Inhibitory action of B-type natriuretic peptide on adrenocorticotropic hormone in patients with acute coronary syndrome.

In addition to the classical actions of hemodynamic regulation, natriuretic peptides (NPs) interact with various neurohumoral factors that are deeply involved in the pathophysiology of cardiovascular diseases. However, their effects on the hypothalamic-pituitary-adrenal (HPA) axis, which is activated under acute high-stress conditions in acute coronary syndrome (ACS), remain largely unknown. We investigated the impact of plasma B-type NP (BNP) on plasma adrenocorticotropic hormone (ACTH)-cortisol levels during the acute phase of ACS ischemic attacks. The study population included 436 consecutive patients with ACS for whom data were collected during emergency cardiac catheterization. Among them, biochemical data after acute-phase treatment were available in 320 cases, defined as the ACS-remission phase (ACS-rem). Multiple regression analyses revealed that plasma BNP levels were significantly negatively associated with plasma ACTH levels only during ACS attacks (P < 0.001), but not in ACS-rem, whereas plasma BNP levels were not significantly associated with plasma cortisol levels at any point. Accordingly, covariance structure analyses were performed to clarify the direct contribution of BNP to ACTH by excluding other confounding factors, confirming that BNP level was negatively correlated with ACTH level only during ACS attacks (ß = -0.152, P = 0.002), whereas BNP did not significantly affect ACTH in ACS-rem. In conclusion, despite the lack of a significant direct association with cortisol levels, BNP negatively regulated ACTH levels during the acute phase of an ACS attack in which the HPA axis ought to be activated. NP may alleviate the acute stress response induced by severe ischemic attacks in patients with ACS.NEW & NOTEWORTHY BNP negatively regulates ACTH during a severe ischemic attack of ACS in which hypothalamic-pituitary-adrenal axis ought to be activated, indicating an important role of natriuretic peptides as a mechanism of adaptation to acute critical stress conditions in humans.

Time-dependent changes in P2Y12 reaction unit values for predicting the different types of cardiovascular events in patients with ischemic heart disease.

Several studies have investigated the association between P2Y12 reaction unit (PRU) value and major adverse cardiovascular events (MACEs) in patients with ischemic heart disease, but there is no well-established consensus on the utility of PRU value. Furthermore, the optimal PRU cut-off value varied with studies. One reason may be that the endpoints and observation periods differed, depending on the study. This study aimed to investigate the optimal cut-off and predictive ability of the PRU value for predicting cardiovascular events, while considering different endpoints and observation periods. We surveyed a total of 338 patients receiving P2Y12 inhibitors and measured PRU during cardiac catheterization. Using time-dependent receiver operating characteristic analysis, we evaluated the cut-off and area under curve (AUC) of the PRU value for two MACEs (MACE ①: composite of death, myocardial infarction, stent thrombosis, and cerebral infarction; MACE ②: composite of MACE ① and target vessel revascularization) at 6, 12, 24 and 36 months after cardiac catheterization. MACE ① occurred in 18 cases and MACE ② in 32 cases. The PRU cut-off values at 6, 12, 24, and 36 months were 257, 238, 217, and 216, respectively, for MACE ① and 250, 238, 209, and 204, respectively, for MACE ②. The AUCs at 6, 12, 24, and 36 months were 0.753, 0.832, 0.718, and 0.717, respectively, for MACE ① and 0.724, 0.722, 0.664, and 0.682, respectively, for MACE ②. The optimal cut-off and predictive ability of PRU values for cardiovascular events varied depending on different endpoints and duration of the observation periods. A relatively high PRU value is effective for short-term event suppression, but a low value is required for long-term event suppression.

Investigation of the small-balloon technique as a method for retrieving dislodged stents.

The small-balloon technique used to retrieve a dislodged coronary stent is less studied. We investigated the small-balloon technique to study the capture force and retrieval rate of dislodged proximal or distal stents. We developed a retrieval model for stent dislodgement and performed bench tests to compare proximal and distal capture. We evaluated capture force by capture site in a fixed stent dislodgement model and capture force and retrieval rate by capture site using a retrieval model of stent dislodgement. Three-dimensional (3D)-micro-computed tomography (CT) was used to scan the captured conditions of the distal (DC) and proximal (PC) groups. Stent, balloon shaft, and guiding catheter (GC) diameters were measured. Retrieval areas within GC were calculated and compared. The force was significantly lower in the PC group than in the DC group (p < 0.01). Successful retrieval was achieved in 100% and 84.8% in the PC and DC groups, respectively. The force required to retrieve the dislodged stent was significantly lower in the PC group than that in the DC group (p < 0.01). The force was significantly lower in the successful cases in the DC group than in the unsuccessful cases (p < 0.01). The retrievable areas in the PC and DC groups were 67.5% and 32.7%, respectively, as calculated from the values measured from the 3D-CT images. The success rate of PC was higher than that of DC using the small-balloon technique. The smaller proximal stent gap in the PC method facilitated the retrieval of the dislodgement stent.

Relationship between haemodynamic indicators and haemogram in patients with heart failure.

AIMS: Pulmonary congestion, reduced cardiac output, neurohumoral factor activation, and decreased renal function associated with decreased cardiac function may have various effects on haemograms. The relationship between these factors and haemograms in patients with heart failure has not been sufficiently investigated. Recently, it was suggested that the lungs are an important site for platelet (Plt) biosynthesis and that it is necessary to study the relationship between pulmonary congestion and Plt count in heart failure in detail. In this study, we examined the relationship between various haemodynamic indicators and haemograms in detail using statistical analyses. METHODS AND RESULTS: A total of 345 patients who underwent cardiac catheterization for the evaluation of cardiac function between 1 January 2015 and 31 December 2020 were included in the study. Haemodynamic indices, including left ventricular end-diastolic pressure (LVEDP) and cardiac index (CI), were measured. Plasma noradrenaline (Nor) concentration, estimated glomerular filtration rate (eGFR), white blood cell (WBC) count, haemoglobin (Hb) level, and Plt count were measured using blood samples collected at the same time. Structural equation modelling (SEM) was used to examine the relationship between LVEDP, CI, plasma Nor concentration, eGFR, WBC count, Hb level, and Plt count. Bayesian inference using SEM was performed for Plt count. A total of 345 patients (mean age: 66.0 ± 13.2 years) were included in this study, and 251 (73%) patients were men. After simple and multiple regression analyses, path diagrams were drawn and analysed using SEM. LVEDP showed a significant negative relationship with Plt count (standardized estimate: -0.129, P = 0.015), and CI showed a significant negative relationship with Hb level (standardized estimate: -0.263, P < 0.001). Plasma Nor concentration showed a significant positive relationship with WBC count (standardized estimate: 0.165, P = 0.003) and Plt count (standardized estimate: 0.198, P < 0.001). The eGFR had a significant positive relationship with Hb level (standardized estimate: 0.274, P < 0.001). Bayesian inference using SEM revealed no relationship between LVEDP and Hb level or WBC count but a significant negative relationship between LVEDP and Plt count. CONCLUSIONS: LVEDP, CI, plasma Nor concentration, and eGFR were related to WBC count, Hb level, and Plt count in patients with heart failure. There was a strong relationship between elevated LVEDP and decreased Plt count, suggesting that pressure overload on the lungs may interfere with the function of the lung as a site of Plt biosynthesis.

Unique crosstalk between platelet and leukocyte counts during treatment for acute coronary syndrome: A retrospective observational study.

In the pathophysiology of acute coronary syndrome (ACS), platelet (PLT) and neutrophil (Neu) crosstalk may be important for activating coagulation and inflammation. It has been speculated that PLTs and Neu may affect each other's cell counts; however, few studies have investigated this hypothesis. In this study, we measured changes in blood cell counts in 245 patients with ACS during treatment and investigated the mutual effects of each blood cell type. Path diagrams were drawn using structural equation modeling, and temporal changes in the count of each blood cell type and the relevance of these changes were analyzed. Throughout the treatment period, the numbers of all blood cell types (red blood cells [RBCs], leukocytes, and PLTs) were associated with each other before and after treatment. A detailed examination of the different cell types revealed that the PLT count at admission had a significant positive effect on the leukocyte (especially Neu) count after treatment. Conversely, the leukocyte (especially Neu) count at admission had a significant positive effect on the PLT count after treatment. During ACS, PLTs and leukocytes, especially Neu, stimulate each other to increase their numbers. The formation of a PLT-leukocyte complex may increase coagulation activity and inflammation, which can lead to a further increase in the counts of both blood cell types.

A pilot cohort study assessing the feasibility of complete revascularization with balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty improves prognosis by alleviating pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension, even with incomplete revascularization. However, hypoxia or the requirement for pulmonary vasodilators often remain even after pulmonary hypertension relief. With this cohort study, we aimed to examine whether complete revascularization by additional balloon pulmonary angioplasty on residual lesions, even after pulmonary hypertension relief, could resolve hypoxia or the requirement for pulmonary vasodilators. During complete revascularization with balloon pulmonary angioplasty in 42 patients with chronic thromboembolic pulmonary hypertension, we investigated therapeutic effects at baseline (T1), pulmonary hypertension relief phase (T2), and at 6 months post-final balloon pulmonary angioplasty (T3). The pulmonary hypertension relief phase was defined as the first time that a mean pulmonary artery pressure ≤ 25 mmHg or pulmonary vascular resistance ≤ 240 dyn-s/cm5 was reached in right heart catheterization before balloon pulmonary angioplasty. The partial pressure of oxygen increased progressively over T1, T2, and T3 (59.2±8.5, 69.0±9.7, and 80.0±9.5 mmHg, respectively; P<0.001 T2 vs. T3). Minimum oxygen saturation levels during the 6-minute walk distance test were 87% (81‒89%), 88% (84‒92%), and 91% (89‒93.3%), respectively (P<0.001 T2 vs. T3), with gradual increase in the 6-minute walk distance (346±125 m, 404±90 m, 454±101 m, respectively; P<0.001 T2 vs. T3). The percentages of patients using pulmonary vasodilators (54.8%, 45.2%, 4.8%, respectively; P<0.001 T2 vs. T3) and requiring oxygen therapy (26%, 26%, 7%, respectively; P = 0.008 T2 vs. T3) decreased significantly without hemodynamic exacerbation or major complications. Despite the discontinuation of pulmonary vasodilators, mean pulmonary artery pressure improved (36.0 [31.0‒41.3], 21.4±4.2, 18.5±3.6 mmHg, respectively; P<0.001 T2 vs. T3). Complete revascularization with balloon pulmonary angioplasty beyond pulmonary hypertension relief benefits patients with chronic thromboembolic pulmonary hypertension; it may improve oxygenation and exercise capacity, and reduce the need for pulmonary vasodilators and oxygen therapy.

A Pilot Evaluation Study of Diffuse Coronary Arterial Contraction Causing Ischemia by Double Measurement of Left Ventriculography Before and After Intracoronary Administration of Nitrates.

Background: Abnormal diffuse coronary artery contraction is not easily diagnosed. In order to evaluate its true risk, we performed double left ventriculography (LVG) before and after intracoronary administration of isosorbide dinitrate (ISDN). We also investigated the relationship between changes in coronary lumen area and changes in left ventricular ejection fraction (LVEF) after ISDN. Methods and Results: The study included 53 patients who underwent an acetylcholine (ACh) provocation test after coronary angiogram and LVG. The second LVG was performed after intracoronary ISDN administration. Coronary lumen area was measured by quantitative coronary arteriography (QCA). Simple and multiple regression analyses showed a significant correlation between changes in total QCA area before and after ISDN administration (pre-and post-total QCA area, respectively) and changes in LVEF. Using structural equation modeling, we observed a negative effect of pre-total QCA area and a positive effect of post-total QCA area on LVEF improvement. Importantly, LVEF improvement was similar between the ACh-positive and -negative groups on the coronary artery spasm test. Receiver operating characteristic curves indicated that the cut-off value at which changes in total QCA area affected changes in LVEF was 5%. Conclusions: Performing double LVG tests before and after ISDN administration may detect myocardial ischemia caused by diffuse coronary artery contraction. The addition of this method to the conventional ACh provocation test may detect the presence of local and/or global myocardial ischemia.

Possible diverse contribution of coronary risk factors to left ventricular systolic and diastolic cavity sizes.

It is generally believed that risk factors damage the coronary arteries, cause myocardial ischemia, and consequently change the shape of the heart. On the other hand, each of the risk factors may also have a negative effect on the heart. However, it is very difficult to examine the effects of each of these risk factors independently. Therefore, it is necessary to select an appropriate statistical method and apply it efficiently. In this study, the effects of coronary risk factors on left ventricular size and cardiac function were investigated using structure equation modeling (SEM), and were shown as Bayesian SEM-based frequency polygons using selected two-dimensional contours. This study showed that each risk factor directly affected the shape of the heart. Because vascular risk and heart failure risk are likely to evolve at the same time, managing risk factors is very important in reducing the heart failure pandemic.

Evaluation of Enhanced Lipid Oxidation and Compensatory Suppression using Natriuretic Peptide in Patients with Cardiovascular Diseases.

Malondialdehyde-modified low-density lipoprotein (MDA-LDL) is recognized as a surrogate marker of lipid oxidation and is associated with arteriosclerosis. However, there are limited reports on the relationship between heart failure and MDA-LDL. Therefore, we aimed to determine whether MDA-LDL is activated in patients with left ventricular (LV) dysfunction and examine our hypothesis that the B-type natriuretic peptide (BNP) masks the enhancement of MDA-LDL in patients with LV dysfunction by its strong antioxidative action. The study population comprised 2,976 patients with various cardiovascular diseases. Patients were divided into four groups depending on the LV ejection fraction (LVEF) or plasma BNP level. A nonparametric analysis with the Kruskal-Wallis test was used to perform an interquartile comparison. In addition, structural equation modeling and Bayesian estimation were used to compare the effects of LVEF and BNP on MDA-LDL. MDA-LDL levels did not significantly change (P > 0.05) with respect to the degree of LVEF among the four groups. In contrast, MDA-LDL levels were significantly decreased (P < 0.001) with respect to the degree of BNP among the four groups. A path model based on structural equation modeling clearly showed a significant effect of LVEF (standardized regression coefficient; ß: -0.107, P < 0.001) and BNP (ß: -0.114, P < 0.001) on MDA-LDL, with a significant inverse association between LVEF and BNP (correlation coefficient -0.436, P < 0.001). MDA-LDL should be activated in patients with LV dysfunction; however, BNP is thought to exert a strong compensatory suppression on lipid oxidation, masking the relationship between heart failure and lipid oxidation.

Possible Association Between Body Temperature and B-Type Natriuretic Peptide in Patients With Cardiovascular Diseases.

BACKGROUND: In addition to various biological effects of natriuretic peptides (NP) on cardiovascular systems, we recently reported that NP raises intracellular temperature in cultured adipocytes. We herein examined the possible thermogenic action of NP in consideration of hemodynamic parameters and inflammatory reaction by proposing structural equation models. METHODS AND RESULTS: The study population consisted of 1985 consecutive patients who underwent cardiac catheterization. Covariance structure analyses were performed to clarify the direct contribution of plasma B-type NP (BNP) to body temperature (BT) by excluding other confounding factors. A hierarchical path model showed increase in BNP, increase in C-reactive protein and decrease in left ventricular ejection fraction were mutually associated. As expected, C-reactive protein was positively correlated with BT. Importantly, despite a negative correlation between BNP and left ventricular ejection fraction, a decrease in the left ventricular ejection fraction was associated with BT decrease, whereas elevation in BNP level was associated with BT increase independently of C-reactive protein level (P = .007). CONCLUSIONS: Patients with LV dysfunction tend to manifest a decrease in BT, whereas BNP elevation is associated with an increase in BT independently of inflammatory response. These findings suggest the adaptive heat-retaining property of NP (and/or NP-associated factors) when BT falls owing to unfavorable hemodynamic conditions in a state of impaired cardiac function.

Increase in oxidized low-density lipoprotein level according to hyperglycemia in patients with cardiovascular disease: A study by structure equation modeling.

AIMS: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) level has been reported to be strongly associated with the pathogenesis of cardiovascular diseases. We focused on diabetic status and investigated its possible contribution to MDA-LDL level. METHODS: The study sample consisted of 2705 patients who were admitted to our hospital and underwent cardiac catheterization. Blood samples were obtained to measure the levels of fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, LDL, MDA-LDL and others. Body mass index (BMI) was also used in constructing structural equation modeling and Bayesian estimation. RESULTS: To explore the factors theoretically associated with MDA-LDL level, we performed structural equation modeling. We generated a path model that revealed that BMI, LDL level and FBS were significantly associated with MDA-LDL level (P < 0.001 for each factor), whereas insulin level and HbA1c level were not significantly associated (P = NS for both factors). Noted above was clearly demonstrated on the image of 2-D contour line by Bayesian structure equation modeling. CONCLUSIONS: This study clearly showed that hyperglycemia affects MDA-LDL level. An interaction between diabetes and dyslipidemia was shown in terms of activation of lipid oxidation.

A Highly-sensitized Response of B-type Natriuretic Peptide to Cardiac Ischaemia Quantified by Intracoronary Pressure Measurements.

B-type natriuretic peptide (BNP) secretion is stimulated by cardiac dysfunction. However, it is unclear how finely myocardial ischaemia contributes to BNP secretion and whether increases in BNP secretion contribute to coronary vasodilation. This study investigated the direct interaction between plasma BNP levels and cardiac ischaemia using the baseline distal-to-aortic pressure ratio (Pd/Pa). We examined the baseline Pd/Pa and fractional flow reserve (FFR) in 167 patients with intermediate coronary stenosis. The plasma BNP level appeared to be associated with the baseline Pd/Pa in the study population, and this association appeared to become clear only in patients with an FFR ≤ 0.80. To examine the effect of the baseline Pd/Pa on the BNP level in these patients, structural equation modeling (SEM) was performed. The baseline Pd/Pa significantly affected the BNP level (ß: -0.37, p = 0.003) and the left ventricular ejection fraction (ß: 0.43, p = 0.001). To examine the role of BNP in coronary vasodilation, we proposed another path model using a novel value obtained by dividing the FFR by the baseline Pd/Pa (FFR/baseline Pd/Pa) as an index of the hyperaemic response. The BNP level significantly affected the FFR/baseline Pd/Pa (ß: 0.48, p = 0.037). This study demonstrated that BNP finely responded to an exacerbation of cardiac ischaemia and that increases in BNP secretion effectively ameliorated coronary vasoconstriction.

Collaborative Activities of Noradrenaline and Natriuretic Peptide for Glucose Utilization in Patients with Acute Coronary Syndrome.

Glucose is an important preferential substrate for energy metabolism during acute coronary syndrome (ACS) attack, although insulin resistance (IR) increases during ACS. Increasing evidence indicates that natriuretic peptides (NP) regulate glucose homeostasis. We investigated possible compensatory actions of NP in collaboration with other neurohumoral factors that facilitate glucose utilization during ACS. The study population consisted of 1072 consecutive cases with ischemic heart disease who underwent cardiac catheterization (ACS, n = 216; non-ACS, n = 856). Among ACS subjects, biochemical data after acute-phase treatment were available in 91 cases, defined as ACS-remission phase (ACS-rem). Path models based on covariance structure analyses were proposed to clarify the direct contribution of B-type NP (BNP) and noradrenaline to glucose and HOMA-IR levels while eliminating confounding biases. In non-ACS and ACS-rem subjects, although noradrenaline slightly increased glucose and/or HOMA-IR levels (P < 0.03), BNP did not significantly affect them. In contrast, in ACS subjects, high noradrenaline was a significant cause of increases in glucose and HOMA-IR levels (P < 0.001), whereas high BNP was a significant cause of decreases in both parameters (P < 0.005). These findings indicate that BNP and noradrenaline coordinately activate glucose metabolism during ACS, with noradrenaline increasing glucose levels, as an energy substrate, while BNP improves IR and promotes glucose utilization.

Association between plasma B-type natriuretic peptide and anaemia in heart failure with or without ischaemic heart disease: a retrospective study.

OBJECTIVES: Anaemia is a risk of worsening heart failure. However, anaemia sometimes remains undetected because the superficial cardiac function does not precisely reflect the adverse impact of anaemia. Plasma B-type natriuretic peptide (BNP) could be helpful in these cases. However, the direct anaemic effects on BNP remain unknown. Herein, we compared the direct effect of anaemia on BNP and left ventricular ejection fraction (LVEF) using an advanced statistical procedure. DESIGN: A retrospective study. SETTING: Secondary care (cardiology), single-centre study. PARTICIPANTS: The study consisted of 3756 inpatients, including 684 without ischaemic heart disease (IHD) and 3072 with IHD. PRIMARY AND SECONDARY OUTCOME MEASURES: Relationship between plasma BNP levels and LVEF values. RESULTS: A path model was constructed to simultaneously examine the adverse impact of anaemia on LVEF and plasma BNP, allowing for renal function. The path model revealed that LVEF increased in response to low haemoglobin (Hb), and the phenomenon was prominent in non-IHD (standardised regression coefficients (St.ß): -0.264, p<0.001) rather than in IHD (St.ß: 0.015, p=0.531). However, the response of BNP was commonly observed in both groups (non-IHD St.ß: -0.238, IHD St.ß: -0.398, p<0.001, respectively). Additionally, this study showed a direct link between low estimated glomerular filtration rate and high BNP independently of LVEF. Incrementally, Bayesian structural equation modelling in covariance structure analysis clearly supported this result. The scatter plots and simple regression analysis revealed that an adequate blood supply was approximately Hb 110 g/L and over in the non-IHD patients, whereas blood was not supplied in sufficient quantities even by Hb 130 g/L in patients with IHD. CONCLUSION: The current study demonstrated that anaemia was a substantial risk for worsening cardiac overload as estimated by plasma BNP. The anaemic response of LVEF likely changed depending on underlying cardiac disorders (IHD or not). However, the response of BNP was robustly observed.

High Serum Uric Acid is Highly Associated with a Reduced Left Ventricular Ejection Fraction Rather than Increased Plasma B-type Natriuretic Peptide in Patients with Cardiovascular Diseases.

High serum uric acid (UA) has been reported to be associated with left ventricular (LV) dysfunction; however, the relationship between UA and plasma B-type natriuretic peptide (BNP), a sensitive biomarker of heart failure, is still unclear. This study investigated their relationship to provide an accurate assessment of high UA. The study patients consisted of 3,077 subjects who underwent cardiac catheterization because of various cardiovascular disorders. Since the explanatory factors of multiple regression analysis were mostly confounding with each other, subgroup analysis was performed by quartering the study population using the respective risk factors and by covariance structure analysis. This analysis revealed that UA was almost always well associated with a reduced LV ejection fraction (LVEF), but generally not with BNP. UA was significantly associated with BNP in lean aged females, but not in obese adolescent males, although LVEF was significantly reduced in response to a high UA in both groups. A high UA is a direct risk factor for cardiac dysfunction from the perspective of BNP; however, augmentation of BNP in response to a high UA would likely be restricted among obese adolescent males. On the other hand, the observed LV systolic dysfunction, such as LVEF, reflects a high UA on an almost constant basis.

Predictors of oxygenation impairment in medical treatment for type B acute aortic dissection.

Lung oxygenation impairment often occurs in patients with type B acute aortic dissection (AAD), necessitating mechanical ventilation. Patients receiving mechanical ventilation are at risk of complications, so a low-oxygen condition requiring mechanical ventilation should be avoided. We explored the predictors of oxygenation impairment. We enrolled 46 patients with type B AAD who had been medically treated and underwent computed tomography. Blood was sampled to measure markers of inflammation, such as the C-reactive protein (CRP) levels and white blood cell count. The arterial partial pressure of oxygen/fraction of inspired oxygen ratio (PaO2/FiO2) was calculated to quantify the severity of respiratory failure. Spearman's rank correlation analysis revealed that the minimum PaO2/FiO2 ratio was significantly correlated with gender, age, and current smoker, and the peak CRP, body temperature, and D-dimer values. A multivariate regression analysis revealed that younger age, male sex, and the peak CRP level were significant predictors of the minimum PaO2/FiO2 ratio (P = 0.01, 0.035 and 0.005, respectively). A covariance structure analysis showed that a younger age and the peak CRP level were significant predictors of oxygenation impairment in type B AAD. Oxygenation impairment in type B AAD is correlated with younger age and a higher peak CRP level. This will enable the identification of patients whose respiratory condition is susceptible to worsening and help prevent mechanical ventilation, leading to the provision of appropriate therapy.

Conflicting relationship between age-dependent disorders, valvular heart disease and coronary artery disease by covariance structure analysis: Possible contribution of natriuretic peptide.

BACKGROUND: It is conceivable that contemporary valvular heart disease (VHD) is affected largely by an age-dependent atherosclerotic process, which is similar to that observed in coronary artery disease (CAD). However, a comorbid condition of VHD and CAD has not been precisely examined. The first objective of this study was to examine a possible comorbid condition. Provided that there is no comorbidity, the second objective was to search for the possible reasons by using conventional risk factors and plasma B-type natriuretic peptide (BNP) because BNP has a potentiality to suppress atherosclerotic development. METHODS: The study population consisted of 3,457 patients consecutively admitted to our institution. The possible comorbid condition of VHD and CAD and the factors that influence the comorbidity were examined by covariance structure analysis and multivariate analysis. RESULTS: The distribution of the patients with VHD and those with CAD in the histograms showed that the incidence of VHD and the severity of CAD rose with seniority in appearance. The real statistical analysis was planned by covariance structure analysis. The current path model revealed that aging was associated with VHD and CAD severity (P < 0.001 for each); however, as a notable result, there was an inverse association regarding the comorbid condition between VHD and CAD (Correlation coefficient [ß]: -0.121, P < 0.001). As the second objective, to clarify the factors leading to this inverse association, the contribution of conventional risk factors, such as age, gender, hypertension, smoking, diabetes, obesity and dyslipidemia, to VHD and CAD were examined by multivariate analysis. However, these factors did not exert an opposing effect on VHD and CAD, and the inverse association defied explanation. Since different pathological mechanisms may contribute to the formation of VHD and CAD, a differentially proposed path model using plasma BNP revealed that an increase in plasma BNP being drawn by VHD suppressed the progression of CAD (ß: -0.465, P < 0.001). CONCLUSIONS: The incidence of VHD and CAD showed a significant conflicting relationship. This result supported the likely presence of unknown diverse mechanisms on top of the common cascade of atherosclerosis. Among them, the continuous elevation of plasma BNP due to VHD might be one of the explicable factors suppressing the progression of CAD.

Close linkage between serum uric acid and cardiac dysfunction in patients with ischemic heart disease according to covariance structure analysis.

High serum uric acid (UA) level has been assumed to be a risk factor for left ventricular (LV) dysfunction; however, the precise relationship between these conditions has not been fully examined because many confounding factors are associated with UA level. We herein examined the precise relationship by proposing structural equation models. The study population consisted of 1432 cases with ischemic heart disease who underwent cardiac catheterization. Multiple regression analyses and covariance structure analyses were performed to elucidate the cause-and-effect relationship between UA level and LV ejection fraction (LVEF). A path model exploring the factors contributing to LVEF showed that high UA was a significant cause of reduced LVEF (P = 0.004), independent of other significant factors. The degree of atherosclerosis, as estimated by the number of diseased coronary vessels, was significantly affected by high UA (P = 0.005); and the number of diseased coronary vessels subsequently led to reduced LVEF (P < 0.001). Another path model exploring the factors contributing to UA level showed that LVEF was a significant cause of high UA (P = 0.001), while other risk factors were also independent contributing factors. This study clearly demonstrated that there was a close link between high UA and LV dysfunction, which was represented by possible cause-and-effect relationship.

Associations between Left Ventricular Cavity Size and Cardiac Function and Overload Determined by Natriuretic Peptide Levels and a Covariance Structure Analysis.

The effects of left ventricular (LV) cavity size on cardiac function and overload have not yet been fully elucidated. We performed a covariance structure analysis and drew theoretical path models to clarify the effects of hemodynamic parameters on the stroke volume index (SVI) as a marker of cardiac function and on the plasma B-type natriuretic peptide (BNP) level as a marker of cardiac overload. We simultaneously measured various hemodynamic parameters and the BNP levels during cardiac catheterization in 1,715 inpatients of our institution. The current path models tested the validity of the Frank-Starling law in patients with heart failure using the SVI, the LV end-systolic volume index (LVESVI) and the LV end-diastolic volume index (LVEDVI). Using the BNP levels, the path models clearly demonstrated that LVESVI substantially augmented cardiac overload, whereas LVEDVI palliated this parameter. These volume indices exerted opposite effects on cardiac function and overload. These results advance the understanding of the relationships between LV cavity size and both cardiac function and overload and indicate the increasing importance of LV diastolic volume in heart failure and the utility of LVESVI as an important marker of cardiac remodeling for further relevant studies.

Manifold implications of obesity in ischemic heart disease among Japanese patients according to covariance structure analysis: Low reactivity of B-type natriuretic peptide as an intervening risk factor.

BACKGROUND/OBJECTIVES: Obesity is believed to be one of the major risk factors for cardiovascular disease in Western countries. However, the effects of obesity should be continuously examined in the Japanese population because the average bodily habitus differs among countries. In this study, we collectively examined the significance of obesity and obesity-triggered risk factors including the low reactivity of B-type natriuretic peptide (BNP), for ischemic heart disease (IHD) in Japanese patients. METHODS AND RESULTS: The study patients consisted of 1252 subjects (IHD: n = 970; non-IHD: n = 282). Multiple logistic regression analysis revealed that dyslipidemia, hypertension, diabetes, and the low reactivity of BNP were significant risk factors for IHD, but body mass index (BMI) was not. A theoretical path model was proposed by positioning BMI at the top of the hierarchical model. Exploratory factor analysis revealed that BMI did not play a causative role in IHD (P = NS). BMI was causatively linked to other risk factors (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP), and these factors played a causative role in IHD (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP). The intrinsic power of the low reactivity of BNP induced by high BMI on the promotion of IHD was fairly potent. CONCLUSION: This study demonstrated that obesity per se is not a strong risk factor for IHD in Japanese patients. However, several important risk factors triggered by obesity exhibited a causative role for IHD. The low reactivity of BNP is a substantial risk factor for IHD.