 55% mediation). In this cross-sectional study, women had higher true aortic SBP than men with similar brachial cuff SBP, an association that was mostly mediated by a shorter stature. This difference in BP measurement may lead to unrecognized undertreatment of women and could partly explain why women are at greater risk for cardiovascular diseases for a given brachial cuff BP than men. These findings may justify the need to study sex-specific BP targets or integration of sex-specific parameters in BP estimation algorithms.

Cardiac alterations with preserved left ventricular ejection fraction association with hepatic steatosis in female prediabetic rats submitted to high-fat-high-sucrose diet

Cardiovascular disease (CVD) is known to be linked with nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes, but few studies are interested in this relationship in prediabetes. This association needs to be explored especially among prediabetic women, who are at greater risk of CVD than men. We aimed to evaluate cardiac alterations and their association with hepatic inflammation and lipid metabolism in prediabetic female rats submitted to 5 months of high-fat-high-sucrose diet (HFS). Wistar female rats were divided in 2 groups fed for 5 months with standard or HFS diet (CTRL/HFS). We analyzed cardiac function, morphology, perfusion and fibrosis by magnetic resonance imaging, then rats underwent an IPGTT. The expression of genes involved in lipid metabolism and inflammation was afterwards studied in liver samples, as well as total lipid mass and triglyceride (TG) contents. Five months of HFS diet induced glucose intolerance ( P < 0.05), and cardiac alterations with increased heart perfusion ( P < 0.01), diastolic and systolic myocardial wall thickness ( P < 0.05 and P < 0.001, respectively) but also increased diastolic left ventricular mass ( P < 0.05). No significant differences were found in left ventricular ejection fraction, cardiac fibrosis, cardiac output and index between groups. HFS diet induced hepatic lipid accumulation with increased total lipid mass ( P < 0.001) and TG contents, but also lipid metabolism adaptations with increased acyl CoA oxidase ( P < 0.0001), CPT1a ( P < 0.0001) and LCAD ( P < 0.0001) expressions. No significant differences were found for FAS, MCAD and inflammatory cytokines (IL-6, TNF-α and MCP1) expressions. HFS diet in female rats induced cardiac alterations associated with hepatic lipid metabolism adaptations characterized by increased lipid peroxidation and β oxidation. Further analyses must be performed to study the relation between cardiac and hepatic alterations observed in female prediabetic rats.

Impacts of Fine Particulate Matter From Wildfire Smoke on Respiratory and Cardiovascular Health in California.

Increases in wildfire activity across the Western US pose a significant public health threat. While there is evidence that wildfire smoke is detrimental for respiratory health, the impacts on cardiovascular health remain unclear. This study evaluates the association between fine particulate matter (PM2.5) from wildfire smoke and unscheduled cardiorespiratory hospital visits in California during the 2004–2009 wildfire seasons. We estimate daily mean wildfire‐specific PM2.5 with Goddard Earth Observing System‐Chem, a global three‐dimensional model of atmospheric chemistry, with wildfire emissions estimates from the Global Fire Emissions Database. We defined a “smoke event day” as cumulative 0‐1‐day lag wildfire‐specific PM2.5 ≥ 98th percentile of cumulative 0–1 lag day wildfire PM2.5. Associations between exposure and outcomes are estimated using negative binomial regression. Results indicate that smoke event days are associated with a 3.3% (95% CI: [0.4%, 6.3%]) increase in visits for all respiratory diseases and a 10.3% (95% CI: [2.3%, 19.0%]) increase for asthma specifically. Stratifying by age, we found the largest effect for asthma among children ages 0–5 years. We observed no significant association between exposure and overall cardiovascular disease, but stratified analyses revealed increases in visits for all cardiovascular, ischemic heart disease, and heart failure among non‐Hispanic white individuals and those older than 65 years. Further, we found a significant interaction between smoke event days and daily average temperature for all cardiovascular disease visits, suggesting that days with high wildfire PM2.5 concentrations and high temperatures may pose greater risk for cardiovascular disease. These results suggest substantial increases in adverse outcomes from wildfire smoke exposure and indicate the need for improved prevention strategies and adaptations to protect vulnerable populations.

Dietary nitrate supplementation attenuates the mechanoflex in older women with early menopause: A pilot study

Women who reached early menopause (EM, 40‐44 yrs) have a greater risk for cardiovascular disease than women with normal menopause (NM, 50‐54 yrs), which may be attributed to a longer duration of estrogen loss and a greater reduction in nitric oxide bioavailability in both the peripherals and center. Previous studies have shown that dietary nitrate supplementation improves cardiovascular function in older women, but how autonomic neural control changes in daily living, such as during exercise, has been involved is unclear. We examined the hypothesis that 2wks continuous use of dietary nitrate supplements would attenuate the exercise pressor reflex in older women with EM.Six EM (65±4 [SD] yrs) and 8 NM (64±2 yrs) women participated in this randomized, placebo‐controlled, double‐blind, cross‐over pilot study. All subjects underwent 2 wks of beetroot juice (BRJ; 140 ml containing ~800 mg nitrate per day) or placebo (140 ml nitrate‐depleted BRJ, daily) intervention with ≥14 days of wash‐out. Before and after each intervention period, subjects performed SHG using the dominant hand at 40% of maximum voluntary contraction (MVC) until fatigue, followed by 2 min of PECA with an upper arm cuff inflated to 250 mmHg. Heart rate (HR; ECG), blood pressure (BP; finger photoplethysmography), muscle sympathetic nerve activity (MSNA; microneurography), and respiration (capnography) were continuously measured. In addition, 24‐h ambulatory BP standard deviation (SD) was monitored before and after each intervention (an indication of BP variability).There were no differences in baseline HR, BP and MSNA, MVC, and the time to fatigue between the EM and NM groups before and after intervention (all p&gt;0.05). At the first 30 s of SHG, the EM group showed significant decreases in MSNA burst frequency (DBF; ‐4.5±6.5 in EM vs. 2.5±6.2 bursts/min in NM, p=0.065) and burst incidence (DBI; ‐10.6±12.6 vs. 2.6±8.4 bursts/100 heartbeats, p=0.037) after BRJ intervention compared with the NM group (Figure1A and B). However, there were no differences between groups at fatiguing exercise and during PECA after the intervention. The interventional changes in 24‐h diastolic BP SD had a positive correlation with ΔMSNA BF (r=0.55, p=0.053) and BI (r=0.58, p=0.036) at the first 30 s of SHG in all subjects and EM individuals were in the left‐lower area (Figure2 A and B).These results suggest that dietary nitrate supplementation may attenuate and mechanoreflex, but not the metaboreflex, in older women with EM during static hand grip, which has a relation with BP variability during ambulation. Certainly, these preliminary observations need to be verified in more older women in future studies.

Effects of Dietary Nitrate Supplements on Morning Blood Pressure Surge and Sympathetic Neural Control during Orthostasis in Post‐menopausal Women

Post‐menopausal women are at greater risk for cardiovascular disease compared with age‐matched men. An exaggerated morning blood pressure surge (MBPS) in post‐menopausal women is well established as an independent risk factor for cardiovascular events. Dietary nitrate supplements such as nitrate‐rich beetroot juice (BRJ) may reduce blood pressure (BP), but no study has investigated the chronic effects of BRJ on MBPS and sympathetic neural control during orthostasis in post‐menopausal women. We hypothesized that dietary nitrate supplements would decrease MBPS and muscle sympathetic nerve activity (MSNA, microneurography) in post‐menopausal women.We performed a double‐blind, placebo‐controlled, cross‐over trial and randomly assigned healthy women [n=14, 64±3 (SD) yr] to either dietary nitrate supplements (140 ml of BRJ; 800 mg nitrate/day) or placebo (140 ml of nitrate‐depleted BRJ daily) for 2 weeks each with ≥2 weeks of washout. Twenty‐four‐hour ambulatory BP monitoring was performed and MBPS was calculated as the morning systolic BP (SBP; averaged for 2 h after wake‐up) minus the lowest nocturnal SBP before and after 2‐week BRJ or placebo intervention. BP, heart rate, and MSNA were measured during 3‐min supine rest and 5‐min 60° head‐up tilt (HUT). Cardiac output (Qc; C2H2 rebreathing) and total peripheral resistance (TPR=mean BP/Qc × 80) were also measured.MBPS decreased after BRJ intervention (Figure A; p=0.043). BRJ did not change hemodynamics or MSNA during supine rest (Figure B‐E; all, p&gt;0.05). However, upright TPR was reduced (Figure C; p=0.007), while Qc trended greater (Figure B; p=0.072) after BRJ intervention. During HUT, MSNA burst frequency (53±15 pre vs. 48±10 bursts/min post, p=0.508 for posture × intervention interaction) and burst incidence (70±17 vs. 63±15 bursts/100 heart beats, p=0.199 for interaction) were similar, but mean burst area (Figure D; p=0.010) and total activity (Figure E; p=0.015) were lower after BRJ intervention. Placebo had no significant impact on hemodynamics and MSNA in the supine position or during HUT in post‐menopausal women (all, p&lt;0.05).Collectively, dietary nitrate supplements decrease morning surge in BP and upright MSNA and vasoconstriction in post‐menopausal women. Whether reductions in sympathetic activation and peripheral vasoconstriction during orthostasis contribute to the reduced MBPS in these women remains to be determined.

Functional Balance among Middle‐aged Adults is a Risk Factor for Cardiovascular Disease

Vascular diseases are associated with falls in older adults (&gt;65 years), but this relationship is not well understood in middle‐aged adults. This study aimed to determine if balance in middle‐aged adults with poor ankle brachial pressure index (ABPI) was impaired compared to those with normal ABPI. We hypothesized middle‐aged adults with vascular disease, measured through ABPI, will fail the Romberg Balance Test at a higher rate compared to those without vascular disease. Data was collected from the 1999‐2000 and 2001‐2002 National Health and Nutrition Examination Survey. Good balance was determined by passing the 4th condition of the Romberg Balance Test; failure wad defined as not passing the 4th condition or any of the preceding conditions. Poor ABPI was classified as ≤0.90 and normal ABPI as &gt;0.90. Middle‐aged adults (50.1 ± 0.23) with poor ABPI have a higher frequency of poor balance (4.2%) compared to good balance (1.3%; p=0.001). Further, individuals with poor ABPI have 3.38 (CI: 1.66, 6.87; p=0.001) times the odds of having poor balance compared to individuals with normal RABPI, which remained significant after adjusting for age and body mass index. Individuals who are at a greater risk for cardiovascular disease, as assessed by ABPI, have higher odds of poor balance. Thus, poor balance appears to be a characteristic of middle‐aged individuals at risk for cardiovascular disease.