Hu Dayi

Efficacy and effectiveness of valsartan/amlodipine and valsartan/amlodipine/hydrochlorothiazide in hypertension: randomized controlled versus observational studies

Abstract Objective: The aim of this post-hoc analysis was to compare the results from randomized controlled trials (RCTs) and real-world evidence (RWE) studies of valsartan/amlodipine (Val/Aml) and valsartan/amlodipine/hydrochlorothiazide (Val/Aml/HCTZ) in patients with uncontrolled hypertension (>140/90 mmHg). Methods: Data was pooled from 15 RCTs (N = 5542) and 8 RWE studies (N = 1397) for Val/Aml; and 2 RCTs (N = 804) and 5 RWE studies (N = 9380) for Val/Aml/HCTZ. Patients who received Val/Aml (80/5, 160/5, 160/10, 320/5, or 320/10 mg), Val/Aml/HCTZ (160/5/12.5, 160/5/25, 160/10/12.5, 160/10/25, or 320/10/25 mg) or placebo were considered for this analysis. Only patients with both baseline and follow-up assessment within 60–90 days after baseline had been included in the analysis. Patients with missing values were excluded from the analysis. Using fitted linear mixed-effects model and random factors, treatment interactions and study design with mean sitting systolic blood pressure (msSBP), diastolic BP (msDBP) and pulse pressure (msPP) reductions from baseline to Week 8–12 of treatment were compared. Results: Baseline demographics and patient characteristics were comparable between RCT and RWE datasets and within Val/Aml and Val/Aml/HCTZ treatment groups. In both RCT and RWE studies, least-squares mean (LSM) reduction in msSBP/msDBP and msPP from baseline were significant (p < .05) across all dosages. The efficacy of Val/Aml in RCTs was statistically significantly greater than in RWE studies for msSBP/msDBP (−23.1/−13.8 vs. −17.9/-9.1 mmHg) but the difference was non-significant for msPP (−8.6 vs. −9.3 mmHg; p = .77). For Val/Aml/HCTZ, no direct comparison was available but a similar trend was observed. The difference observed for msSBP and msDBP may be due to routine practice setting, larger populations may have more confounders and different behaviors towards treatment adherence. Conclusion: These findings demonstrate that the efficacy of Val/Aml and Val/Aml/HCTZ in RCTs was more pronounced compared with their effectiveness in RWE studies in different ethnic populations although the overall benefit was not different.

GW24-e2249 One-year cardiovascular event rates in patients with atherothrombotic disease in China

Objectives We sought to assess the risk profile, management and subsequent 1-year cardiovascular (CV) event rates in Chinese patients who had a history of established atherosclerotic arterial disease, including coronary artery disease (CAD), stroke, peripheral vascular disease (PAD), or with two or more cardiovascular risks. Methods From Oct. 2004 to Jan. 2005, 3732 Chinese patients with either atherosclerotic arterial disease (CAD, stroke, PAD; n = 2689) or at least 2 risk factors for atherothrombosis (n = 734) were sequentially enrolled in the study. Outcomes of interest included CV death, myocardial infarction (MI), stroke and hospitalisation for atherothrombotic events. Results During a mean follow-up time of 13.6 ± 1.5 months, 309 participants (8.3%) were lost. Overall, the all cause death rate was 8.6% (294 deaths), with CV deaths accounting for 41.2% (121 deaths; 3.5% overall). CV death was 4.4% for those with atherosclerotic arterial disease vs 1.1% for patients with multiple risk factors only. Among patients with established disease, CV death was 4.2% for patients with CAD, 5.0% for patients with stroke, and 6.3% for patients with PAD. For the end point of CV death/MI/stroke/hospitalisation for atherothrombotic events, the highest event rate occurred among patients with 3 vascular disease locations (34.3%), followed by those with 2 (27.6%), 1 location (21.0%) and those with risk factors only (12.7%, P < 0.001). A large percentage of patients did not reach the therapeutic target values specified in current guidelines. Conclusions In Chinese patients with established atherosclerotic arterial disease, or at risk of atherothrombosis, a substantial increase in cardiovascular event rates with increasing numbers of affected arterial beds. PAD patients appeared to be at an especially high risk. Our study suggests a need to improve detection and consequent medical treatment of multi-site atherosclerotic arterial disease.

GW24-e3931 Correlation Analysis Between Hyperuricemia and Cardiovascular Disease Risk Factors in Population of Healthy Examination

Objectives To understand the relationship between hyperuricemia and cardiovascular disease risk factors. Methods 468 cases with hyperuricemia (HUA) screened out from a company on-the-job personnel healthy medical information, and 508 cases with normal serum uric acid levels (NUA) were randomly selected from the same healthy medical information. Two groups of cardiovascular risk factors were compared with. After an accurate clinical examination and a biochemical evaluation, the results were analysed. Results Participants with hyperuricemia compared to those with normal serum uric acid levels had higher in SBP, DBP, TG, LDL- C and BMI (p < 0.01). Multiple regression analysis showed significant correlation of serum uric acid level and DBP, BMI, TG and fasting glucose levels (p < 0.01 or p < 0.05). Conclusions Serum uric acid concentration are significantly association with cardiovascular disease (CVD) risk factors, and increase risk of CVD.

GW24-e3523 Association of dysglycemia and all-cause mortality across the spectrum of coronary artery disease

Objectives To assess the association between fasting plasma glucose (FPG) and all-cause mortality across the spectrum of coronary artery disease (CAD). Methods There were 18999 patients in this study. The primary end points were in-hospital and follow-up all-cause mortality. According to the quartiles of FPG levels, patients were categorised into 4 groups: Q1, <5.1 mmol/L (to convert to mg/dL, multiply by 18); Q2, 5.1 - 5.9 mmol/L; Q3, 5.9 - 7.5 mmol/L; and Q4, ≥7.5 mmol/L. Q1 was recognised as the lower glycemic group, Q2/Q3 as the normoglycemic groups, and Q4 as the higher glycemic group. Results In patients with acute myocardial infarction (AMI), all-cause mortality for the dysglycemic groups were higher than normoglycemic groups (in-hospital mortality for Q1 to Q4 was 1.0%, 0.9%, 0.2%, and 1.5%, respectively, P value = 0.001; follow-up mortality for Q1 to Q4 was 1.7%, 0.9%, 0.3%, and 1.8%, respectively, P value <0.001). In patients with stable coronary artery disease (SCAD), there were no significant differences in mortality among groups. While in patients with unstable angina pectoris (UAP), the normoglycemic groups were associated with lower follow-up mortality and roughly equal in-hospital mortality compared with the dysglycemic groups. After adjusting for confounding factors, this observation persisted. Conclusions The association between lower glycemia and mortality differed across the spectrum of CAD. In patients with AMI, there was a U-shaped relationship. In patients with SCAD or UAP, mildly to moderately decreasing FPG was associated with neither higher nor lower all-cause mortality.

GW24-e2974 Elevated Serum levels of TNF-alpha in Patients with diastolic dysfunction and Hepatitis C Virus Infection

Objectives Prior study showed HCV-infected patients exhibited evidence of left ventricular diastolic dysfunction (LVDD), but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between TNF-α and LVDD in HCV-infected patients. Methods A total of 120 HCV-infected patients and 120 control healthy individuals were enrolled and examined for circulating TNF-α. Results Serum TNF-α level was significantly higher in patients group (5.67 ± 1.64 pg/mL vs. 2.23 ± 1.26 pg/mL; P <0.001). After adjusting for confounding factors, TNF-α was still associated with NT-proBNP in patients group (β′ = 0.037, P = 0.046). Simple regression analysis demonstrated a correlation between TNF-α vs. E/E′ (r = 0.114, P = 0.024), TNF-α vs. E/A (r = 0.023, P = 0.047), and TNF-α vs. DT (r = 0.148, P< 0.001). Patients with E/E′ ratio > 15, classified as LVDD, had higher TNF-α (7.4 pg/mL vs. 3.2 pg/mL P < 0.001) compared to those with normal diastolic function (E/E′ < 8). In a multivariate regression analysis adjusting for all the factors associated with LVDD, TNF-α was still significantly associated with LVDD (OR: 2.4, 95% CI: 1.34∼2.17, P < 0.001). Conclusions We found increased serum levels of TNF-α were associated with LVDD in HCV-infected patients, which suggest a link between inflammation and the presence of LVDD.

GW24-e3148 A RyR2-V1810L mutation identified in a Chinese patient with clinic manifestation of postural orthostatic tachycardia syndrome

Objectives Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder characterised by an increase heart rate, syncope and an elevated plasma norepinephrine in response to posture change. None of mutations were directly associated with POTS, although some variations have been identified in the norepinephrine transporter gene. Mutations in any gene related to autonomic nervous system and cardiovascular system could promote the development of POTS, even be the pathogenic gene. Methods We studied twentyfour probands suspected of suffering from channelopathy enrolled in the National Channellopathy Registry Study. The clinical characteristic was investigated, including family and personal medical histories, 12-lead electrocardiography and 24-hour ambulatory electrocardiography. DNA samples of the probands and their parents were extracted from serum leukocyte. LQTS1-3 genes and 45 exons of RYR2 gene where the known mutation clusters located were first identified by direct DNA-sequencing. Mutation analysis for the probands’ families would proceed if the results of proband were positive. Results LTQS13 genes tests were negative and a heterozygous mutation (c.5428G>C) in RyR2 gene was identified to cause acid amino missense mutation (p. V1810L) and absent in 200 reference alleles. The mutated residues exhibit high conservation across species. p. V1810L was found a paternally inherited missense mutation. The proband was a twelve-year old girl. She has experienced recurrent episode of syncope at the time of her position change since she was nine years old. The electrocardiogram documented a prolonged QT interval of 548ms when she was in standing position and a diagnosis of Long QT syndrome (LQTS) was assumed. However, the QT interval was not prolonged in supine position and a heart rate increase at least 35bpm was documented in a upright test, which were not the typical features of LQTS. RyR2 gene was known as a susceptibility gene of catecholaminergic polymorphic ventricular tachycardia (CPVT) Conclusions The symptom of orthostatic tachycardia indicates a diagnosis of POTS. LQTS, CPVT and POTS are different disease, but all of them are associated with increased sympathetic activation. Because ion channel has a pivotal role in cardiac systole, we hypothesise that RyR2 gene mutation could cause a clinic manifestation of POTS, even be another POTS-associated gene. Although no study has reported that RyR2 gene is associated with POTS, our finding provides new insights into the mechanism of POTS.

DO HYPOGLYCAEMIA AND HYPERGLYCAEMIA HAVE SIMILAR EFFECTS ON ALL-CAUSE MORTALITY ACROSS THE SPECTRUM OF SEVERITY OF CORONARY ARTERY DISEASE?

Objectives We have previously reported that in older patients with acute myocardial infarction (AMI), increased as well as mildly decreased admission fasting plasma glucose (FPG) levels could predict higher in-hospital and 3-year mortality. Although more attention has been paid to glucose level abnormalities, many missing links in the chain of evidence remain in our understanding of the association between glycaemia and prognosis. The aim of this study therefore was to assess the association between admission FPG levels and all-cause mortality among patients with stable coronary artery disease (SCAD), unstable angina pectoris (UAP) and acute myocardial infarction (AMI) by analysing data from the Beijing Heart and Metabolism Survey (BHMS). Methods A total of 18 999 consecutive patients were recruited. According to the quartiles of FPG levels, patients were categorised into 4 groups: Q1, FPG<5.1 mmol/l; Q2, 5.1 mmol/l≤FPG<5.9 mmol/l; Q3, 5.9 mmol/l≤FPG<7.5 mmol/l; and Q4, FPG≥7.5 mmol/l. Q1 was recognised as the hypoglycaemic group, Q2/Q3 as the relatively euglycemic groups, and Q4 as the hyperglycaemic group. The primary end point was in-hospital and 2-year all-cause mortality. Results Both the hypo- and hyperglycaemic groups were associated with higher in-hospital and 2-year all-cause mortality in the overall cohort. However, the association between hypoglycemia and mortality varied across the CAD severity spectrum. In patients with AMI, in-hospital mortality for Q1 to Q4 was 1.0%, 0.9%, 0.2%, and 1.5%, respectively (p value=0.001); and 2-year mortality for Q1 to Q4 was 1.7%, 0.9%, 0.3%, and 1.8%, respectively (p value <0.001). In patients with SCAD, in-hospital mortality for Q1 to Q4 was 0.3%, 0.3%, 0.2%, and 0.5%, respectively (p value=0.691); and 2-year mortality for Q1 to Q4 was 0.3%, 0.7%, 0.7%, and 0.5%, respectively (p value=0.566). After adjusting for confounding factors, this observation persisted in multivariable analysis. Conclusions The association between hypoglycemia and mortality differed across the CAD severity spectrum. In patients with AMI, there was a U-shaped relationship between admission FPG levels and short- and long-term mortality. In patients with SCAD or UAP, mild to moderately decreasing FPG level (<5.1 mmol/l) was neither associated with higher mortality nor with reduced short- and long-term mortality as traditionally understood. An initial admission FPG level of 5.1–7.5 mmol/l may be desirable because it was associated with better clinical outcomes.

BILATERAL CORONARY ARTERY FISTULA AS A CAUSE OF ANGINA PECTORIS

Objectives A 75-year-old female patients was admitted to our hospital presenting with episodes of exhausted chest pain for 2 years. Methods A continuous murmur was heard over the precordium. The repeated ECG and echocardiograms were normal. At cardiac catheterisation, a left-to-right shunt of 1.33:1 (Qp:Qs) was found. Coronary angiography showed one fistula arising in left anterior descending artery (LAD) ending in the left atrium, and a second fistula arising in right coronary artery (RCA) and terminating in the pulmonary artery. Multislice computed tomographic angiography showed the left and right fistulas entering the left atrium and the pulmonary artery, respectively. The patient was referred for surgical ligation of the fistulas. Two weeks later the patient was discharged and she has shown symptom-free at follow-ups. Results Generally, most coronary artery fistulas (CAFs) manifest as a single fistula and drain into one of the cardiac chambers; cases of multiple fistulas are rare. According to the site of drainage, CAFs have varied physiologic presentations. A fistula that drains into the left atrium does not result in a left-to-right shunt, but rather causes a volume load similar to mitral regurgitation. The CAFs that drain into the pulmonary arteries are similar hemodynamically to a patent ductus arteriosus. Most CAFs are often clinically silent and inconsequential. However, bilateral CAFs may have a clinical and embryological significance on the basis of coronary steal phenomenon. Conclusions There appears to be good consensus that all symptomatic patients should undergo closure of mediumor large CAFs.

Influence of abnormal fasting plasma glucose on left ventricular function in older patients with acute myocardial infarction

Objective We assessed whether the admission fasting plasma glucose (FPG) levels were associated with all-cause mortality and left ventricular (LV) function in older patients with acute myocardial (AMI). Methods A total of 1854 consecutive patients were categorised into four groups: hypoglycaemia, euglycemia, mild hyperglycemias and severe hyperglycemias. The primary outcomes were in-hospital/3-year mortality and LV function. Results There was a near-linear relationship between FPG and Killip class. However, no significant correlation was found between FPG levels and LV ejection fraction. Both FPG levels and Killip classes were all independent significant predictors for mortality. Compared with the euglycemia group, both the hypo- and hyperglycemias were associated with higher in-hospital and 3-year mortality. Conclusions In older patients with AMI, FPG values had differential influences on LV function and mortality. There was a U-shaped relationship between FPG and in-hospital/3-year mortality, and a near-linear relationship between increased admission glucose levels and higher Killip classification.

Visualisation of expanded conus branch for overfilled with contrast medium

Case Study A 74-year-old male was admitted with atypical chest pain. Transradial coronary angiography revealed that there was no obstructive disease in left anterior descending artery (LAD) or circumflex artery (LCX; figure A). When performing right coronary angiography with a five French Tiger shaped universal catheter (Terumo Corporation, Japan), the conus branch was super selected. Furthermore, expansion of conus branch was observed after overfilling with contrast medium (white arrow in panel B of the Figure). The catheter was removed immediately. Visualisation of expanded conus branch persisted for about 40 s, then the stain disappeared radically (Figure C). Under the circumstances, there was no significant change in symptoms, vital signs or electrocardiogram. Then the angiography was continued and revealed a nearly normal right coronary artery and conus branch (Figure D). Serial ultrasound cardiogram tests were performed and no pericardial effusion were found. We deduced that expansion of conus branch should be attributed to the artery overfilling with contrast medium. Special curve of the universal catheter facilitated super selection of conus branch when performing right coronary angiography, and overfilling with contrast medium could result in conus branch expansion, rupture, malignant arrhythmia, etc. This is a profound example of this phenomenon. And as far as we know, this is the first report in the literature. We should do our best to avoid super selection of conus branch and overfilling with contrast medium in order to decrease such complications.