The effects of atorvastatin treatment on the fibrinolytic system in dyslipidemic patients

Statins have pleiotrophic effects related to the pathogenesis of atherosclerosis and thrombogenicity of the vessel wall beyond lipid lowering. The aim of the present study was to examine the effect of atorvastatin treatment on the fibrinolytic system in patients with dyslipidemia. The investigation was carried out on 41 dyslipidemic patients (21 males and 20 females) with a mean age of 53.8 years (range, 30-76). The patients were divided into subgroups according to their cholesterol and triglyceride levels as hypercholesterolemic (n = 26) and mixed-type hyperlipidemic (n = 15) and their risk factors for coronary heart disease including age, sex, hypertension, obesity, smoking, and family history. The patients were started on atorvastatin 10 mg/day, and evaluated within 6-12 weeks to assess the changes in fibrinolytic parameters including global fibrinolytic capacity, plasminogen activator inhibitor type-1 and tissue plasminogen activator, and lipids. After successful lipid-lowering therapy, global fibrinolytic capacity (P = 0.003) and tissue plasminogen activator levels (P = 0.04) were found to be increased and plasminogen activator inhibitor type-1 levels (P = 0.02) decreased in dyslipidemic patients. Global fibrinolytic capacity levels increased (P < 0.001) and plasminogen activator inhibitor type-1 levels decreased (P = 0.01) in patients with hypercholesterolemia (n = 26). However, no significant changes were observed in fibrinolytic parameters in patients with mixed-type hyperlipidemia (n = 15). When the patients were separately evaluated according to risk factors, significant beneficial effects on the fibrinolytic system were observed, especially in patients without obesity and hypertension as well as in older patients and males. These findings suggest that atorvastatin treatment has a beneficial effect on the fibrinolytic system in patients with hypercholesterolemia, but not in patients with mixed-type hyperlipidemia. Further studies are needed to show whether higher doses and longer periods of lipid lowering treatment have beneficial effects in patients with mixed type hyperlipidemia and some risk factors.     

Associations between elevated resting heart rate and subclinical atherosclerosis in asymptomatic Korean adults undergoing coronary artery calcium scoring

Elevated resting heart rate (RHR) and the presence of coronary artery calcium (CAC) are closely related with inflammatory activity and cardiovascular disease outcomes. To date, however, the relationship between a high RHR and CAC has not been well studied, especially in non-western populations. We therefore aimed to examine the cross-sectional relationship between high RHR and the burden of subclinical atherosclerosis as measured by CAC score in a large sample of Korean adults. A total 26,018 subjects were enrolled and underwent CAC screening as part of a broader general health examination. RHR was categorized into four groups as: <60, 60–69, 70–79, and ≥80 beats per minute. Multivariable logistic regression models were employed to estimate the odds of having a CAC score of either >0, >100, or >400 based on RHR. Mean age of the study population was 53.9?±?8.2 years, and 79.7?% were male. After adjustment, each 10 beat per minute increment in RHR was associated with greater odds of having a CAC score above 100 (OR 1.13, 95?% CI 1.08–1.18) or 400 (OR 1.22, 95?% CI 1.13–1.31). Likewise, following adjustment, the odds of having a CAC >100 or >400 for those with a RHR ≥80 beats per minute were 1.42 (95?% CI 1.19–1.69) and 1.86 (95?% CI 1.42–2.47), respectively, compared with those who had a RHR <60 beats per minute. In a large cohort of Korean adults, elevations in the RHR, particularly above 80 beats per minute, were found to be independently associated with the presence of subclinical atherosclerosis as measured by CAC scoring.     

<Emphasis Type="Italic">HLA-B27</Emphasis> Homozygosity and Clinical Features of Ankylosing Spondylitis

Osteoporosis (OP) is a frequent complication of ankylosing spondylitis (AS), even in early stages of the disease, and is associated with elevated levels of biochemical markers of bone turnover, proinflammatory cytokines, and acute-phase reactants. This suggests that systemic inflammatory mediators, such as interleukin-6 and tumor necrosis factor-α, may be involved. Various factors that conceivably work in conjunction with one another also cause bone loss in AS (eg, genetic polymorphisms of vitamin D, low levels of osteoprotegerin and sex steroid hormones, and impaired calcium and vitamin D absorption). Dual x-ray absorptiometry for assessing bone mineral density (BMD) has limitations in patients with AS because of unreliability of spinal measurements, particularly in advanced disease with new bone formation. Femoral neck BMD is reduced and correlates with increased risk of vertebral fractures. Hence, measurement of BMD at the femoral neck may provide the most accurate means of detecting osteopenia and OP and could assess fracture risk in AS patients. No guidelines are available for detection and treatment of OP in AS, and most patients are young men, who are less likely to be screened. The only evidence-based recommendation is that optimal control of disease activity in AS prevents bone loss. A recent study showed a beneficial effect of infliximab therapy on bone turnover markers and BMD in AS. Also, bisphosphonates may be useful in managing OP in AS.     

In vitro sensitivity of Blastocystis hominis to garlic, ginger, white cumin, and black pepper used in diet

To determine the growth pattern and in vitro susceptibility of Blastocystis hominis to metronidazole (MTZ), garlic, ginger, white cumin, and black pepper. Stool specimens were collected from 16 irritable bowel syndrome (IBS) and 10 controls between July–November 2010. Stool microscopy and culture for B. hominis was performed. Drug susceptibility assays was done using 0.01 and 0.1 mg/ml of MTZ, garlic, ginger, white cumin, and black pepper. Effect was assessed on B. hominis culture after 48 h. Stool DNA was extracted using stool DNA extraction kit (Qiagen) and polymerase chain reaction (PCR) done using subtype-specific sequence-tagged-site primers. B. hominis genotype 3 and coinfection of 1 and 3 tended to grow well in culture compared to isolated type 1 infection. Exposed to MTZ at a concentration of 0.01 mg/ml, 38% (6/16) B. hominis from IBS did not grow in culture compared to 100% (10/10) of B. hominis from control (p = 0.001). When they were exposed to MTZ at 0.1 mg/ml, 56% (9/16) B. hominis from IBS did not grow in cultures compared to 100% (10/10) from control (p = 0.01). Forty-four percent (7/16) B. hominis from IBS did not grow in culture compared to 100% (10/10) B. hominis from control when exposed to garlic at a concentration of 0.01 mg/ml (p = 0.003) and following exposure to garlic at 0.1 mg/ml, 38% (6/16) B. hominis from IBS did not grow in cultures compared to 100% (10/10) from control (p = 0.001). B. hominis isolates from IBS had a cell count of 6,625 at a MTZ concentration of 0.01 mg/ml that reduced to 1,250 as MTZ concentration was increased to 0.1 mg/ml (p = 0.08). B. hominis from IBS with a mean cell count of 3 × 10⁵ at baseline decreased to 1 × 10⁴ when exposed to garlic at 0.01 mg/ml (p < 0.001) and to 1 × 10³ (p < 0.001) when garlic was 0.1 mg/ml. B. hominis from IBS cell count decreased to 1 × 10⁵ when exposed to white cumin at 0.01 mg/ml (p = 0.01) and to 1 × 10⁵ (p < 0.001) when white cumin was 0.1 mg/ml. Exposed to black pepper at 0.1 mg/ml, cell count of B. hominis from IBS decreased to 1 × 10⁵ (p = 0.01). B. hominis from IBS decreased to 1.3 × 10⁵ exposed to ginger at 0.01 mg/ml (p = 0.001). B. hominis isolates were mostly genotypes 3, type 1 and 3 coinfection, and non-typeable B. hominis isolates. B. hominis isolates from IBS mostly genotype 1 demonstrated an increased sensitivity to garlic at 0.01 mg/ml with a B. hominis cell count of 3,714 compared to 6,142 when exposed to 0.01 mg/ml of MTZ. However, this sensitivity did not increase as garlic concentration was increased to 0.1 mg/ml, for B. hominis cell count was 6,000 compared to 1,428 as MTZ was increased to 0.1 mg/ml.     

Changes in Serum and Renal Vitamin E Levels in Deoxycorticosterone Acetate-Salt Hypertensive Rats

Background

Hypertension is an important risk factor for the progression of chronic renal disease, which may result in the development of end-stage renal disease. Since reactive oxygen species are implicated in the induction of hypertension, antioxidants have been used to reduce blood pressure and renal impairment in animal models and in human hypertension. However, the available data are not conclusive.

Methods

To investigate oxidative stress in hypertension, we evaluated renal and serum vitamin E levels as the most effective antioxidant to reduce lipid peroxidation by high-performance liquid chromatography among rats subjected to deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks. Renal levels of malondialdehyde (MDA) as a marker of cell lipid peroxidation were also assayed in treated rats. Systolic blood pressure (SBP) was measured in conscious rats by the tail-cuff method using a PowerLab/4sp data acquisition system.

Results

SBP increased significantly in DOCA-salt-treated rats compared to the sham group after 4 weeks of treatment. Serum vitamin E levels were significantly lower and renal MDA concentrations significantly higher in treated compared to sham rats. However, renal vitamin E levels were also significantly higher among treated compared to sham rats.

Discussion

Decreased plasma vitamin E levels and increased renal MDA levels show systemic and local oxidative stress in DOCA-salt-treated rats. However, the higher renal vitamin E level suggested a local compensatory mechanism. Vitamin E administration might be appropriate, as significant decreases in vitamin E levels were observed in the serum of DOCA-salt-treated rats.     

Transient apical ballooning: sheep in wolves' garb

Takotsubo cardiomyopathy is a unique acute cardiac syndrome characterized by typical ischemic chest symptoms, an elevated ST segment on the electrocardiogram, and elevated cardiac disease markers. It is often misdiagnosed as acute myocardial infarction. Coronary angiography usually shows no evidence of obstructive atherosclerotic coronary artery disease. Left ventriculography and echocardiography reveal a peculiar regional systolic dysfunction with akinesis of the midventricle and apex and compensatory hyperkinesis of the basal ventricular segments. This syndrome has been shown to have a distinct temporal relationship with intense emotional stressors, and is characterized by an excellent clinical recovery when appropriate conservative measures are taken during the acute phase of the illness. In this review, we highlight the proposed pathophysiology and clinical manifestations of this recognized reversible form of myocardial failure.     

Infective endocarditis in patients with congenitally malformed hearts: characterization of the syndrome in a developing country

OBJECTIVE: Cardiac surgery for correction or palliation of congenital cardiac disease in infancy and childhood remains a privilege that is rarely accessible to two-thirds of the world's population. This imbalance has created a unique spectrum of illness in patients with underlying congenital cardiac disease and complicating infective endocarditis in developing countries, including Pakistan. In this study, we characterize endocarditis as seen in such patients presenting in Karachi. PATIENTS AND SETTINGS: We reviewed retrospectively patients admitted to Aga Khan University with underlying congenitally malformed hearts and endocarditis between 1991 and 2004. RESULTS: We identified 48 patients with endocarditis according to the modified Duke Criterions, with just over half the cases (54%) classified as definite endocarditis. Of the patients, 23 (49%) patients were more than 16 years old. Uncorrected left-to-right-shunts, tetralogy of Fallot, and congenital mitral valvar disease were the most common underlying defects. Patients with cyanotic defects, particularly of the complex type, were underrepresented (4%). Only 11 (22.9%) of the patients had a previous palliative or corrective surgery. In one-third of the patients (16), streptococcal species were identified as the microbiologic cause of endocarditis, and 22 (45.8%) had culture-negative endocarditis. In contrast, Staphylococcus aureus and enterococci caused endocarditis in only one patient each. There were no differences in mortality or complications between cyanotic and acyanotic congenital defects. Surgery was performed in nine (18.7%) patients with endocarditis, and of these, 13 (27.1%) died. CONCLUSIONS: In contrast to the developed world, endocarditis in the developing countries, such as Pakistan, complicates uncorrected left-to-right shunts and tetralogy of Fallot, probably because patients with complex cyanotic defects fail to survive long after birth due to the lack of available surgery. Almost half of patients had culture-negative endocarditis, likely related to several factors.     

Progress in shivering control

Hypothermia is a potent neuroprotectant and induced hypothermia holds great promise as a therapy for acute neuronal injury. Thermoregulatory responses, most notably shivering, present major obstacles to therapeutic temperature management. A review of thermoregulatory physiology and strategies aimed at controlling physiologic responses to hypothermia is presented.     

Intraluminal filling defects on coronary angiography: more than meets the eye

Intraluminal filling defects are occasionally encountered on coronary angiography and often related with coronary thrombi. However, other conditions affecting the coronary arteries may present with similar angiographic findings causing diagnostic uncertainty. Accurate characterization of the angiographic filling defect is critical, particularly in patients planned for a percutaneous coronary intervention (PCI), as diagnosis of a coronary thrombus not only increases the risk of post procedural adverse events but also requires a specific therapeutic approach. In this paper, we report three patients in whom coronary angiography revealed intraluminal filling defects mimicking coronary thrombi. When further investigated with intravascular ultrasound (IVUS) as a part of the planned PCI, the thrombus was excluded and alternate etiology of the filling defect was confirmed in all patients. The angiographic "pseudothrombi" were produced by coronary dissection in one and by heavy calcification within the atherosclerotic plaque in two patients. The use of IVUS allowed accurate characterization of the angiographic filling defect and provided important information to guide management and optimize therapeutic approach.