Central aortic pulse pressure, thrombogenicity and cardiovascular risk.

High central aortic pulse pressure (CPP) and thrombin-induced platelet-fibrin clot strength (TIP-FCS) have been associated with ischemic outcomes in patients with coronary artery disease in separate studies. But, the ischemic risk associated with these factors has never been analyzed in a single study and their interrelation is unknown. The primary aim of the study was to establish cut points for CPP and TIP-FCS measured at the time of catheterization associated with long term major adverse cardiovascular events. We enrolled 334 consecutive patients undergoing cardiac catheterization and assessed thrombogenicity by thrombelastography. Patients were followed up to 3 years. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and ischemic stroke and the secondary endpoint was occurrence of the primary endpoint or recurrent ischemic events requiring hospitalization. Patients with primary and secondary endpoint occurrence had higher CPP (83 ± 20 vs. 60 ± 18 mmHg, p < 0.0001; 70 ± 21 vs. 59 ± 18 mmHg, p < 0.0001, respectively) and TIP-FCS (68.5 ± 5.8 vs. 65.5 ± 5.0 mm, p = 0.008; 67.4 ± 5.9 vs. 65.2 ± 4.8 mm, p = 0.001, respectively). CPP >60 mmHg and TIP-FCS >69 mm were both independent predictors of primary endpoint occurrence (p = 0.0001 and p = 0.02, respectively). ROC analysis for CPP and TIP-FCS showed a C-statistic of 0.81 (p < 0.0001) and 0.68 (p = 0.007) for the primary endpoint, respectively. Patients with CPP >60 mmHg had higher TIP-FCS (66.8 ± 5.1 vs. 64.8 ± 5.0 mm, p < 0.001) and primary and secondary endpoint occurrence (13 vs. 1.1%, p < 0.0001 and 31.8 vs. 14.4%, p = 0.0002, respectively). CPP >60 mmHg + TIP-FCS > 69 mm was associated with a markedly increased risk of primary endpoint occurrence [HR (95% CI) 5.4(2.3-12.5), p = 0.0001]. High CPP and thrombogenicity are interrelated; each are independently associated with increased cardiovascular risk; and simultaneous presence markedly enhances risk. The mechanistic link between CPP and thrombogenicity deserves further study.

[Distribution laws of Chinese medical syndrome types and analyses of risk factors in senile hypertension patients: a clinical study].

OBJECTIVE: To explore the distribution laws of TCM syndrome types and to analyze the distribution of dynamic blood pressure curve, atherosclerosis, and age in senile hypertension patients. METHODS: Totally 1 131 senile hypertension patients were recruited from 7 provinces and municipal cities. Features of TCM syndromes, classification and distribution curves, and syndrome distribution laws were observed. The distribution curves of dynamic blood pressure, carotid atherosclerosis, and age were compared in each TCM syndrome types. RESULTS: There were four main syndrome types in 736 cases (56.15%), i.e., excessive accumulation of phlegm-dampness syndrome (210 cases, 16.02%), yin deficiency and hyperactivity of yang syndrome (177 cases, 13.50%), Gan-Shen yin deficiency syndrome (79 cases, 6.03%), and deficiency of qi and yin syndrome (252 cases, 19.22%). Besides, there were two more sub-types, i.e., collateral obstruction by blood stasis syndrome and collateral obstruction by phlegm and stasis. Circadian blood pressure monitor was completed in 211 cases. Of them, abnormal circadian blood pressure occurred in 152 cases (accounting for 72. 38%); yin deficiency and hyperactivity of yang syndrome, excessive accumulation of phlegm-dampness syndrome, deficiency of qi and yin syndrome plus collateral obstruction by blood stasis syndrome were most often seen. Color ultrasound of carotid artery was performed in 660 patients of main syndromes. The incidence was quite higher in those of excessive accumulation of phlegm-dampness syndrome (182 cases, 27. 58%), deficiency of qi and yin syndrome plus collateral obstruction by blood stasis syndrome or collateral obstruction by phlegm and stasis (322 cases, 48.79%). Yin deficiency and hyperactivity of yang syndrome was dominant in patients 60 -79 years old, while deficiency of qi and yin syndrome and Gan-Shen yin deficiency syndrome were dominant in patients older than 80 years. CONCLUSIONS: Excessive accumulation of phlegm-dampness syndrome, yin deficiency and hyperactivity of yang syndrome, Gan-Shen yin deficiency syndrome, and deficiency of qi and yin syndrome were main syndrome types in senile hypertension patients. There was statistical difference in the distribution curves of blood pressure, atherosclerosis, and age of various TCM syndrome types.

Relationship between 24 h blood pressure variability and mortality in acute myocardial infarction patients.

BACKGROUND: In recent years, the mortality of patients with AMI has not declined significantly. The relationship between blood pressure variability (BPV) and acute myocardial infarction (AMI) is unclear. We explored the relationship between 24-h BPV and mortality in patients with AMI. HYPOTHESIS: The mortality of patients with AMI is related to BPV. We hope to provide therapeutic ideas for reducing the risk of death in patients with AMI. METHODS: This is a retrospective cohort study. We extracted and analyzed data from the MIMIC-IV 2.0, which was established in 1999 under the auspices of the National Institutes of Health (America). The average real variability (ARV) was calculated for the first 24-h blood pressure measurement after patients with AMI were admitted to the intensive care unit (ICU). Patients were divided into four groups according to ARV quartiles. The outcomes were 30-day, 1-year, and 3-year all-cause mortalities. Data were analyzed using Cox regression, Kaplan-Meier curves, and restricted cubic spline (RCS) curves. RESULTS: We enrolled 1291 patients with AMI, including 475 female. The patients were divided into four groups according to the qualities of diastolic blood pressure (DBP)-ARV. There were significant differences in the 30-day, 1-year and 3-year mortality among the four groups (p = .02, p < .001, p < .001, respectively). After adjustment for confounding factors, systolic blood pressure (SBP)-ARV could not predict AMI patient mortality (p > .05), while the highest DBP-ARV was associated strongly with increased 30-day mortality (HR: 2.291, 95% CI 1.260-4.168), 1-year mortality (HR: 1.933, 95% CI 1.316-2.840) and 3-year mortality (HR: 1.743, 95% CI 1.235-2.461). Kaplan-Meier curves demonstrated that, regardless of SBP or DBP, the long-term survival probabilities of patients in the highest ARV group were significantly lower than that of those in other groups. RCS curves showed that the death risk of patients with AMI first decreased and then increased with the increase in ARV when DBP-ARV < 8.04. The 30-day death risk first increased and then decreased, and the 1-year and 3-year death risks increased and then stabilized with ARV increase when DBP-ARV > 8.04. CONCLUSION: This study showed that patients with AMI may have an increased risk of short- and long-term death if their DBP-ARV is higher or lower during the first 24-h in ICU.

Clinical characteristics of primary aldosteronism screened from Chinese patients with hypertension: The China primary aldosteronism prospective study.

We investigated the clinical characteristics of primary aldosteronism (PA) screened from patients with hypertension in China. The participants were hypertensive patients who were suspected of PA and registered in the China Primary Aldosteronism Prospective Study. Plasma aldosterone-to-renin ratio (ARR) was used as the screening test. In patients screened positive for PA, that is, an ARR exceeding the thresholds and plasma aldosterone concentration (PAC) > 100 pg/mL, a confirmatory test was performed for diagnosis. Patients with PA underwent a CT scan and adrenal venous sampling for subtyping. Of the 1497 screened patients, 754 (50.4%) had an ARR exceeding the diagnostic threshold and 637 (84.5% of those eligible) were registered. These registered hypertensive patients with suspected PA had a mean (standard deviation) age of 52.6 ± 12.1 years, and included 442 (58.6%) women. In multiple stepwise logistic regression, the significant odds ratios for the presence of diagnosed (n = 490) versus suspected and non-diagnosed PA (n = 147) were 4.54 (95% CI: 2.78-7.39) for a history of hypokalemia, 0.79 (95% CI: 0.64-0.98) for a 0.9 mmol/l higher serum total cholesterol, and 2.25 (95% CI: 1.63-3.10) for a doubling of PAC in the supine or standing/sitting position. In multiple stepwise logistic regression, the significant odds ratios for the presence of unilateral (n = 135) versus bilateral PA (n = 53) were 3.04 (95% CI: 1.90-4.87) for a 0.4 mmol/l lower minimum serum potassium concentration and 1.86 (95% CI: 1.20-2.86) for a 0.3 mmol/l higher serum high-density lipoprotein cholesterol. PA might be a biochemical continuum in the adrenal hypersecretion of aldosterone as well as hypokalemia.

[Association between left ventricular diastolic function and blood pressure variability in essential hypertensive patients].

OBJECTIVE: To investigate the relationship between blood pressure variability (BPV) and left ventricular diastolic function in patients with essential hypertension. METHODS: Left ventricular diastolic function of 252 hypertensive patients were assessed by early (E) diastolic transmitral flows to early diastolic mitral annular velocity (Ea) (E/Ea) ratio derived from Doppler echocardiography. Patients were divided into two groups according to normal left ventricular diastolic function group (E/Ea<15, n = 168) and left ventricular diastolic dysfunction group (E/Ea ≥ 15, n = 84). All patients were monitored by ambulatory blood pressure. Standard deviation (SD) and coefficient of variation (CV) of blood pressure were calculated as the BPV. Relationship between BPV and left ventricular diastolic function were analyzed by multivariate logistic regression analysis. RESULTS: All-day average diastolic blood pressure(DBP), the day systolic blood pressure (SBP), night SBP, night DBP, SBPSD, DBPSD and DBPCV in the left ventricular diastolic dysfunction group were significantly higher than in the normal diastolic function group (all P < 0.05). Multivariate logistic regression analysis showed that left ventricular diastolic dysfunction was associated with SBPSD (OR:1.126, 95%CI:1.054-1.203, P < 0.01), SBPCV (OR:1.127, 95%CI:1.036-1.225, P < 0.01) in this patient cohort. CONCLUSION: High variability of SBP is correlated with left ventricular diastolic dysfunction in hypertensive patients.

Extracorporeal Cardiopulmonary Resuscitation in Children of Asia Pacific: A Retrospective Analysis of Extracorporeal Life Support Organization Registry.

BACKGROUND: Recent advances in extracorporeal membrane oxygenation (ECMO) have led to increasing interest in its use during cardiopulmonary resuscitation (CPR). However, decisions regarding extracorporeal CPR (ECPR) in children are difficult as a result of limited studies, especially in Asia Pacific. The objective of this study was to investigate trends in survival and demographic details for children with ECPR in Asia Pacific recorded in the Extracorporeal Life Support Organization (ELSO) registry from 1999 to 2016 and identify the risk factors associated with in-hospital mortality. METHODS: The data of children younger than 18 years of age who received ECPR over the past 18 years in Asia Pacific were retrospectively analyzed. The data were extracted from the ELSO registry and divided into two 9-year groups (Group 1: 1999-2007 and Group 2: 2008-2016) to assess temporal changes using univariate analysis. Then, univariate and multiple logistic regression analyses were performed between survivors and nonsurvivors to identify factors independently associated with in-hospital mortality. RESULTS: A total of 321 children were included in final analysis, with an overall survival rate of 50.8%. Although survival rates were similar between Group 1 and Group 2 (43.1% vs. 52.5%, χ2 = 1.67, P = 0.196), the median age (1.7 [0.3, 19.2] months for Group 1 vs. 5.6 [0.8, 64.9] months for Group 2, t = -2.93, P = 0.003) and weight (3.7 [3.0, 11.5] kg for Group 1 vs. 6.0 [3.4, 20.3] kg for Group 2, t = -3.14, P = 0.002) of children increased over time, while the proportion of congenital heart disease (75.9% for Group 1 vs. 57.8% for Group 2, χ2 = 6.52, P = 0.011) and cardiogenic shock (36.2% for Group 1 vs. 7.2% for Group 2, χ2 = 36.59, P < 0.001) decreased. Patient conditions before ECMO were worse, while ECMO complications decreased across time periods, especially renal complications. Multiple logistic regression analysis of ECMO complications showed that disseminated intravascular coagulation (DIC), myocardial stunning, and neurological complications were independently associated with increased odds of hospital mortality. CONCLUSIONS: The broader indications and decreased complication rates make EPCR to be applicated more and more extensive in children in Asia Pacific region. ECMO complications such as myocardial stunning are independently associated with decreased survival.

[Expression of peroxisome proliferator-activated receptors Y changes with age in vascular smooth muscle cells of spontaneously hypertensive rat].

OBJECTIVE: In order to elucidate the relationship between PPAR-gamma and the development of hypertension, we detected the expression of peroxisome proliferator-activated receptors gamma (PPAR-gamma) in the vascular smooth muscle cells (VSMCs) and the VSMC proliferation of spontaneously hypertensive rats (SHR) at different ages. METHODS: The expression of PPAR-gamma in the intact vascular tissues of rats at different ages were detected by immunohistochemistry. Aortic VSMCs were cultured. PPAR-gamma mRNA in primary and low-passage cultured VSMCs of various ages were determined by RT-PCR, and proteins were evaluated by immunohistochemistry and age matched Western Blot. Age matched Wistar-Kyoto rats (WKY) were used as control. RESULTS: This experiment demonstrated that the expression of PPAR-gamma increased with age in the intact aorta tissues of SHR. The expression of PPAR-gamma did not continuously increase in 24w-old SHR when compared with that in 16w-old SHR. No difference between 4w-, 24w-old SHR and age matched WKY was observed, but the expression of PPAR-gamma was greater in 8w- and 16w old SHR than in age matched WKY. In primary and low-passage cultured VSMCs, the expression of PPAR-gamma mRNA and protein increased with age both in SHR VSMCs and WKY VSMCs of 4w, 8w and 16w old, and no difference between 4w- and 24w-old SHR and WKY was noted, but the expression of PPAR-gamma was higher in 8w- and 16w-old SHR than in age matched WKY. PPAR-gamma expression in 24w-old SHR did not increase and it was equal to 16w-old SHR and 24w-old WKY. CONCLUSION: These datas on SHR suggest that the expression of PPAR-gamma changes with age and the development of high blood pressure. PPAR-gamma expression may play a compensatory role in hypertension, but this compensatory action is limited.

[The effects of angiotensin II receptor blockers in hypertensive patients complicating hyperuricaemia].

OBJECTIVE: To study the effects of angiotensin II receptor blockers (ARB), losartan and irbesartan, on blood pressure and serum uric acid (SUA) level in mild to moderate essential hypertensive patients complicating hyperuricaemia. METHODS: A total of 351 eligible patients were recruited in this multi-center, randomized, double-blind parallel clinical trial. After 1 week screening and a 2 week single-blinded placebo wash-out period, patients were randomly assigned to receive losartan 50 mg (n=76) or irbesartan 150 mg (n=175) once daily for 4 weeks, followed by a double-dose for another 4 weeks in patients whose seated DBP were >or=90 mm Hg or SBP>or=140 mm Hg at the end of 4 weeks. The SUA concentration and blood pressure were measured at baseline, 4 and 8 weeks post therapy. RESULTS: Three hundred and twenty-five patients completed the study (162 in the losartan group and 163 in the irbesartan group). Both groups were well matched for baseline clinical characteristics and demographics. SUA was significant reduced in losartan group (430.93 micromol/L vs 372.35 micromol/L, P<0.0001), but not in Irbesartan group (430.46 micromol/L vs 420.67 micromol/L, P>0.05) 8 weeks post therapy compared to baseline level. Blood pressure was significantly and equally reduced in both groups after 8 weeks treatment compared to baseline level (P<0.0001). CONCLUSION: Losartan is an optimum choice of medication for patients with mild-to-moderate hypertension complicating hyperuricemia.

Antiplatelet Effect Durability of a Novel, 24-Hour, Extended-Release Prescription Formulation of Acetylsalicylic Acid in Patients With Type 2 Diabetes Mellitus.

High platelet reactivity and high platelet turnover have been implicated in incomplete platelet inhibition during immediate-release acetylsalicylic acid therapy in patients with type 2 diabetes mellitus (DM). An extended-release acetylsalicylic acid (ER-ASA; Durlaza) formulation was developed to provide 24-hour antithrombotic effects with once-daily dosing. The objective of the study was to evaluate the antiplatelet effects of ER-ASA in patients with DM. In this open-label, single-center study, patients with DM (n = 40) and multiple cardiovascular risk factors received ER-ASA 162.5 mg/day for 14 ± 4 days. Multiple platelet function tests, serum and urinary thromboxane B2 metabolites, prostacyclin metabolite, and high-sensitive C-reactive protein levels were assessed at 1, 12, 16, and 24 hours post-dose. Patients with high platelet turnover and/or high platelet reactivity were treated with ER-ASA 325 mg/day for 14 ± 4 days, and laboratory analyses were repeated. All patients responded to ER-ASA 162.5 mg/day as measured by arachidonic acid-induced aggregation, and there was no loss of the platelet inhibitory effect of ER-ASA 162.5 mg/day over 24 hours post-dose (p = not significant). The antiplatelet effect was sustained over 24 hours for all platelet function measurements. Mean 1- to 24-hour serum thromboxane B2 levels were low with both doses and were lower with ER-ASA 325 mg/day compared with 162.5 mg/day therapy (p = 0.002). In conclusion, ER-ASA 162.5 mg daily dose provided sustained antiplatelet effects over 24 hours in patients with type 2 DM and multiple cardiovascular risk factors and had a favorable tolerability profile.

Vorapaxar in the secondary prevention of atherothrombosis.

Dual antiplatelet therapy with aspirin, a platelet cyclooxygenase-1 inhibitor and P2Y12 receptor blockers, remains the major drug strategy to prevent ischemic event occurrence in patients with acute coronary syndromes and in patients undergoing coronary stenting, but there some limitations that can be overcome by targeting novel targets. Unlike direct thrombin inhibitors that bind directly to thrombin, targeting the platelet thrombin receptor, protease activated receptor (PAR)-1, may offer a better choice for the attenuation of atherosclerosis progression, thrombus-mediated ischemic events and restenosis without interfering with primary hemostasis. Vorapaxar - a synthetic analogue of himbacine, is a high affinity and highly selective PAR-1 antagonist that can effectively inhibit thrombin-induced platelet aggregation. In the TRACER trial, the addition of vorapaxar to standard therapy in patients with non-stent thrombosis-elevation- acute coronary syndromes did not significantly reduce the primary composite end point occurrence of cardiovascular (CV) death, myocardial infarction (MI), stroke, hospitalization for ischemia, or urgent revascularization, but significantly increased the GUSTO moderate and severe bleeding (p < 0.001) and intracranial hemorrhage (ICH). In the TRA 2°P-TIMI 50 trial, in patients with a history of MI and peripheral arterial disease (PAD) (67% of the total population), the end point of CV death, MI, or stroke was significantly (20%) reduced with vorapaxar whereas GUSTO moderate or severe bleeding was increased (1.5-fold), but not ICH or fatal bleeding and the net clinical outcome favoring the vorapaxar therapy. Based on these favorable results, the FDA approved vorapaxar for the reduction of thrombotic cardiovascular events in patients with prior MI or with PAD for long term therapy. A careful patient selection is needed to balance efficacy versus safety. At this time, patients with high risk for recurrent ischemic event occurrence such as patients with diabetes mellitus and previous MI can be safely treated with vorapaxar for long-term therapy.