[Relationship between EPA or EPA/AA and arteriosclerosis in elderly patients over 80 years old].

AIM: Fish oil is associated with decreased arteriosclerosis, cardiovascular disease and the prevention of cellular aging. Most studies of n-3 PUFA (polyunsaturated fatty acid) have been conducted in patients under 80 years of age, and there are few studies of subjects ≥80 years of age. This study investigated the relationship between eicosapentaenoic acid (EPA) or arachidonic acid (AA) and arteriosclerosis in elderly patients ≥80 years of age. METHOD: We enrolled 150 patients ≥80 years of age (average, 85±4 years) not taking EPA that presented or were admitted to our hospital. Their EPA or AA levels were measured to investigate the relationship between EPA or EPA/AA and cardiovascular disease or cerebrovascular disease. In addition, we investigated whether the ratio of EPA/AA was associated with estimated glomerular filtration rate (eGFR). RESULTS: The mean EPA level was 55.9±34.5 µg/dL, the mean AA level was 145.1±45.4 µg/dL and the mean EPA/AA was 0.40±0.24 (mean±SD). There were no significant differences between the EPA/AA and EPA values in patients with cardiovascular disease and those in patients without cardiovascular disease. Moreover, there were no significant differences between the EPA/AA and EPA values in patients with cerebrovascular disease and those in patients without cerebrovascular disease. There were no statistically significant correlations between EPA/AA or EPA and eGFR. CONCLUSION: Individuals may achieve a peak value of EPA or EPA/AA in their 70s and there is little change in those levels in patients aged over 80. No relationship was identified between EPA/AA and arteriosclerosis in subjects aged over 80 compared with those under 80 years of age.

Hypertensive encephalopathy in patients with chronic renal failure caused by stopping antihypertensive agents: a report of two cases.

We herein report two cases of patients with chronic kidney disease who developed hypertensive encephalopathy, which occurred after a sudden discontinuance of antihypertensive agents. Both patients underwent care at our hospital after experiencing neurological abnormalities. In both patients, magnetic resonance imaging (MRI) revealed edema in the cerebral white matter and cortices, basal ganglia, brainstem, and cerebellum. Though recently the number of reports about hypertensive encephalopathy has decreased, we describe two case reports and also review the pertinent literature.

Comparison of the effect of lipophilic and hydrophilic statins on serum adiponectin levels in patients with mild hypertension and dyslipidemia: Kinki Adiponectin Interventional (KAI) Study.

The plasma level of adiponectin, which is known as an anti-atherogenic adipocytokine, correlates inversely with the progression of atherosclerosis. An increase in the serum adiponectin level has been reported after the administration of hydrophilic pravastatin, but not after the administration of lipophilic statins thus far. We investigated whether hydrophilic pravastatin acts distinctly from simvastatin, which has the highest lipophilicity, on the favorable effect on adiponectin in dyslipidemic patients. A total of 27 dyslipidemic patients with mild hypertension were enrolled in this study. The patients were initially treated with simvastatin 10 mg/day for six months or more (mean 7.1 months), and then were switched to pravastatin 20 mg/day. The serum adiponectin, cholesterol fractionated components, and C-reactive protein (CRP) were evaluated after six-month intervals. Switching from simvastatin to pravastatin caused little change in the low-density lipoprotein cholesterol levels (103 mg/dl to 104 mg/dl, p = 0.782) and blood pressure (133/70 mmHg to 132/69 mmHg), while the serum adiponectin level significantly increased (11.9 mug/ml to 13.1 mug/ml, p = 0.009, respectively), and the serum CRP significantly decreased (0.078 mg/dl to 0.062 mg/dl, p = 0.040, respectively). Hydrophilic pravastatin increased the serum adiponectin level and decreased the CRP after switching from lipophilic simvastatin in the absence of any difference in the low-density lipoprotein cholesterol level and blood pressure. It remains possible, however, that this difference was due not only to pharmacologic lipophilicity, but also to some other specific characteristics such as the formula of statins, the subject characteristics, race, body size, high-density lipoprotein cholesterol, etc.

Inhibition of nitrate tolerance without reducing vascular response during eccentric dosing of nitrates.

It has been reported that the nitrate tolerance related to continuous dosing of nitrates reduces drug efficacy, and therefore eccentric dosing of nitrates is recommended. In this study, we investigated the appearance of nitrate tolerance related to continuous dosing of nitrates and prevention of nitrate tolerance during eccentric dosing by comparing the grade of coronary dilatation after sublingual nitroglycerin. Of 26 patients with ischemic heart disease who underwent elective cardiac catheterization, 8 patients were continuously administered nitrates, 8 patients were eccentrically administered nitrates, and 10 patients were not treated. We compared the coronary response to sublingual nitroglycerin among the 3 groups. In a coronary vessel without significant stenosis, the coronary vessel area, coronary lumen area, and mean coronary blood flow velocity after sublingual nitroglycerin were measured using intravascular ultrasound (IVUS). In the continuous dosing group, the maximal rate of change in the vessel area after sublingual nitroglycerin was 105 +/- 1 (mean +/- SEM) %, significantly lower than those in the untreated group and the eccentric dosing group (114 +/- 2%, 114 +/- 2%) (p < 0.01, respectively). In conclusion, eccentric dosing of nitrates inhibited the appearance of nitrate tolerance without reducing vascular response.

Comparison of risk factors in acute myocardial infarction and unstable angina pectoris in patients < or =66 versus >66 years of age.

A prospective study was conducted of the differences in clinical characteristics between patients with acute myocardial infarction and those with unstable angina pectoris admitted to hospitals in the South-Osaka district of Japan. Gender and smoking were identified as discriminant risk factors for the incidence of acute myocardial infarction in patients < or =66 years with acute coronary syndromes; however, age alone affected the mode of presentation in older patients.

Eccentric dosing of nitrates does not increase cardiac events in patients with healed myocardial infarction.

This study was performed to investigate the risk of cardiac events by eccentric or continuous dosing of nitrates in patients with healed myocardial infarction. A total of 573 patients with healed myocardial infarction were assigned to one of two groups: a nitrate-treatment (n =239) and a nontreatment (n =334) group. The nitrate-treatment group was further subdivided into a group receiving eccentric dosing of nitrates (n =153) and a group receiving continuous dosing of nitrates (n =86). The mean observation period was 11.2+/-8.2 months. The cardiac events investigated were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, sudden death, worsening angina and rebound angina. Baseline characteristics were also compared among the three groups to determine any effects on outcome. Among the patients receiving eccentric or continuous dosing of nitrates, the rates of cardiac events were 12.7/1,000 person.year and 67.4/1,000 person.year, respectively, whereas the rate was 19.7/1,000 person.year in the nontreated patients. The incidence of cardiac events was significantly greater in patients receiving continuous dosing of nitrates than in the nontreated patients (p <0.05). Continuous dosing of nitrates thus increases cardiac events, and while eccentric dosing of nitrates does not increase them, it is also not effective at preventing them in patients with healed myocardial infarction.

Increased cardiac mortality in women compared with men in patients with acute myocardial infarction.

OBJECTIVE: It has been reported that women with acute myocardial infarction (AMI) have a higher short-term mortality rate than men, but the reason is not known. The profile in relation to age, gender and risk factors was evaluated to compare AMI and unstable angina pectoris (UAP). METHODS: Findings from 984 patients including 580 patients with AMI (129 women, 451 men) and 404 patients with UAP (131 women, 273 men) were analyzed by the South Osaka Acute Coronary Syndrome Study Group (SACS). The primary endpoint of the study was in-hospital death. The primary endpoints of interest (cardiac death) were fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. RESULTS: Cardiac death during hospitalization within 30 days in AMI was higher in women than in men (12.4% vs 6.7%, p < 0.05). On the other hand, in UAP there was no significant difference between women and men (1.5% vs 0.7%, NS). The incidence of cardiac death in AMI was significantly higher for patients 75 years old and older (19.0%) than for patients less than 55 years old (4.2%), 55-64 years old (3.5%) and 65-74 years old (4.7%) (p < 0.001, respectively). CONCLUSIONS: Cardiac death was higher for women compared with men in patients with AMI. The worse prognosis for the AMI women patients was likely to be derived from less performance of percutaneous coronary intervention, and a high incidence of severe myocardial infarction. Further research should be focused on the analysis of various clinical backgrounds.

Haziness on coronary angiogram after percutaneous transluminal coronary angioplasty evaluated with angioscopy.

Coronary angiograms obtained after percutaneous transluminal coronary angioplasty are often hazy due to uneven distribution of contrast medium at the angioplasty site, In this study, structural changes resulting in haziness after percutaneous transluminal coronary angioplasty were identified angioscopically. The affected coronary arteries of 35 patients who underwent successful percutaneous transluminal coronary angioplasty were examined with angioscopy. Coronary angioscopic examination of the sites subjected to percutaneous transluminal coronary angioplasty revealed large surface disruptions in 17 cases, small surface disruptions in four cases, and thrombi in 24 cases. Angiographic haziness was recognized in 24 of 35 patients after percutaneous transluminal coronary angioplasty. Haziness on angiography was more significant in patients who exhibited large surface disruption (88% vs 50%, p < 0.05), and was significantly greater in patients who exhibited white thrombus (100% vs 56%, p<0.05). Moreover, it appears that percutaneous transluminal coronary angioplasty-induced large surface disruption and white thrombus likely play an important role in increasing haziness.

Long-term, continuous treatment with both oral and transdermal nitrates increases cardiac events in healed myocardial infarction patients.

This study was performed to investigate the effects of continuous dosing of oral, transdermal (patch), and a combination of the two with nitrate treatments on cardiac events in patients with healed myocardial infarction. In total, 1,291 patients with healed myocardial infarction were assigned 2 groups: treatment with nitrates (n=713) or nontreatment (n=578). Nitrate treatment was subdivided into 3 groups: patch group (n=149), oral group (n=504), and combination group (n=60). The mean observation period was 17.4 +/- 21.1 months. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. Baseline characteristics were also compared among the 4 groups to determine any effects on outcome. Among the patients with patch, oral, and combination groups, cardiac events occurred 3.4%, 6.7%, 10.0%, respectively, whereas only 2.9% of the patients treated without nitrates had cardiac events. The incidence of cardiac events was significantly greater in patients with oral nitrates and combination groups compared to patients without nitrates (p<0.01, respectively). Continuous dosing of long-term treatment with both oral and transdermal nitrates increased cardiac events in healed myocardial infarction patients.

Efficacy of coronary angioplasty following conventional coronary thrombolysis in patients with acute myocardial infarction.

The efficacy of combined thrombolysis and angioplasty for the purpose of coronary reperfusion after acute myocardial infarction has been controversial. The present study was conducted, therefore, to evaluate the effects of angioplasty following administration of conventional thrombolytic agents on the long-term prognosis of acute myocardial infarction patients. A total of 409 patients admitted to the hospital within 12 hours of the onset of infarction between January 1990 and May 2001 were studied retrospectively. These included 151 patients treated with thrombolysis alone (group T), 73 patients treated with angioplasty alone (group A), and 35 patients treated with angioplasty after thrombolysis (group T&A). Group T&A had shorter intervals from onset to initial treatment than group A (3.0 hours vs 6.3 hours, p < 0.01), a higher reperfusion success rate than group T (91.4% vs 74.8%, p < 0.01), and more improved left ventricular wall motion than group A. One-year cardiac mortality rates tended to be higher in group T, which had a higher rate of unsuccessful reperfusion than groups T&A or A (8.1% vs 3.4% vs 3.5%). The frequencies of hemorrhagic complications were similar among the 3 groups. From these findings, we conclude that thrombolytic therapy with subsequent angioplasty is an effective strategy for achieving cardiac reperfusion following acute myocardial infarction.

Effects of increasing the dose of pravastatin on serum adiponectin level in Japanese mild hypercholesterolemic and hypertensive patients.

The plasma level of adiponectin (CAS 1070484-33-1), known as an anti-atherogenic adipocytokine, inversely correlates with the progression of atherosclerosis. The reported effects of statins on the serum level of adiponectin include significant increases in the adiponectin levels caused by pravastatin (CAS 81131-70-6). In this study, increasing the dosage of pravastatin was investigated to determine whether it had a clearly favorable effect on the adiponectin level in hypercholesterolemic patients. A total of 26 mild hypercholesterolemic and hypertensive patients were enrolled in this study. The patients were initially treated with pravastatin 10 mg/day for 6 months or more, and then increased to pravastatin 20 mg/day. Serum adiponectin, cholesterol fractionated components, and lipoprotein components were evaluated after 6 months. Increasing the dose of pravastatin from 10 to 20 mg/day caused the low-density lipoprotein cholesterol levels to decrease (from 130 to 104 mg/dL, p < 0.001), and thereafter the serum adiponectin levels, particularly the high-molecular-weight adiponectin levels significantly increased (from 10.9 to 12.6 microg/mL, p = 0.022; from 6.6 to 7.6 microg/mL, p = 0.022, respectively). Pravastatin increased the serum adiponectin level after increasing the dosage from 10 to 20 mg/day. It remains possible, however, that the difference was due not only to pharmacologic effects, but also to other specific characteristics such as the subject characteristics, viz.; race, body size, high-density lipoprotein cholesterol, etc.

Beta-blockers prevent cardiac events in Japanese patients with myocardial infarction.

BACKGROUND: Although the favorable effects of beta-blockers in the treatment of myocardial infarction (MI) have been repeatedly demonstrated in Western countries, administration of this drug has been limited in Japan. METHODS AND RESULTS: The study group of 1,896 patients with MI was retrospectively divided into 1,029 patients treated by beta-blockers and 867 not treated by beta-blockers, and the incidences of cardiac events, consisting of recurrent MI, death because of worsening heart failure, and sudden death, and cardiovascular events, comprising cardiac events and stroke, were compared in both groups. There were 45 cardiac events (4.4%, 30.1 patients/1,000 patients. year) among the beta-blocker group, which was significantly less than the 56 cardiac events (6.5%, 52.3 patients/1,000 patients. year) among the no-beta-blocker group (p<0.05). The total mortality was 92 (8.9%, 61.6 patients/1,000 patients. year) and 124 (14.3%, 115.8 patients/1,000 patients. year), respectively, and cardiac death occurred in 42 (4.1%, 28.1 patients/1,000 patients. year) and 53 (6.1%, 49.5 patients/1,000 patients. year), respectively, indicating that both these events occurred significantly less in the beta-blocker group (p<0.01 and p<0.05). CONCLUSIONS: Beta-blockers prevent cardiac events in Japanese patients with MI. However, a placebo-controlled, double-blind, multicenter, clinical trial conducted on a large scale in Japan would further contribute more precise information of the useful effects of beta-blockers.

A 7-day administration of tPA or heparin in the prevention of intimal hyperplasia following vascular injury in atherosclerotic rabbits.

The effects on intimal hyperplasia of tissue plasminogen activator (tPA) and heparin following vascular injury were investigated. A common iliac artery in 34 hereditary hypercholesterolemic rabbits was injured by three successive 60-second balloon inflations to a pressure of 6 atm. Thereafter, two groups were continuously infused with tPA for 7 days at rates of 2 mg/kg per 24 hours (tPA-H) or 0.6 mg/kg per 24 hours (tPA-L), and two groups received intraarterial infusions of 750 U/kg (heparin-H) or 150 U/kg (heparin-L) heparin, followed by 625 U/kg or 125 U/kg subcutaneously twice daily for the same period, respectively. Twenty-eight days after injury, the intimal areas of the tPA-H (0.07 +/- 0.13 mm2), tPA-L (0.11 +/- 0.08 mm2), heparin-H (0.17 +/- 0.08 mm2), and heparin-L (0.28 +/- 0.27 mm2) groups were all significantly (P < 0.01) smaller than the controls (0.57 +/- 0.23 mm2), as were the intimal/medial cross-sectional area ratios (0.10 +/- 0.14, 0.21 +/- 0.20, 0.28 +/- 0.10, and 0.50 +/- 0.54 vs 1.13 +/- 0.74, respectively). Thus, attenuation of platelet aggregation by tPA or heparin inhibited medial smooth muscle cell proliferation and intimal hyperplasia in balloon injured arteries.

Modification of treatment strategies over a period of 14 years has markedly reduced cardiac events among post-myocardial infarction patients.

Recent trends in the treatment of post-myocardial infarction (MI) patients and the factors accounting for the improvement in outcome are presented. A total of 6,602 post-MI patients (5,320 males, 1,282 females; 58.9 +/- 10.4 years of age) enrolled between 1986 and 1999 were followed up for an average of 12.6 +/- 16.3 months. The incidence of cardiac events, which included fatal and nonfatal recurrent MIs, sudden death and death by congestive heart failure, was highest (44.9 events/1,000 person year) in 1986-1987, but decreased steadily to 22.5 events/1,000 person year by 1997-1999 (Trend p<0.0001). This trend accompanied the increased use of coronary thrombolysis, percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery, increased prescription of antiplatelet agents (51.5%-83.4%), lipid-lowering agents (29.8%-52.6%) and angiotensin-converting enzyme inhibitors (5.3%-->41.0%), and reduced prescription of calcium antagonists (68.5%-41.0%) and nitrates (60.7%-->45.7%). These changes in treatment have led to a decreased incidence of angina pectoris, wall motion abnormalities and abnormal Q waves on electrocardiograms. The decline in the incidence of cardiac events among post-MI patients in the 14 years between 1986 and 1999 reflects implementation of new therapeutic modalities proven to be effective in clinical trials and in daily practice.

Pravastatin reduces the incidence of cardiac events among patients with myocardial infarction.

We retrospectively compared the incidence of cardiac events in myocardial infarction (MI) patients treated in our departments between 1990 and 1999 with pravastatin or without cholesterol-lowering agents. Our aim was to evaluate the efficacy of pravastatin in the secondary prevention of MI. Cardiac events--defined as fatal or nonfatal recurrent MI, sudden cardiac death, and death from congestive heart failure--occurred in 8 (2.2%) of 356 MI patients treated with pravastatin (17.1 cases/1.000 person x year) and in 39 (5.6%) of 700 MI patients not treated with cholesterol-lowering agents (54.3 cases/1000 person x year), which represented a significant decline among those taking pravastatin (P < 0.05, odds ratio: 0.39, 95% (CI: 0.18-0.84). Likewise, total mortality was significantly lower among patients treated with pravastatin (18 cases, 5.1%; 38.4 cases/1,000 person x year vs 77 cases, 11.0%; 107.2 cases/1,000 person x year, P < 0.01, odds ratio: 0.43, 95% CI: 0.25-0.73). Subgroup analysis revealed a significantly lower incidence or cardiac events in the pravastatin group for 6 of the items among 53 patient characteristics, and was lower but not significant for 45 items and was greater but not significant only for 2 items. Furthermore, multivariate analysis confirmed pravastatin to be a useful factor for preventing the occurrence of cardiac events in MI patients (P < 0.05, odds ratio: (0.44, 95% CI: 0.20-0.95), and Kaplan-Meier curves also showed pravastatin to significantly reduce the incidence of both cardiac events and total mortality. These findings are consistent with those previously reported by several large-scale clinical trials carried out in Western countries, and demonstrate that pravastatin is useful for secondary prevention of MI in Japanese patients.