Hirofumi Kawamata

Treatment of coronary spastic angina with a statin in addition to a calcium channel blocker: a pilot study.

Combined therapy with a statin and a calcium channel blocker, which can improve lipid metabolism and reduce oxidative stress, may attenuate coronary vasoconstriction in patients with coronary spastic angina (CSA). After 6 months of therapy with benidipine and pravastatin, an acetylcholine provocation test was performed a second time in 25 patients with CSA. The patients were divided into 2 groups according to whether the result of this second test was positive (n = 13) or negative (n = 12). The test was designated as positive when the intracoronary injection of acetylcholine induced angiographically demonstrable total or subtotal occlusion (positive-test group). In the negative-test group, significant decrease in the plasma levels of low-density lipoprotein (LDL) cholesterol (−20.7 ± 11.1%, P < 0.01 versus baseline) were observed along with a dramatic increase in the serum level of high-density lipoprotein (HDL) cholesterol (26.8 ± 13.2%, P < 0.01 versus baseline). Furthermore, a significant decrease of the malondialdehyde-modified low-density lipoprotein (MDA-LDL) level, a marker of oxidative stress, was also observed (-22.6 ± 14.1%, P < 0.01 versus baseline) in this group. In the positive-test group, however, no significant changes were found in any of the aforementioned parameters. The results showed that improvement of lipid metabolism, especially an increase of HDL cholesterol level and a reduction of MDA-LDL, may inhibit vascular contractility.

Association of plasma level of malondialdehyde-modified low-density lipoprotein with coronary plaque morphology in patients with coronary spastic angina: implication of acute coronary events.

BACKGROUND Focal vasospasm is reportedly involved in a high incidence of acute coronary syndrome (ACS) as compared with diffuse vasospasm. No adequate studies have been conducted on the mechanism underlying the higher incidence of ACS involving focal vasospasm than of those involving diffuse vasospasm in patients with coronary spastic angina. METHODS AND RESULTS Blood samples were collected from the aortic root (Ao) and the coronary sinus (CS) before provoking left coronary vasospasm using intracoronary administration of acetylcholine. After relief of vasospasm, volumetric analyses of vasospastic lesions were evaluated with 3-dimensional intravascular ultrasound in 64 patients. The percent plaque volume was more prominent in focal (n=31) than in diffuse vasospasm (n=33) (40.9+/-9.4 vs. 23.3+/-9.2%, p<0.0001). The Cs-Ao difference of malondialdehyde-modified low-density lipoprotein (MDA-LDL) level, as a marker of atherothrombosis, in focal vasospasm increased significantly as compared with diffuse vasospasm (6.9+/-6.7 vs. 1.2+/-5.7 U/L, p=0.001). In a multiple-logistic regression analysis with the traditional risk factors, the Cs-Ao difference of MDA-LDL level was a variable differing independently between the 2 types of vasospasm. CONCLUSIONS Higher MDA-LDL levels were observed in the coronary circulation in patients with focal vasospasm than in those with diffuse vasospasm. Under these conditions, the dramatically increased percent plaque volume in cases with focal vasoconstriction may play an important role in the development of acute coronary events.

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.

Efficacy of Calcium Channel Blocker in the Secondary Prevention of Myocardial Infarction

BACKGROUND Calcium channel blockers (CCBs) may have a positive influence on the long-term prognosis of Japanese patients with ischemic heart disease. METHODS AND RESULTS The effect of nifedipine-retard (NR) (n=202) compared with that of non-CCB treatment (n=92) on the secondary prevention of myocardial infarction (MI) was retrospectively investigated in patients who had survived acute MI between 1987 and 1996. The primary endpoint was the occurrence of cardiac death or non-fatal MI. The median follow-up was 6.3+/-2.4 years. The incidence of cardiac events was 8.9% in the NR group and 14.1% in the non-CCBs group (p=0.14, odds ratio (OR): 0.584, 95% confidence interval (CI): 0.286-1,193). However, subanalysis revealed that NR significantly reduced the incidence of cardiac events in patients aged less than 55 years (4.2 vs 18.2%, p=0.016, OR: 0.180, 95%CI: 0.045-0.721) and those who did not smoke (8.6 vs 16.4%, p=0.048, OR: 0.462, 95%CI: 0.203-0.999). CONCLUSION Although this was a retrospective analysis, it showed that NR did not cause an increase in the incidence of cardiac events in post-MI patients; it even prevented cardiac events, especially in those who were less than 55 years of age and in non-smokers, suggesting the potential usefulness of CCBs in the secondary prevention of MI in Japan.

Antihypertensive Efficacy of the Direct Renin Inhibitor Aliskiren as Add-on Therapy in Patients with Poorly Controlled Hypertension

OBJECTIVE A direct renin inhibitor, aliskiren, has a longer stable antihypertensive effect compared with other renin-angiotensin-aldosterone system (RAAS) inhibitors. METHODS This study was a 6-month, single-center, open trial conducted between December 2010 and November 2011 to assess the antihypertensive effect of adding aliskiren (300 mg) to the treatment of essential hypertension patients whose target blood pressure (BP) had not been achieved and to assess whether it was possible to reduce the amount of antihypertensive drugs used. RESULTS The results showed an overall improvement in the target BP achievement rate of 60% for clinic BP and 52% for home BP measurements (75 cases total). The mean number of drugs before treatment with aliskiren was 3.28±1.52, whereas at the end of the six months the mean number of drugs prescribed other than aliskiren was 2.85±1.72 (p<0.0001). Moreover, no worsening of the renal function was observed in patients with diabetes or chronic kidney disease (CKD) who were being treated with other RAAS inhibitors in combination to aliskiren. CONCLUSION These results showed that when aliskiren was added to the treatment of poorly controlled hypertension, the BP achievement rate increased, and it was possible to reduce the amount of antihypertensive drugs used in combination with aliskiren. Moreover, as a result of careful monitoring of the renal function or decreasing the amounts of drugs used in combination, no worsening of the renal function was observed even in the cases complicated by diabetes or CKD being treated with other RAAS inhibitors.