Past History Of Cardiovascular Disease Research Articles

Propensity Score Matching Comparing Asciminib Versus Ponatinib in Chronic Myeloid Leukemia Patients Who Failed Prior Tyrosine Kinase Inhibitor Therapy

Background ASCEMBL trial has demonstrated superior efficacy of Asciminib (ASC) over Bosutinib in terms of molecular response, and event-free survival. Furthermore, ASC could reduce discontinuation rates due to lower occurrences of adverse events (7% vs 25%). However, it remains to be established how ASC would compare to Ponatinib (PON), which is frequently used in chronic myeloid leukemia (CML) practice for patients (pts) failing multiple lines of tyrosine kinase inhibitor (TKI) therapy. No prospective study has been performed or is ongoing comparing ASC vs PON, but alternatively, observational data can provide valuable insight on this topic. The propensity score is the probability of therapy assignment conditional on observed baseline characteristics. We performed a propensity score matching (PSM) analysis to balance the variables affecting the treatment choice among ASC vs PON therapy. The present study aimed to compare the therapeutic efficacy of ASC to PON in CML pts who failed prior TKIs concerning molecular response, failure-free survival (FFS), progression, and overall survival (OS). Patients and methods A total of 426 CML pts who had been treated with ASC or PON in 6 countries (Canada, Netherlands, Czech Republic, France, Argentine, and Italy) were included. In this preliminary report, data from 394 pts were analyzed. Primary endpoint was FFS at 1 year which was defined as the interval from TKI therapy start until treatment failure or death. Treatment outcomes were assessed for molecular response and long-term outcomes such as MR2 (BCR::ABL1 <1%IS or molecular response 2 log or deeper), MMR (BCR::ABL1 <0.1%IS or molecular response 3 log or deeper), MR4 (BCR::ABL1 <0.01%IS or molecular response 4 log or deeper), FFS, Progression, and OS. These parameters were evaluated in the overall population (n=394), resistant (n=254), or intolerant subgroups (n=126), T315I mutated (n=89) or non-T315I mutated subgroups (n=304), those having a past history of cardiovascular disease (CVD) (n=89) or not (n=304). For propensity score calculation, the following pre-treatment variables were selected using a binary logistic regression model: age, history of cardiovascular disease (CVD), disease phase, T315I mutation, and reason for failure to prior TKI line. 160 pts (i.e. 80 case-control pairs) were finally extracted through the PSM process within 0.2 of caliper difference. Results Significant differences were observed in various factors between ASC vs PON group, such as age (p<0.01), past history of CVD (p<0.01), previous TKI lines (p<0.01), presence of mutations (p=0.034), and reason for failure to prior TKI line (p<0.01). These differences ceased to exist when PSM was applied (Table 1). In the overall population, at 12 months, FFS was 46.7%, 95%CI [40.0-52.0%], MR2 62.6% [57.1-67.6%], MMR 44.7% [39.2-50.1%], MR4 28.6% [23.9-33.6%]), and OS 88.1% [84.1-91.1%]. In the overall population, PON group showed a lower FFS than ASC group (HR of PON 1.61, 95%CI [1.14-2.28], p=0.006), but, this difference was no significant when limited to the PSM selected pts. Figure 1 illustrates FFS in Asciminib vs Ponatinib-treated patients. In a subgroup of pts without T315I mutation, those on ASC showed higher FFS (HR of PON 1.82, [1.21-2.71], p=0.003), higher MR2 rate (HR of PON 0.69, [0.511-0.94], p=0.020), and higher MMR rate (HR of PON 0.677, [0.47-0.97], p=0.035). Additionally, in a subgroup of pts with a history of CVD those on ASC showed higher FFS (HR of PON 2.21, [1.19-4.10], p=0.011). Also, in pts in the chronic phase, ASC group showed higher FFS (HR of PON 1.77, [1.18-2.65], p=0.005), MR2 rate (HR of PON 0.73, [0.55-0.97], p=0.032), and MMR rate (HR of PON 0.71, [0.52-0.99], p=0.047). In the PSM balanced population, only MR2 rate was found to be significantly higher in favor of ASC (HR of PON 0.6, [0.39-0.93], p=0.022), while no significant differences were observed in all the other endpoints of interest. Conclusion From our current preliminary results, it can be established that ASC has at least equal efficacy to PON regarding FFS, MMR, MR4, progression, and OS which was confirmed in a PSM cohort. These findings contribute valuable insights to the understanding of ASC and PON treatments in pts with specific disease characteristics and may have implications for personalized therapy decisions in the absence of clinical trials comparing these drugs. Our aim is to expand our PSM cohort.

P‐BB‐54 | Loss of Consciousness Reactions in Donors Reporting Current or Past History of Cardiovascular Disease

P‐BB‐54 | Loss of Consciousness Reactions in Donors Reporting Current or Past History of Cardiovascular Disease

OA18 Small vessel and large vessel vasculitis due to rheumatoid vasculitis: a case of mononeuritis multiplex with pulseless foot leading to amputation

Abstract Introduction Rheumatoid vasculitis occurs in patients with longstanding severe seropositive rheumatoid arthritis. The incidence has reduced drastically with availability of more effective medication. Rheumatoid vasculitis primarily affects small and medium vessels, and rarely large vessels as well. Case description This 77-year-old lady with deforming seropositive rheumatoid arthritis was stable on methotrexate under the care of multiple Trusts for the last 30 years. Methotrexate had been stopped a year ago due to pancytopenia and she was started on prednisolone and hydroxychloroquine. While on these medications she flared with arthralgia and had difficulty in walking attributed to ankle synovitis. She was started on adalimumab, after 3 doses of which she developed widespread skin psoriasis leading to discontinuation. Subsequently, she was admitted to our Trust with left foot gangrene and was referred to rheumatology. Further questioning revealed that numbness in both lower limbs, inability to walk and frequent falls had started following the cessation of methotrexate. On examination, there was bilateral foot drop, worse on the right side. The left foot was gangrenous with diminished pulses in dorsalis pedis and posterior tibial arteries with preserved all other pulses. There was no vasculitic rash or nail fold infarcts. Psoriatic rash had resolved and there was no active synovitis in the joints. Nerve conduction test revealed severe ongoing axonal degenerative type sensory and motor polyneuropathy in the lower limbs without any upper limb involvement. CT angiogram showed multifocal stenoses, more so in the left common iliac, external iliac and superficial femoral artery. There were no conventional vascular risk factors such as hypertension, diabetes, dyslipidaemia or smoking, and there was no past history of cardiovascular disease. PET-CT scan did not reveal any features of vasculitis or aortitis. The vasculitis screening was negative including cryoglobulins. Initially she was on IV antibiotics for left foot cellulitis, hence she was managed with steroids without any potent immunosuppressive agents. Subsequently, she underwent left sided below knee amputation. After the wound had healed, she was started on IV rituximab with low-dose methotrexate and steroid taper. Discussion Although rare, rheumatoid vasculitis can cause significant morbidity and complications. Rheumatoid vasculitis tends to occur in patients with so-called ‘burnt-out’ RA and strongly associated with seropositivity. While it can affect many organ systems, skin and the peripheral nervous system are most frequently affected. Cutaneous vasculitis occurs in around 90% of patients and is the most common clinical manifestation. This includes parable purpura, leg ulcers and nailfold infarcts. It may lead to digital ischaemia, necrosis and gangrene if large vessels are involved. Another common manifestation is a vasculitic neuropathy due to involvement of the vaso nervorum. Around 40% have a sensory neuropathy and 20% have a mixed sensory motor neuropathy like the index patient. Ocular manifestations such as scleritis have been described and may be the first indication of rheumatoid vasculitis. Aortitis in rheumatoid vasculitis may present with aortic insufficiency and aneurysm formation. Pericarditis has also been described as a possible disease manifestation in patients with rheumatoid vasculitis. Our patient did not have any of these clinical features and the PET-CT scan was unremarkable, which could have been due to the steroids she was on prior to the scan. Clinically, there was pulseless gangrene of the left foot with CT angiogram showing multiple stenosis suggesting large vessel involvement in the absence of conventional vascular risk factors. Renal involvement in rheumatoid vasculitis is very rare. PAN like renal involvement and glomerulonephritis has been described. Our patient did not have any haematuria or any significant proteinuria, and imaging did not reveal any renovascular aneurysms. Isolated nailfold infarcts do not require any systemic treatment. Systemic involvement with rheumatoid vasculitis requires aggressive treatment with high-dose steroids with cyclophosphamide or rituximab. Our patient had neuropathy and gangrene of the left foot, hence she was started on rituximab accordingly. Key learning points Rheumatoid vasculitis is a rare but serious complication which can present with a vasculitic neuropathy/mononeuritis multiplex. Rarely, it can cause ischemia and gangrene. If there is systemic involvement, aggressive therapy with steroids, cyclophosphamide or rituximab is needed.

Validation of interpretation of ST-elevation myocardial infarction using the smartphone based 12 lead electrocardiograms in comparison to the cardiologist-a cross sectional study, validation study, single-center study

Background: In patients experiencing an ST-elevation myocardial infarction (STEMI), rapid diagnosis leads to optimal clinical outcomes. Recent technology has provided access to a reliable means of obtaining an ECG reading through a smartphone application (app) that works with an attachment providing all 12-leads of a standard ECG system. We developed a 12-lead smartphone-based electrocardiogram (ECG) called “Spandan”, and an application to accurately assess the presence of STEMI in patients presenting with chest pain. Objectives of study was to perform clinical observation studies on the patients screened for STEMIs and evaluate the variation in the diagnosis of STEMIs detected in both 12-lead gold standard and Spandan 12 lead ECG. Methods: This single-center study was carried out at Shri Mahant Indresh hospital (SMIH), Dehradun, Uttarakhand, India from April-2022 to November-2022. All patients (n=278) visiting the ECG room with symptoms of chest pain, shortness of breath and past history of cardiovascular disease at the department of cardiology of the SMIH, Dehradun were included in the study. Results: Mean age (SD) was 53.96±15.31 years. The male gender participants was 75.17%. 14.3% were STEMI patients as per the standard 12 lead interpretation, smartphone ECG interpreted 7.1% of the participants as STEMI and cardiologist interpreted nearly 15.4% of the participants of STEMI. Conclusions: This study confirmed the potential of a smartphone ECG for evaluation of STEMI and the feasibility of studying this technology further to define the diagnostic accuracy, limitations, and appropriate use of this new technology.

Cardiovascular risk among patients recovered from COVID-19 in the short and medium term: what does the current evidence conclude?

Cardiovascular risk and diseases among patients recovered from COVID-19 is a recent field of study in the world medical literature and is also of vital importance because a large number of patients develop complications once the acute phase of the disease is over. The broad spectrum of myocardial injury in cardiovascular diseases can range from theasymptomatic elevation of cardiac troponin levels to the development of fulminant myocarditis and/or circulatory shock, which can leave significant sequelae. Despite the fact that there is no clear strategy to treat cardiac events that occur during COVID-19 infection and taking into account that treatment is mainly aimed at relieving patients’ symptoms as they arise, the objective of this work was to find out and collect current evidence on this subject, so that readers can be offered a reference guide in Spanish that contributes to the development of their health profession. The methodology used was a literature search in databases including Medline, Scopus and ScienceDirect within a time window between 2019 and 2022. The main results revealed that the molecular and pathophysiological mechanisms involved in post-COVID-19 syndrome include the renin-angiotensin-aldosterone system since SARS-CoV-2 tropism is linked to angiotensin-converting enzyme 2. This causes an alteration of the neurohumoral response of the cardiovascular, renal and digestive systems,generating deficits in the signaling pathways and causing direct damage to the heart, lungs and other organs. Post-COVID-19 syndrome, in general, is defined as the occurrence or persistence of symptoms three or four weeks after the acute phase of the disease. This could then be considered as a time window of risk and strict follow-up to assess in apersonalized way the risk among the different groups of patients, especially those with a past history of cardiovascular disease. The main results revealed disorders such as heart failure, arrhythmias, pericarditis and myocarditis, which require early detection and occur days or even weeks after the acute phase of COVID-19.

Issue of Waist Circumference for the Diagnosis of Metabolic Syndrome Regarding Arterial Stiffness: Possible Utility of a Body Shape Index in Middle-Aged Nonobese Japanese Urban Residents Receiving Health Screening

Introduction: Abdominal obesity as a risk factor for diagnosing metabolic syndrome (MetS) is evaluated using waist circumference (WC), although WC does not necessarily reflect visceral adiposity. This cross-sectional study aimed to clarify whether replacing WC with “A Body Shape Index (ABSI),” an abdominal obesity index, in MetS diagnosis detects individuals with arterial stiffening assessed by cardio-ankle vascular index (CAVI). Methods: A retrospective cross-sectional study was conducted in 46,872 Japanese urban residents (median age 40 years) who underwent health screening. Exclusion criteria were current treatments and a past history of cardiovascular disease (CVD). The Japanese, International Diabetes Federation, and NCEP-ATPIII criteria were used to diagnose MetS. High CAVI was defined as CAVI ≥9.0. Results: CAVI correlated positively with ABSI (β = 0.127), but negatively with WC (β = −0.186), independent of age, sex, systolic blood pressure, fasting plasma glucose, and high-density lipoprotein--cholesterol. Receiver operating characteristic (ROC) analysis showed that ABSI had a stronger contribution to high CAVI (area under the ROC curve [AUC] = 0.730) than WC (AUC = 0.595) and body mass index (AUC = 0.520). ABSI ≥0.080 was defined as abdominal obesity based on the results of ROC analysis for high CAVI and estimated glomerular filtration rate <60 mL/min/1.73 m2. Logistic regression analysis revealed that replacing high WC with ABSI ≥0.080 in MetS diagnosis enhanced the detection of subjects with high CAVI. Discussion/Conclusion: Use of ABSI can detect subjects with arterial stiffening, which may lead to efficient stratification of CVD risk. Further studies are needed to confirm whether MetS diagnosis using ABSI predicts CVD morbidity and mortality.

The distribution of eGFR by age in a community-based healthy population: the Japan specific health checkups study (J-SHC study)

Renal function gradually declines with age. However, the association between changes in renal function and healthy aging has not been determined. This study examined the distribution of estimated glomerular filtration rate (eGFR) values in healthy subjects by age using large-scale cross-sectional data of health check-up participants in Japan. Among the 394,180 health check-up participants, 75,217 (19.1%) subjects without hypertension, diabetes, hyperlipidemia, obesity, proteinuria, smoking, past history of cardiovascular diseases, and renal failure/not undergoing dialysis were included in the healthy group. The distribution of eGFR values was determined at each age between 39 and 74years. in healthy subjects, the mean (± 2 SD range) values of eGFR (mL/min/1.73m2) at ages 40, 50, 60, and 70 were 88.0 (55.4-121.7), 82.3 (51.2-113.3), 77.8 (48.1-107.6), and 72.9 (44.7-101.1), respectively. The difference in the mean eGFR by age was almost constant across all ages. In the linear regression analysis adjusted for sex, the regression coefficient of mean eGFR for a one-year increase in age was -0.46mL/min/1.73m2 in healthy subjects (P < 0.001). By sex, the distribution of eGFR and the 1-year change in eGFR showed similar results in both men and women. Renal function slowly declined with age in a healthy population; however, it was relatively preserved until the mid 70s. This result suggests that a decline in renal function often observed in the elderly does not attribute to aging alone, and further examination might be required to clarify the cause of renal impairment.

MO509DOSE-RESPONSE RELATIONSHIP BETWEEN ALCOHOL CONSUMPTION AND THE RISK OF DEVELOPING CKD: RETROSPECTIVE COHORT STUDY

Abstract Background and Aims Drinking habits are one of the most important modifiable lifestyle factors to prevent the development of chronic kidney disease (CKD). Previous studies showed that it was inversely associated with the risk of developing CKD, but the dose-response relationship between alcohol consumption and the development of CKD is still controversial. In the present study, we aimed to examine whether the amount of alcohol consumed at one time is associated with new onset of CKD in general population. Method Study subjects were 11,162 Japanese aged 45 to 74 years, with an estimated glomerular filtration rate ≥60 mL/min/1.73m2, no proteinuria, no past history of cardiovascular disease, COPD or liver disease. The drinking status was obtained by self-administered questionnaires. We categorized the study subjects into four groups based on the amount of alcohol consumption: &amp;lt;20g/time of ethanol equivalent (lowest); 20-40g/time (low intermediate); 40-60g/time (high intermediate); &amp;gt;60g/time (highest). We set non-drinkers as a reference category. The primary outcome was the incidence of CKD, defined as 25% reduction of eGFR and to less than 60 mL/min/1.73 m2 and/or a dipstick urinalysis score of 1+ or greater (equivalent to ≥30 mg/dL) during the follow up period. We employed Cox proportional hazards regression models to examine the dose-response relationship between baseline alcohol consumption and the risk of CKD. Trend tests were performed using Cox proportional hazards regression models that treated alcohol consumption as a continuous linear term. Results Lowest and low intermediate groups were significantly associated with a decreased risk of CKD (hazard ratio [HR] 0.84; 95% confidence interval [CI], and 0.71–0.99; HR 0.79; 95% CI, 0.66–0.96, respectively) compared to non-drinkers. High intermediate group was associated with a decreased risk of CKD (HR 0.92; 95% CI, 0.70–1.21), and highest group was associated with an increased risk of CKD (HR 1.28; 95% CI, 0.84–1.95), but these associations did not reach statistical significance. There was no dose-response relationship between baseline alcohol consumption and risk of CKD (P-trend = 0.30). Conclusion A J-shape association was observed between self-reported alcohol intake and the incidence of CKD. Moderate alcohol consumption at one time may help reduce the risk of CKD.

Clinical Profile and Outcome of COVID 19 Patients at Tertiary Cardiovascular Center of Nepal.

Background and Aims: Cardiovascular comorbidities are common in patients with COVID-19 and these patients are at higher risk of morbidity and mortality. It is not known if the presence of cardiovascular co-morbid conditions poses independent risk or whether this is mediated by other factors.&#x0D; Methods: This is a retrospective follow up study done at Shahid Gangalal National Heart Centre (SGNHC). The main objective of this study was to study the clinical profile, baseline comorbidities, and outcome of cardiac patients and health care worker diagnosed with COVID 19. This study retrospectively evaluated case records of all cardiovascular disease (CVD) patients admitted at SGNHC with COVID 19 cases from 1st case diagnosed on July at SGNHC till September 2020.&#x0D; Results: During this study period, 90 patients with COVID 19 with cardiovascular disease were admitted. The mean age of the study population was 52.3±19 years with 65.6% being male. Among the study population 52 (57.8%) had past history of cardiovascular disease, hypertension in 18 (20%) cases, diabetes in 8 (8.9%) cases. Among the patients with cardiovascular diagnosis, acute coronary syndrome was most common cardiovascular diagnosis in 23 (25.6% cases) followed by rheumatic heart disease in 21 (23.4%) cases, dilated cardiomyopathy in 7 (7.8% cases), ischemic cardiomyopathy with reduced ejection fraction (EF) in 7 (7.8%) cases, post coronary artery bypass graft (CABG) in 8 (8.9%), post valve replacement in 5 (5.5%), congenital heart disease in 3.3% cases and complete heart block in 3.3% cases. Most of the cases were symptomatic with moderate illness in 46.7% cases, mild illness in 41.4% cases and severe/critical illness in 11.1% cases. Among COVID patients with cardiovascular disease, the mortality was 11.1%.&#x0D; Conclusion: Patients with cardiovascular disease with COVID 19 have more severe COVID 19 symptoms and has higher COVID 19 related death, so strict vigilance and early intervention is needed to improve its outcome.

Albumin Is a Non-GFR, Time-Dependent Determinant of Cystatin C in Functionally Anephric Dialysis Patients

BACKGROUND: The serum concentration of cystatin C (CysC) is a better glomerular filtration rate (GFR) estimator than creatinine (Cr), but CysC is still influenced by several factors other than GFR. The present study aimed to identify the non-GFR determinants of CysC in anuric dialysis patients without being confounded by GFR. METHODS: Chronic hemodialysis (HD) and peritoneal dialysis (PD) patients with a daily urine amount ＜ 100 mL were enrolled for the measurement of serum CysC levels at the time of enrollment, at the sixth, and the twelfth month of the study. The generalized estimating equation model was used to test the time-dependent association of CysC or Cr with other parameters. RESULTS: Of the 105 functionally anephric dialysis patients (79 on HD, 26 on PD) with an average dialysis duration of 4.84 ± 2.83 years, serum CysC and serum Cr both had a time-dependent, increasing positive correlation with serum albumin levels. The past history of cardiovascular (CV) disease correlated positively with CysC but reversely with Cr. In the subgroup analyses, the same pattern of associations presented in the HD patients, yet only CysC but not Cr of the PD patients presented significant time-dependent associations with albumin and the past history of CV diseases. CONCLUSION: Our study found albumin a novel determinant of serum CysC in a manner of positive time-dependent association. Whether CysC is viewed as an alternative nutritional marker such as Cr in dialysis patients deserves further studies.

New index of abdominal obesity, a body shape index, is BMI-independently associated with systemic arterial stiffness in real-world Japanese population.

To clarify that the new index of abdominal obesity, a body shape index (ABSI), is associated with obesity-related metabolic disorders and arterial stiffness. We analyzed the cross-sectional data from 62,514 Japanese subjects (mean age 44.4years, mean body mass index (BMI) 22.2kg/m2) without a past history of cardiovascular disease, stroke, or treatment for obesity-related metabolic disorders. Various body adiposity indices including BMI, waist circumference (WC), and ABSI were evaluated for abilities to indicate metabolic disorders and arterial stiffness assessed by cardio-ankle vascular index (CAVI). WC, WC/height ratio, and WC/BMI ratio correlated with BMI regardless of gender or obesity, whereas ABSI hardly correlated with BMI. ROC analyses demonstrated that ABSI had the highest discriminatory power in predicting high CAVI (≥90th percentile) compared to other body adiposity indices, and the cut-off value was 0.080. Increases in ABSI as well as BMI reflected severity of metabolic disorders. After adjusting for confounders identified by multiple regression analysis, adjusted CAVI correlated positively with ABSI, whereas an inverted relationship was observed between adjusted CAVI and BMI. Additionally, the contribution of high ABSI (≥0.080) for high CAVI was independent of gender, age, obesity, and obesity-related metabolic disorders in the multivariate logistic regression model. ABSI is an easily calculated index of abdominal obesity which reflects metabolic disorders and systemic arterial stiffening, and may be useful in primary health screening even without any medical equipment for visceral fat quantification.

Cardiac injuries in coronavirus disease 2019 (COVID-19)

As the coronavirus disease 2019 (COVID-19) epidemic worsens, this global pandemic is impacting more than 200 countries/regions and more than 4,500,000 confirmed cases worldwide. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which might attack not only the respiratory system, but also the other important organs, including the heart. It was reported that COVID-19 patients with a past history of cardiovascular diseases would have a higher mortality. Meanwhile, elevated troponin levels were frequently observed in COVID-19 cases. Besides the comprehensive treatments for COVID-19, as a cardiologist, we should also remain vigilant about the cardiac injuries, especially those with severe emergent cardiovascular symptoms.

P1264LOW PHOSPHATE AND LOW CALCIUM LEVELS PREDICT A HIGHER RISK FOR CARDIOVASCULAR EVENTS OF MAINTENANCE HEMODIALYSIS PATIENTS

Abstract Background and Aims It has been reported that higher serum levels of phosphate (P) and calcium (Ca) are associated with a higher risk of cardiovascular disease (CVD) and premature death of maintenance hemodialysis (MHD) patients. Thus, several clinical guidelines recommend that serum P and Ca levels in MHD patients be maintained within the optimal range. However, in the current situation in which the guidelines have penetrated widely, there are few reports that have investigated the association between chronic kidney disease (CKD)-mineral and bone disorder (MBD)-related factors and adverse events in MHD patients. Method The study design was a 3-year multicenter, observational study. A total of 989 MHD patients were enrolled in this study. The blood levels of Hb, ferritin, iron, total iron-binding capacity, β2-microglobulin, creatinine, total protein, albumin, total cholesterol, Ca and P were measured every 3 months. The blood levels of high-sensitivity C-reactive protein (hCRP) and intact parathyroid hormone (int-PTH) were also measured every six months. The correlation between CKD-MBD factors and adverse events was evaluated by the time-dependent Cox hazard model. Results In 82% of patients, 83% of patients, and 78% of patients, serum P levels, serum Ca levels, and int-PTH levels, respectively, were maintained in the target ranges (3.5≤P≤6.0 mg/dL, 8.4≤Ca≤10.0 mg/dL, 60≤int-PTH≤240 pg/mL) that were recommended by the 2012 guidelines of the Japanese Society for Dialysis Therapy. After correcting for age, sex, past history of CVD, Hb, albumin, and hCRP, compared with the patients with target levels of P, patients with low P levels (&amp;lt;3.5 mg/dL) had a significantly higher risk for CVD (P=0.042, HR: 2.27), hospitalization (P=0.034, HR: 2.44), and all-cause mortality (P=0.03, HR: 2.29). On the other hand, there was no association between higher serum P levels and adverse events. Compared with the patients who maintained target int-PTH levels, patients with lower (&amp;lt;60) (P=0.025, HR: 1.46) and higher (&amp;gt;240 pg/mL) (P=0.04, HR: 1.44) int-PTH levels had a significantly higher risk for hospitalization. There was no significant correlation between serum Ca and adverse events. Furthermore, compared with the patients who maintained the target levels of both Ca and P, the patients with target Ca and low P levels (P=0.042, HR: 2.75) had a significantly higher risk for CVD. Compared with the patients who maintained the target levels of both Ca and P, the patients with low Ca and low P levels (P&amp;lt;0.001, HR: 4.4) and target Ca and low P levels (P=0.22, HR: 2.0) had a significantly higher risk for hospitalization. Conclusion After correcting for several clinical factors, we found that patients who maintained low serum P levels had a significantly higher risk for CVD and all-cause mortality than patients who maintained higher Ca and P levels. Undoubtedly, extremely high serum P, Ca, and int-PTH levels should be treated according to the guidelines. However, in the current situation in which the guidelines have penetrated widely, CKD-MBD management, in which the clinical conditions of low P, Ca, and int-PTH are considered, is needed.

P1433VALIDATION OF A SERUM CALCIFICATION PROPENSITY TEST FOR THE PREDICTION OF ALL-CAUSE MORTALITY AMONG DIALYSIS PATIENTS

Abstract Background and Aims Vascular calcification as cause of vascular stiffness is a major contributor to the high cardiac burden among stage 5 chronic kidney disease dialysis (CKD5HD) patients. Early identification of patients with high calcification propensity is crucial for proper risk stratification and management of these patients. Recently, a novel in vitro test (T50-test) was developed which determines calcification propensity of human serum and predicts mortality among ND-CKD (non-dialysis chronic kidney disease) patients, kidney transplant recipients and CKD5HD patients suffering from secondary hyperparathyroidism. We now evaluated whether these results can be confirmed in an unselected cohort of CKD5HD patients and can be used in the future for improving care of these patients. Method This prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 Fresenius Medical Care NephroCare centers in Cataluña (Spain). T50 was determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database (EuCliD®). After their baseline T50 measurement, patients were followed for two years for the occurrence of the primary endpoint all-cause mortality. The association between T50 and all-cause mortality was examined by using proportional subdistribution hazards regression modelling accounting for kidney transplantation as competing event. In sensitivity analyses we adjusted for age, sex, vascular access (fistula/graft, catheter), treatment modality (HD, HDF), Charlson comorbidity index and dialysis vintage. Results Mean age of the study population was 72.2 years and 63.8% were male. 42.5% had diabetes and 55.0% past history of cardiovascular disease. Mean T50 was 283.4 min among the total cohort. During follow-up, 185 (23.8%) patients died. Patients who reached the endpoint had a significantly lower T50 at baseline as compared to those who survived during follow-up (269.6 vs 287.7 min, p = 0.001). A cross-validated model (mean c statistic: 0.5767) identified T50 as a linear predictor of all-cause-mortality (subdistribution hazard ratio (per min): 0.9957, 95% CI [0.9933;0.9981]). T50 remained a significant predictor of all-cause mortality after adjusting for relevant confounding in sensitivity analyses. Conclusion In this prospective study, we confirmed that T50 is an independent predictor of all-cause mortality among a large unselected cohort of hemodialysis patients. T50 may be used to identify patients with high vascular calcification propensity and mortality risks and may help physicians to implement a personalized and more precise renal replacement therapy option.

Abstract P3009: Stenostiffness Approach for Cardiovascular Disease Risk Assessment in Primary Prevention

Background: The Japan Brachial-Ankle pulse wave VELocity individual participant data meta-analysis of prospective studies (J-BAVEL) studies are a series of individual participant data meta-analyses carried out to demonstrate the predictive ability, individually, of the inter-arm blood pressure difference (IAD), ankle-brachial pressure index (ABI), and brachial-ankle pulse wave velocity (brachia-ankle PWV) for the prediction of cardiovascular events in Japanese subjects. Purposes: Based on the findings of the J-BAVEL study series, we discuss here a strategy for integrating IAD, ABI, and brachial-ankle PWV (i.e., steno-stiffness approach) with the conventional cardiovascular disease (CVD) risk prediction model to improve the accuracy of CVD risk prediction in primary prevention. Methods and Results: The data of 1,1726 subjects without a past history of cardiovascular disease (CVD) in J-BAVEL study were re-analyzed. The IAD &gt; 15 mm Hg (IAD15) was associated with a significant Cox stratified adjusted hazard ratio (HR) for subsequent stroke [2.42; 95% confidence interval (CI), 1.27-4.60; P &lt;0.01]. The adjusted odds ratio of IAD10 for ABI ≤0.90 in the binary logistic regression analysis was 3.42 (95% CI 2.13-5.50; P &lt; 0.001). Furthermore, among 10,512 subjects of J-BAVEL study cohort, subjects having either ABI ≤0.90 {n = 123 (1.2%)} or brachial-ankle PWV ≥15.9 m/sec {n = 3,837 (36.5%)} were defined as abnormal steno-stiffness markers. The addition of abnormal steno-stiffness marker to a model including the FRS improved the accuracy of prediction of the development of CVD (category-free net reclassification improvement: 0.391 [95% CI, 0.266-0.517], P &lt; 0.001; integrated discrimination index: 0.0021 [95% CI, 0.0004-0.0038], P = 0.02). Conclusion: Steno-stiffness approach (i.e., IAD, ABI, and brachial-ankle PWV) to CVD risk assessment in primary prevention may be efficient. The IAD is a simply measured useful physiological marker of subclinical PAD (IAD10) or stroke (IAD15). Furthermore, the ABI ≤0.90 or brachial-ankle PWV &gt; 15.9 m/sec may be efficient for the improvement of CVD risk assessment by conventional risk prediction model in primary prevention.

High Concentration of Serum Aspartate Aminotransferase in Older Underweight People: Results of the Kanagawa Investigation of the Total Check-Up Data from the National Database-2 (KITCHEN-2).

Background: Aspartate aminotransferase (AST) is pivotal in amino acid metabolism. However, the serum activity of AST, which leaks from multiple organs, including liver and skeletal muscle, is unknown in older underweight people, who are at high risk of skeletal muscle mass loss. Therefore, we measured the serum activities of AST and alanine aminotransferase (ALT), a liver-specific transaminase, in a large, community-based cross-sectional study. Methods: Clinical parameters and lifestyles were characterized in 892,692 Japanese people with a wide range of body mass indexes (BMIs; 13–39.9 kg/m2), aged 40–74 years old, who were undergoing a medical checkup. A general linear model was used to calculate the estimated mean of serum AST (EM-AST) in each BMI category after adjustment for confounding factors, including past history of cardiovascular disease and waist circumference. Results: Severe underweight (BMI 13–14.9 kg/m2) was present in 910 subjects (0.1%). Raw serum AST showed a J-shaped relationship with BMI, which was blunted in older subjects (60–74 years), and similar, but less curved relationships were identified for raw serum ALT and gamma-glutamyl transferase. These J-shaped relationships in serum AST were not altered when subjects were classified by sex, past history of cardiovascular and cerebrovascular diseases, and habitual exercise. EM-AST showed a U-shaped relationship, with a minimum at BMI 21–22.9 kg/m2, regardless of age and waist circumference. Conclusions: High serum AST but normal serum ALT is highly prevalent in older underweight people and might reflect skeletal muscle pathology.

Difference in positive relation between cardio-ankle vascular index (CAVI) and each of four blood pressure indices in real-world Japanese population.

This study aimed to investigate the association of cardio-ankle vascular index (CAVI), an arterial stiffness parameter, with four blood pressure (BP) indices, systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and mean BP (MBP), in real-world population including untreated hypertension. We analyzed the cross-sectional data from 23,257 Japanese subjects (12,729 men and 10,528 women, aged 47.1 years) without a past history of cardiovascular disease, stroke, hypertension, diabetes or dyslipidemia. Gender differences in four BP indices were slight, but significant for SBP, DBP and MBP. All four BP indices increased linearly with age. After adjusting for confounders comprising gender, age, HDL-C and BMI identified by multiple regression analysis, CAVI was lower in normotensive subjects compared to hypertensive subjects. Trend test detected an almost linear relation of adjusted CAVI with each of four BP indices even within ideal range. Exceptionally, the increment in adjusted CAVI reached its peak over 140 mm Hg range in SBP. Logistic regression models showed that 1-SD increment in each BP index contributed independently to high CAVI (≥90th percentile), whereas that in PP showed a somewhat lower contribution. Subgroup analyses revealed that older age, dyslipidemia and hypertension were independently associated with relatively small contributions to high CAVI per 1-SD increment in SBP. PP might be less useful to assess arterial stiffness compared to other BP indices. Besides, the contribution of SBP increment to arterial stiffening was relatively large in normotensive, normolipidemic non-elderly subjects, whose individual transition of SBP should be noticed.

Factors associated with intra-individual visit-to-visit variability of blood pressure in four countries: the INTERMAP study.

Several studies demonstrated that visit-to-visit variability of blood pressure (BP) predicted future events of total death, stroke and cardiovascular disease. Little is known about factors associated with visit-to-visit BP variability in different countries. We recruited participants aged 40-59 years from four countries (Japan, the People's Republic of China [PRC], the United Kingdom [UK] and the United States [US]). At each study visit, BP was measured twice by trained observers using random zero sphygmomanometers after five minutes resting. We defined visit-to-visit BP variability as variation independent of mean (VIM) by using average systolic BP of 1st and 2nd measurement across four study visits. Data on 4680 men and women were analyzed. Mean ± standard deviation of VIM values among participants in Japan, the PRC, the UK and the US were 5.44 ± 2.88, 6.85 ± 3.49, 5.65 ± 2.81 and 5.84 ± 3.01, respectively; VIM value in the PRC participants was significantly higher. Sensitivity analyses among participants without antihypertensive treatment or past history of cardiovascular disease yielded similar results. Higher VIM value was associated with older age, female gender, lower pulse rate and urinary sodium excretion and use of antihypertensive agents such as angiotensin converting enzyme inhibitors, beta blockers and calcium channel blockers. The difference of visit-to-visit BP variability between PRC and other countries remained significant after adjustment for possible confounding factors. In this large international study across four countries, visit-to-visit BP variability in the PRC was higher than in the other three countries. Reproducibility and mechanisms of these findings remain to be elucidated.

Simultaneously Measured Interarm Blood Pressure Difference and Stroke: An Individual Participants Data Meta-Analysis.

We conducted individual participant data meta-analysis to examine the validity of interarm blood pressure difference in simultaneous measurement as a marker to identify subjects with ankle-brachial pressure index <0.90 and to predict future cardiovascular events. We collected individual participant data on 13 317 Japanese subjects from 10 cohorts (general population-based cohorts, cohorts of patients with past history of cardiovascular events, and those with cardiovascular risk factors). Binary logistic regression analysis with adjustments identified interarm blood pressure difference >5 mm Hg as being associated with a significant odds ratio for the presence of ankle-brachial pressure index <0.90 (odds ratio, 2.19; 95% confidence interval, 1.60-3.03; P<0.01). Among 11 726 subjects without a past history of cardiovascular disease, 249 developed stroke during the average follow-up period of 7.4 years. Interarm blood pressure difference >15 mm Hg was associated with a significant Cox stratified adjusted hazard ratio for subsequent stroke (hazard ratio, 2.42; 95% confidence interval, 1.27-4.60; P<0.01). Therefore, interarm blood pressure differences, measured simultaneously in both arms, may be associated with vascular damage in the systemic arterial tree. These differences may be useful for identifying subjects with an ankle-brachial pressure index of <0.90 in the overall study population, and also a reliable predictor of future stroke in subjects without a past history of cardiovascular disease. These findings support the recommendation to measure blood pressure in both arms at the first visit.

Low sleep quality is associated with progression of arterial stiffness in patients with cardiovascular risk factors: HSCAA study

Background and aimsImprovement in sleep quality is considered to be a viable target for prevention and treatment of cardiovascular diseases. To gain insight into its underlying mechanisms, we evaluated the significance of objectively measured sleep quality in patients with regard to progression of arterial stiffness over a 3-year follow-up period. MethodsThis prospective cohort study included 306 serial patients registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) study. In addition to classical cardiovascular risk factors (body mass index, current smoking, past history of cardiovascular disease, dyslipidemia, diabetes mellitus), the participants were examined for ambulatory blood pressure (BP), apnea-hypopnea index (AHI), standard deviation of the NN (RR) interval (SDNN) for heart rate variability (HRV), and objective sleep quality using actigraphy findings. Brachial-ankle pulse wave velocity (baPWV) was measured at both baseline and follow-up (36.6 ± 6.8 months) as a parameter of arterial stiffness. ResultsIncreases in PWV (%) were greater (p = 0.03) in the low sleep quality (LSQ) group (5.75 ± 1.15%) as compared to the normal sleep quality group (2.69 ± 0.85%). Patients with the greatest increase (≥20%) from baseline exhibited a significantly (p < 0.05) larger percentage of LSQ (75% vs. 49.6%) as compared to those without PWV progression (<0%), with the association still significant (odds ratio 3.62, 95% confidence interval 1.04–12.55, p = 0.04) even after adjustment for other clinical risk factors. For all subjects, univariate logistic regression analyses showed that diabetes and LSQ were significantly associated with the greatest increase of PWV. Comparisons of characteristics among specific subgroups showed more prominent associations of LSQ with the greatest increase of PWV in patients with greater age, dyslipidemia, and higher AHI. ConclusionsLSQ was associated with progression of arterial stiffness over a 3-year period, independent of cardiovascular risk factors such as BP, AHI, and HRV.