Plasma alpha-tocopherol and coronary endothelium-dependent vasodilator function.

BACKGROUND: In the presence of atherosclerosis, the coronary endothelial vasomotor response to acetylcholine is frequently abnormal but is variable between patients. We tested the hypothesis that the plasma concentration of alpha-tocopherol is associated with the preservation of nitric oxide-mediated endothelium-dependent vasomotion. METHODS AND RESULTS: We studied 15 men and 6 women (mean age 61+/-10 years) at coronary angiography who were not taking vitamin supplements. Coronary endothelium-dependent and -independent vasomotion was assessed by intracoronary infusions of acetylcholine and nitroglycerin. The vasomotor responses were compared with the plasma concentration of alpha-tocopherol and the plasma alpha-tocopherol concentration relative to total lipid (total cholesterol plus triglycerides). The mean plasma alpha-tocopherol was 25.6+/-6.1 micromol/L, total cholesterol 193+/-27 mg/dL, triglycerides 115+/-66 mg/dL, and alpha-tocopherol to total lipid 4. 2+/-0.9 micromol. L(-1). (mmol/L)(-1). The mean vasomotor response to acetylcholine was -1% (range -33% to 28%) and to nitroglycerin 22% (range 0% to 54%). Plasma alpha-tocopherol was significantly correlated with the acetylcholine response (r=0.49, P<0.05) but not the nitroglycerin response (r=0.13, P>0.05). The acetylcholine response remained significant after adjustment for other potential sources of oxidant stress (total cholesterol, diabetes mellitus, smoking, angina class) (P<0.01). The relative concentration of alpha-tocopherol to total lipid was not related to endothelial function (r=0.24, P=0.3, n=20). CONCLUSIONS: alpha-Tocopherol may preserve endothelial vasomotor function in patients with coronary atherosclerosis. This effect may be related primarily to the action of alpha-tocopherol in the vascular wall. Further studies that assess the impact of alpha-tocopherol supplementation as therapy of endothelial dysfunction are justified.

Role of endothelin-1 in the active constriction of human atherosclerotic coronary arteries.

BACKGROUND: Atherosclerotic coronary arteries are prone to constriction but the underlying causes are incompletely understood. We tested the hypothesis that endothelin-1 (ET-1), a potent vasoconstrictor, contributes to the heightened tone of atherosclerotic human coronary arteries. METHODS AND RESULTS: In 8 patients with coronary artery disease (CAD) and 8 patients with angiographically smooth coronary arteries (normal), we infused BQ-123, an antagonist of the ET(A) receptor, into a major coronary artery (infused artery) at 40 nmol/min for 60 minutes. The infused artery in the CAD patients contained a >50% stenosis. Using quantitative angiography, we compared the dilation of the infused artery with another, noninfused coronary artery. To estimate the magnitude of the contribution of ET-1 to coronary tone, we compared the dilation to BQ-123 with that elicited by intracoronary nitroglycerin (200 microgram). BQ-123 induced significant dilation in the normal arteries (7.3% at 60 minutes, P<0.001 versus noninfused arteries) and a greater dilation in the CAD arteries (16.3% at 60 minutes, P<0.001 versus infused normal arteries). The dilation at stenoses was particularly pronounced (21.6% at 60 minutes, P<0.001 versus infused CAD arteries). Compared with the dilation from nitroglycerin, ET-1 contributed to 39% of the coronary tone in normal arteries, 74% of tone in CAD arteries, and 106% of tone at stenoses (P<0.01). CONCLUSIONS: ET-1 accounts for nearly all the resting tone in atherosclerotic coronary arteries, especially at stenoses. Inhibitors of ET-1, by relieving constriction, may significantly lessen the hemodynamic significance of coronary stenoses and thereby reduce myocardial ischemia.

Risk of primary and recurrent acute myocardial infarction from lipoprotein(a) in men and women.

OBJECTIVES: This study sought to examine whether lipoprotein(a) concentrations were risk factors for a first acute and recurrent myocardial infarction. BACKGROUND: There is conflicting evidence concerning the risk of acute myocardial infarction from lipoprotein(a). No studies have examined the risk of recurrent acute myocardial infarction from lipoprotein(a), and few have addressed the risk in women. METHODS: This was a population-based case-control study of 893 men and women 35 to 69 years old participating in the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Project in Newcastle, Australia in 1993 to 1994. Case and control patients were classified into those with and without a previous myocardial infarction, and median lipoprotein(a) concentrations were compared after adjusting for other variables. Quintiles of lipoprotein(a) concentration were also examined. RESULTS: Compared with control subjects without a previous myocardial infarction, median lipoprotein(a) concentrations increased from case patients with a first myocardial infarction (15 mg/liter higher, 95% confidence interval [CI] -36 to 60) to control patients with a previous myocardial infarction (159 mg/ liter higher, 95% CI 40 to 278) and case patients with a previous myocardial infarction (60 mg/liter higher, 95% CI -16 to 136, p < 0.01, test for trend). Women had significantly higher lipoprotein(a) concentrations than men (median 71 mg/liter higher, 95% CI 23 to 118). The highest quintile of lipoprotein(a) (>550 mg/liter) was a significant risk factor for a first acute myocardial infarction (odds ratio [OR] 1.77, 95% CI 1.03 to 3.03); but in those with a previous myocardial infarction, the highest quintile was not associated with recurrent myocardial infarction (OR 0.84, 95% CI 0.30 to 2.37). CONCLUSIONS: High lipoprotein(a) concentrations may be a marker of vascular or tissue injury or may be associated with other genetic or environmental factors that cause acute myocardial infarction. Currently, lipoprotein(a) measurement cannot be recommended for assessment of risk for acute myocardial infarction.

Effect of transient abrupt vessel closure during otherwise successful angioplasty for unstable angina on clinical outcome at six months. Hirulog Angioplasty Study Investigators.

OBJECTIVES: The objective of this study was to identify predictors of major adverse cardiac events after successful coronary angioplasty. BACKGROUND: The acute complications of angioplasty are related to baseline clinical and angiographic variables, and early complications adversely affect long-term outcome. However, the predictors of enduring success after uncomplicated angioplasty are less well defined. METHODS: Of 4,098 patients undergoing angioplasty in the Hirulog Angioplasty Study, 3,899 (95%) had a successful procedure without in-hospital death, emergent bypass surgery or clinical evidence of myocardial infarction. Baseline and procedural variables for these 3,899 patients were examined. RESULTS: Major adverse cardiac events occurred in 22% of the patients with initially successful procedures at 6 months: death in 1%, myocardial infarction in 2% and repeat revascularization in 21%. Univariable predictors of increased events included successful salvage from abrupt vessel closure (p < 0.001), emergency stenting (p < 0.001), multilesion angioplasty (p < 0.001), diabetes (p=0.02), target lesion in the left anterior descending artery (p=0.02), unstable angina (p=0.03) and smaller final luminal diameter (p=0.04). There was a trend toward increased events among patients with prior angioplasty (p=0.08), but asymptomatic elevation of the creatine kinase was not predictive (p=0.5). In a multivariable model, abrupt vessel closure was the strongest independent predictor of major adverse cardiac events at 6 months (p < 0.001; odds ratio [95% confidence interval]=3.6 [2.5 to 5.1]), while multivessel angioplasty, target lesion in the left anterior descending artery and diabetes also remained independent predictors (all p < or = 0.02). CONCLUSIONS: This analysis suggests that "uncomplicated" abrupt vessel closure is a powerful predictor of adverse clinical outcome following successful angioplasty. Improved techniques to reduce abrupt closure during angioplasty are thus urgently needed, and patients who experience "uncomplicated" closure require closer surveillance during follow-up.

Relationship of clinical presentation and calcification of culprit coronary artery stenoses.

Coronary artery calcification is increased in the presence of atherosclerosis. However, there is great variability in the calcification of individual coronary stenoses, and the clinical significance of this finding remains unknown. We tested the hypothesis that culprit lesions associated with myocardial infarction or unstable angina are less calcified than are stenoses associated with stable angina. The study consisted of 78 patients who underwent intravascular ultrasound imaging of culprit stenoses after the placement of a stent. Seventeen patients presented with stable angina; 43, with unstable angina; and 18, with myocardial infarction. The extent of coronary calcification was measured by the angle of its arc and was quantified with a computer-based protractor. The arc of calcium was measured in the stented area at the point of maximal calcification and also as an average of the calcification found at proximal, middle, and distal stent segments. The maximal arc of calcium decreased progressively from patients with stable angina (91+/-10 degrees ) to those with unstable angina (59+/-8 degrees ) and to those with myocardial infarction (49+/-11 degrees, P=0.014). Similarly, the average arc of calcium was greatest (32+/-7 degrees ) in patients with stable angina, less (15+/-4 degrees ) in patients with unstable angina, and least (10+/-5 degrees ) in patients with acute myocardial infarction (P=0.014). These associations remained significant after adjustment for other factors that potentially affect arterial calcification. Acute coronary syndromes are associated with a relative lack of calcium in the culprit stenoses compared with stenoses of patients with stable angina. These findings have implications for the understanding of the biology of acute coronary syndromes as well as for the identification of coronary stenoses by methods that rely solely on the presence of calcium.

Role of endothelial dysfunction in coronary artery disease and implications for therapy.

Atherosclerosis is a complex process that is characterized by the accumulation of modified low-density lipoprotein (LDL), local inflammatory and immune responses, and reduced nitric oxide bioavailability within the arterial wall. These cellular changes lead to endothelial vasomotor dysfunction, plaque instability, and the development of clinical events such as stable angina and the acute coronary syndromes. The vascular endothelium plays a critical role in modulating both the inflammatory response and vasomotor abnormalities that occur in those with coronary artery disease or risk factors for disease. In these conditions, endothelial cells are activated by cytokines to express cellular adhesion molecules that facilitate the adhesion of leukocytes to the endothelium, and their migration into the subintimal space. Cytokines stimulate inflammatory and smooth muscle cells in the intima to produce degradative enzymes, including metalloproteinases that can weaken the fibrous cap of atherosclerotic lesions and make them vulnerable to rupture. Endothelial cells also regulate vascular tone by the synthesis of nitric oxide. Atherosclerosis and other conventional risk factors for coronary artery disease are associated with endothelial vasodilator dysfunction in the coronary epicardial and resistance vessels, which likely contributes to myocardial ischemia. Several studies have demonstrated that lowering serum total and LDL cholesterol reverses endothelial vasomotor dysfunction, reduces myocardial ischemia, and lowers the risk of the acute coronary syndromes or need for revascularization. Improving endothelial function, for example, by lowering blood cholesterol should now be regarded as a goal of therapy in the treatment of coronary artery disease.

Relation between endothelial dysfunction and the acute coronary syndrome: implications for therapy.

Endothelial dysfunction is present in patients with atherosclerosis, even in the early stages of disease, before plaque formation. Thus, it is a useful marker for early cardiovascular disease. In recent studies, statin therapy has been shown to improve endothelial function by increasing production of nitric oxide, a key vasodilator, from the endothelium. The improvement in endothelial function occurs by lipid lowering as well as by nonlipid mechanisms. These effects begin early in treatment, supporting prompt initiation of statin therapy. The functional benefits that result from an improvement in endothelial dysfunction include enhanced myocardial perfusion, reduced duration and burden of transient myocardial ischemia, and reduced angina pectoris. As dysfunctional endothelium encourages the recruitment of leukocytes into the arterial wall and thereby predisposes to inflammation and plaque disruption, improvement in endothelial function leads to plaque stabilization.

Usefulness of intravascular ultrasound in preventing stenting of hazy areas adjacent to coronary stents and its support of support spot-stenting.

The uncertain significance of hazy areas at the margins of coronary stents may lead to further, at times unnecessary, stenting. However, the risk of restenosis increases substantially when additional stents are deployed. We used intravascular ultrasound (IVUS) to identify the causes of hazy segments adjacent to stents. We identified 13 cases with hazy regions adjacent to coronary stents and 20 controls without hazy regions matched by age, gender, and vessel stented. Hazy regions were defined from the angiogram as reduced contrast density without a clearly defined intimal tear, dissection, thrombus, or stenosis (> 50%). IVUS images were obtained from the reference, stent, and hazy and control regions adjacent to the stent. Computerized planimetery was used to measure the vessel, lumen, and plaque cross-sectional areas (CSAs), the maximum arc of calcium, and the eccentricity ratio (minimum:maximum lumen diameter). There were no significant differences between hazy and control segments in the vessel, lumen, and plaque CSAs. All lumen CSAs were >4.0 mm2. Compared with control regions, the hazy regions had calcified plaque more often (69% vs 25%; odds ratio [OR] 6.75, 95% confidence intervals [CI] 1.82 to 25.0]) and more frequent intimal tears (23% vs 0%, OR 6.67, 95% CI 1.98 to 35.0). Haziness was particularly associated with calcified plaque and eccentric lumen (p = 0.037). Thus, haziness at the margins of coronary stents is often caused by calcified plaque. IVUS can differentiate calcified plaques from intimal tears and thereby obviate unnecessary stenting.

Cell dysfunction in atherosclerosis and the ischemic manifestations of coronary artery disease.

Many of the cellular mechanisms and dysfunctions that underlie atherosclerotic plaque formation have been identified, including adverse interactions between atherogenic lipids and the arterial endothelium, loss of endothelium-dependent dilation, accumulation of inflammatory cells and mediators of inflammation in the intima of the arteries, and a decline in anticoagulant defenses. Several studies have shown that these mechanisms, which appear to be active throughout the pathogenesis and progression of atherosclerosis, are reversible within days, weeks, or months with effective lipid-lowering therapy. In addition, the findings of large-scale trials of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors suggest that the rapid improvement observed in trial participants is attributable to a reversal of endothelial and vascular wall dysfunctions rather than to a reduction in plaque size. The accumulated evidence indicates that improved endothelial function can benefit patients who have angina pectoris and/or are at risk for myocardial infarction. Current understanding of the cellular mechanisms of atherogenesis also suggests avenues of future research to refine treatment approaches and further improve outcomes for patients with coronary artery disease.

Chlamydia pneumoniae infection is frequent but not associated with coronary arteriosclerosis in cardiac transplant recipients.

We sought to explore the relation between Chlamydia pneumoniae, cytomegalovirus (CMV), and cardiac transplant-associated arteriosclerosis. Serologic evidence of past Chlamydia pneumoniae infection was investigated in 3 patient groups at the time of cardiac catheterization: cardiac transplant recipients (n=49), patients having coronary artery bypass grafting (CABG) (n=39), and a control group free of angiographic coronary artery disease (n=21). High Chlamydia pneumoniae immunoglobulin G titers (> or =1:160) were more frequently observed in cardiac transplant recipients (odds ratio[OR] 13.7; 95% confidence intervals [CI] 1.6 to 117.4, p <0.05) and CABG patients (OR 21.7; 95% CI 1.6 to 287.0, p <0.05) than in controls. However, high Chlamydia pneumoniae titers did not distinguish between cardiac transplant recipients with or without angiographic transplant-associated arteriosclerosis or CABG patients with or without bypass vein graft disease. Furthermore, there was no significant relation between elevated Chlamydia pneumoniae titers and the presence or progression of transplant-associated arteriosclerosis in the subgroup of patients who were also CMV positive. Yet, analysis of the same angiograms demonstrated an association between CMV infection and the recent progression of transplant-associated arteriosclerosis. Thus, patients with cardiac transplantation have evidence of past Chlamydia pneumoniae and CMV infection but Chlamydia pneumoniae does not appear to have an independent role or synergistic relation to CMV in the development of transplant-associated arteriosclerosis.

Lipid-lowering therapy after coronary revascularization.

Atherosclerosis is often asymptomatic, unrecognized, and undertreated. Lumen irregularities are important angiographic findings that should be addressed aggressively through risk factor modification, medical therapy, and coronary revascularization. Both angiographic and clinical benefits have been demonstrated with lipid reduction therapy in randomized clinical trials. Coronary revascularization is indicated for symptom relief and improvement in quality of life in patients with acute coronary syndromes at "intermediate" and "high" risk of subsequent death or myocardial infarction. In patients following percutaneous coronary intervention (PCI), future cardiac events may be related to lumen renarrowing or to progression of atherosclerotic disease at sites remote from the site of coronary revascularization. The time course of restenosis is relatively self-limiting, generally occurring within 6-12 months after the procedure. Clinical events occurring > 1 year after PCI generally relate to new lesions or progression of existing atherosclerotic disease. Patients with diabetes mellitus may be at higher risk for late coronary events than nondiabetic patients. In post-coronary artery bypass surgery (CABG) patients, the majority of late events relate to degeneration of saphenous vein grafts. Lipid lowering therapy after coronary revascularization has been shown to prevent clinical events related to plaque instability and inhibit progression of saphenous vein graft disease. Thus, there are 2 goals in management of patients with symptomatic coronary artery disease: (1) to relieve the flow-limiting stenosis, and (2) to prevent future clinical events with aggressive lipid lowering and modification of other risk factors. Patients, specialists, and primary care physicians each need to take accountability for this risk-factor modification.

Effect of wetting the mouth on aortic blood pressure just before taking sublingual nitrates.

The absorption of sublingual nitrate tablets is sometimes variable. We performed a randomized controlled trial to determine whether wetting the mouth improved the decrease in aortic systolic blood pressure (BP) from sublingual nitrate tablet or spray. The 100 patients undergoing routine diagnostic cardiac catheterization were allocated to control (no nitrate), 0.3 mg sublingual nitrate tablet, 0.4 mg sublingual nitrate spray, water + 0.3 mg sublingual nitrate tablet, or water + 0.4 mg sublingual nitrate spray. Aortic systolic and diastolic BP were recorded using a fluid-filled catheter and measured off-line blind to the treatment group. Compared with control subjects, there were significant decreases in aortic systolic BP with both nitrate preparations (tablet = -7.1 mm Hg, 95% confidence interval [CI] = -12.5 to -1.6 mm Hg; spray = -8.0 mm Hg, 95% CI = -13.4 to -2.5 mm Hg). On average, water significantly increased the fall in aortic systolic BP with nitrate tablets (-5.5 mm Hg, 95% CI = -10.9 to -0.1 mm Hg, p = 0.044) but did not significantly enhance the effect of nitrate spray (-2.8 mm Hg, 95% CI = -8.3 to 2.6 mm Hg). Water significantly increased the fall in aortic diastolic BP with tablets only (-2.9 mm Hg, 95% CI = -5.5 to -0.2), and had no significant effect on heart rate. Water had a consistently larger influence on the hemodynamic effects of nitrate tablets than on the effects of nitrate spray. Patients with a dry mouth will have an increased effect from sublingual nitrate tablets if they wet their mouth before using sublingual nitrate tablets. Water does not appear to assist in the action of sublingual spray.

The validity of estimating heart disease reduction from a Framingham logistic equation.

We compared two ways in which a logistic equation could be used to estimate the number of heart disease events prevented after lowering blood cholesterol levels. Men were selected from an Australian population survey who met the entry criteria of the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). The numbers of heart disease events expected over 7.4 years were calculated from the logistic equation after reducing the men's blood cholesterol by the amounts achieved in the LRC-CPPT placebo and treatment groups (our simulated placebo and treatment groups). The number of events prevented was calculated as the absolute difference between the simulated groups (9.48 per 1000 men per 7.4 years) and the percentage difference of the simulated groups multiplied by the observed incidence rate in the LRC-CPPT placebo group (13.66 per 1000 men per 7.4 years). The second estimate was closer to that observed in the LRC-CPPT (17.10 per 1000 men per 7.4 years), and we recommend this approach in cost-effectiveness studies.

Where do developing World clinicians obtain evidence for practice: a case study on pneumonia.

There are few data on the practice of evidence based medicine in the developing world, nor on the actual sources of evidence that clinicians use in practice. To test the hypothesis that there was variation between and within developing countries in the proposed management of a patient with hospital acquired pneumonia, and that part of the variation can be explained by the sources of evidence used. Questionnaire responses to hypothetical case history. Investigators from 6 centres within the International Clinical Epidemiology Network (INCLEN) in China, Thailand, India, Egypt, and Kenya. Doctors chosen to represent primary and secondary hospital practice in the regions of the study centres. Investigations and initial treatments which would be ordered for a hypothetical 60-year-old woman who develops pneumonia 5 days after hospital admission, whether local data on antibiotic sensitivities are available and where information would be obtained to guide management. Chest x-ray and sputum gram stain/culture were consistently the most commonly ordered investigations, there being much greater variation in the initial treatment choices with either penicillin, a third-generation cephalosporin or aminoglycoside being the most popular choice. Textbooks were the commonest form of information source, and access to a library, textbooks and journals were statistically significantly associated with appropriate choice of investigations, but not treatment. Access to local antibiotic sensitivities was associated with appropriate initial treatment choice. Improving access to information in the literature and to local data may increase the practice of evidence-based medicine in the developing world.

A new method of estimating cost effectiveness of cholesterol reduction therapy for prevention of heart disease.

The purpose of this study was to demonstrate a new method of estimating the cost effectiveness of interventions that lower blood cholesterol levels in the prevention of coronary heart disease (CHD) at the community level. The participants in the study were 67 651 men aged 35 to 64 years in the Lower Hunter region of New South Wales, Australia. Census data, risk factor profiles and CHD event rates from community surveillance, plus costs in 1988-1989 Australian dollars, were used as inputs to a computer program that used a logistic equation. The output estimated the CHD events avoided and the cost effectiveness of an intervention that identified and treated men with cholesterol levels greater than 6.5 mmol/L with dietary modification and cholestyramine. The cost of implementation of the intervention was $A50.1 million to prevent 104 CHD events. The cost-effectiveness ratio was $A482 224 per CHD event avoided (SD = $A24 761) and the direct medical costs avoided were approximately $A500 000 over a 5-year period ($A4535.07 per CHD event avoided). Drug acquisition costs contributed substantially (88%) to the total costs of interventions that rely on screening to identify individuals with high cholesterol for intensive treatment.

Lipid lowering improves endothelial functions.

The healthy endothelium usually provides an anticoagulant, vasodilatory and anti-inflammatory spectrum of functions that are central in vascular homeostasis. Dysfunction of the endothelium is a common feature of all phases of atherosclerosis. Hypercholesterolemia provokes many aspects of endothelial dysfunction before and during the development of atheroma. For example, a high cholesterol diet leads to the formation of a fatty streak and the recruitment and binding of blood leukocytes to the artery wall. This process requires expression by the endothelial cells of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1). In rabbits that are fed an atherogenic diet, the aortic endothelium, which usually expresses little VCAM-1, shows foci of VCAM-1 expression soon after initiating this diet. Furthermore, lowering plasma cholesterol by diet or drugs down-regulates the expression of VCAM-1 and reduces the density of inflammatory cells in the atherosclerotic plaque. Hypercholesterolemia also attenuates normal vasodilatation to several stimuli such as exercise and acetylcholine. In healthy subjects, the vascular endothelium produces the vasodilator nitric oxide. In atherosclerosis, however, nitric oxide bioavailability is impaired. As a result, atherosclerotic coronary arteries commonly display a vasoconstrictor response when challenged with acetylcholine. Lipid lowering appears to favorably influence endothelial vasomotor and inflammatory functions in ways that may benefit patients with coronary artery disease. Continued probing of the basic mechanisms of endothelial dysfunction and its treatment may lead to new therapies that offer clinical benefits in patients with atherosclerosis, including reductions in coronary events.

Percutaneous coronary intervention and subsequent endovascular beta-radiation brachytherapy in a 14-year-old with repaired anomalous left coronary artery from pulmonary artery.

Anomalous origin of the left coronary artery from pulmonary artery (ALCAPA) is a rare congenital anomaly. Re-establishment of the dual coronary system is the standard treatment, although the long-term outcome after surgical repair is not well defined. We report a case in which coronary stenting was performed to treat left anterior descending artery lesions eight months after surgical repair of ALCAPA. The patient then developed rapid in-stent restenosis within three months, which was successfully treated by rotational atherectomy, balloon angioplasty, and catheter-based beta-radiation brachytherapy. Follow-up angiograms after three and six months showed no recurrent in-stent restenosis. This represents the first report of coronary stenting in the setting of ALCAPA, and the first report of catheter-based intracoronary radiation therapy in a pediatric patient.

Risk factors for mastitis in breastfeeding women: results of a prospective cohort study.

OBJECTIVES: To identify potential risk factors for the development of mastitis in breastfeeding women. METHODS: A prospective cohort study with questionnaire and telephone follow-up was conducted. Women were recruited after delivery at either the teaching hospital or the only private hospital with an obstetric service during May to December 1994 in Newcastle, New South Wales and were followed up at home for six months. 1,075 breastfeeding women were recruited and were sent follow-up questionnaires at three, eight and 26 weeks post-delivery. RESULTS: Mastitis occurred in 20% (95% CI 18-22%) of women during the first six months. Factors that were statistically significantly and independently related to mastitis were: past history of mastitis (adjusted Hazard Ratio=1.74, 1.07-2.81), university or college education (HR=1.93, 1.18-3.16), blocked duct (HR=2.43, 1.68-3.49), cracked nipples (HR=1.44, 1.00-2.07), use of creams on nipples (HR=1.83, 1.22-2.73), particularly papaya cream (Relative Risk = 1.83, 1.36-2.47), and always starting with the alternate breast on consecutive feeds (HR=2.28, 1.50-3.44). CONCLUSIONS: Women with a past history of mastitis had an increased risk of developing mastitis. Blocked ducts and cracked nipples serve as warning signs for mastitis. Use of some creams may increase the risk of mastitis and their value should be tested in clinical trials. IMPLICATIONS: We have identified several pre-natal and post-natal markers for increased risk of mastitis that may assist in its early identification and treatment. The use of creams on nipples may introduce pathogens that cause mastitis and should be avoided.

Lack of compensatory enlargement at sites of coronary vasospasm: identification by ultrasound and successful treatment with stenting.

The case of a young man with spontaneous vasospasm at two sites in his left anterior descending coronary artery is described. Intravascular ultrasound demonstrated mild eccentric atherosclerosis with smaller total artery cross-sectional area (defined as the external elastic membrane) compared with reference segments. Impaired compensatory enlargement (remodeling) in response to mild atherosclerosis may derive from one or more biologic mechanisms that are also responsible for vasospasm. This characteristic is easily identified by intravascular ultrasound. In this case, coronary stenting of the vasospastic sites led to excellent long-term control of symptoms more than 1 year after intervention.

Early statin therapy in acute coronary syndromes.

Patients who survive an acute coronary syndrome are at much higher risk of a recurrent event within the following year than patients with stable coronary syndromes. Risk factor modification, including statin therapy, lowers the risk of recurrent events over many years, but also to reduces the high risk of an another event within the weeks to months following the initial acute coronary syndrome. The mechanisms that contribute to this benefit are likely related to improvements in endothelial function, a decrease in vascular inflammation, and reduced prothrombotic factors. The effects of statins may be mediated by cholesterol reduction, cholesterol-independent effects (particularly by decreasing isoprenoids), and mechanisms that are independent of inhibiting HMG CoA reductase. Observational studies show an early reduction in mortality with statin therapy started before discharge from hospital after an acute coronary syndrome. Several randomized controlled trials also support a rapid reduction in the risk of recurrent events after starting statins during the hospital admission for an acute coronary syndrome. Early statin therapy is also related to improved compliance and use of statins several years after a coronary event. Thus early statin therapy may improve both early and long-term secondary prevention efforts.