Cardiac Acoustic Biomarkers in Patients with Heart Failure during Cardiopulmonary Exercise Testing: An Exploratory Study.

Objective Exercise therapy as part of cardiac rehabilitation is one of the most effective treatments for patients with chronic heart failure (HF). The anaerobic threshold (AT) determined by an exhaled gas analysis during cardiopulmonary exercise testing (CPX) is used to prescribe the appropriate level of exercise therapy. However, CPX using an exhaled gas analysis is not widely performed because of its cost, complexity, and the need for skilled staff. Therefore, a simpler and inexpensive method for determining AT without respiratory gas measurements is required in patients with HF. The present study elucidated the relationship between the AT determined by the CPX ventilatory method (CPX-AT) and the AT determined by cardiac acoustic biomarkers (CABs), which are measured by acoustic cardiography (CAB-AT), in HF patients. Methods Patients underwent symptom-limited ramp CPX twice using a cycle ergometer. The ATs determined from the exhaled gas analysis were identified by three independent physicians. CABs, including S1 and S2 intensities (peak-to-peak amplitudes), electromechanical activation time (EMAT) defined as the time interval from the Q wave onset on electrocardiography to the first heart sound (S1), heart rate (HR), and other parameters, were collected during CPX. Patients Forty patients with HF were included in this study. Results A significant correlation (R=0.70; p<0.001) was found between CPX-AT and CAB-AT, using the double product of S1 intensity and heart rate. CAB-AT using S1 intensity also showed a significant correlation with CPX-AT (R=0.71; p<0.001). Conclusion The present study suggests a possible new method for determining AT without respiratory gas measurements in patients with HF.

Association of ambient temperature and acute heart failure with preserved and reduced ejection fraction.

AIMS: Evidence on the association between ambient temperature and the onset of acute heart failure (AHF) is scarce and mixed. We sought to investigate the incidence of AHF admissions based on ambient temperature change, with particular interest in detecting the difference between AHF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Individualized AHF admission data from January 2015 to December 2016 were obtained from a multicentre registry (Tokyo CCU Network Database). The primary event was the daily number of admissions. A linear regression model, using the lowest ambient temperature as the explanatory variable, was selected for the best-estimate model. We also applied the cubic spline model using five knots according to the percentiles of the distribution of the lowest ambient temperature. We divided the entire population into HFpEF + HFmrEF and HFrEF for comparison. In addition, the in-hospital treatment and mortality rates were obtained according to the interquartile ranges (IQRs) of the lowest ambient temperature (IQR1 <5.5°C; IQR25.5-13.3°C; IQR3 13.3-19.7°C; and IQR4 >19.7°C). The number of admissions for HFpEF, HFmrEF and HFrEF were 2736 (36%), 1539 (20%), and 3354 (44%), respectively. The lowest ambient temperature on the admission day was inversely correlated with the admission frequency for both HFpEF + HFmrEF and HFrEF patients, with a stronger correlation in patients with HFpEF + HFmrEF (R2  = 0.25 vs. 0.05, P < 0.001). In the sensitivity analysis, the decrease in the ambient temperature was associated with the greatest incremental increases in HFpEF, followed by HFmrEF and HFrEF patients (3.5% vs. 2.8% vs. 1.5% per -1°C, P < 0.001), with marked increase in admissions of hypertensive patients (systolic blood pressure >140 mmHg vs. 140-100 mmHg vs. <100 mmHg, 3.0% vs. 2.0% vs. 0.8% per -1°C, P for interaction <0.001). A mediator analysis indicated the presence of the mediator effect of systolic blood pressure. The in-hospital mortality rate (7.5%) did not significantly change according to ambient temperature (P = 0.62). CONCLUSIONS: Lower ambient temperature was associated with higher frequency of AHF admissions, and the effect was more pronounced in HFpEF and HFmrEF patients than in those with HFrEF.

Clinical Significance of the Controlling Nutritional Status (CONUT) Score in Patients with Infective Endocarditis.

Risk stratification of patients with infective endocarditis (IE) is difficult. The Controlling Nutritional Status (CONUT) score is an index of immune function and nutritional status. We investigated the prognostic value of the CONUT score in IE and whether its prognostic value differed between IE patients with and without indications for surgery.Clinical records were retrospectively evaluated for 92 patients with IE treated at Nihon University Itabashi Hospital and Nihon University Hospital between January 2014 and May 2019. The CONUT score was determined upon admission, and patients were divided into two groups at the median score (≤ 7 [n = 50] and ≥ 8 [n = 42]). The primary outcome was all-cause mortality at 90 days after admission.The high CONUT group had significantly higher C-reactive protein and N-terminal pro-brain natriuretic peptide levels, as well as a significantly lower hemoglobin and estimated glomerular filtration rate (all P < 0.05), and considerably more valve perforation (26% versus 8%, P < 0.05). Kaplan-Meier analysis revealed that mortality was significantly higher in the high CONUT group (P < 0.001). Even after adjusting for the propensity score based on IE risk factors, a higher CONUT score was still associated with mortality. A receiver-operating characteristic analysis revealed that a CONUT score ≥ 8 had a sensitivity of 86% and specificity of 76% for predicting all-cause mortality. A CONUT score ≥ 8 was most strongly associated with mortality in patients with surgical indications (P < 0.001).In patients with IE, a higher CONUT score was significantly associated with inflammation, heart failure, renal dysfunction, anemia, valve dysfunction, and short-term mortality, especially in patients with surgical indications.

Benefit and harm of intravenous vasodilators across the clinical profile spectrum in acute cardiogenic pulmonary oedema patients.

BACKGROUND: The absence of high quality, large-scale data that indicates definitive mortality benefits does not allow for firm conclusions on the role of intravenous vasodilators in acute heart failure. We aimed to investigate the associations between intravenous vasodilators and clinical outcomes in acute heart failure patients, with a specific focus on patient profiles and type of vasodilators. METHODS: Data of 26,212 consecutive patients urgently hospitalised for a primary diagnosis of acute heart failure between 2009 and 2015 were extracted from a government-funded multicentre data registration system. Propensity scores were calculated with multiple imputations and 1:1 matching performed between patients with and without vasodilator use. The primary endpoint was inhospital mortality. RESULTS: On direct comparison of the vasodilator and non-vasodilator groups after propensity score matching, there were no significant differences in the inhospital mortality rates (7.5% vs. 8.8%, respectively; P=0.098) or length of intensive/cardiovascular care unit stay and hospital stay between the two groups. However, there was a substantial difference in baseline systolic blood pressure by vasodilator type; favourable impacts of vasodilator use on inhospital mortality were observed among patients who had higher systolic blood pressures and those who had no atrial fibrillation on admission. Furthermore, when compared to nitrates, the use of carperitide (natriuretic peptide agent) was significantly associated with worse outcomes, especially in patients with intermediate systolic blood pressures. CONCLUSIONS: In acute heart failure patients, vasodilator use was not universally associated with improved inhospital outcomes; rather, its effect depended on individual clinical presentation: patients with higher systolic blood pressure and no atrial fibrillation seemed to benefit maximally from vasodilators. TRIAL REGISTRATION: UMIN-CTR identifier, UMIN000013128.

Younger- vs Older-Old Patients with Heart Failure with Preserved Ejection Fraction.

OBJECTIVES: Heart failure with preserved ejection fraction (HFpEF) is now recognized as a geriatric syndrome with multifactorial pathophysiology and clinical heterogeneity rather than a solely left ventricular diastolic dysfunction. Because the pathophysiology of HFpEF is suggested to differ by age, this study compared the clinical characteristics and prognostic factors between HFpEF patients aged 65 to 84 years and those aged 85 years or older. DESIGN: Retrospective cohort study. SETTING: The Tokyo CCU Network including 73 hospitals in Tokyo, Japan. PARTICIPANTS: Individuals aged 65 years or older with HFpEF (N = 4305). MEASUREMENTS: Very old patients were defined as those aged 85 years or older. Potential risk factors for in-hospital mortality were selected by univariate analyses, and those with a P value <.10 were used in multivariate Cox regression analysis with forward selection (likelihood ratio) to identify significant factors. RESULTS: Prevalence of hypertension was significantly higher in very old patients, whereas prevalence of coronary artery disease, diabetes mellitus, hyperlipidemia, and smoking was significantly higher in patients aged 65 to 84 years. In very old patients, low systolic blood pressure (hazard ratio [HR] = .988), high serum creatinine level (HR = 1.34), and coexisting chronic obstructive pulmonary disease (COPD; HR = 2.01) were identified as independent risk factors for in-hospital mortality. In contrast, low systolic blood pressure (HR = .987) and low body mass index (HR = .935) were identified as independent risk factors in patients aged 65 to 84 years. CONCLUSION: Significant differences were observed in the clinical characteristics and prognostic factors for in-hospital mortality between HFpEF patients aged 65 to 84 and those 85 years and older. Of note, coexisting COPD was associated with significantly lower survival rate only in patients aged 85 years and older, suggesting the prognostic impact of concomitant pulmonary disease in HFpEF may increase with age. These results have implications for future research and management of older HFpEF patients. J Am Geriatr Soc 00:1-6, 2019. J Am Geriatr Soc 67:2123-2128, 2019.

Different prognostic associations of beta-blockers and diuretics in heart failure with preserved ejection fraction with versus without high blood pressure.

OBJECTIVE: No agents have been proven to improve survival in heart failure with preserved ejection fraction (HFpEF), but the phenotypic diversity of HFpEF suggests it may be possible to identify specific HFpEF phenotypes that will benefit from certain treatments. This study compared the risk factors for and prognostic impacts of treatments on in-hospital mortality between HFpEF patients with (+) and without (-) high blood pressure (HBP). METHODS: Data on 2238 consecutive HFpEF patients were extracted from Tokyo CCU Network data registry and analysed. HFpEF was defined as an ejection fraction greater than or equal to 50%; HBP was defined as elevated systolic blood pressure (>140 mmHg) at admission. Potential risk factors for in-hospital mortality were selected by univariate analyses and those with P < 0.10 were used in multivariate Cox regression analysis with forward selection (likelihood ratio) to identify significant factors. RESULTS: In-hospital mortality was significantly lower for HFpEF + HBP than HFpEF - HBP patients (log-rank, P < 0.001). Independent risk factors for in-hospital mortality in HFpEF + HBP patients were older age (hazard ratio 1.069) and in-hospital treatment without beta-blockers (hazard ratio 7.946), whereas older age (hazard ratio 1.035), higher C-reactive protein (hazard ratio 1.047), higher B-type natriuretic peptide (hazard ratio 1.000) and in-hospital treatment without diuretics (hazard ratio 4.201) were identified as independent risk factors in HFpEF - HBP patients. CONCLUSION: There were significant differences in prognostic factors, including beta-blocker and diuretic treatments, for in-hospital mortality between HFpEF patients with and without HBP. These findings suggest possible individualized therapies for patients with HFpEF.

Effects of glycemic control on in-hospital mortality among acute heart failure patients with reduced, mid-range, and preserved ejection fraction.

The relationship between glycemic control and outcome in patients with heart failure (HF) remains contentious. A recent study showed that patients with HF with mid-range ejection fraction (HFmrEF) more frequently had comorbid diabetes relative to other patients. Herein, we examined the association between glycosylated hemoglobin (HbA1c) and in-hospital mortality in acute HF patients with reduced, mid-range, and preserved EF. A multicenter retrospective study was conducted on 5205 consecutive patients with acute HF. Potential risk factors for in-hospital mortality were selected by univariate analyses; then, multivariate Cox regression analysis with backward stepwise selection was performed to identify significant factors. Kaplan-Meier survival curves and log-rank testing were used to compare in-hospital mortality between groups. Across the study cohort, 44% (2288 patients) had reduced EF, 20% had mid-range EF, and 36% had preserved EF. The overall in-hospital mortality rate was 4.6%, with no significant differences among the HF patients with reduced, mid-range, and preserved EF groups. For patients with HFmrEF, higher HbA1c level was a significant risk factor for in-hospital mortality (hazard ratio 1.387; 95% confidence interval 1.014-1.899; P = 0.041). In contrast, HbA1c was not an independent risk factor for in-hospital mortality in HF patients with preserved or reduced EF. In conclusion, HbA1c is an independent risk factor for in-hospital mortality in acute HF patients with mid-range EF, but not in those with preserved or reduced EF. Elucidation of the pathophysiological mechanisms behind these findings could facilitate the development of more effective individualized therapies for acute HF.

Impact of Triggering Events on Outcomes of Acute Heart Failure.

BACKGROUND: The onset of acute heart failure is known to be associated with increased physical activity and other specific behaviors that can trigger hemodynamic deterioration. This analysis aimed to describe the distribution of triggers in patients hospitalized for acute heart failure, and investigate their effects on in-hospital outcomes. METHODS: Consecutive patients hospitalized for acute heart failure between 2010 and 2014 were registered in a multicenter data registration system (72 institutions within Tokyo, Japan). Baseline demographics and in-hospital mortality were extracted from 17,473 patients. Patients with a trigger were grouped based on their triggering event: those with onset during (a) physical activity; (b) sleeping; (c) eating or watching television; (d) bathing or excretion (use of restrooms); and (e) engaging in other activities. These patients were compared with patients without identifiable triggers. Multiple imputation was used for missing data. RESULTS: Patients were predominantly men (57.1%), with a mean age of 76.0 ± 13.0 years; a triggering event was present in 49.1%. No significant difference in baseline characteristics was noted between groups except for younger age, higher blood pressure, and prevalence of signs of congestion in the trigger-positive group. In-hospital mortality rate was 7.9%. Presence of triggers was positively associated with a reduced risk of in-hospital mortality (adjusted odds ratio 0.79; 95% confidence interval, 0.70-0.90; P = .0003). In a delta-adjusted pattern mixture model, the effect of a triggering event on in-hospital mortality remained consistently significant. CONCLUSION: Triggering events for acute heart failure can provide additional information for risk prediction. Efforts to identify the triggers should be made to classify patients according to risk group.

Effect of Heart Failure Secondary to Ischemic Cardiomyopathy on Body Weight and Blood Pressure.

Both the obesity paradox and blood pressure (BP) paradox remain ill defined. Because both obesity and hypertension are well-known predictors of coronary artery disease (CAD) and acute heart failure (HF), in the present study, we compared the obesity paradox and the BP paradox between patients with acute HF with and without a history of CAD. A multicenter retrospective study was conducted on 3,204 consecutive patients with acute HF. Potential risk factors for in-hospital mortality were selected by univariate analyses; multivariate Cox regression analysis with backward stepwise selection was then used to identify significant factors. Kaplan-Meier survival curves and log-rank testing were used to compare in-hospital mortality between groups. Across the study cohort, 27% of patients had a history of CAD, and the all-cause in-hospital mortality rate was 5%. In-hospital mortality was significantly lower for patients with obesity than in those without obesity (log-rank, p = 0.033). However, this obesity paradox disappeared in the group with HF and CAD (log-rank, p = 0.740). In contrast, in-hospital mortality was significantly lower for patients with high BP at admission, regardless of the presence of a history of CAD (log-rank, p <0.001 for both groups). In conclusion, a history of CAD canceled the obesity paradox in patients with acute HF, whereas the BP paradox persisted regardless of a history of CAD.

Association of plasminogen activator inhibitor-1 and low-density lipoprotein heterogeneity as a risk factor of atherosclerotic cardiovascular disease with triglyceride metabolic disorder: a pilot cross-sectional study.

BACKGROUND: We hypothesized that an increase in plasminogen activator inhibitor 1 (PAI-1) might reduce low-density lipoprotein (LDL) particle size in conjunction with triglyceride (TG) metabolism disorder, resulting in an increased risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This study was carried out as a hospital-based cross-sectional study in 537 consecutive outpatients (mean age: 64 years; men: 71%) with one or more risk factors for ASCVD from April 2014 to October 2014 at the Cardiovascular Center of Nihon University Surugadai Hospital. The estimated LDL-particle size was measured as relative LDL migration using polyacrylamide gel electrophoresis with the LipoPhor system.The plasma PAI-1 level, including the tissue PA/PAI-1 complex and the active and latent forms of PAI-1, was determined using a latex photometric immunoassay method. RESULTS: A multivariate regression analysis after adjustments for ASCVD risk factors showed that an elevated PAI-1 level was an independent predictor of smaller-sized LDL-particle in both the overall patients population (ß=0.209, P<0.0001) and a subset of patients with a serum low-density lipoprotein cholesterol (LDL-C) level lower than 100 mg/dl (ß=0.276, P<0.0001). Furthermore, an increased BMI and TG-rich lipoprotein related markers [TG, remnant-like particle cholesterol, apolipoprotein (apo) B, apo C-II, and apo C-III] were found to be independent variables associated with an increased PAI-1 level in multivariate regression models. A statistical analysis of data from nondiabetic patients with well-controlled serum LDL-C levels yielded similar findings. Furthermore, in the 310 patients followed up for at least 6 months, a multiple-logistic regression analysis after adjustments for ASCVD risk factors identified the percent changes of the plasma PAI-1 level in the third tertile compared with those in the first tertile as being independently predictive of decreased LDL-particle size [odds ratio (95% confidence interval): 2.11 (1.12/3.40), P=0.02]. CONCLUSION: The plasma PAI-1 levels may be determined by the degree of obesity and TG metabolic disorders. These factors were also shown to be correlated with a decreased LDL-particle size, increasing the risk of ASCVD, even in nondiabetic patients with well-controlled serum LDL-C levels.

Correlation of Pre- and In-Hospital Systolic Blood Pressure in Acute Heart Failure Patients and the Prognostic Implications　- Report From the Tokyo Cardiac Care Unit Network Emergency Medical Service Database.

BACKGROUND: Systolic blood pressure (SBP) is an important prognostic indicator for patients with acute heart failure (AHF). However, its changes and the effects in the different phases of the acute management process are not well known.Methods and Results:The Tokyo CCU Network prospectively collects on-site information about AHF from emergency medical services (EMS) and the emergency room (ER). The association between in-hospital death and SBP at 2 different time points (on-site SBP [measured by EMS] and in-hospital SBP [measured at the ER; ER-SBP]) was analyzed. From 2010 to 2012, a total of 5,669 patients were registered and stratified into groups according to both their on-site SBP and ER-SBP: >160 mmHg; 100-160 mmHg; and <100 mmHg. In-hospital mortality rates increased when both on-site SBP and ER-SBP were low. After multivariate adjustment, both SBPs were inversely associated with in-hospital death. Notably, the risk for patients with ER-SBP of 100-160 mmHg (intermediate risk) differed according to their on-site SBP; those with on-site SBP <100 or 100-160 mmHg were at higher risk (OR, 7.39; 95% CI, 4.00-13.6 and OR, 2.73; 95% CI, 1.83-4.08, respectively [P<0.001 for both]) than patients with on-site SBP >160 mmHg. CONCLUSIONS: Monitoring changes in SBP assisted risk stratification of AHF patients, particularly patients with intermediate ER-SBP measurements. (Circ J 2016; 80: 2473-2481).

Complete occlusion of the left main trunk coronary artery by a cardiac papillary fibroelastoma in a hemodynamically unstable patient.

Papillary fibroelastomas are benign cardiac tumors with high embolic potential. The majority of cases of complete obstruction of the left main trunk (LMT) of the coronary artery are diagnosed via autopsy following sudden death; survival is rare in this setting. We present the case of a 60-year-old woman who underwent stent placement in the LMT three years prior to developing chest pain and cold sweats. On coronary arteriography, the catheter could not be advanced into the LMT due to resistance in the ostium. Insertion of the catheter was achieved after the resolution of resistance via catheterization of the LMT by means of an intra-aortic balloon pump drive system. The LMT was normal, and the patient's circulatory failure improved. The cause of the LMT embolism was a cardiac papillary fibroelastoma. Primary surgical excision is the recommended therapy for symptomatic cardiac papillary fibroelastoma. If the patient is hemodynamically stable, it may be possible to delay surgery. However, the patient in question developed cardiogenic shock secondary to two-vessel obstruction by the tumor. Therefore, even if the tumor had been removed using an intra-aortic balloon pump, the patient may not have survived until surgery. .

Time Interval from Symptom Onset to Hospital Care in Patients with Acute Heart Failure: A Report from the Tokyo Cardiac Care Unit Network Emergency Medical Service Database.

AIMS: There seems to be two distinct patterns in the presentation of acute heart failure (AHF) patients; early- vs. gradual-onset. However, whether time-dependent relationship exists in outcomes of patients with AHF remains unclear. METHODS: The Tokyo Cardiac Care Unit Network Database prospectively collects information of emergency admissions via EMS service to acute cardiac care facilities from 67 participating hospitals in the Tokyo metropolitan area. Between 2009 and 2011, a total of 3811 AHF patients were registered. The documentation of symptom onset time was mandated by the on-site ambulance team. We divided the patients into two groups according to the median onset-to-hospitalization (OH) time for those patients (2h); early- (presenting ≤2h after symptom onset) vs. gradual-onset (late) group (>2h). The primary outcome was in-hospital mortality. RESULTS: The early OH group had more urgent presentation, as demonstrated by a higher systolic blood pressure (SBP), respiratory rate, and higher incidence of pulmonary congestion (48.6% vs. 41.6%; P<0.001); whereas medical comorbidities such as stroke (10.8% vs. 7.9%; P<0.001) and atrial fibrillation (30.0% vs. 26.0%; P<0.001) were more frequently seen in the late OH group. Overall, 242 (6.5%) patients died during hospitalization. Notably, a shorter OH time was associated with a better in-hospital mortality rate (odds ratio, 0.71; 95% confidence interval, 0.51-0.99; P = 0.043). CONCLUSIONS: Early-onset patients had rather typical AHF presentations (e.g., higher SBP or pulmonary congestion) but had a better in-hospital outcome compared to gradual-onset patients.

Takotsubo cardiomyopathy in two patients with microvascular angina.

We present two cases in which takotsubo cardiomyopathy (TC) developed immediately after a diagnosis of microvascular angina had been established. One patient who had been diagnosed as having endothelium-dependent microvascular angina (microvascular spasm) developed TC three weeks after the initial admission. The other patient was diagnosed as having endothelium-independent microvascular angina (decreased coronary flow reserve) and subsequently developed TC after the discontinuation of nicorandil treatment. These cases may provide insight into the possible mechanisms underlying the pathophysiological findings of TC. .

Development of a model for prediction of coronary atherosclerotic regression: evaluation of high-density lipoprotein cholesterol level and peripheral blood monocyte count.

Monocytes and high-density lipoprotein cholesterol (HDL-C) play important roles in the process of coronary atherosclerosis. We hypothesized that a reasonable predictive model of coronary plaque regression might be constructed using the change in the peripheral monocyte count and the serum HDL-C level. The plaque volume, as assessed by volumetric intravascular ultrasound, was measured at the baseline and after 6 months of pravastatin therapy in 114 patients with coronary artery disease. After 6 months of pravastatin therapy, a significant decrease of the plaque volume by 9.9% (p < 0.0001, vs. baseline) was observed; furthermore, a corresponding increase of the serum HDL-C level and decrease of the peripheral blood monocyte count were also seen (12.5%, p < 0.01 and -7.3%, p < 0.0001). In a multivariate regression analysis using the serum lipids and traditional risk factors as the covariates, the increase in the serum HDL-C (ß -0.56, p < 0.0001) and the decrease in monocyte count (ß 0.23, p = 0.03) were identified as independent predictors of the plaque regression. A model for the prediction of plaque regression according to whether the achieved the change in (Δ) monocyte count and ΔHDL-C were above or below the median values was prepared. Among the four groups, the group with ΔHDL-C ≥8.8% and Δmonocyte count ≤-8.6% showed the largest plaque regression (-20.4%), and the group with ΔHDL-C <8.8% and Δmonocyte count >-8.6% showed the increase of the plaque volume (2.6%). In view of the inflammatory nature of atherosclerosis, the model constructed using the two predictors may be a useful model for the prediction of plaque regression.

Low-density lipoprotein cholesterol/apolipoprotein B ratio may be a useful index that differs in statin-treated patients with and without coronary artery disease: a case control study.

Low density lipoproteins (LDLs) are heterogeneous aggregations of molecules of different particle sizes, and small-size LDLs are more potent risk factors for atherosclerosis. We examined the qualitative characteristics of LDLs in patients with stable coronary artery disease (CAD) receiving statin therapy. LDL-particle size was estimated based on the LDL-cholesterol/apolipoprotein B ratio (LDL-C/apoB) in 214 age-adjusted men receiving statin therapy. The LDL-C/apoB ratio was significantly lower in the CAD (+) group (n = 107) than in the CAD (-) group (n = 107) (median, 1.17 versus 1.19, P = 0.0095). LDL-C/apoB was significantly lower in patients with serum TG ≥ 150 mg/dL than in those with serum TG < 150 mg/dL, and in patients with serum HDL-C < 40 mg/dL than in those with serum HDL-C ≥ 40 mg/dL (1.06 versus 1.18, P = 0.012; 1.08 versus 1.22, P = 0.0023). Stepwise logistic regression analysis revealed that elevated serum TG was an independent predictor for smaller sizes of LDLs, both in the overall subjects (ß : -0.165, P = 0.02) as well as in the subset with serum LDL-C < 100 mg/dL (ß : -0.252, P = 0.011). This study demonstrated that not only the absolute serum LDL-C level, but also the qualitative characteristics of LDL may be monitored for secondary prevention of CAD. Such monitoring is particularly important in patients with elevated serum TG levels, which is associated with smaller sizes of LDL-particles.

Coronary plaque regression and lifestyle modification in patients treated with pravastatin. - Assessment mainly by daily aerobic exercise and an increase in the serum level of high-density lipoprotein cholesterol -.

BACKGROUND: The purpose of this study was to explore the effect of lifestyle modification, mainly daily aerobic exercise, on coronary atherosclerosis in patients with coronary artery disease (CAD). METHODS AND RESULTS: A 6-month prospective observational study was conducted with 84 CAD patients receiving pravastatin treatment in order to evaluate the relationship between lifestyle modification, in particular aerobic exercise, and plaque volume as assessed by intravascular ultrasound (IVUS). Lifestyle during the study period was assessed by the-lifestyle modification score. A significant decrease in plaque volume by 12.9% was observed after 6 months of pravastatin therapy (P<0.0001 vs baseline). The change in plaque volume correlated with the change in the serum level of high-density lipoprotein cholesterol (HDL-C) (r=-0.549, P<0.0001), non-HDL-C (r=0.248, P=0.03), low-density lipoprotein cholesterol/HDL-C (r=0.505, P<0.0001), apolipoprotein (apo) A-1 (r=-0.335, P=0.007) and apoB/apoA-1 (r=0.335, P=0.007), and lifestyle modification score (r=-0.616, P<0.0001). There was a clear positive correlation between a change in the serum HDL-C level and lifestyle modification score. Multivariate regression analysis revealed that the increase in serum HDL-C level and lifestyle modification score were independent predictors of coronary plaque regression. CONCLUSIONS: An appropriate combination of statin therapy and lifestyle modification, in particular, physical activity, may result in coronary plaque regression. This combined treatment strategy, inducing an increase of the serum HDL-C, may contribute to coronary plaque regression.

Relation of change in apolipoprotein B/apolipoprotein A-I ratio to coronary plaque regression after Pravastatin treatment in patients with coronary artery disease.

Some investigations have looked into the ability of measurements of apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio to predict cardiovascular events. We hypothesized that a decrease in the apoB/apoA-1 ratio by statin therapy would act on suppression of coronary plaque progression. A 6-month prospective study was conducted of 64 patients with coronary artery disease treated with pravastatin. The plaque volume, assessed by volumetric intravascular ultrasonography, had decreased significantly by 12.6% (p <0.0001 vs baseline). Although a significant decrease of 6.4% and 14.6% was found in the serum level of apoB and the apoB/apoA-1 ratio (p = 0.0001 and p <0.0001, respectively, vs baseline), a significant increase of 14.0% of and 12.0% in the level of apoA-I and apoA-II (both p <0.0001 vs baseline). No significant changes were found in the level of apoC-II or apoE. A stepwise regression analysis revealed that the change in the apoB/apoA-1 ratio was an independent predictor of the change in coronary plaque volume (beta coefficient 0.386; p = 0.0023). In conclusion, our results have indicated that the decrease in the apoB/apoA-I ratio is a simple predictor for coronary atherosclerotic regression: the lower the apoB/apoA-I ratio, the lower the risk of coronary atherosclerosis.