Occurrence Of Acute Cardiovascular Events Research Articles

Curcumin Equipped Nanozyme-Like Metal-Organic Framework Platform for the Targeted Atherosclerosis Treatment with Lipid Regulation and Enhanced Magnetic Resonance Imaging Capability.

Atherosclerotic cardiovascular disease (ASCVD) has become the leading cause of death worldwide, and early diagnosis and treatment of atherosclerosis (AS) are crucial for reducing the occurrence of acute cardiovascular events. However, early diagnosis of AS is challenging, and oral anti-AS drugs suffer from limitations like imprecise targeting and low bioavailability. To overcome the aforementioned shortcomings, Cur/MOF@DS is developed, a nanoplatform integrating diagnosis and treatment by loading curcumin (Cur) into metal-organic frameworks with nanozymes and magnetic resonance imaging (MRI) properties. In addition, the surface-modification of dextran sulfate (DS) enables PCN-222(Mn) effectively target scavenger receptor class A in macrophages or foam cells within the plaque region. This nanoplatform employs mechanisms that effectively scavenge excessive reactive oxygen species in the plaque microenvironment, promote macrophage autophagy and regulate macrophage polarization to realize lipid regulation. In vivo and in vitro experiments confirm that this nanoplatform has outstanding MRI performance and anti-AS effects, which may provide a new option for early diagnosis and treatment of AS.

SUN-566 Metabolic Effects of Cross-Hormone Treatments in Transgender Individuals in Taiwan

Objective:Many biological differences seen in men and women are driven by relative different level of estrogen and testosterone. Transgender individuals may need gender-affirming intervention like inhibiting of endogenous sex hormones or replenishing cross-hormone to induce physical change to stimulate their expressed or experienced gender. However, recent study has concluded that the incidences of acute cardiovascular events are higher in transwomen receiving transgender hormone therapy (1). Transgender therapy for adults with Testosterone in female to male (FtM); with Estrogen and anti-androgen in male to female (MtF) are frequently prescribed in Taiwan. The aim of this study is to investigate metabolic effects of an altered sex hormone profile on different gender.Methods:The study is a retrospective study conducted in a tertiary medical center in Northern Taiwan analyzing biological differences over time for 65 FtM and 45 MtF patients in our endocrine out-patient department. The results from the exams are analyzed separately using paired t-test compared to baseline visit. The transgender individuals are examined at four time points; before the cross-hormone therapy, three, six, and twelve months following sex hormone treatment.Results:The primary outcome was that FtM patients showed significant increases in BMI (22.6±0.3 v.s. 23.3±0.4 kg/m2; P<0.001; t=6M), low density lipoprotein cholesterol (124±3 vs.131±3 mg/dL; P=0.03; t=12M), creatinine (0.75±0.01 vs.0.83±0.14 mg/dL; P<0.001; t=12M), and hemoglobin (13.5±0.7 v.s. 15.2±0.19 g/dL; P<0.001; t=12M) compared to the baseline; decreases of high density lipoprotein cholesterol (57±2.1 v.s. 51±2.0 mg/dL; <0.001; t=12M) was also revealed. Patients in MtF group disclosed declines in low density lipoprotein cholesterol (104±3 v.s. 100±3 mg/dL; P=0.05; t=3M), hemoglobin (14.0±0.1 v.s. 13.5±0.1 g/dL; P=0.008; t=12M), uric acid (5.3±0.2 v.s. 4.7±0.2mg/dL; P=0.03; t=12M) and creatinine (0.82±0.01 v.s. 0.79±0.14 mg/dL; P<0.001; t=6M) compared to baseline data. In addition, most of these metabolic effects persisted the follow-up period.Conclusion:This observational study revealed the role of cross-hormone treatment in increasing relative cardiovascular risk in FtM transgender individuals.Reference:1. Nota, N. M., et al. (2019). “Occurrence of Acute Cardiovascular Events in Transgender Individuals Receiving Hormone Therapy: Results From a Large Cohort Study.” Circulation 139(11): 1461-1462. Nothing to Disclose: LYL, YHL, THW, YCL

Lipoprotein-associated phospholipase A2 predicts cardiovascular events in dialyzed patients.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a serine lipase that enhances the instability of the atherosclerotic plaques. While in the general and cardiac population Lp-PLA2 is recognized as an important determinant of cardiovascular (CV) accidents, no data are available for the renal population. The aim of this study was to evaluate the relationship between Lp-PLA2 and acute CV events in hemodialyzed patients. We enrolled 102 dialyzed patients, 63% male, age 71years (59-78), 35% with diabetes, 54% hypertension, 40% coronary artery disease and 31% peripheral vascular disease. They were investigated for Lp-PLA2 (cut-off < 194nmol/min/ml), lipoprotein profile and the occurrence of acute CV events and death in the subsequent 3years of follow-up. The median (interquartile ranges) levels of Lp-PLA2, total-, HDL-, LDL-cholesterol and ApoB/ApoA lipoprotein ratio were 184.5 (156.5-214.5) nmol/min/ml, 158 (127-191) mg/dl, 41 (33-51) mg/dl, 79 (63-102) mg/dl and 0.72 (0.58-0.89), respectively. In 42% of patients, Lp-PLA2 was > 194nmol/min/ml and total- and LDL-cholesterol were higher, as well as CV morbidity and mortality. During follow-up, 51% of patients developed at least one CV event; the median survival time was 36 months, with a total and CV mortality of 42 and 29%, respectively. At multivariate Cox regression, Lp-PLA2 > 194nmol/min/ml (HR = 2.98, p = 0.005), age (HR = 1.03, p = 0.029), diabetes (HR = 2.86, p = 0.002) and hypertension (HR = 2.93, p = 0.002) were independently associated with time to CV events. Lp-PLA2 activity is elevated among dialyzed patients and is an independent risk factor for acute CV events in a mean follow-up of 3years.

A New Perspective for Chinese Medicine Intervention for Coronary Artery Disease: Targeting Inflammation.

Inflammation, which plays a critical role in atherosclerosis and the occurrence of acute cardiovascular events, may be a new target for treatment of coronary artery disease (CAD) to reduce residual cardiovascular risk. Recently, Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease (CANTOS), the largest scale clinical trial that targeted inflammation but not lipids, has affirmed for the first time the inflammatory hypothesis of artherosclerosis and marked the advent of an exciting era of targeting inflammation for the prevention and treatment of cardiovascular diseases. Chinese medicine (CM) is a promising adjuvant therapy for CAD in light of its safety and pleiotropic effect of anti-inflammation, anti-platelet, lipid-regulating, endothelium-protection, microcirculation-improving, etc. In recent years, exploration of anti-inflammatory treatment of CAD with CM has been going on from theory to practice. Taking CANTOS as an example, the design strategy to combine CM and Western medicine to inhibit inflammation were discussed in this paper, which might provide a new perspective for CM intervention on CAD.

Vasa Vasorum Angiogenesis: Key Player in the Initiation and Progression of Atherosclerosis and Potential Target for the Treatment of Cardiovascular Disease.

Plaque microvascularization and increased endothelial permeability are key players in the development of atherosclerosis, from the initial stages of plaque formation to the occurrence of acute cardiovascular events. First, endothelial dysfunction and increased permeability facilitate the entry of diverse inflammation-triggering molecules and particles such as low-density lipoproteins into the artery wall from the arterial lumen and vasa vasorum (VV). Recognition of entering particles by resident phagocytes in the vessel wall triggers a maladaptive inflammatory response that initiates the process of local plaque formation. The recruitment and accumulation of inflammatory cells and the subsequent release of several cytokines, especially from resident macrophages, stimulate the expansion of existing VV and the formation of new highly permeable microvessels. This, in turn, exacerbates the deposition of pro-inflammatory particles and results in the recruitment of even more inflammatory cells. The progressive accumulation of leukocytes in the intima, which trigger proliferation of smooth muscle cells in the media, results in vessel wall thickening and hypoxia, which further stimulates neoangiogenesis of VV. Ultimately, this highly inflammatory environment damages the fragile plaque microvasculature leading to intraplaque hemorrhage, plaque instability, and eventually, acute cardiovascular events. This review will focus on the pivotal roles of endothelial permeability, neoangiogenesis, and plaque microvascularization by VV during plaque initiation, progression, and rupture. Special emphasis will be given to the underlying molecular mechanisms and potential therapeutic strategies to selectively target these processes.

Allopurinol use and the risk of acute cardiovascular events in patients with gout and diabetes

BackgroundFew studies, if any, have examined cardiovascular outcomes in patients with diabetes and gout. Both diabetes and gout are risk factors for cardiovascular disease. The objective of this study was to examine the effect of allopurinol on the risk of incident acute cardiovascular events in patients with gout and diabetes.MethodsWe used the 2007–2010 Multi-Payer Claims Database (MPCD) that linked health plan data from national commercial and governmental insurances, representing beneficiaries with United Healthcare, Medicare, or Medicaid coverage. In patients with gout and diabetes, we assessed the current allopurinol use, defined as a new filled prescription for allopurinol, as the main predictor of interest. Our outcome of interest was the occurrence of the first Incident hospitalized myocardial infarction (MI) or stroke (composite acute cardiovascular event), after which observations were censored. We employed multivariable-adjusted Cox proportional hazards models that simultaneously adjusted for patient demographics, cardiovascular risk factors and other medical comorbidities. We calculated hazard ratios [HR] (95% confidence intervals [CI]) for incident composite (MI or stroke) acute cardiovascular events. We performed sensitivity analyses that additionally adjusted for the presence of immune diseases and colchicine use, as potential confounders.ResultsThere were 2,053,185 person days (5621.3 person years) of current allopurinol use and 1,671,583 person days (4576.5 person years) of prior allopurinol use. There were 158 incident MIs or strokes in current and 151 in prior allopurinol users, respectively. Compared to previous allopurinol users, current allopurinol users had significantly lower adjusted hazard of incident acute cardiovascular events (incident stroke or MI), with an HR of 0.67 (95% CI, 0.53, 0.84). Sensitivity analyses, additionally adjusted for immune diseases or colchicine use, confirmed this association.ConclusionsCurrent allopurinol use protected against the occurrence of acute cardiovascular events in patients with gout and diabetes. The underlying mechanisms for this potential cardio-protective effect of allopurinol need further exploration.

Seasonal Variation in Heart Failure Hospitalization

A seasonal variation has been reported for occurrence of acute cardiovascular events, such as myocardial infarction, sudden death, and rupture/dissection of aortic aneurysms. The aim of this study was to determine whether a seasonal variation exists for heart failure (HF) hospitalization. The study included all cases of HF admissions to Ferrara Hospital between January 2002 and December 2009. The sample was divided into subgroups by gender, age, cardiovascular risk factors, patients' outcome, and order of ICD-9 codes (first diagnosis, accessory diagnosis). On the basis of date of admission, cases have been analyzed for seasonal variation and annual frequency. For seasonal analysis, monthly cases were categorized into four 3-month intervals by seasons. Moreover, monthly admissions have been also adjusted for number of days, and the average number of admissions per month has been used. The database included 15,954 patients with the ICD-9-CM codes of HF (420-429). Hospital admissions for HF were most frequent in winter (28.4%) and least in summer (20.4%). Chronobiological analysis yielded a significant peak in January for total cases and all subgroups considered. No differences were found for subgroups by gender, age, fatal cases, presence of hypertension and diabetes mellitus, patients' outcome, and order of ICD-9 codes (first diagnosis, accessory diagnosis). A seasonal periodicity for HF hospitalization was demonstrated, with a peak in winter months, independent of gender, age, major cardiovascular risk factor, and patients' outcome. These data could be useful for practitioners to improve causative prevention measures, therapeutic management, and educational strategies.

Endothelial dysfunction and erectile dysfunction in the aging man

Penile erection is a vascular event that requires an intact endothelium to occur. A dysfunctional endothelium is an early marker for the development of atherosclerotic changes and can also contribute to the occurrence of acute cardiovascular events. The pathogenesis of both endothelial and erectile dysfunction (ED) is intimately linked through decreased expression and activation of endothelial nitric oxide (NO) synthase, and the subsequent blunted physiological actions of NO naturally occurring with aging. It is now well-understood that ED is a symptom of underlying disease rather than a disease itself; for this reason in the near future both general practitioners, internal medicine practitioners and many specialists will have to interplay with sexual medicine. Aging in the man is also associated with several changes in arterial structure and function, part of them related to the decline of circulating levels of steroids, that is, testosterone and estradiol. These changes may be responsible, in part, for the lack of efficacy of ED treatments. The recent discovery that chronic administration of phosphodiesterase type 5 inhibitors may improve erectile and endothelial responsiveness of men previously non-responsive to on-demand regimes, and the knowledge that testosterone is one of the main modulators of the expression of penile phosphodiesterase type 5 isoenzyme, opens a new scenario in the treatment of men with ED and co-morbidities. The aim of this review is to discuss the pathophysiology of endothelial dysfunction and its relationship with ED in the aging male, and to suggest possible strategies to improve arterial function with regard to sexual dysfunctions.

Adherence to Antihypertensive Medications and Cardiovascular Morbidity Among Newly Diagnosed Hypertensive Patients

Nonadherence to antihypertensive treatment is a common problem in cardiovascular prevention and may influence prognosis. We explored predictors of adherence to antihypertensive treatment and the association of adherence with acute cardiovascular events. Using data obtained from 400 Italian primary care physicians providing information to the Health Search/Thales Database, we selected 18,806 newly diagnosed hypertensive patients >or=35 years of age during the years 2000 to 2001. Subjects included were newly treated for hypertension and initially free of cardiovascular diseases. Patient adherence was subdivided a priori into 3 categories-high (proportion of days covered, >or=80%), intermediate (proportion of days covered, 40% to 79%), and low (proportion of days covered, <or=40%)-and compared with the long-term occurrence of acute cardiovascular events through the use of multivariable models adjusted for demographic factors, comorbidities, and concomitant drug use. At baseline (ie, 6 months after index diagnosis), 8.1%, 40.5%, and 51.4% of patients were classified as having high, intermediate, and low adherence levels, respectively. Multiple drug treatment (odds ratio, 1.62; 95% CI, 1.43 to 1.83), dyslipidemia (odds ratio, 1.52; 95% CI, 1.24 to 1.87), diabetes mellitus (odds ratio, 1.40; 95% CI, 1.15 to 1.71), obesity (odds ratio, 1.50; 95% CI, 1.26 to 1.78), and antihypertensive combination therapy (odds ratio, 1.29; 95% CI, 1.15 to 1.45) were significantly (P<0.001) associated with high adherence to antihypertensive treatment. Compared with their low-adherence counterparts, only high adherers reported a significantly decreased risk of acute cardiovascular events (hazard ratio, 0.62; 95% CI, 0.40 to 0.96; P=0.032). The long-term reduction of acute cardiovascular events associated with high adherence to antihypertensive treatment underscores its importance in assessments of the beneficial effects of evidence-based therapies in the population. An effort focused on early antihypertensive treatment initiation and adherence is likely to provide major benefits.

Non-invasive Methods for Cardiovascular Risk Assessment in Asymptomatic Type 2 Diabetes Mellitus

Cardiovascular disease (CVD) is the major cause of mortality in type 2 diabetes mellitus. CVD is a clinical manifestation of atherosclerosis, a chronic and progressive inflammatory disease characterized by a long asymptomatic phase. Progression of atherosclerosis can lead to the occurrence of acute cardiovascular events. Atherosclerosis can be identified during the subclinical phase by several methods, including using biomarkers, pulse wave velocity, augmentation index, flow-mediated dilation, carotid ultrasound, and calcium score. The appropriate criteria for identifying asymptomatic patients with type 2 diabetes who should undergo CVD screening and therapeutic intervention remain controversial. Non-invasive methods, such as markers of subclinical atherosclerosis, may aid in risk stratification and the design of tailored therapies for patients with type 2 diabetes mellitus.

Circadian variation in vascular tone and endothelial cell function in normal males

The existence of circadian rhythms in the time of onset of acute cardiovascular events has been described previously. This report describes the circadian variation in endothelial cell products, such as nitric oxide (NO) and endothelin-1 (ET-1) levels, and endothelium-dependent and -independent vasodilation in normal males. Plasma ET-1 and NO were measured every 4 h in nine subjects (20-41 years old) over a 24 h period. Endothelium-dependent and -independent vascular responses were measured in the forearm skin every 4 h using laser Doppler imaging after iontophoresis of increasing doses of acetylcholine (ACh) and sodium nitroprusside respectively. A statistically significant circadian variation was demonstrated for the mean ACh response (P=0.0001, ANOVA). The peak response [in arbitrary perfusion units (AU)] occurred at 16.00 hours (8.90+/-1.91 AU) and the lowest response at 08.00 hours (4.57+/-0.66 AU). A significant circadian variation was also seen for the highest dose of sodium nitroprusside (P=0.036, ANOVA), the peak occurred at 16.00 hours (3.97+/-1.80 AU), and the lowest at 04.00 hours (2.62+/-0.58 AU) and 08.00 hours (2.58+/-1.16 AU). There was a significant circadian variation in the ET-1 levels (P=0.04) with two peaks, one at 20.00 hours (0.80+/-0.28 pg/ml) and the other at 08.00 hours (0.84+/-0.15 pg/ml). The lowest value occurred at 16.00 hours (0.61+/-0.24 pg/ml). There was also a borderline trend for a circadian variation in NO levels (P=0.06), with higher levels at 20.00 hours (15.53+/-8.42 micromol/l), and low levels at 04.00 hours (10.87+/-4.70 micromol/l) and 08.00 hours (9.82+/-3.15 micromol/l). ACh responses were significantly correlated with ET-1 (r=-0.3, P=0.02) and NO (r=0.30, P=0.02) levels. Our findings suggest that endothelial activity has a circadian variation with attenuation in the morning. These circadian variations in endothelial activity might play an important role in the occurrence of acute cardiovascular events at this time, which are precipitated through the interplay between ET-1, NO and vascular function.

Morning attenuation of endothelium-dependent, flow-mediated dilation in healthy young men: possible connection to morning peak of cardiac events?

Brachial artery flow-mediated dilation (FMD), a noninvasive, widely used clinical index of endothelial function and magnitude of FMD, has been reported to be closely related to many coronary risk factors and coronary atherosclerosis. However, there has been no study that examines the diurnal change of FMD. We designed this study to reveal the diurnal variation of FMD in healthy volunteers. We examined FMD in response to reactive hyperemia by high resolution ultrasound in 13 healthy young men (age 25-32) at four different times over the course of a day. Mean measures of brachial artery FMD was 4.0% at 8:00, 5.3% at 12:00, 9.7% at 17:00, and 6.9% at 21:00 hours. Flow-mediated dilation at 8:00 and at 12:00 hours was significantly lower than that at 17:00 (p < 0.05). These results show that endothelial function has diurnal variation and is significantly attenuated in the morning. Morning attenuation of endothelial function should be recognized in clinical research and may play an important role in the circadian variation of the occurrence of acute cardiovascular events.