Onset Of Cardiovascular Events Research Articles

#2850 Elevation of serum indoxyl-sulfate in mice with normal kidney function triggers cardiac and vascular dysfunctions

Abstract Background and Aims Acute kidney disease (AKD) is associated with a long-term risk of cardiovascular mortality and major cardiovascular events, particularly heart failure and acute myocardial infarction. To date, the underlying mechanisms responsible for this elevated cardiovascular risk remain poorly understood. Patients with AKD show increased circulating levels of indoxyl-sulfate (IS), a uremic toxin known to promote oxidative stress, inflammation and apoptosis in cultured vascular and cardiac cells. In this context, we hypothesized that IS elevation during AKD might promote acute myocardial and vascular lesions, which over time favour the onset of cardiovascular events. In a first attempt to test this hypothesis, we aimed to verify whether IS elevation in mice with normal renal function induces myocardial and vascular dysfunctions similar to that observed in AKD. Method Thirty female C57BL6J mice were divided into three groups: control (CT, n = 10), IS (n = 10) and AKD (n = 10). AKD was induced by 5/6 nephrectomy. Blank surgeries were performed in the CT and IS groups. IS was administered continuously for 15 days via drinking water (2.5 g/L) to reach, in IS mice, the IS serum concentrations found in AKD mice, as monitored by a validated high-performance liquid chromatography-tandem mass spectrometry method. Cardiac and vascular functions were assessed by echocardiography at baseline and at D15. Expression of markers of contractility (SERCA-2a for myocardium, αSMA for aorta), inflammation (TNF-α, IL-1β), and endothelial dysfunction (VCAM-1, ICAM-1, iNOS) were assessed by qRT-PCR and western blot. The presence of cardiac lesions was assessed histologically. Results Elevation of serum IS concentrations was similar in IS and AKD mice (serum IS: 10.7 ± 3.4 µg/mL in IS-group and 10.9 ± 5.8 µg/mL in AKD-group vs. 4.0 ± 2.1 µg/mL in CT-group (p < 0.001 in CT vs IS and AKD group). Compared with CT mice, IS and AKD mice showed systolic and diastolic dysfunctions as evidenced by decreased ejection fraction (EF: 62.4% [58.0-72.3] in CT vs. 50.1% [45.0-57.0] in IS (p < 0.05 vs CT) and 51.3% [45.6-57.1] in AKD (p < 0.01 vs CT)), decreased fractional shortening (FS: 33.6% [30.1-40.4] in CT vs. 24.8% [21.9-29.7] in IS (p < 0.05 vs CT) and 25.8% [22.4-29.6] in AKD (p < 0.01 vs CT)) and increased isovolumic relaxation time (IVRT: 17.2 ± 1.6 ms in CT vs. 20.7 ± 1.3 ms in IS (p < 0.001 vs CT) and 19.0 ± 1.7 ms in AKD (p < 0.05 vs CT)), respectively. For all echocardiographic parameters assessed, there were no significant differences observed between IS and AKD mice. Myocardium from IS and AKD mice showed decreased expression of SERCA-2a and elevated expression of both IL-1β and TNF-α at the mRNA and protein levels compared to CT mice. Aortas from IS and AKD mice also showed decreased mRNA expression of α-SMA and increased mRNA expression of IL-1β, VCAM-1, and iNOS compared to aortas from CT mice. The mRNA and protein expression of these inflammatory and contractile markers were not statistically different in the hearts and aortas from IS compared to AKD mice. No signs of vascular dysfunction were observed in either of the groups on ultrasound. Conclusion Systemic exposure to IS in mice without renal failure leads to significant cardiac and vascular dysfunctions that were similar to those observed in mice with AKD. Additional studies are needed to confirm the causal role of IS in the cardiovascular impact of AKD, and to determine whether IS could represent a valuable prognostic tool and therapeutic target for preventing AKD-associated cardiovascular complications.

Arterial Stiffness is an early vascular complication in menopause associated with high levels of asprosin

Background: Menopause is a biological phenomenon experienced by women on average at 51 years of age. The negative impact of menopause on the health of women left without treatment is now recognized but still remains understudied. Menopause is characterized by a decline in ovarian function and estrogen levels that is associated with weight gain and an increased risk of cardiovascular events. Because cardiovascular disease clinically presents 7-10 years following menopause, research on the early onset of cardiovascular events in menopause is urgently needed. Asprosin has been recently identified as an adipokine secreted by white adipose tissue and its levels are increased in obesity. Whether asprosin production is increased in menopause remains unknown. We hypothesize that arterial stiffness is an early vascular complication and is associated with high levels of asprosin in menopause. Methods: 8-week-old female C57BL/6 mice were randomized into two experimental groups: Control Group (n=9) and Ovariectomized (OVX) Group (n=8). The OVX group received surgical ovariectomies and the Control Group underwent surgery without ovary removal. The experimental protocol spanned 22 weeks. Carotid-femoral and intracarotid pulse wave velocity (PWV) measurements, the gold standard to measure arterial stiffness, were obtained. At terminal experiments, thoracic aortas were isolated and mounted on a wire myograph for vascular reactivity studies. Acetylcholine and sodium nitroprusside concentration-response curves were used to assess endothelium-dependent and endothelium-independent relaxation, respectively. Gonadal white adipose tissue (gWAT) was collected for further asprosin measurements. Results: The OVX Group exhibited a significant reduction in uterus weight (59.87 ± 19.62 mg vs. 162.8 ± 16.37 mg controls, p<0.05), validating our menopause model. At week 16, the OVX group exhibited a significant increase in carotid-femoral PWV (3.03 ± 0.09 m/s vs. 2.7 ± 0.11 m/s controls, p<0.05) as well as intracarotid PWV (5.09 ± 0.35 m/s vs 2.5 ± 0.23 m/s controls, p<0.05), confirming arterial stiffness. No differences in endothelium-dependent and endothelium-independent relaxation were observed between the experimental groups, indicating that the menopausal mice had not developed endothelial dysfunction at week 22. As expected, the OVX group showed a significant increase in body weight (24.7 ± 0.26 g vs. 22.2 ± 0.42 g controls, p<0.05) and BMI (0.27 ± 0.002 kg/m2 vs. 0.24 ± 0.005 kg/m2 controls, p<0.05), confirming obesity. The increased weight of gWAT in the OVX group (0.69 ± 0.15 g vs. 0.26 ± 0.02 g controls, p<0.05) was accompanied by elevated asprosin expression (1.14-fold increase, p<0.05). Conclusion: nt of endothelial dysfunction in menopause. Increased asprosin is novel and represents a potential link between adiposity and arterial stiffness in menopause. Future directions will investigate the relationship between arterial stiffness and hypertension in menopause. NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Fucoidan-induced reduction of lipid accumulation in foam cells through overexpression of lysosome genes

Atherosclerosis (AS) is the common basis for the onset of cardiovascular events. The lipid metabolism theory considers foam cell formation as an important marker for the initiation of AS. Fucoidan is an acidic polysaccharide that can reduce lipid accumulation in foam cells. Studies show that tea polysaccharides can be transported to lysosomes via the tubulin pathway. However, the specific mechanism of action of fucoidan on foam cells has not been extensively studied. Therefore, we further explored the mechanism of action of fucoidan and evaluated whether it could reduce lipid accumulation in foam cells by affecting the expression of lysosomal pathway–related genes and proteins. In this study, three inhibitors, CPZ, EIPA, and colchicine, were used to inhibit endocytosis, macropinocytosis, and the tubulin pathway, respectively, to study the pathways of action. Transcriptomics and proteomics analysis, as well as western blotting and qRT-PCR were used to determine the effects of fucoidan and the inhibitors on lysosomal genes and proteins. Fucoidan could enter foam cells through both endocytosis and via macropinocytosis, and then further undergo intracellular transport via the tubulin pathway. After fucoidan treatment, the expression of lysosomal pathway–related genes and proteins including LAMP2, AP3, AP4, MCOLN1, and TFEB in foam cells increased significantly (P < 0.01). However, the expression of lysosomal genes and proteins after colchicine intervention was comparable with that in the model group. Therefore, the tubulin pathway inhibited by colchicine is an important pathway for the transport and distribution of fucoidan within cells. In summary, fucoidan may be transported to lysosomes via the tubulin pathway and may enhance the expression of lysosomal genes, promoting autophagy, thereby accelerating lipid clearance in foam cells. Due to its significant lipid-lowering effect, it can be used in the clinical treatment of AS.

Early onset of cardiovascular events in women with hypertensive disorders of pregnancy: The nationwide CONCEPTION study

Early onset of cardiovascular events in women with hypertensive disorders of pregnancy: The nationwide CONCEPTION study

The menopausal transition period and cardiovascular risk.

The menopausal transition period spans, on average, 2-8 years before the final menstrual period and is associated with an increase in clinical and subclinical cardiovascular risk. In this Review, we discuss the metabolic and cardiovascular changes that occur during the menopausal transition period and the role of ovarian ageing, chronological ageing and other ageing-related risk factors in mediating these changes. Disentangling the relative contributions of chronological and reproductive ageing to cardiovascular risk is challenging, but data from longitudinal studies in women transitioning from premenopause to post-menopause have provided valuable insights. We also discuss evidence on how cardiovascular risk is altered by premature or early menopause, surgical menopause, and vasomotor and other menopausal symptoms. Whether targeted interventions can slow the progression of atherosclerosis and subclinical disease during the menopausal transition, thus delaying or preventing the onset of cardiovascular events, remains to be determined. Furthermore, we consider the recommended strategies for cardiovascular risk reduction in women undergoing menopausal transition using the framework of the American Heart Association's Life's Essential 8 key measures for improving and maintaining cardiovascular health, and discuss the cardiovascular risks and benefits of menopausal hormone therapy. Finally, we also discuss novel therapies that might benefit this population in reducing cardiovascular risk.

Artificial Intelligence in Medicine: Revolutionizing Healthcare for Improved Patient Outcomes

Artificial Intelligence in Medicine: Revolutionizing Healthcare for Improved Patient Outcomes

Salt-induced maladaptive innate immune memory impedes stroke recovery

Abstract A high salt diet (HSD) is a top risk factor for human mortality. Beyond its heavily implicated role in hypertension, it is now linked to the development of inflammatory diseases before the onset of cardiovascular events. Even after salt reduction, HSD can induce prolonged tissue damage, yet the mechanisms by which HSD induces persistent negative effects on immune system are largely unexplored. While HSD is an established risk factor for stroke, its impact on long-term stroke recovery is unknown. Here, we model two major stroke types, intracerebral hemorrhage, and cerebral ischemia, to investigate how HSD induces unfavorable immune responses and subsequently impacts long-term tissue repair. We found HSD exclusively hampers alternative activation in monocytes-derived macrophages (MDMs) while sparing the major parenchymal macrophage—microglia—in the stroke brain. HSD induces innate immune memory in the hematopoietic stem and progenitor cells through downregulating mitochondrial oxidative phosphorylation and NR4a orphan nuclear receptors expression. This immunological memory was retained in the brain-infiltrating MDMs and restrained their reparative functions. Consequently lead to impaired tissue repair and neurobehavioral recovery during stroke recovery phase. Pharmacological treatment with NR4a1 activator and genetic overexpression of NR4a1 restored MDMs reparative phenotype suppressed by HSD and enabled stroke recovery. These findings establish a new mechanism linking HSD-induced maladaptive innate immune memory to a hindered macrophage alternative activation and delayed tissue recovery. Our data unveil innate immune memory and NR4a1 as potential therapeutic targets for treating HSD-associated diseases.

Is there a role in acute kidney injury for FGF23 and Klotho?

Cardio-renal syndrome is a clinical condition that has recently been well defined. In acute kidney disease, this interaction might trigger chronic processes determining the onset of cardiovascular events and the progression of chronic kidney disease. Moreover, the high mortality rate of acute kidney injury (AKI) is also linked to the fact that this condition is often complicated by dysfunctions of other organs such as lungs or heart, or is associated with septic episodes. In this context the role and the potential link between bone, heart and kidney is becoming an important topic of research. The aim of this review is to describe the cardiac alterations in the presence of AKI (cardiorenal syndrome type 3) and explore how bone can interact with heart and kidney in determining and influencing the trend of AKI in the short and long term. The main anomalies of mineral metabolism in patients with AKI will be reported, with specific reference to the alterations of fibroblast growth factor 23 and Klotho as a link between the bone-kidney-heart axis.

Possibilities of dispensary observation in reducing mortality from coronary heart disease

Dispensary observation of patients with coronary artery disease can significantly reduce the likelihood of cardiovascular complications onset. Active outpatient monitoring allows to correct the main risk factors for cardiovascular complications, to estimate the risk of unfavorable cardiovascular events onset and to identificate patients who will get benefit of coronary revascularization. The introduction of a comprehensive assessment of cardiovascular risk and the development of remote monitoring technologies will improve the long-term results of outpatient follow-up of patients with coronary artery disease at high cardiovascular risk.

PS-C22-10: SERUM SOLUBLE (PRO)RENIN RECEPTOR CONCENTRATION AS A PROGNOSTIC FACTOR IN PATIENTS UNDERGOING MAINTENANCE HEMODIALYSIS

Objective: The (pro)renin receptor [(P)RR)] is a multifunctional protein with roles in angiotensin II-dependent and -independent intracellular cell signaling and as an adaptor protein between the Wnt receptor complex and vacuolar proton-translocating adenosine triphosphatase. The (P)RR is cleaved to generate soluble (P)RR [s(P)RR], reflecting the status of the tissue renin-angiotensin system and/or activity of the (P)RR. Patients undergoing hemodialysis (HD) have poor prognosis because of the increased prevalence of cardiovascular and malignant diseases. This study was conducted to investigate whether the s(P)RR level is associated with new onset of cardiovascular events or malignant diseases and prognosis in patients undergoing HD. Design and method: A total of 258 patients undergoing maintenance HD who were enrolled in our cohort study investigating the relationships between serum s(P)RR levels and background factors were prospectively followed up for 60 months. We investigated the relationships between s(P)RR levels and new onset of cardiovascular events or malignant diseases and mortality during the follow-up period. Results: The cumulative incidence of new onset of cardiovascular events (P = 0.009) and cardiovascular deaths (P &lt; 0.001), but not of malignant diseases, was significantly greater in patients with higher serum s(P)RR level (≧ 29.8 ng/ml) than in those with lower s(P)RR level (&lt; 29.8 ng/ml). A high serum s(P)RR level was independently correlated with cardiovascular mortality (95% CI 1.001 - 1.083, P = 0.046). Conclusions: These data showed that the serum s(P)RR level is associated with cardiovascular events and mortality, suggesting that the serum s(P)RR level could be used as a biomarker for selecting patients requiring intensive care.

2 ABSENCE OF MAJOR CARDIOVASCULAR EVENT IN A GROUP OF PATIENTS FOLLOWED FOR MORE THAN ONE YEAR AFTER SEVERE COVID-19 PNEUMONIAE

Abstract Introduction The Coronavirus disease 2019 (COVID-19), doesn't affect only respiratory system, but it also involves other organs including cardiovascular system, possibly causing acute or chronic cardiovascular events. Preexisting cardiovascular diseases enhance COVID-19 morbidity, as well. Aim In this retrospective analysis we investigated the onset of cardiovascular events during a time-span of more than one year since hospitalization (384 days). Methods The analysis included 43 patients, who were hospitalized in Internal Medicine Department of Montichiari Hospital (ASST Spedali Civili of Brescia) for moderate to severe SARS-CoV2 related pneumonia treated with high-flow oxygen support (ranging from 40% fraction of inspired oxygen to non-invasive ventilation) Mean age was 63 years, 28% (12/43) were female and 72% (31/43) were male. Thirty-five percent of the patients suffered from heart diseases, 56% of them were hypertensives and 23% had type 2 diabetes; 12% had chronic kidney disease (CKD) and 5% an active neoplasm. 49% of the sample was obese. Nineteen percent took ACE inhibitors and 19% was on ARBs. Statins were taken by 37% of the patients; an antiaggregant by 21%, and an anticoagulant by 2% (see table) Results The follow-up visit included the evaluation of post-covid infection quality-of-life, standard laboratory tests, chest computed tomography, spirometry with evaluation of DLCO. The onset of cardiovascular events during the average period of 384 days was evaluated. None of the 43 patients had major cardiovascular events: coronary heart disease, cerebrovascular disease, peripheral arterial disease, deep vein thrombosis and pulmonary embolism. Conclusions Even if this study failed to demonstrate new-onset CV events, longer follow-up studies performed to evaluate cardiovascular risk following SARS-CoV1 infection showed persistent hyperlipidemia, cardiovascular system abnormalities, and glucose metabolism disorders in a very high number of patients. Further analyses are needed to further investigate longer term cardiovascular consequences of SARS-CoV2 infection.

Insufficient blood pressure control is independently associated with increased arterial stiffness.

Hypertension is a risk factor for atherosclerosis. Achieving the therapeutic target value of blood pressure (BP) prevents the onset of cardiovascular events; however, it is not clear how antihypertensive drug use and BP control status relate to arterial stiffness. The purpose of this study is to investigate the relationship between BP control status with or without antihypertensive drugs and arterial stiffness. Nine hundred eighty individuals (mean age: 68 ± 11 years) who participated in a community-based cohort study were enrolled. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). Higher BP was defined as a systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. Participants were divided into four groups: normal, non higher BP without antihypertensive drugs (n = 421); untreated, higher BP without antihypertensive drugs (n = 174); good control, non higher BP with antihypertensive drugs (n = 209); and poor control, higher BP with antihypertensive drugs (n = 176). In multivariable logistic analysis adjusted for age, sex, dyslipidemia and diabetes mellitus medication use, obesity, smoking, alcohol drinking, and heart rate at the CAVI measurement for a high CAVI-using a borderline cutoff value of 8.0-the other three groups were significantly associated with a high CAVI when compared with the normal group. By contrast, multivariable logistic analysis of a high CAVI using an abnormal cutoff value of 9.0 demonstrated that the poor control and untreated groups were significantly associated with a high CAVI, whereas the good control group was not. In conclusion, even with antihypertensive drugs, poor BP control is independently associated with a high CAVI.

Prognostic value of soluble ST2, high-sensitivity cardiac troponin, and NT-proBNP in type 2 diabetes: a 15-year retrospective study

BackgroundPatients with type 2 diabetes (T2DM) present an increased risk of cardiovascular (CV) disease and excess CV-related mortality. Beyond the established role of brain natriuretic peptide (BNP) and cardiac troponins (cTn), other non-cardiac-specific biomarkers are emerging as predictors of CV outcomes in T2DM.MethodsSerum levels of soluble suppression of tumorigenesis 2 (sST2), high-sensitivity (hs)-cTnI, and N-terminal (NT)-proBNP were assessed in 568 patients with T2DM and 115 healthy controls (CTR). Their association with all-cause mortality and the development of diabetic complications was tested in T2DM patients over a median follow-up of 16.8 years using Cox models and logistic regressions.ResultssST2 followed an increasing trend from CTR to uncomplicated T2DM patients (T2DM-NC) to patients with at least one complication (T2DM-C), while hs-cTnI was significantly higher in T2DM-C compared to CTR but not to T2DM-NC. A graded association was found between sST2 (HR 2.76 [95% CI 1.20–6.33] for ≥ 32.0 ng/mL and 2.00 [1.02–3.94] for 16.5–32.0 ng/mL compared to < 16.5 ng/mL, C-statistic = 0.729), NT-proBNP (HR 2.04 [1.90–4.55] for ≥ 337 ng/L and 1.48 [1.05–2.10] for 89–337 ng/L compared to < 89 ng/L, C-statistic = 0.741), and 15-year mortality in T2DM, whereas increased mortality was observed in patients with hs-cTnI ≥ 7.8 ng/L (HR 1.63 [1.01–2.62]). A ‘cardiac score’ based on the combination of sST2, hs-cTnI, and NT-proBNP was significantly associated with all-cause mortality (HR 1.35 [1.19–1.53], C-statistic = 0.739) and development of CV events.ConclusionssST2, hs-cTnI, and NT-proBNP are associated with 15-year mortality and onset of CV events in T2DM. The long-term prognostic value of sST2 and its ability to track variables related to insulin resistance and associated metabolic disorders support its implementation into routine clinical practice.

Genetic susceptibility, screen-based sedentary activities and incidence of coronary heart disease

BackgroundWhether the associations of time spent in screen-based sedentary activities with CHD vary by genetic susceptibility is currently unknown. The objective of this study was to examine the interplay of genetic susceptibility to CHD and two prevalent types of screen-based sedentary activities (television [TV] viewing and computer use) for CHD incidence.MethodsThis prospective cohort study included 373,026 individuals of European ancestry without prevalent CHD/stroke from UK Biobank data. Genetic susceptibility to CHD was assessed using weighted polygenic risk scores, calculated by summing the number of risk-increasing alleles among 300 single-nucleotide polymorphisms, multiplied by their corresponding effect estimates. TV viewing and computer use were assessed through touch-screen questionnaires. CHD incidence (n=9185) was adjudicated over a median 12.6-year follow-up.ResultsCompared with ≥4h/day of TV viewing, the hazard ratio of CHD was 0.84 (95% confidence interval [CI] 0.79–0.90) and 0.94 (0.90–0.99) for ≤1h/day and 2–3h/day of TV viewing, respectively, after adjusting for confounders including the genetic risk. CHD hazards were higher for medium and high genetic risk than for low genetic risk. Across all levels of genetic risk including high-genetic risk, ≤1h/day of TV viewing had lower CHD hazards, compared with ≥4h/day: no evidence of interaction between genetic risk and TV viewing (p value: 0.362). Estimates of the population attributable fraction (PAF) suggested that 10.9% (95% CI 6.1–15.3%) of CHD could be prevented if TV viewing time were reduced to ≤1h/day, assuming causality. The PAF values were relatively larger for medium-to-high genetic risk than for low genetic risk, although the CIs were wide and overlapping. No associations were observed for computer use.ConclusionsLess TV viewing time was associated with lower CHD risk independently of genetic risk. Clinical trials targeted at individuals with high genetic susceptibility should consider reducing TV viewing as as a behavioural target for prevention of an early onset of cardiovascular events.

Diastolic Pressure and ACR Are Modifiable Risk Factors of Arterial Stiffness in T2DM Without Cardiovascular Disease.

To evaluate early, before the onset of cardiovascular events and of chronic renal insufficiency, the association between chronic kidney disease (CKD)-mineral bone disorder (MBD) biomarkers and vascular stiffness [Cardio Ankle Vascular Index (CAVI)] in the course of type 2 diabetes (T2DM). We evaluated 174 T2DM patients [median age 56 years; male/female (M/F) 100/74] with diabetes duration < 10 years and without decreased estimated glomerular filtration rate (eGFR; ≥60 mL/min/1.73 m2) or macrovascular complications. Thirty-four age-matched healthy subjects [M/F 13/21; age 53.5 (50.0-57.7) years; eGFR 107.5 (97.0-119.7) mL/ min1.73 m2] served as local reference control for CAVI (pathological: ≥8) and the novel CKD-MBD biomarkers. Albumin-to-creatinine ratio (ACR) averaged 8.5 mg/g (5.6-17.2) with 12.6% of the patients showing pathologic values, indicative of incipient diabetic nephropathy. Serum parathyroid hormone, fibroblast growth factor 23, and sclerostin were higher while 1,25-dihydroxyvitamin D and Klotho were lower than a control group. CAVI was normal (<8) in only 54% and correlated positively with age (P < 0.001), hemoglobin 1A1c (P = 0.036), and systolic (P = 0.021) and diastolic blood pressure (DBP) (P = 0.001) and negatively correlated with 25-hydroxyvitamin D (P = 0.046). In multivariate analysis, age, DBP, ACR, and serum Klotho were independent positive predictors of CAVI. In the absence of overt cardiovascular disease and of chronic renal insufficiency, CAVI is frequently pathologic in T2DM. DBP and ACR are modifiable risk factors of vascular stiffness in T2DM, thus warranting optimal assessment.

Association between vascular lesion and penile erection hardness in Japanese patients with erectile dysfunction

ABSTRACT Introduction It is generally recognized that erectile dysfunction (ED) is largely attributable to vascular endothelial dysfunction which develops secondary to atherosclerotic changes and blood flow disorder. It is suggested that many patients with ED usually have advanced atherosclerosis because both ED and atherosclerosis share common risk factors. Objective Many erectile dysfunction(ED) cases are attributed to vascular endothelial dysfunction and impaired blood flow due to arteriosclerotic changes. In this study, we examined the association among the erection hardness score (EHS), Pulse Wave Velocity(PWV), and the presence of carotid artery plaques. Materials and Methods The study was enrolled 67 patients who visited our hospital with the chief complaint of ED. Based on the history at the first visit, 28 of the 67 patients were categorized into the EHS 3-4 group and the remaining 39 into the EHS 0-2 group. The two groups were retrospectively analyzed. Results The PWV points were significantly higher in the EHS 0-2 group than in the EHS 3-4 group (P = 0.047). In consideration for error in age, the modified points (PWV at the first visit - reference PWV by age) were significantly higher in the EHS 0-2 group than in the EHS 3-4 group (P = 0.026). This group also showed a higher detection rate of plaques by carotid ultrasound (66.7%). Conclusions This study showed that patients with lower points of EHS had higher PWV and were more likely to have carotid artery plaques. While ED has occasionally been considered as an early risk marker for the onset of cardiovascular events, this study suggests that the hardness of the penis can be an easier-to-measure and more sensitive index. Disclosure Work supported by industry: no.

Short-Term Prognostic Factors in Hospitalized Herpes Zoster Patients and Its Associated Cerebro-Cardiovascular Events: A Nationwide Retrospective Cohort in Japan.

BackgroundShort-term mortality and incidence of cerebrovascular and cardiovascular events (C-CVE) during hospitalization of patients with severe herpes zoster (HZ) have not been sufficiently investigated. We aimed to investigate short-term prognosis and incidence of C-CVE associated with HZ in hospitalized patients.MethodsThis retrospective cohort study from April 2016 to March 2018 included HZ inpatient cases selected from the Diagnosis Procedure Combination database—a Japanese nationwide inpatient database. HZ and C-CVE were diagnosed based on the 10th revision of the International Classification of Diseases and Injuries codes. The definition of primary exposure was that treatments were initiated within 7 days of admission, and antivirals were administered for ≥7 days. Main Outcomes were in-hospital deaths and C-CVE onset after hospitalization.ResultsAmong 16,811,501 in-hospital cases registered from 1,208 hospitals, 29,054 cases with HZ were enrolled. The median age was 71.0 years, 15,202 cases (52.3%) were female, and the HZ types were the central nervous system (n=9,034), disseminated (n=3,051), and ophthalmicus (n=1,069) types. There were 301 (1.0%) in-hospital deaths and 385 (1.3%) post-hospitalization onset of C-CVE. The 30-day in-hospital survival rates with or without underlying disease were 96.8% and 98.5%, respectively. Age ≥75 years (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.55–3.05), liver cirrhosis or hepatic failure (HR, 5.93; 95% CI, 2.16–16.27), chronic kidney disease (HR, 1.82; 95% CI, 1.24–2.68), heart failure (HR, 1.65; 95% CI, 1.22–2.24), and old cerebrovascular events (HR, 1.92; 95% CI, 1.10–3.34) were associated with poor short-term prognosis. Age ≥75 years (odds ratio [OR], 1.70; 95% CI, 1.29–2.24), diabetes (OR, 1.50; 95% CI, 1.19–1.89), dyslipidemia (OR, 1.95; 95% CI, 1.51–2.51), hyperuricemia (OR, 1.63; 95% CI, 1.18–2.27), hypertension (OR, 1.76; 95% CI, 1.40–2.20), heart failure (OR, 1.84; 95% CI, 1.32–2.55), and glucocorticoid administration (OR, 1.59; 95% CI, 1.25–2.01) were associated with increased risks for in-hospital C-CVE onset.ConclusionsThe underlying diseases that could influence the short-term mortality of severe HZ were identified. Glucocorticoid is a possible risk factor for the in-hospital onset of C-CVE after severe HZ development.

Short-term exposure to ambient ozone associated with cardiac arrhythmias in healthy adults

ObjectiveThe exact biological mechanism whereby exposure to ambient ozone (O3) may contribute to clinical onset of cardiovascular events remains unclear. In this study, we aim to examine the impacts of O3 exposure on cardiac arrhythmias and potential pathways involved through autonomic dysfunction and myocardial injury. MethodsSeventy-three non-smoking healthy adults were followed with 4 repeated measurements of 24-hour ambulatory arrhythmias, heart rate variability, ST-segment deviation, and blood pressure (BP) in Beijing, China, 2014‒2016. Generalized additive mixed models coupled with distributed lag nonlinear models were constructed to evaluate the associations and potential interlinks between O3 exposure and outcome measurements. ResultsDuring the study period, 24-hour average concentrations of ambient O3 were 47.4 µg/m3 (ranging from 1.0 to 165.9 µg/m3). Increased risks of premature ventricular contraction and ventricular tachycardia were associated with interquartile range increases in O3 exposure during the last 5 days before each participant's clinic visit, with relative risks of 2.14 (95% confidence interval [CI]: 1.95 to 2.32) and 5.47 (95% CI: 3.51 to 7.43), respectively. Mediation analyses further showed that sympathetic activation, parasympathetic inhibition, and elevated BP levels, as well as heightened risks of ST-segment depression could mediate up to 47.74% of the risks of arrhythmias attributable to O3 exposure. ConclusionOur results suggest that short-term exposure to ambient O3 could prompt the genesis of arrhythmias partially through worsening autonomic function and myocardial burden.

Adverse pregnancy and postpartum outcomes among women with chronic hypertension in France (2010–2018): The nationwide CONCEPTION study

In France, 1.5% of primiparous women has a chronic hypertension (HT) before pregnancy. Its impact on fetal and maternal outcomes remains unclear. We aimed to estimate the impact of chronic hypertension on the onset of cardiovascular events during pregnancy and postpartum (PP). We identified every primiparous woman who gave birth in France between 2010 and 2018, using data from the French National Health Insurance Information System database. Chronic HT before pregnancy and maternal cardiovascular outcomes were identified by deliveries of anti-HT drugs and hospital diagnosis codes. Renin-angiotensin-blockers were considered strictly contra-indicated during the 2nd and 3rd trimesters of pregnancy. We used Poisson models to estimate incidence relative risk (IRR) of adverse pregnancy and PP outcomes among women with chronic HT. Overall, 2,825,529 women were included. Among them, 42,919 (1.5%) had chronic HT and 25,636 were treated during pregnancy (60% of chronic HT). Women with chronic HT were older and were more likely to smoke, to be socially deprived, to be obese, diabetic, and to have previous cardiovascular, venous or renal medical history. In fully-adjusted models, the IRR [95% confidence interval] of maternal cardiovascular events were: 5.7 [5.5–5.8] for preeclampsia, 1.0 [1.0–1.1], 1.4 [0.9–2.2] for stroke, 1.5 [1.2–1.8] for venous thromboembolism, 2.3 [0.9–6.2] for acute coronary syndrome, 3.2 [2.6–3.9] for heart failure and 2.6 [1.4–4.7] for death during PP. The IRR of preeclampsia in women treated during pregnancy vs. women with no HT (5.29 [5.07–5.53]) was significantly higher than in untreated women (3.16 [2.97–3.36]). Among women treated for HT during pregnancy, 435 (2.3%) and 123 (0.7%) bought a renin-angiotensin-blocker at least once during the 2nd and 3rd trimesters, respectively ( Fig. 1 ). Chronic hypertension before pregnancy is a major risk factor of pregnancy and PP adverse outcomes.

Abstract 10851: Statin Shows Significant Antiatherosclerosis and Anti-Inflammatory Effect in Kawasaki Disease Model Mouse

Introduction: Kawasaki disease (KD) is an acute systemic vasculitis, which might promote atherosclerosis in adulthood. The purpose of this study is to verify long-term effect of HMG-CoA inhibitor (statin) for the vasculitis. Hypothesis: Statins suppressed inflammatory cell infiltration and plaque arteriosclerosis in KD, and might have a preventive effect on the onset of cardiovascular events in the chronic phase. Methods: Candida albicans water-soluble fraction (CAWS) was injected intraperitoneally in 5-week-old male apoE -/- mice to create KD-like vasculitis. All mice were fed a high-fat diet 2 weeks after the first injection. Divided into 3 groups, PBS (P), CAWS (C), and CAWS with statin (CS) (orally administered atorvastatin 10mg/kg/day), and sacrificed 6 or 10 weeks after injection and obtained the aorta with the heart (from root to iliac bifurcation). The lipid plaque lesion on the aorta was stained with Oil Red O and the inflammatory cells in aortic root sections were stained with hematoxylin and eosin. These area ratios were quantified and compared. Results: Both atherosclerosis and inflammatory cell infiltration were significantly promoted by CAWS (p&lt;0.01). Statin significantly suppressed plaque area after 10 weeks (C 33±1.5%, CS 18±1.7%) and inflammatory cell infiltration after 6, 10 weeks (C 16±0.6%, CS 7.8±0.9% after 6 weeks, and C 20±2.1%, CS 10±1.0 after 10 weeks, respectively). We examined the statistical correlation between the plaque lesion and the inflammatory cell area, so it revealed the trend between the two groups (r=0.97, P&lt;0.001). Conclusions: CAWS vasculitis, KD-like vasculitis, promoted the development of atherosclerosis in apoE -/- mice. It was newly revealed that long-term oral administration of statin significantly suppressed not only atherosclerosis but also inflammatory cell infiltration. Statin treatment might be expected for secondary prevention of the onset of cardiovascular events in the chronic phase of KD.