Comparison of the effects of pitavastatin versus pravastatin on coronary artery plaque phenotype assessed by tissue characterization using serial virtual histology intravascular ultrasound.

Thin-cap fibroatheroma (TCFA) is the most common type of vulnerable plaque and is the precursor of plaque rupture. However, rupture of a TCFA is not the only mechanism underlying thrombus formation or acute coronary syndrome. Although statin therapy changes the composition of coronary artery plaques, the effects of statins, particularly different types of statins, on plaque phenotype have not been fully examined. This study compared the effects of pitavastatin versus pravastatin on coronary artery plaque phenotype assessed by virtual histology (VH) intravascular ultrasound (IVUS) in patients with angina pectoris (AP). Coronary atherosclerosis in nonculprit lesions was evaluated using VH-IVUS at baseline and 8 months after statin therapy; analyzable IVUS data were obtained from 83 patients with stable AP (39 patients treated with pitavastatin and 44 with pravastatin) and 36 patients with unstable AP (19 patients treated with pitavastatin and 17 with pravastatin). Pitavastatin had a strong effect on reducing pathologic intimal thickening (PIT), especially in patients with unstable AP, but had no impact on VH-TCFA or fibroatheroma (FA). By contrast, pravastatin had weak effects on reducing PIT, VH-TCFA, or FA. Increases in the number of calcified plaques were observed for both statins. In conclusion, pitavastatin and pravastatin changed coronary artery plaque phenotype as assessed by VH-IVUS in patients with AP. However, the effects of these statins on coronary artery plaque phenotype were different.

Low serum docosahexaenoic acid is associated with progression of coronary atherosclerosis in statin-treated patients with diabetes mellitus: results of the treatment with statin on atheroma regression evaluated by intravascular ultrasound with virtual histology (TRUTH) study.

BACKGROUND: Diabetes mellitus (DM) accelerates plaque progression despite the use of statin therapy. The purpose of the present study was to evaluate the determinants of atheroma progression in statin-treated patients with DM. METHODS: Coronary atherosclerosis in nonculprit lesions in a vessel undergoing percutaneous coronary intervention (PCI) was evaluated using virtual histology intravascular ultrasound. The study included 50 patients with DM who had been taking statin therapy for 8 months at the time of PCI. RESULTS: Twenty-six patients (52%) showed atheroma progression (progressors) and the remaining 24 patients (48%) showed atheroma regression (regressors) after 8 months of follow-up. Fewer progressors than regressors received intensive lipid-lowering therapy with pitavastatin (31% vs. 50%, p = 0.17) and the frequency of insulin use was higher in progressors (31% vs. 13%, p = 0.18). However, neither of these differences reached statistical significance. Risk factor control at baseline and at the 8-month follow-up did not differ between the 2 groups except for serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Univariate regression analysis showed that serum EPA (r = -0.317, p = 0.03) and DHA (r = -0.353, p = 0.02) negatively correlated with atheroma progression. Multivariate stepwise regression analysis showed that low serum DHA and pravastatin use were significant independent predictors for atheroma progression during statin therapy (DHA: ß = -0.414, type of statin: ß = -0.287, p = 0.001). CONCLUSIONS: Low serum DHA is associated with progression of coronary atherosclerosis in statin-treated patients with DM. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN ID: C000000311.

Impacts of age on coronary atherosclerosis and vascular response to statin therapy.

Age is a well-established risk factor for cardiovascular disease. Recent trials using intravascular ultrasound (IVUS) have shown that lipid-lowering therapy with statins halts the progression or induces the regression of coronary artery plaques. However, impacts of age on coronary atherosclerosis and vascular response to statin therapy have not been fully evaluated. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology-IVUS. IVUS data were analyzed from 119 patients who were divided into two groups according to age: elderly patients (≥65 years, n = 72) and non-elderly patients (<65 years, n = 47). No patients were taking statins or other lipid-lowering therapies at baseline. At baseline, external elastic membrane (EEM) volume (17.27 vs. 14.95 mm(3)/mm, p = 0.02) and plaque volume (9.49 vs. 8.11 mm(3)/mm, p = 0.03) in the elderly patients were significantly greater than in the non-elderly patients. The EEM volume (-2.4 %, p = 0.007) and plaque volume (-3.1 %, p = 0.007) after 8-month of statin therapy had significantly decreased in the non-elderly patients but not in the elderly patients. A significant positive correlation was observed between age and percentage change in plaque volume (r = 0.265, p = 0.004). A multivariate regression analysis showed that age was a significant predictor of the percentage change in plaque volume during statin therapy (ß = 0.223, p = 0.02). Coronary atherosclerosis was more advanced and vascular responses to statin therapy were attenuated in the elderly patients compared to the non-elderly patients.

Lipoprotein(a) is associated with necrotic core progression of non-culprit coronary lesions in statin-treated patients with angina pectoris.

BACKGROUND: Statin therapy results in regression and stabilization of coronary artery plaques, and reduces the incidence of coronary artery disease. However, statin therapy does not effectively halt the accumulation of necrotic core in all patients. The purpose of the present study was to identify the predictors associated with necrotic core progression during statin therapy. METHODS: Coronary atherosclerosis in non-culprit lesions was evaluated using virtual histology intravascular ultrasound at baseline and 8 months after statin therapy. One hundred nineteen patients were divided into 2 groups based on necrotic core progression or regression during an 8-month follow-up period. RESULTS: Patients with necrotic core progression had higher serum lipoprotein(a) [Lp(a)] levels than patients with regression at baseline (16 mg/dL vs. 12 mg/dL, p = 0.02) and at the 8-month follow-up (17 mg/dL vs. 10 mg/dL, p = 0.006). Patients with necrotic core progression had a higher fibro-fatty plaque volume (1.28 mm³/mm vs. 0.73 mm³/mm, p = 0.002), and less necrotic core (0.56 mm³/mm vs. 1.04 mm³/mm, p < 0.0001) and dense calcium (0.35 mm³/mm vs. 0.56 mm³/mm, p = 0.006) plaque volumes at baseline than patients with regression. Multivariate logistic regression analysis showed that Lp(a) was a significant independent predictor associated with necrotic core progression during statin therapy (odds ratio [OR]: 3.514; 95% confidence interval [CI]: 1.338-9.228; p = 0.01). CONCLUSIONS: Serum Lp(a) is independently associated with necrotic core progression in statin-treated patients with angina pectoris.

Statin treatment for coronary artery plaque composition based on intravascular ultrasound radiofrequency data analysis.

BACKGROUND: Systemic therapy with statin has been shown to lower the risk of coronary events; however, the in vivo effects of statin therapy on plaque volume and composition are less understood. METHODS: We conducted a prospective, open-labeled, randomized, multicenter study in 11 centers in Japan. A total of 164 patients were randomized to receive either 4 mg/d of pitavastatin (intensive lipid-lowering therapy) or 20 mg/d of pravastatin (moderate lipid-lowering therapy). Analyzable intravascular ultrasound data were obtained for 119 patients at baseline and at 8-month follow-up. The primary end point was the difference of volume changes in each of the 4 main plaque components (fibrosis, fibrofatty, calcium, and necrosis), assessed by virtual histology intravascular ultrasound, between the 2 groups. RESULTS: The mean low-density lipoprotein cholesterol level at follow-up was significantly lower in the pitavastatin than in the pravastatin group (74 vs 95 mg/dL, P < .0001). During the 8-month follow-up period, statin therapy reduced the absolute and relative amount of fibrofatty component (pitavastatin: from 1.09 to 0.81 mm(3)/mm, P = .001; pravastatin: from 1.05 to 0.83 mm(3)/mm, P = .0008) and increased in the amount of calcium (pitavastatin: from 0.42 to 0.55 mm(3)/mm, P < .0001; pravastatin: from 0.44 to 0.55 mm(3)/mm, P = .005), whereas volume changes in both plaque components were not statistically different between the 2 groups. CONCLUSIONS: Both pitavastatin and pravastatin altered coronary artery plaque composition by significantly decreasing the fibrofatty plaque component and increasing the calcified plaque component.

Optimal initial diagnostic strategies for the evaluation of stable angina patients: a multicenter, prospective study on myocardial perfusion imaging, computed tomographic angiography, and coronary angiography.

BACKGROUND: For stable patients suspected of having coronary artery disease (CAD), myocardial perfusion imaging (MPI) or computed tomographic angiography (CT) is used for initial evaluation, while coronary angiography (CAG) is used for confirming the diagnosis. The choice of the initial diagnostic test might influence the treatment strategy. METHODS AND RESULTS: Patients scheduled for MPI, CT, or CAG as the initial diagnostic test were enrolled. The primary and secondary end-points were a major adverse cardiac event (MACE) and revascularization, respectively. Of the 2,878 patients enrolled, 2,825 underwent initial diagnostic tests, and 2,780 were followed up for 1.42±0.49 years. After adjustment for CAD severity, Cox proportional hazard regression analysis showed that the risk of MACE in the MPI and CT groups were similar and significantly less than that in the CAG group (hazard ratio, 0.82 vs. 2.19; 95% confidence interval [CI], 0.43-1.58 vs. 1.40-3.44). Furthermore, the rate of revascularization in the MPI group was less than that of the CT (odds ratio, 1.62; 95% CI, 1.20-2.18) and CAG (odds ratio, 5.36; 95% CI, 4.07-7.05) groups. CONCLUSIONS: These data indicate that for stable patients with suspected CAD, the use of MPI or CT as the initial diagnostic test was associated with better prognosis than the use of CAG, and that initial evaluation with MPI was associated with a lower requirement of coronary intervention.

Impact of diabetes mellitus on coronary atherosclerosis and plaque composition under statin therapy ­ subanalysis of the TRUTH study ­.

BACKGROUND: Patients with diabetes mellitus (DM) have a markedly increased incidence of adverse cardiovascular events, but the mechanisms have not been well-characterized. METHODS AND RESULTS: The TRUTH study evaluated the effects of 8-month statin therapy on coronary artery plaque composition using virtual histology intravascular ultrasound (IVUS). Analyzable IVUS data were obtained from 119 patients, including 50 DM patients. The pattern of arterial remodeling, extent of coronary atherosclerosis, and plaque composition were compared in subjects with and without DM. Significant decreases in atheroma volume (-2.3%, P=0.02) and external elastic membrane volume (-1.7%, P=0.02) were observed only in the non-DM group. Although statin therapy significantly decreased the fibro-fatty component in both groups, this component at follow-up was significantly greater in the DM group (0.99 mm(3)/mm vs. 0.70 mm(3)/mm, P=0.03). Multivariate regression analysis showed that the presence of DM was associated with greater atheroma volume (ß=0.203, P=0.02), particularly fibro-fatty plaque volume at follow-up (ß=0.215, P=0.01). CONCLUSIONS: DM attenuated the degree of regression of coronary atherosclerosis under statin therapy. A large amount of fibro-fatty plaque volume under statin therapy may affect the development of coronary events in patients with DM.

Association of the extent of myocardial ischemia with outcomes in patients with suspected coronary artery disease in Japan.

BACKGROUND: There is an ongoing controversy regarding the necessity of single-photon emission computed tomography (SPECT) for patients with ischemic heart diseases after the publication of the results of the ISCHEMIA trial. We aimed to evaluate the association of the extent of myocardial ischemia with outcomes in patients with suspected coronary artery disease in Japan. METHODS: From the data of 2780 patients with stable angina who were enrolled prospectively between January 2006 and March 2008 in Japan and had undergone physician-referred non-invasive imaging tests (Japanese Coronary-Angiography or Myocardial Imaging for Angina Pectoris Study), 1205 patients managed with SPECT were stratified by 10 % myocardial ischemia. Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalization for heart failure, and late revascularization, were followed-up for 1 year. RESULTS: Patients with ≥10 % myocardial ischemia (n = 173) were less likely to be women than patients with <10 % myocardial ischemia (n = 1032) and had a significantly higher 1-year cumulative incidence of MACEs (6.9 % vs. 1.8 %, p < 0.0001). After adjusting for confounders, the risk of ≥10 % myocardial ischemia relative to <10 % myocardial ischemia for MACEs remained significant [adjusted hazard ratio (95 % confidence interval), 2.40 (1.09-5.26), p = 0.029]. After adjusting including treatments, the risk of MACEs became insignificant between the ≥10 % myocardial ischemia group and the <10 % myocardial ischemia group [adjusted hazard ratio (95 % confidence interval), 1.04 (0.45-2.45), p = 0.92]. CONCLUSION: The presence of ≥10 % myocardial ischemia at diagnosis was significantly associated with the 1-year risk for MACEs in Japanese patients with suspected coronary artery disease.

Efficacy of paclitaxel-eluting stent implantation in hemodialysis patients.

Hemodialysis patients were recognized as a high-risk group for restenosis after percutaneous coronary intervention in the era of the bare-metal stent. Recently, sirolimus-eluting stents (SES) have reduced restenosis and target lesion revascularization (TLR); however, it has been reported that their efficacy in hemodialysis patients is limited. The purpose of this study was to investigate whether paclitaxel-eluting stents (PES) improved angiographic outcomes of hemodialysis patients compared with SES. This study is a retrospective cohort study. We analyzed 54 hemodialysis patients with 87 lesions implanted with PES from February 2007 to September 2008, and 49 hemodialysis patients with 68 lesions implanted with SES from August 2004 to January 2007. Angiographic follow-up after 8-10 months was obtained for 59 lesions (67.8%) in the PES group and 43 lesions (63.2%) in the SES group. At baseline, the PES patients had more peripheral artery disease compared with the SES group (66.7 vs. 34.7%; p = 0.0012). There were no significant differences in the angiographic characteristics or procedural index. The binary restenosis rate was lower in lesions implanted with PES than in those with SES (13.6 vs. 39.5%; p = 0.034). Accordingly, the TLR rate was lower in lesions implanted with PES than with SES (9.3 vs. 26.5%; p = 0.041). Our results suggest that PES is more effective than SES in reducing restenosis and TLR in hemodialysis patients.

Association of coronary revascularisation after physician-referred non-invasive diagnostic imaging tests with outcomes in patients with suspected coronary artery disease: a post hoc subgroup analysis.

OBJECTIVE: We aimed to evaluate the association of the prognostic impact of coronary revascularisation with physician-referred non-invasive diagnostic imaging tests (single photon emission CT (SPECT) vs coronary CT angiography) for coronary artery disease. DESIGN: A post hoc analysis of a subgroup from the patient cohort recruited for the Japanese Coronary-Angiography or Myocardial Imaging for Angina Pectoris Study. SETTING: Multiple centres in Japan. PARTICIPANTS: From the data of 2780 patients with stable angina, enrolled prospectively between January 2006 and March 2008 in Japan, who had undergone physician-referred non-invasive imaging tests, 1205 patients with SPECT as an initial strategy and 625 with CT as an initial strategy were analysed. We assessed the effect of revascularisation (within 90 days) in each diagnostic imaging stratum and the interaction between the two strata. PRIMARY AND SECONDARY OUTCOME MEASURES: Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalisation for heart failure and late revascularisation, were followed up for 1 year. The χ2 test, Student's t-test, Kaplan-Meier analysis, log-rank test and multivariable Cox proportional hazard model were used in data analysis. RESULTS: A total of 210 (17.4%) patients in the SPECT stratum and 149 (23.8%) in the CT stratum underwent revascularisation. Although in each stratum, the cumulative 1 year incidence of MACEs was significantly higher in patients who underwent revascularisation than in those who did not (SPECT stratum: 9.1 vs 1.2%, log-rank p<0.0001; CT stratum: 6.1 vs 0.8%, log-rank p=0.0001), there was no interaction between the risk of revascularisation and the imaging strata (SPECT stratum: adjusted HR (95% CI), 4.25 (1.86-9.72); CT stratum: 4.13 (1.16-14.73); interaction: p=0.97). CONCLUSION: The association of revascularisation with the outcomes of patients with suspected coronary artery disease was not different between SPECT-first and CT-first strategies in a physician-referred fashion.

Impact of renal dysfunction on the choice of diagnostic imaging, treatment strategy, and outcomes in patients with stable angina.

We investigated the interaction between the prognostic impact of a decrease in eGFR and the choice of initial diagnostic imaging modality for coronary artery disease. Out of 2878 patients who enrolled in the J-COMPASS study, 2780 patients underwent single photon emission computed tomography (SPECT), coronary computed tomography (CT) angiography, or coronary angiography (CAG) as an initial diagnostic test. After excluding patients with routine hemodialysis or lacked serum creatinine levels, 2096 patients in the non-decreased eGFR group (eGFR ≥ 60 ml/min/1.73 m2) and 557 patients in the decreased eGFR group (eGFR < 60 ml/min/1.73 m2) were analyzed in this study. Major adverse cardiac events, including death, myocardial infarction, heart failure hospitalization, and late revascularization, were followed, with a median follow-up duration of 472 days. SPECT or CAG was preferable to CT in patients in the decreased eGFR group (p < 0.0001 and p = 0.0024, respectively). There was a marginally significant interaction between the prognostic impact of a decrease in eGFR and the choice of diagnostic imaging modality (interaction-p = 0.056). A decrease in eGFR was not associated with a poor outcome in patients who underwent CT, while a decrease in eGFR was associated with poor outcomes in patients who underwent SPECT or CAG. In conclusion, the prognostic impact of a decrease in eGFR tended to be different among the initial imaging modalities.

Polyunsaturated Fatty Acid Impact on Clinical Outcomes in Acute Coronary Syndrome Patients With Dyslipidemia: Subanalysis of HIJ-PROPER.

Background This study aimed to examine the impact of baseline eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio on clinical outcomes of patients with acute coronary syndrome. Methods and Results In the HIJ-PROPER (Heart Institute of Japan Proper Level of Lipid Lowering With Pitavastatin and Ezetimibe in Acute Coronary Syndrome) study, 1734 patients with acute coronary syndrome and dyslipidemia were randomly assigned to pitavastatin+ezetimibe therapy or pitavastatin monotherapy. We divided the patients into 2 groups based on EPA/AA ratio on admission (cutoff 0.34 µg/mL as median of baseline EPA/AA ratio) and examined their clinical outcomes. The primary end point comprised all-cause death, nonfatal myocardial infarction, nonfatal stroke, unstable angina pectoris, or ischemia-driven revascularization. Percentage reduction of low-density lipoprotein cholesterol and triglyceride from baseline to follow-up was similar regardless of baseline EPA/AA ratio. Despite the mean low-density lipoprotein cholesterol level during follow-up being similar between the low- and high-EPA/AA groups, the mean triglyceride levels during follow-up were significantly higher in the low- than in the high-EPA/AA group. After 3 years of follow-up, the cumulative incidence of the primary end point in patients with low EPA/AA was 27.2% in the pitavastatin+ezetimibe group compared with 36.6% in the pitavastatin-monotherapy group (hazard ratio 0.69; 95% CI, 0.52-0.93; P=0.015). However, there was no effect of pitavastatin+ezetimibe therapy on the primary end point in patients with high EPA/AA (hazard ratio 0.92; 95% CI, 0.70-1.20; P=0.52). Conclusions Among acute coronary syndrome patients who have dyslipidemia and low EPA/AA ratio, adding ezetimibe to statin decreases the risk of cardiovascular events compared with statin monotherapy. Clinical Trial Registration URL: http://www.umin.ac.jp/ctr. Unique identifier: UMIN000002742.

Clinical characteristics of hospitalized heart failure patients with preserved, mid-range, and reduced ejection fractions in Japan.

AIMS: There are regional differences in the patient characteristics, management, and outcomes of hospitalized patients with heart failure (HF). The aim of this study was to evaluate the clinical characteristics and outcomes of Japanese patients who are hospitalized with HF on the basis of the left ventricular ejection fraction (LVEF) stratum. METHODS AND RESULTS: We retrospectively conducted a multicentre cohort study of 1245 hospitalized patients with decompensated HF between 2013 and 2014. Of these patients, 36% had an LVEF < 40% [HF with reduced ejection fraction (HFrEF), median age 72 years, 71% male], 21% had an LVEF 40-49% [HF with mid-range EF (HFmrEF), 77 years, 56% male], and 43% had an LVEF ≥ 50% [HF with preserved EF (HFpEF), 81 years, 44% male]. The primary outcome was death from any cause, and the secondary outcomes were cardiac death and re-hospitalization due to worsened HF after hospital discharge. There were high proportions of non-ischaemic cardiomyopathy (32%) in HFrEF patients, coronary artery disease (44%) in HFmrEF patients, and valvular disease (39%) in HFpEF patients. The frequencies of intravenous diuretic and natriuretic peptide administration during hospitalization were 66% and 30%, respectively. The median hospital stay for the overall population was 19 days, and the length of stay was >7 days for >90% of patients. In-hospital mortality was 7%, but was not different among the LVEF groups (HFrEF 7%, HFmrEF 6%, and HFpEF 8%). After a median follow-up of 19 months (range, 3-26 months), 192 (17%) of the 1156 patients who were discharged alive died, and 534 (46%) were re-hospitalized after hospital discharge. There were no significant differences in mortality after hospital discharge among the three LVEF groups (HFrEF 18%, HFmrEF 16%, and HFpEF 16%). There were no differences in cardiac death or re-hospitalization due to worsened HF after hospital discharge among the LVEF groups (cardiac death: HFrEF 8%, HFmrEF 7%, and HFpEF 7%; re-hospitalization due to worsened HF: HFrEF 19%, HFmrEF 16%, and HFpEF 17%). Multivariable-adjusted analyses showed that the HFmrEF and HFrEF groups, compared with the HFpEF group, were not associated with an increased risk for in-hospital death or death after hospital discharge. Non-cardiac causes of death and re-hospitalization after hospital discharge accounted for 35% and 38%, respectively. CONCLUSIONS: Our results revealed different clinical characteristics but similar mortality rates in the HFrEF, HFmrEF, and HFpEF groups. The most common cause of death and re-hospitalization after hospital discharge was HF, but non-cardiac causes also contributed to their prognosis. Integrated management approaches will be required for HF patients.

Long-term events after physician-referred initial tests by myocardial perfusion imaging or computed tomography coronary angiography in patients with suspected coronary artery disease.

BACKGROUND: The effects of initial tests on long-term events have been unknown. PATIENTS AND METHODS: In this observational retrospective study, we analyzed the effects of initial noninvasive tests by myocardial perfusion imaging (MPI) and computed tomography angiography (CTA) on long-term major adverse cardiac events (MACEs) among patients with suspected coronary artery disease during a median follow-up of 8.1 years (interquartile range: 7.7-8.9). RESULTS: Sex difference in the rate of abnormal findings on initial tests was observed in both the MPI (female vs. male: 32.6 vs. 55.5%; P<0.0001) and CTA groups (30.6 vs. 47.9%; P<0.0001). Early revascularization in the MPI was significantly lower than that in the CTA (16 vs. 23%; P=0.0005). A total of 109 MACEs (39 of 1830 patients during the original follow-up period and 70 of 616 patients during the extended follow-up period) occurred: 77 MACEs (6.4%) in the MPI group and 32 (5.1%) in the CTA group (adjusted hazard ratio for MPI: 0.78; 95% confidence interval: 0.50-1.23; P=0.29). In the total cohort, the risk-adjusted MACE rate in the females was ∼50% of the males. CONCLUSION: The long-term MACE rates did not differ between physician-referred initial tests of MPI and CTA despite a higher frequency of early revascularization in the CTA group. In this extended cohort, female sex was associated with a lower rate of positive findings and a lower MACE rate compared with the male sex.

Efficacy of Statin Therapy in Inducing Coronary Plaque Regression in Patients with Low Baseline Cholesterol Levels.

AIM: The efficacy of statin therapy in inducing coronary plaque regression may depend on baseline cholesterol levels. We aimed to determine the efficacy of statin therapy in inducing coronary plaque regression in statin-naïve patients with low cholesterol levels using serial intravascular ultrasound (IVUS) data from the treatment with statin on atheroma regression evaluated by virtual histology IVUS (TRUTH) study. METHODS: The TRUTH study is a prospective, multicenter trial, comparing the efficacies of pitavastatin and pravastatin in coronary plaque regression in 164 patients. All patients were statin-naïve and received statin therapy only after study enrollment. The primary endpoint was the observation of coronary plaque progression, despite statin therapy. RESULTS: Serial IVUS data, at baseline and after an 8-month follow-up, were available for 119 patients. The patients were divided into three groups based on non-high-density lipoprotein cholesterol (HDL-C) levels-low: ≤140 mg/dl, n=38; moderate: 141-169 mg/dl, n=42; and high: ≥170 mg/dl, n=39. Coronary plaque progression was noted in the low cholesterol group, whereas plaque regression was noted in the moderate and high cholesterol groups [%Δplaque volume: 2.3±7.4 vs. －2.7± 10.7 vs. －3.2±7.5, p=0.004 (analysis of variance)]. After adjusting for all variables, a low non-HDL-C level (≤140 mg/dl) was identified as an independent predictor of coronary plaque progression [odds ratio, 3.7; 95% confidence interval, 1.5-9.1, p=0.004]. CONCLUSION: Serial IVUS data analysis indicated that statin therapy was less effective in inducing coronary plaque regression in patients with low cholesterol levels but more effective in those with high cholesterol levels at baseline.University Hospital Medical Information Network (UMIN) (UMIN ID: C000000311).

C-reactive protein and future cardiovascular events in statin-treated patients with angina pectoris: the extended TRUTH study.

AIM: The TRUTH trial demonstrated that 8-month statin therapy alters the composition of coronary artery plaque using virtual histology (VH)-intravascular ultrasound (IVUS). The extended TRUTH study was conducted to evaluate the relationship between changes in coronary atherosclerosis and mid-term clinical outcomes and identify the factors associated with cardiovascular events. METHODS: Of 164 patients with angina pectoris who participated in the TRUTH trial, 119 subjects with analyzable IVUS data at both enrollment and the 8-month follow-up were enrolled and observed for at least two years. The primary end point was the time to first occurrence of cardiovascular composite events, including cardiovascular death, nonfatal myocardial infarction, nonfatal cerebral infarction, unstable angina and ischemic-driven revascularization, except for target lesion revascularization. RESULTS: The frequency of reaching the primary end point was 13% (16/119), with a mean follow-up period of 41.9±9.4 months. Although plaque regression and changes in plaque composition were not associated with future cardiovascular events, the serum high-sensitivity C-reactive protein (hs-CRP) levels at the start of the extended TRUTH study were significantly higher in the event group than in the event-free group (1.43 mg/L vs. 0.58 mg/L, p=0.01). A multivariate logistic regression analysis showed that the hs-CRP level was an independent significant predictor of cardiovascular events (odds ratio: 1.69; 95% confidence interval: 1.14-2.50, p=0.01). CONCLUSIONS: Coronary artery plaque regression and changes in plaque composition during statin therapy do not predict future cardiovascular events in patients with angina pectoris. Instead, the serum hs-CRP level can be used as a predictor of cardiovascular events.

Comparison of effects of serum n-3 to n-6 polyunsaturated fatty acid ratios on coronary atherosclerosis in patients treated with pitavastatin or pravastatin undergoing percutaneous coronary intervention.

A low n-3 to n-6 polyunsaturated fatty acid (PUFA) ratio is associated with cardiovascular events. However, the effects of this ratio on coronary atherosclerosis have not been fully examined, particularly in patients treated with different types of statins. This study compared the effects of n-3 to n-6 PUFA ratios on coronary atherosclerosis in patients treated with pitavastatin and pravastatin. Coronary atherosclerosis in nonculprit lesions in the percutaneous coronary intervention vessel was evaluated using virtual histology intravascular ultrasound in 101 patients at the time of percutaneous coronary intervention and 8 months after statin therapy. Pitavastatin and pravastatin were used to treat 51 and 50 patients, respectively. Changes in the docosahexaenoic acid (DHA)/arachidonic acid (AA) and eicosapentaenoic acid+DHA/AA ratios were not correlated with the percentage change in plaque volume in the pitavastatin group, whereas the percentage change in plaque volume and the changes in the DHA/AA ratio (r = -0.404, p = 0.004) and eicosapentaenoic acid+DHA/AA ratio (r = -0.350, p = 0.01) in the pravastatin group showed significant negative correlations. Multivariate regression analysis showed that age (ß = 0.306, p = 0.02), the presence of diabetes mellitus (ß = 0.250, p = 0.048), and changes in the DHA/AA ratio (ß = -0.423, p = 0.001) were significant predictors of the percentage change in plaque volume in patients treated with pravastatin. In conclusion, decreases in n-3 to n-6 PUFA ratios are associated with progression in coronary atherosclerosis during pravastatin therapy but not during pitavastatin therapy.

Effects of serum n-3 to n-6 polyunsaturated fatty acids ratios on coronary atherosclerosis in statin-treated patients with coronary artery disease.

A low ratio of n-3 to n-6 polyunsaturated fatty acids has been associated with cardiovascular events. However, the effects of this ratio on coronary atherosclerosis have not been fully examined. The purpose of the present study was to evaluate the correlations between the n-3 to n-6 polyunsaturated fatty acid ratio and coronary atherosclerosis. Coronary atherosclerosis in nonculprit lesions in the percutaneous coronary intervention vessel was evaluated using virtual histology intravascular ultrasound in 101 patients at the time of percutaneous coronary intervention and 8 months after statin therapy. Forty-six patients (46%) showed atheroma progression and the remaining 55 patients (54%) showed atheroma regression at 8-month follow-up. Significant negative correlations were observed between percentage change in plaque volume and change in the eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio (r = -0.190, p = 0.05), docosahexaenoic acid (DHA)/AA ratio (r = -0.231, p = 0.02), and EPA+DHA/AA ratio (r = -0.240, p = 0.02). Furthermore, percentage change in the fibrous component volume was negatively and significantly correlated with change in the EPA/AA ratio (r = -0.206, p = 0.04) and EPA+DHA/AA ratio (r = -0.217, p = 0.03). Multivariate regression analysis showed that change in the EPA+DHA/AA ratio was a significant predictor of percentage change in plaque volume and fibrous component volume (ß = -0.221, p = 0.02, and ß = -0.200, p = 0.04, respectively). In conclusion, decreases in serum n-3 to n-6 polyunsaturated fatty acid ratios are associated with progression in coronary atherosclerosis evaluated using virtual histology intravascular ultrasound in statin-treated patients with coronary artery disease.

Comparison of change in coronary atherosclerosis in patients with stable versus unstable angina pectoris receiving statin therapy (from the Treatment With Statin on Atheroma Regression Evaluated by Intravascular Ultrasound With Virtual Histology [TRUTH] study).

Although statin-induced regression in coronary atherosclerosis seems to be greater in patients with acute coronary syndrome than in those with stable coronary artery disease, no reports have examined this. The purpose of the present study was to compare the changes in coronary atherosclerosis in patients with stable versus unstable angina pectoris (AP). The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology intravascular ultrasound, and analyzable intravascular ultrasound data were obtained from 119 patients (83 patients with stable AP and 36 with unstable AP). A significant decrease in plaque volume was observed in patients with unstable AP (-2.2%, p = 0.02) but not in patients with stable AP. A significant increase in the necrotic-core component (0.30 mm(3)/mm, p = 0.009) was observed only in patients with unstable AP. Significant positive correlations were observed between the percentage of change in platelet-activating factor acetylhydrolase and the percentage of change in plaque volume (r = 0.346, p = 0.05) in patients with unstable AP. No significant correlations were observed in patients with stable AP. Multivariate regression analyses showed that a reduction in platelet-activating factor acetylhydrolase was associated with regression in coronary atherosclerosis, particularly of the fibrous component (ß = 0.443, p = 0.003), in patients with unstable AP. In conclusion, regression of the coronary artery plaque volume was greater, although statin therapy did not halt the increases in plaque vulnerability, in patients with unstable AP compared to those with stable AP. A reduction in the serum platelet-activating factor acetylhydrolase level was associated with regression in coronary atherosclerosis, particularly the fibrous plaque volume, in patients with unstable AP.

Effects of statins on serum n-3 to n-6 polyunsaturated fatty acid ratios in patients with coronary artery disease.

BACKGROUND: A low n-3 to n-6 polyunsaturated fatty acids (PUFAs) ratio is reported to be associated with cardiovascular events. However, the effects of statins on this ratio have not been fully examined. METHODS: A total of 101 patients with coronary artery disease, who were not receiving lipid-lowering therapy were randomly assigned to receive either 4 mg/day of pitavastatin or 20 mg/day of pravastatin. Serum PUFA levels were measured at baseline and 8 months after treatment with statins. RESULTS: Pitavastatin was used to treat 51 patients and the remaining 50 patients were treated using pravastatin. A significant positive correlation was observed between the percent change in low-density lipoprotein cholesterol and that in dihomogamma-linolenic acid (r = .376, P = .007), arachidonic acid (AA; r = .316, P = .02), eicosapentaenoic acid (EPA; r = .408, P = .003), or docosahexaenoic acid (DHA; r = .270, P = .056) in the pitavastatin group. However, these correlations were not observed in the pravastatin group. The DHA/AA ratio decreased significantly in the pitavastatin group only (from 0.96 to 0.83, P = .0002) and the DHA/AA ratio was significantly lower in the pitavastatin group at 8 months (0.83 vs 0.96, P = .03). The EPA/AA ratio did not show significant changes in either group. CONCLUSIONS: Pitavastatin decreased the serum DHA/AA ratio, whereas pravastatin had no effect on this ratio. Neither pitavastatin nor pravastatin had an effect on the serum EPA/AA ratio in patients with coronary artery disease.