A randomized, prospective, double-blind, placebo-controlled trial of the effect of diltiazem gel on pain after hemorrhoidectomy.

BACKGROUND: Spasm of the internal anal sphincter is considered to be one of the causes of pain in anal diseases. We have evaluated the effects of topical diltiazem on postoperative pain after hemorrhoidectomy. METHODS: Sixty-two patients were randomly assigned to receive a 2 % diltiazem gel (n = 32) or a placebo gel (n = 30) after hemorrhoidectomy. Patients applied the gel to the anal region three times per day for 14 days. Pain both in the resting state and on defecation ranged from 0 to 10 on a numerical rating scale, and the number of prescribed loxoprofen tablets (Loxonin) were recorded and confirmed daily by telephone. Any morbidity during the follow-up period was recorded. RESULTS: Both pain scores during defecation and the number of analgesic tablets consumed tended to be lower in the diltiazem group, although they did not reach statistical significance (P = 0.09, P = 0.12, respectively). Total number of complications was significantly higher in the diltiazem group, but each incidence of complications, including itching sensation, headache, and dizziness was not statistically different. CONCLUSIONS: Perianal application of 2 % diltiazem gel after hemorrhoidectomy has the potential to reduce postoperative pain during defecation.

Quality of life in patients with chronic anal fissure after topical treatment with diltiazem.

AIM: To assess the physical and mental health of fissure patients before and after topical treatment with diltiazem. METHODS: Consecutive patients were enrolled prospectively into the study. Quality of life was measured with the short-forum 36 health survey (SF-36) before and after 6-wk treatment with diltiazem. Patients scored symptoms of pain, bleeding, and irritation using numeral rating scales at the initial and follow-up visits. Fissure healing was assessed and side effects were noted. RESULTS: Fissures healed in 21 of 30 (70%) patients. There were significant reductions in the scores of pain, bleeding, and irritation after 1 wk of treatment, respectively. Four patients experienced perianal itching and one patient reported headache. When measured at baseline, pain and irritation showed a negative impact on two of the eight subscales on the SF-36, respectively (bodily pain and social functioning for pain; vitality and mental health for irritation). Repeating the SF-36 showed an improvement in bodily pain (P = 0.001). Patients whose fissures healed reported an improvement in bodily pain, health-perception, vitality, and mental health (P < 0.05). CONCLUSION: Successful treatment of chronic anal fissure with topical diltiazem leads to improvement in health-related quality of life.

Prevalence of coronary heart disease in patients with aortic aneurysm and/or peripheral artery disease.

Although the presence of coronary heart disease (CHD) was the major determinant of perioperative mortality and long-term prognosis in patients with aortic aneurysm (AA) and peripheral artery disease (PAD), the prevalence and severity of CHD in patients with individual vascular diseases was unknown. Adenosine triphosphate-loading myocardial single-photon emission computed tomography therefore was performed in 788 patients with vascular diseases of the aorta and peripheral arteries, with AA in 500, PAD localized in the lower-limb arteries in 183, and combined AA and PAD in 105. Patients with known CHD, such as those with previous myocardial infarction or revascularization procedures, were excluded. Myocardial single-photon emission computed tomography was analyzed using a 20-segment model, and summed stress scores and summed difference scores were calculated. Stress-induced myocardial ischemia was defined as a summed difference score >or=2. The presence of myocardial ischemia was highest in patients with combined PAD and AA (73%), followed by PAD (55%; p = 0.005), and the lowest in patients with AA (37%; p <0.0001). Summed stress score was also the highest in patients with combined PAD and AA (11.6 +/- 9.9), followed by PAD (7.8 +/- 8.8; p <0.0001), and the lowest in patients with AA (4.0 +/- 6.2; p <0.0001 for both). Similarly, summed difference score was the highest in patients with combined PAD and AA (6.4 +/- 6.1), followed by PAD (4.4 +/- 5.7; p = 0.001) and AA (2.3 +/- 4.0; p <0.0001 for both). In conclusion, the prevalence of CHD in patients with PAD was >50%, and although myocardial ischemia was observed in only (1/3) of patients with AA, its prevalence not only doubled, but also indicated extensive myocardial ischemia when combined with PAD. Thus, cardiac evaluation was particularly important in patients with combined AA and PAD.

Important parameters in the detection of left main trunk disease using stress myocardial perfusion imaging.

OBJECTIVES: We sought noninvasively to diagnose left main trunk (LMT) disease using myocardial perfusion imaging (MPI). METHODS: Five hundred and eight patients with suspected coronary artery disease (CAD) underwent both stress MPI and coronary angiography. The extent and severity of perfusion abnormalities were assessed using a 20-segment model. In addition, perfusion defects in both left anterior descending and left circumflex arterial territories were defined as a left main (LM) pattern defect, and those in 3-coronary arterial territories as a 3-vessel pattern defect. RESULTS: In 42 patients with LMT disease, a summed stress score (19.4 ± 10.0 vs. 13.5 ± 10.0; p < 0.0001) and a summed rest score (12.1 ± 9.7 vs. 7.0 ± 7.8; p = 0.002) were greater than in 466 patients without LMT disease, while a summed difference score was similar (7.3 ± 7.7 vs. 6.5 ± 6.1; p = NS). The prevalence of an LM-pattern defect was low in both groups (12% vs. 8%; p = NS). However, a 3-vessel pattern defect (33% vs. 7%; p < 0.0001), lung uptake of radiotracers (38% vs. 11%; p < 0.0001), and transient ischemic dilation (31% vs. 13%; p = 0.003) were more frequently observed in patients with LMT disease than in those without. Logistic regression analysis showed that a 3-vessel pattern defect (OR=3.5, 95% CI = 1.4-8.8; p = 0.007), lung uptake of radiotracers (OR = 2.5, 95% CI = 1.1-5.7; p = 0.03), and previous myocardial infarction (MI) (OR = 2.4, 95% CI = 1.0-5.7; p = 0.05) were the most important parameters to detect LMT disease. After excluding 163 patients with previous MI, a repeat analysis revealed that lung uptake of radiotracers (OR = 8.2, 95% CI = 2.3-29.2; p = 0.001) and an LM-pattern defect (OR = 6.3, 95% CI = 1.4-27.2; p < 0.02) were independent predictors for LMT disease. CONCLUSION: In the identification of LMT disease, lung uptake of radiotracers was a single best parameter, which was independent of the presence or absence of previous MI.

The diagnostic utility of the Heston index in gated SPECT to detect multi-vessel coronary artery disease.

OBJECTIVES: Although the Heston index, derived left ventricular (LV) volumetric analysis, is reported to best represent transient LV dilation on non-gated single-photon emission computed tomography (SPECT), its diagnostic performance has not been proven to identify extensive coronary artery disease (CAD) as assessed by coronary angiogram. Accordingly, we sought to evaluate the diagnostic utility of Heston index to detect multi-vessel CAD. METHODS: Post-stress and resting electrocardiogram-gated 99mTc-sestamibi SPECT was performed in 223 patients with suspected or known CAD. All of the patients underwent coronary angiography within 3 months of gated SPECT. The summed stress, summed rest, and summed difference scores were calculated using a 20-segment model. The left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were calculated automatically with the QGS program. In addition, stress-to-rest ratios of EDV, ESV, and (ESVx5+EDV) were calculated; the latter was defined as Heston index. RESULTS: In the 104 patients with multi-vessel CAD, the summed stress score (17.5+/-10.0 vs. 11.7+/-9.2, p<0.001), the summed difference score (9.1+/-6.3 vs. 4.3+/-4.2, p<0.0001), the Heston index (1.17+/-0.15 vs. 1.02+/-0.13, p<0.0001), the stress-to-rest ratio of EDV (1.05+/-0.10 vs. 0.99+/-0.09; p<0.0001), and that of ESV (1.23+/-0.21 vs. 1.04+/-0.17; p<0.0001, respectively) were greater than in the 119 patients with one-vessel CAD or insignificant lesion. The best cut-off value was determined as 1.09 for Heston index, giving a sensitivity of 76%, specificity of 77% for detection of multi-vessel CAD. Multiple stepwise logistic regression analysis showed that Heston index >or =1.09, summed stress score > or =14, and summed difference score > or =9 were the independent predictors of detecting multi-vessel CAD, yielding a sensitivity of 76% and specificity of 77% (global chi 2, 88.8). CONCLUSIONS: The Heston index is simple and achieves higher diagnostic value in the detection of multi-vessel CAD, compared with conventional analysis alone.

Do eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia?: A preliminary study.

The present study was conducted to examine the effect of eicosapentaenoic acid supplements on pulse wave velocity (PWV) in patients with dyslipidemia as a prospective open-labeled study. Eicosapentaenoic acid supplements (1,800 mg/day) were prescribed to 40 patients, and diet therapy in consultation with a nutritionist was conducted in 44 patients as a control group. These interventions were continued for 12 months, and PWV and blood examinations were performed at the start and end of these interventions. PWV increased in the control group but not in the eicosapentaenoic acid group. After adjustment for age, gender, the initial PWV, and the changes in mean blood pressure during the study period, a general linear model univariate analysis post hoc comparison demonstrated that the change in PWV during the period of study was significantly larger in the control group (42 +/- 20 cm/s) than in the eicosapentaenoic acid group (-9 +/- 19 cm/s) (p<0.05). Thus, this preliminary study suggested that eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia. A further study with a larger number of subjects is proposed to confirm this beneficial effect of eicosapentaenoic acid supplements on arterial stiffness.

[Effects of acute administration of beraprost sodium on parameters related to atherosclerotic vascular damage in coronary artery disease].

OBJECTIVES: The present study was conducted to examine the effects of acute administration of prostacyclin derivatives on plasma levels of adhesion molecules, endothelial function, and pulse wave velocity in patients with coronary heart disease. METHODS: In 20 patients with coronary heart disease, plasma levels of vascular cell adhesion molecule-1, P-selectin, and beta-thromboglobulin, endothelial function, and pulse wave velocity were assessed before and after the cold pressor test. These assessments were performed again 2 hr after the oral administration of prostacyclin derivatives (beraprost sodium 40 micrograms) or placebo. Endothelial function was assessed by changes in forearm blood flow before and after reactive hyperemia. Pulse wave velocity was determined by the volume rendering method. RESULTS: Prostacyclin derivatives significantly improved endothelial function and decreased plasma beta-thromboglobulin level, but did not affect blood pressure and pulse wave velocity. Prostacyclin derivatives did not prevent the elevations of blood pressure and pulse wave velocity induced by the cold pressor test, but did prevent the elevations of P-selectin and beta-thromboglobulin induced by the cold pressor test. CONCLUSIONS: Prostacyclin derivatives improved endothelial function and prevented platelet activation induced by the cold pressor test. Prostacyclin apparently has an anti-atherogenic effect.

Brachial-ankle pulse wave velocity as a marker of atherosclerotic vascular damage and cardiovascular risk.

The measurement of brachial-ankle pulse wave velocity (baPWV) is simple and applicable for general population studies. The present study was conducted to evaluate the applicability of baPWV for screening cardiovascular risk as well as for use as a marker of the severity of atherosclerotic vascular damage in a general population. baPWV was measured in a cross-sectional study involving two cohorts constituting a total of 10,828 subjects who underwent annual health screening check up examinations (6,716 males and 4,112 females; age 30 to 74 years). The Framingham risk score and Pocock's score were obtained. Multivariate analysis demonstrated that baPWV was associated with both scores, independently from conventional atherosclerotic risk factors. The receiver-operator characteristic curve demonstrated that a baPWV of 14.0 m/s is useful for risk stratification by Framingham score and to discriminate patients with either stroke or coronary heart disease (n=143), but the likelihood ratios were less than 5.0. Logistic regression analysis demonstrated that a baPWV>14.0 m/s is an independent variable for the risk stratification by Framingham score and for the discrimination of patients with atherosclerotic cardiovascular disease. Thus, baPWV has potential as a new marker of cardiovascular risk and may be more useful than other conventional markers; in addition, baPWV is easy to obtain and serves as an indicator of either atherosclerotic cardiovascular risk or severity of atherosclerotic vascular damage; thus it is useful to screen the general population. While the discriminating powers are not sufficiently high, a cutoff value of 14.0 m/s serves to screen subjects, especially in middle-aged ones, of either gender.

Increased pulse wave velocity associated with reduced calcaneal quantitative osteo-sono index: possible relationship between atherosclerosis and osteopenia.

Although the associations between arterial calcification or advanced atherosclerosis and osteopenia have been well documented, it is not clear whether the one is the result of the other or they coprogress from the early stages through common mechanisms. Thus, we measured pulse wave velocity (PWV), which reflects earlier phase atherosclerosis, and osteo-sono assessment index (OSI), which correlates with bone mineral density, in 7865 Japanese subjects (4183 males and 3682 females, aged 50 +/- 12 yr) and analyzed their association. PWV was determined by the volume rendering method; OSI was measured by the calcaneal quantitative ultrasound method. We evaluated the influence of age, gender, menopausal state, and established atherosclerotic risk factors on this association. In a linear regression analysis, OSI negatively correlated with PWV in both genders, and this association was more prominent in females (r = -0.38, P < 0.01) than in males (r = -0.17, P < 0.01). In females, this relationship was stronger after the menopause. In a multivariate analysis, PWV was significantly associated with OSI independent of age and conventional atherosclerotic risk factors. In females, this association was independent from menopause. These results suggest that common or related mechanisms, which may be accelerated after menopause, control both atherosclerosis and osteoporosis from the early stages.

Influences of age and gender on results of noninvasive brachial-ankle pulse wave velocity measurement--a survey of 12517 subjects.

The present study was conducted to evaluate the influences of age and gender on the results of noninvasive brachial-ankle pulse wave velocity (baPWV). In 12517 subjects who had no medication and no history of cardiovascular diseases, multiple regression analysis demonstrated that age, blood pressure, body mass index, triglycerides, blood glucose, and uric acid were significant variables for baPWV in both genders. From this population, we extracted 7881 "healthy subjects" (4488 males and 3393 females, 25-87 years) without any of the atherogenic risk factors, and the results of baPWV were analyzed chronologically in 5-year age intervals. baPWV was lower in females than in males until age 60, and became similar in both genders over age 60. Multiple regression analysis demonstrated that not only the value of R(2) but also the coefficient of the effect of age on baPWV are larger in females than in males. In the estimation of the regression curve, the relationship between age and baPWV demonstrated a quadratic curve in both genders. Thus, aging influences baPWV, and its effect is more prominent in female. Menopause seems to be the crucial phenomenon to explain the augmented increase in arterial stiffness with aging in females.

Hepatitis C virus seropositivity, but not hepatitis B virus carrier or seropositivity, associated with increased pulse wave velocity.

Immune mechanisms have important roles in the pathogenesis of atherosclerosis. The present study was conducted to evaluate the association of pulse wave velocity (PWV) with either hepatitis C or B. In 7514 subjects, we determined the PWV, as well as the plasma levels of hepatitis B virus antigen and antibody and of hepatitis C virus antibody. The results of multiple regression analysis showed that seropositivity for hepatitis C virus was a significant variable for PWV independent from atherosclerotic risk factors. Thus, hepatitis C virus seropositivity was associated with increased PWV.

Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement.

The present study was conducted to evaluate the validity and reproducibility of noninvasive brachial-ankle pulse wave velocity (baPWV) measurements and to examine the alteration of baPWV in patients with coronary artery disease (CAD). Simultaneous recordings of baPWV by a simple, noninvasive method and aortic pulse wave velosity (PWV) using a catheter tip with pressure manometer were performed in 41 patients with CAD, vasospastic angina, or cardiomyopathy. In 32 subjects (15 controls and 17 patients with CAD), baPWV was recorded independently by two observers in a random manner. In 55 subjects (14 controls and 41 patients with CAD), baPWV was recorded twice by a single observer on different days. baPWV were compared among 172 patients with CAD (aged 62 +/- 8 years); 655 age-matched patients without CAD but with hypertension, diabetes mellitus, or dyslipidemia; and 595 age-matched healthy subjects without these risk factors. baPWV correlated well with aortic PWV (r=0.87, p<0.01). Pearson's correlation coefficients of interobserver and intraobserver reproducibility were r=0.98 and r=0.87, respectively. The corresponding coefficients of variation were 8.4% and 10.0%. baPWV were significantly higher in CAD patients than in non-CAD patients with risk factors, for both genders (p<0.01). In addition, baPWV were higher in non-CAD patients with risk factors than in healthy subjects without risk factors. Thus, the validity and reproducibility of baPWV measurements are considerably high, and this method seems to be an acceptable marker reflecting vascular damages. baPWV measured by this simple, noninvasive method is suitable for screening vascular damages in a large population.