Effects of Calcium-Channel Blocker Benidipine-Based Combination Therapy on Cardiac Events　- Subanalysis of the COPE Trial.

BACKGROUND: The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial was conducted to compare the effects of regimens combining the dihydropyridine calcium-channel blocker benidipine with each of 3 secondary agent types (an angiotensin-receptor blocker (ARB), a ß-blocker and a thiazide) in Japanese hypertensive outpatients who did not achieve target blood pressure (<140/90 mmHg) with benidipine 4 mg/day alone. The analysis included 3,293 patients (ARB, 1,110; ß-blocker, 1,089; thiazide, 1,094) with a median follow-up of 3.61 years. The main results of the COPE trial demonstrated that the incidences of hard cardiovascular composite endpoints and fatal or non-fatal strokes were significantly higher in the benidipine/ß-blocker group than in the benidipine/thiazide group.Methods and Results:We further evaluated the treatment effects on different cardiac events among the 3 benidipine-based regimens.We observed a total of 50 cardiac events, 4.2 per 1000 person-years. The incidences of total cardiac events and each cardiac event were similarly low among the 3 treatment groups. Unadjusted and multi-adjusted hazard ratios for total cardiac events showed no significant difference among the 3 treatment groups. CONCLUSIONS: This subanalysis of the COPE trial demonstrated that blood pressure-lowering regimens combining benidipine with an ARB, ß-blocker or thiazide diuretic were similarly effective for the prevention of cardiac events in Japanese hypertensive outpatients.

A bedtime dose of ARB was better than a morning dose in improving baroreflex sensitivity and urinary albumin excretion--the J-TOP study.

The hypothesis that the bedtime dosing of angiotensin receptor blocker (ARB) is superior to morning dose in improving baroreflex sensitivity (BRS) and urinary albumin/creatinine ratio (UACR) was tested in this study. Baroreflex sensitivity was measured at baseline and at 6th month (N = 109) and was found to increase in the bedtime-dose group (P = .004), but not in the morning-dose group. The correlations between the change in BRS and the change in UACR were insignificant in the morning-dose group (r = 0.17, P = .26), but were significant in the bedtime-dose group (r = -0.29, P = .04). In conclusion, the improvement of BRS could be one of the mechanisms by which bedtime dosing of ARB confers renal protection.

Intensive or standard blood pressure control in patients with a history of ischemic stroke: RESPECT post hoc analysis.

The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study and its pooled analysis showed that intensive blood pressure (BP) lowering reduced recurrent stroke risk by 22% in patients with a history of stroke. Here, we report the effect of intensive BP lowering on the risk of recurrent stroke subtypes in patients with a history of ischemic stroke. RESPECT was a randomized clinical trial among 1280 people with a history of cerebral infarction or intracerebral hemorrhage. Participants were assigned to the intensive blood pressure control group (blood pressure < 120/80 mmHg) or standard blood pressure control group (blood pressure < 140/90 mmHg). In this post hoc analysis, we analyzed 1074 patients with a history of cerebral infarction. The mean BP at baseline was 140.7/81.4 mmHg. Throughout the follow-up period, the mean BP was 133.4/77.5 (95% CI, 132.7-134.1/76.9-78.2) mmHg in the standard group and 126.7/74.1 (95% CI, 126.0-127.4/73.5-74.8) mmHg in the intensive group. During a mean follow-up of 3.9 years, 78 first recurrent strokes occurred. Intensive treatment tended to reduce overall annual stroke recurrence (1.74% in intensive vs. 2.17% in standard; P = 0.351 by log-rank test) and did not change the risk of ischemic stroke (1.74% vs. 1.75%, P = 0.999) but markedly reduced the risk of hemorrhagic stroke (0.00% vs. 0.39%, P = 0.005). Beneficial effects of intensive BP control were observed for the risk of hemorrhagic stroke in patients with a history of ischemic stroke. The findings of this study indicate the benefit of intensive BP control for patients with a history of ischemic stroke at high risk of hemorrhagic stroke.

Preventive effects of eicosapentaenoic acid on coronary artery disease in patients with peripheral artery disease.

BACKGROUND: The JELIS trial examined the preventive effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD) in hypercholesterolemia. Previous investigators have reported that patients with peripheral artery disease (PAD) have a poor prognosis due to the potential risk for CAD. We conducted a subanalysis to examine whether the incidence of CAD was high in patients with PAD and whether EPA prevented the occurrence of CAD. METHODS AND RESULTS: Of 18,645 the Japan EPA lipid intervention study (JELIS) patients, 223 had PAD (control group; complicated (n=77), newly diagnosed (n=29), EPA group; complicated (n=96), newly diagnosed (n=21)). We analyzed the incidence of major coronary events (MCE) in the 2 groups. Cox proportional hazard ratio adjusted for baseline risk factor levels was used to test differences between the 2 groups. The incidence of MCE in the control group was significantly higher in patients complicated with PAD and in those newly diagnosed with PAD than in patients without PAD (complicated: hazard ratio 1.97, P=0.039; newly diagnosed: hazard ratio 2.88, P=0.030). As for patients with PAD, the EPA group had a significantly lower MCE hazard ratio than the control group (hazard ratio 0.44, 95% confidence interval 0.19-0.97, P=0.041). CONCLUSIONS: Subanalysis of the JELIS trial demonstrated that in patients with PAD the incidence of CAD was higher than in controls, and that EPA markedly reduced the occurrence of CAD in those patients.

Influence of blood pressure on the effects of low-dose asprin in elderly patients with multiple atherosclerotic risks.

OBJECTIVE: We examined whether the efficacy of low-dose acetylsalicylic acid (aspirin) for primary prevention of cardiovascular events is influenced by blood pressure (BP) using data from patients aged 60-85 years with hypertension, dyslipidemia, and/or diabetes, but without cardiovascular disease of the Japanese Primary Prevention Project. METHODS: All patients had received aspirin (100 mg/day) or no aspirin. BP subgroups were defined as low (average SBP from the baseline to the year of the events <130 mmHg), moderate (≥130 and <140 mmHg), and high (≥140 mmHg). The mean duration of follow-up was 5.02 years. RESULTS: In hypertensive patients (n = 12 278) aspirin had no significant impact on the primary outcome of death from cardiovascular disease, nonfatal stroke, and nonfatal myocardial infarction. On the other hand, aspirin increased the incidence of serious extracranial hemorrhage [hazard ratio, 1.81; 95% confidence interval (CI), 1.18-2.77; P = 0.0064] and tended to increase hemorrhagic stroke (hazard ratio, 1.75; CI, 0.99-3.07; P = 0.053). Aspirin had no effect on the primary outcome in any of the BP subgroups, and was associated with increased hemorrhagic stroke in the high BP group (hazard ratio, 3.51; CI, 1.29-9.51; P = 0.014); serious extracranial hemorrhage was elevated or tended to elevate in the moderate (hazard ratio, 2.53; CI, 1.18-5.45; P = 0.017) and high (hazard ratio, 2.14; CI, 1.00-4.56; P = 0.050) BP groups. CONCLUSION: In aged Japanese hypertensive patients, these data demonstrated no overall benefit of low-dose aspirin therapy although treatment was associated with an elevated risk of hemorrhagic events.

Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.

BACKGROUND: Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease. We aimed to test the hypothesis that long-term use of eicosapentaenoic acid (EPA) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish. METHODS: 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999. Patients were randomly assigned to receive either 1800 mg of EPA daily with statin (EPA group; n=9326) or statin only (controls; n=9319) with a 5-year follow-up. The primary endpoint was any major coronary event, including sudden cardiac death, fatal and non-fatal myocardial infarction, and other non-fatal events including unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting. Analysis was by intention-to-treat. The study was registered at ClinicalTrials.gov, number NCT00231738. FINDINGS: At mean follow-up of 4.6 years, we detected the primary endpoint in 262 (2.8%) patients in the EPA group and 324 (3.5%) in controls-a 19% relative reduction in major coronary events (p=0.011). Post-treatment LDL cholesterol concentrations decreased 25%, from 4.7 mmol/L in both groups. Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events. Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group. Sudden cardiac death and coronary death did not differ between groups. In patients with a history of coronary artery disease who were given EPA treatment, major coronary events were reduced by 19% (secondary prevention subgroup: 158 [8.7%] in the EPA group vs 197 [10.7%] in the control group; p=0.048). In patients with no history of coronary artery disease, EPA treatment reduced major coronary events by 18%, but this finding was not significant (104 [1.4%] in the EPA group vs 127 [1.7%] in the control group; p=0.132). INTERPRETATION: EPA is a promising treatment for prevention of major coronary events, and especially non-fatal coronary events, in Japanese hypercholesterolaemic patients.

Changes in self-monitored pulse pressure correlate with improvements in B-type natriuretic Peptide and urinary albumin in treated hypertensive patients.

BACKGROUND: Pulse pressure (PP) is an independent marker of cardiovascular risk, even in treated hypertensive subjects, but is often little changed by antihypertensive treatment. We assessed the hypothesis that changes in PP during antihypertensive therapy correlate with changes in surrogate markers of target-organ damage. METHODS: We studied 540 treated hypertensive subjects whose home systolic blood pressure (SBP) was >/=135 mm Hg. They were followed for 6 months after allocation to either a control group or an added treatment group (doxazosin, 1 to 4 mg plus beta-blocker when needed). The changes in PP and various blood pressure (BP) measures, including mean BP (MP), SBP, and diastolic BP (DBP) during follow-up, were related to changes in plasma B-type natriuretic peptide (BNP) and the urine albumin-creatinine ratio (UAR). RESULTS: Although self-measured MP was significantly lowered in the added treatment group, PP was not changed overall, although some patients showed a decrease, and others showed an increase. In multivariable analyses, changes in both clinic and home PP were positively associated with changes in log BNP, such that increases in clinic and home PP were paralleled by corresponding increases in BNP. However, no such corresponding relationships were observed when home PP decreased. The change in home PP, but not clinic PP, was positively and linearly associated with the change in UAR. CONCLUSIONS: Changes in PP during antihypertensive treatment are important because PP may increase in some patients, in whom there are adverse changes in surrogate markers of target-organ damage. These changes of PP are best evaluated by home monitoring.

The differential effects of angiotensin II type 1 receptor blockers on microalbuminuria in relation to low-grade inflammation in metabolic hypertensive patients.

BACKGROUND: A dual angiotensin type 1 receptor blocker (ARB)/peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist telmisartan may be more useful for microalbuminuria reduction than ARBs with no PPARgamma agonistic action. We investigated whether there is a difference between the effects of telmisartan and valsartan with respect to microalbuminuria reduction, and the association with improvement of metabolic features or suppression of the inflammatory state. METHODS: Fifty-three patients who had metabolic syndrome and had been taking valsartan were recruited. All of these patients were randomly assigned to replace valsartan by telmisartan (telmisartan group; n = 30) or to keep taking valsartan (control group; n = 21). Various parameters were measured at baseline and 12 weeks after randomization. RESULTS: There were no significant changes in blood pressure (BP), glucose, and lipid parameters between baseline and 12 weeks after randomization in either group. There was a significant increase in high molecular weight adiponectin in the telmisartan group (4.6 v 5.0 microg/mL, P = .024), whereas there was no significant change in the control group. The reductions of microalbuminuria and high-sensitivity C-reactive protein (hs-CRP) were significant in the telmisartan group (28.1 v 18.9 mg/g.Cr and 0.77 v 0.60 mg/L, respectively, P = .001 and P = .022), whereas there was no significant change in the control group. The reductions of microalbuminuria and hs-CRP were significantly correlated with each other (gamma = 0.413, P = .003). CONCLUSIONS: The dual ARB/PPARgamma agonist telmisartan achieved more microalbuminuria reduction than an ARB with no PPARgamma agonistic action, possibly through suppression of the inflammatory state in metabolic hypertensive patients.

Masked nocturnal hypertension and target organ damage in hypertensives with well-controlled self-measured home blood pressure.

It has been reported that masked hypertension, a state in which patients show normal clinic blood pressure (BP) but elevated out-of-clinic BP by self-measured home BP, is a predictor of cardiovascular morbidity much like sustained hypertension. In addition, nocturnal BP is closely associated with cardiovascular disease. This might mean that ambulatory and self-measured home BP monitoring each provide independent information. We performed ambulatory BP monitoring, self-measured home BP monitoring, echocardiography and carotid ultrasonography in 165 community-dwelling subjects. We subclassified the patients according to the ambulatory and self-measured home BP levels as follows: in the masked nocturnal hypertension group, the self-measured home BP level was <135/85 mmHg and the ambulatory nocturnal BP level was >or=120/75 mmHg; in the normotensive group, the self-measured home BP level was <135/85 mmHg and the ambulatory nocturnal BP level was <120/75 mmHg. The intima-media thickness (IMT) and relative wall thickness (RWT) were greater in the masked nocturnal hypertension group than in the normotensive group (IMT: 0.76+/-0.20 vs. 0.64+/-0.14 mm, p<0.05; RWT: 0.50+/-0.14 vs. 0.41+/-0.10, p<0.05). Even in hypertensives with well-controlled self-measured home BP, elevated ambulatory nocturnal BP might promote target organ damage. We must rule out masked hypertension using self-measured home BP monitoring, and we might also need to rule out nocturnal masked hypertension using ambulatory BP monitoring.

Comparison of olmesartan combined with a calcium channel blocker or a diuretic in elderly hypertensive patients (COLM Study): safety and tolerability.

The cardiovascular effects of combined therapy with the angiotensin receptor blocker (olmesartan) and a dihydropyridine calcium channel blocker (CCB) or a diuretic were compared in high-risk elderly Japanese hypertensive patients by performing a randomized, open label, blinded-endpoint study of morbidity and mortality (the COLM study). Here we report the results obtained with respect to safety and tolerability. High-risk hypertensive patients aged 65-84 years were enrolled and were randomized to receive olmesartan combined with either a CCB (amlodipine or azelnidipine) or a low-dose diuretic for at least 3 years. The primary endpoint was a composite of fatal and non fatal cardiovascular events, whereas adverse events (AEs) and the percentage of patients who discontinued the allocated treatment were evaluated as secondary endpoints. A total of 5141 patients were randomized. Both combination regimens achieved a similar reduction of cardiovascular morbidity and mortality. The incidences of AEs, serious AEs, drug-related serious AEs and discontinuation due to serious AEs were lower in the olmesartan plus CCB group than in the olmesartan plus diuretic group. Serum levels of uric acid and creatinine were significantly higher in the olmesartan plus diuretic group than in the olmesartan plus CCB group. Olmesartan combined with a CCB was significantly superior to olmesartan plus a diuretic with regard to the frequency of AEs and discontinuation of treatment.

Comparison of valsartan and amlodipine on ambulatory and morning blood pressure in hypertensive patients.

BACKGROUND: Cardiovascular events occur most frequently in the morning. We aimed to study the effects of monotherapy with the long-acting angiotensin II receptor blocker valsartan compared with the long-acting calcium antagonist amlodipine on ambulatory and morning blood pressure (BP). METHODS: We performed ambulatory BP monitoring before and after once-daily dose of valsartan (valsartan group, n = 38) and amlodipine (amlodipine group, n = 38) therapy in 76 hypertensive patients. To achieve the target BP of < or =140/90 mm Hg, valsartan was titrated from 40 mg/day to 160 mg/day (mean dose 124 mg/day) and amlodipine was titrated from 2.5 mg/day to 10 mg/day (mean dose 6.4 mg/day). RESULTS: Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (P <.002). However, the antihypertensive effect of amlodipine was superior to that of valsartan in clinical SBP (-26 mm Hg v -13 mm Hg, P =.001) and 24-h SBP (-14 mm Hg v -7 mm Hg, P =.008). In addition, morning SBP was significantly reduced by amlodipine from 156 to 142 mm Hg (P <.001) but not by valsartan. Both agents reduced lowest night SBP to a similar extent (amlodipine 121 to 112 mm Hg, P <.001; valsartan 123 to 114 mm Hg, P <.002). Reduction in morning SBP surge (morning SBP minus lowest night SBP) was significantly greater in patients treated with amlodipine compared with those treated with valsartan (-6.1 mm Hg v +4.5 mm Hg, P <.02). CONCLUSIONS: Amlodipine monotherapy was more effective than valsartan monotherapy in controlling 24-h ambulatory BP and morning BP in hypertensive patients.

Effects of bedtime vs. morning administration of the long-acting lipophilic angiotensin-converting enzyme inhibitor trandolapril on morning blood pressure in hypertensive patients.

Cardiovascular events occur most frequently in the morning. To study the effects of the long-acting lipophilic angiotensin-converting enzyme (ACE) inhibitor trandolapril on morning blood pressure (BP), we performed ambulatory BP monitoring (ABPM) before and after administration of trandolapril just before going to bed (bedtime-administered group: n=17) or in the morning (morning-administered group: n=20) in 37 hypertensive patients. Both sets of ABPM data were available in 30 patients. The 24-h systolic BP (SBP) levels were significantly decreased by 7.2 mmHg in the morning-administered group (p=0.02) and by 5.2 mmHg in the bedtime-administered group (p=0.04). In the bedtime-administered group, prewaking SBP (the average of the 2-h SBP values just before waking) and morning SBP (the average of the 2-h SBP values just after waking) were significantly decreased by 11 mmHg (p=0.005) and by 8.4 mmHg (p=0.03), respectively. On the other hand, in the morning-administered group, the reduction of prewaking SBP (3.9 mmHg, n.s.) and morning SBP (6.6 mmHg, n.s.) did not reach the level of statistical significance. However, the differences in the reductions of prewaking and morning SBPs between the two groups were not statistically significant. There was no additional reduction of the nighttime lowest BP in either administration group. In conclusion, bedtime administration of the long-acting ACE inhibitor trandolapril seems to be a safe and effective means of controlling morning BP in hypertensive patients without an excessive fall in nocturnal BP.

Combination therapy for hypertension in patients with CKD: a subanalysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events trial.

The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial was a multicenter, randomized, three-arm comparative study (N=3293) undertaken to determine the optimal combination therapy, based on the occurrence of cardiovascular events in patients treated with an angiotensin II receptor blocker (ARB), a ß-blocker (BB) or a thiazide diuretic (TD) in addition to the calcium antagonist benidipine as baseline medication. This subanalysis was conducted to compare the efficacy of three combination therapies in a subset of 834 patients with chronic kidney disease (CKD) (287 patients treated with benidpine-ARB, 283 patients treated with benidipine-BB and 264 patients treated with benidipine-TD). The incidence of composite cardiovascular events as the primary end point did not differ among these three groups. The incidence of hard end points and cerebrovascular events among these groups did not differ either, although the incidence among all patients in the COPE trial was lower in the benidipine-TD group than in the benidipine-BB group. The incidence of new-onset diabetes mellitus was higher in the benidipine-TD group than in the benidipine-ARB group among patients with CKD. The estimated glomerular filtration rate (eGFR) was maintained even after 12 months of treatment in patients with a baseline eGFR <60 ml min(-1) per 1.73 m(2) regardless of the treatment group, although the eGFR decreased over time in all patients in the three groups. In conclusion, in patients with CKD, all of the tested combination therapies demonstrated comparable efficacy in terms of prevention of cardiovascular events as well as maintenance of eGFR.

Efficacy and safety of diuretics in combination with perindopril in hypertensive stroke patients: Results of the Japan Perindopril and Diuretics on Cerebrovascular Disease Study (J-PADOC).

AIMS: An international randomized controlled trial has shown that anti-hypertensive therapy using perindopril and indapamide significantly reduces the recurrence of stroke. To evaluate the efficacy and safety of diuretics given as add-on therapy to stroke patients, as needed, to perindopril, we conducted a prospective multicenter observational study. METHODS: A total of 3825 hypertensive patients with a history of stroke were enrolled. The patients received a two-step therapy, starting with perindopril alone, and those who failed to achieve the blood pressure target were subsequently given a diuretic. Each group was followed for 6 months. RESULTS: 62.8% of the patients achieved the blood pressure goal. The incidence of adverse events was significantly higher in the perindopril plus diuretic combination therapy group than in the perindopril monotherapy group. Although these results may reflect that severely hypertensive patients were selectively assigned to combination therapy, the observed differences were essentially elevated serum creatinine, triglycerides, blood urea nitrogen and uric acid, whereas no significant inter-group difference was noted in total cholesterol and blood glucose. CONCLUSIONS: If adequate care of compromised renal function is taken, perindopril plus diuretic combination therapy exerts potent hypotensive effects without posing significant safety problems in patients with a history of stroke.

Suppressive effect of EPA on the incidence of coronary events in hypercholesterolemia with impaired glucose metabolism: Sub-analysis of the Japan EPA Lipid Intervention Study (JELIS).

BACKGROUND: JELIS was a large-scale clinical trial that investigated the effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD). In this paper, the data of patients registered in JELIS were analysed to compare the incidence of CAD between patients with impaired glucose metabolism (IGM) and normoglycemic (NG) patients. The effect of EPA on the incidence of CAD in patients with IGM was also assessed. METHODS: The 18,645 hypercholesterolemic patients registered in JELIS were divided into two groups. One group consisted of patients with IGM (n=4565), which included the patients who had diabetes mellitus and patients who had a fasting plasma glucose of 110mg/dL or higher, either at the time of registration or after 6 months. The other group consisted of NG patients (n=14,080). CAD incidence of the two groups over the average 4.6-year follow-up period was compared, and the effect of EPA was assessed. RESULTS: Compared to NG patients, IGM patients had a significantly higher CAD hazard ratio (1.71 in the non-EPA group and 1.63 in the EPA group). The treatment with EPA resulted in a 22% decrease in the CAD incidence (P=0.048) in IGM patients and an 18% decrease (P=0.062) in NG patients. CONCLUSIONS: It was found that the CAD risk in IGM patients is higher than in NG patients, and that highly purified EPA is very effective in decreasing the incidence of CAD among Japanese IGM patients, even though the intake of fish is high.

Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS).

BACKGROUND: Japan EPA Lipid Intervention Study (JELIS) was a large-scale clinical trial examining the effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD) in hypercholesterolemic patients. Herein, we focused on risk factors other than low-density lipoprotein cholesterol (LDL-C) to investigate the effects of EPA on CAD among JELIS primary prevention cases. METHODS: Hypercholesterolemic patients on statin therapy but without evidence of CAD (n=14,981) were randomly assigned to an EPA group (n=7503) or a control group (n=7478). The relationships between incident CAD, the number of CAD risk factors (hypercholesterolemia; obesity; high triglyceride (TG) or low high-density lipoprotein cholesterol (HDL-C); diabetes; and hypertension) and EPA treatment were investigated. RESULTS: For the control and EPA groups combined, a higher number of risk factors was directly associated with an increased incidence of CAD. Incidence was lower for the EPA group than for the control group regardless of the numbers of risk factors. Compared to patients with normal serum TG and HDL-C levels, those with abnormal levels (TG >or=150 mg/dL; HDL-C <40 mg/dL) had significantly higher CAD hazard ratio (HR: 1.71; 95% CI: 1.11-2.64; P=0.014). In this higher risk group, EPA treatment suppressed the risk of CAD by 53% (HR: 0.47; 95% CI: 0.23-0.98; P=0.043). CONCLUSIONS: Multiple risk factors besides cholesterol are associated with markedly increased incidence of CAD. High TG with low HDL-C represents a particularly potent risk factor. EPA was effective in reducing the incidence of CAD events for patients with this dyslipidemic pattern, suggesting that EPA may be especially beneficial in patients who with abnormal TG and HDL-C levels.

Inhibition of the renin-angiotensin system: no effect on circulating macrophage colony-stimulating factor levels in acute myocardial infarction.

Macrophage colony-stimulating factor, which induces proliferation and differentiation, and activation of monocytes and macrophages, plays an important role in the vulnerability of atheromatous plaques as well as the formation of atherosclerotic lesions. We measured serum concentrations of macrophage colony-stimulating factor in patients with acute myocardial infarction and also investigated the effects of early administration of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker on circulating macrophage colony-stimulating factor levels in these patients. The patients were divided randomly into 3 therapeutic groups; perindopril, candesartan, and control (without perindopril and candesartan) groups, and the drugs were administered within 24 to 36 hours after the onset of acute myocardial infarction. Serum macrophage colony-stimulating factor concentrations in acute myocardial infarction patients at the time of admission were significantly higher than those in healthy control subjects. The macrophage colony-stimulating factor levels in the patients decreased gradually after admission, but remained significantly higher than those in control subjects for 14 days. There were no significant differences in serum macrophage colony-stimulating factor levels among the 3 therapeutic groups during this study period. In conclusion, circulating macrophage colony-stimulating factor levels are elevated during the course of acute myocardial infarction, and inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitor or angiotensin receptor blocker does not affect these levels.