Risk factors for non-haemorrhagic stroke in patients with coronary heart disease and the effect of lipid-modifying therapy with pravastatin

Objective To determine the relative importance of recognised risk factors for non-haemorrhagic stroke, including serum cholesterol and the effect of cholesterol-lowering therapy, on the occurrence of non-haemorrhagic stroke in patients enrolled in the LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease) study. Design The LIPID study was a placebo-controlled, double-blind trial of the efficacy on coronary heart disease mortality of pravastatin therapy over 6 years in 9014 patients with previous acute coronary syndromes and baseline total cholesterol of 4-7 mmol/l. Following identification of patients who had suffered non-haemorrhagic stroke, a pre-specified secondary end point, multivariate Cox regression was used to determine risk in the total population. Time-to-event analysis was used to determine the effect of pravastatin therapy on the rate of non-haemorrhagic stroke. Results There were 388 non-haemorrhagic strokes in 350 patients. Factors conferring risk of future non-haemorrhagic stroke were age, atrial fibrillation, prior stroke, diabetes, hypertension, systolic blood pressure, cigarette smoking, body mass index, male sex and creatinine clearance. Baseline lipids did not predict non-haemorrhagic stroke. Treatment with pravastatin reduced non-haemorrhagic stroke by 23% (P= 0.016) when considered alone, and 21% (P= 0.024) after adjustment for other risk factors. Conclusions The study confirmed the variety of risk factors for non-haemorrhagic stroke. From the risk predictors, a simple prognostic index was created for nonhaemorrhagic stroke to identify a group of patients at high risk. Treatment with pravastatin resulted in significant additional benefit after allowance for risk factors. (C) 2002 Lippincott Williams Wilkins.

Effects of the vasopeptidase inhibitor, omapatrilat, in 723 patients with coronary heart disease

Introduction Among individuals with a history of myocardial infarction (MI), higher levels of blood pressure (BP) are associated with increased long-term risks of death from coronary heart disease. Treatment with a BP-lowering regimen, based on omapatrilat may result in greater clinical benefits than treatment with a regimen based on a regular angiotensin-converting enzyme (ACE) inhibitor because of more favourable effects on the renin-angiotensin-aldosterone system. Methods Seven hundred and twenty-three clinically stable patients with a history of MI or unstable angina, and a mean entry BP of 134/77 mmHg, were randomised to six months treatment with omapatrilat 40 mg, omapatrilat 20 mg, or matching placebo. Results After six months, mean BP levels (systolic/diastolic) in the omapatrilat 40 mg group were reduced by 4.3/ 2.9 mmHg (95% confidence interval 1.3 to 7.2/1.2 to 4.6). Mean BP levels in the omapatrilat 20 mg group were reduced by 4.6/1.0 mmHg (1.6 to 7.6/-0.7 to 2.6) in comparison with the placebo group. Both doses of omapatrilat also produced significant decreases in plasma ACE activity and significant increases in levels of plasma renin activity, atrial natriuretic peptide, endothelin and homocysteine (p

The genetics of coronary heart disease: the contribution of twin studies

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.

A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention

PURPOSE: To determine the effects of aggressive lipid lowering on markers of ischemia, resistance vessel function, atherosclerotic burden, and Symptom status in patients with symptomatic coronary artery disease. METHODS: Sixty consecutive patients with coronary artery disease that was unsuitable for revascularization were assigned randomly to either usual therapy of lipids for patients with a low-density lipoprotein (LDL) cholesterol target level <116 mg/dL, or to a, more aggressive lipid-lowering strategy involving up to 80 mg/d of atorvastatin, with a target LDL cholesterol level <77 mg/dL. The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function.(brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, patients in the aggressive therapy group had a significantly greater decrease in mean (+/- SD) LDL cholesterol level than those in the usual care group (29 +/- 38 mg/dL vs. 7 +/- 24 mg/dL, P = 0.03). Patients in the aggressive therapy group had a reduction in the number of ischemic wall segments (mean between-group difference of 1.3; 95% confidence interval: 0.1 to 2.0; P = 0.04), flow-mediated dilatation (mean between-group difference of 5.9%; 95% confidence interval: 2.5% to 9.4%; P = 0.001), and angina score after 12 weeks. There were no significant changes in atherosclerotic burden in either group. CONCLUSION: Patients with symptomatic coronary artery disease who are treated with aggressive lipid lowering have improvement of symptom status and ischemia that appears to reflect improved vascular function but not atheroma burden. Am J Med. 2003;114:445-453. (C) 2003 by Excerpta Medica Inc.

Association of severe coronary stenosis with subclinical left ventricular dysfunction in the absence of infarction

Background. Regional left ventricular (LV) dysfunction may occur in patients with coronary artery disease (CAD) in the absence of infarction, but the causes of this phenomenon are unclear. We sought to identify whether changes in regional LV function were related to stenosis severity, using sensitive new ultrasound markers of function. Methods: We studied 67 individuals with no history of infarction and with normal LV systolic function: 49 patients with CAD and 18 control subjects without CAD. All patients underwent color Doppler tissue imaging, integrated backscatter (IB), anatomic M-mode echocardiography, and strain rate imaging to detect changes in structure and function. Peak early and late diastolic myocardial velocity, cyclic variation of IB, wall thickness, and percent wall thickening were measured in each basal and mid segment. Strain rate and peak systolic strain were calculated in each wall. CAD was defined as greater than or equal to 50% diameter stenosis. Normokinetic segments (n = 354) subtended by CAD were divided according to stenosis severity into 3 groups: group 1 (subtended by 50%-69% stenosis); group 2 (subtended by 70%-98% stenosis); and group 3 (subtended by greater than or equal to99% stenosis). Each parameter in each group was compared with that in 216 segments from control subjects. Results: Segments subtended by significant CAD showed lower peak early and late diastolic myocardial velocity compared with control segments. Group 3 showed significantly lower myocardial velocities than group 2 for both peak early (4.8 +/- 1.8 vs 6.0 +/- 2.0 cm/s, P

Effects of combined low-density lipoprotein apheresis and aggressive statin therapy on coronary calcified plaque as measured by computed tomography

Eight patients with heterozygous familial hypercholesterolemia who received combined long-term low-density lipoprotein apheresis and high-dose statin therapy showed a significant decrease in volume of coronary calcium over a period of 29 months as measured by, computed tomography. This suggests that the effects of aggressive lipid-lowering therapy can be assessed non-invasively and may be used as surrogate end points when testing new therapies.

Kidney targeting and puncturing during percutaneous nephrolithotomy: recent advances and future perspectives

Background and Purpose: Precise needle puncture of the kidney is a challenging and essential step for successful percutaneous nephrolithotomy (PCNL). Many devices and surgical techniques have been developed to easily achieve suitable renal access. This article presents a critical review to address the methodologies and techniques for conducting kidney targeting and the puncture step during PCNL. Based on this study, research paths are also provided for PCNL procedure improvement. Methods: Most relevant works concerning PCNL puncture were identified by a search of Medline/PubMed, ISI Web of Science, and Scopus databases from 2007 to December 2012. Two authors independently reviewed the studies. Results: A total of 911 abstracts and 346 full-text articles were assessed and discussed; 52 were included in this review as a summary of the main contributions to kidney targeting and puncturing. Conclusions: Multiple paths and technologic advances have been proposed in the field of urology and minimally invasive surgery to improve PCNL puncture. The most relevant contributions, however, have been provided by the applicationofmedical imaging guidance, newsurgical tools,motion tracking systems, robotics, andimage processing and computer graphics. Despite the multiple research paths for PCNL puncture guidance, no widely acceptable solution has yet been reached, and it remains an active and challenging research field. Future developments should focus on real-time methods, robust and accurate algorithms, and radiation free imaging techniques

Collecting system percutaneous access using real-time tracking sensors: first pig model in vivo experience

Purpose: Precise needle puncture of the renal collecting system is an essential but challenging step for successful percutaneous nephrolithotomy. We evaluated the efficiency of a new real-time electromagnetic tracking system for in vivo kidney puncture. Materials and Methods: Six anesthetized female pigs underwent ureterorenoscopy to place a catheter with an electromagnetic tracking sensor into the desired puncture site and ascertain puncture success. A tracked needle with a similar electromagnetic tracking sensor was subsequently navigated into the sensor in the catheter. Four punctures were performed by each of 2 surgeons in each pig, including 1 each in the kidney, middle ureter, and right and left sides. Outcome measurements were the number of attempts and the time needed to evaluate the virtual trajectory and perform percutaneous puncture. Results: A total of 24 punctures were easily performed without complication. Surgeons required more time to evaluate the trajectory during ureteral than kidney puncture (median 15 seconds, range 14 to 18 vs 13, range 11 to 16, p ¼ 0.1). Median renal and ureteral puncture time was 19 (range 14 to 45) and 51 seconds (range 45 to 67), respectively (p ¼ 0.003). Two attempts were needed to achieve a successful ureteral puncture. The technique requires the presence of a renal stone for testing. Conclusions: The proposed electromagnetic tracking solution for renal collecting system puncture proved to be highly accurate, simple and quick. This method might represent a paradigm shift in percutaneous kidney access techniques

Kidney targeting and puncturing during percutaneous nephrolithotomy:recent advances and future perspectives

Precise needle puncture of the kidney is a challenging and essential step for successful percutaneous nephrolithotomy (PCNL). Many devices and surgical techniques have been developed to easily achieve suitable renal access. This article presents a critical review to address the methodologies and techniques for conducting kidney targeting and the puncture step during PCNL. Based on this study, research paths are also provided for PCNL procedure improvement. Methods: Most relevant works concerning PCNL puncture were identified by a search of Medline/PubMed, ISI Web of Science, and Scopus databases from 2007 to December 2012. Two authors independently reviewed the studies.

Collecting system percutaneous access using real-time tracking sensors: first pig model in vivo experience

Purpose: Precise needle puncture of the renal collecting system is an essential but challenging step for successful percutaneous nephrolithotomy. We evaluated the efficiency of a new real-time electromagnetic tracking system for in vivo kidney puncture. Materials and Methods: Six anesthetized female pigs underwent ureterorenoscopy to place a catheter with an electromagnetic tracking sensor into the desired puncture site and ascertain puncture success. A tracked needle with a similar electromagnetic tracking sensor was subsequently navigated into the sensor in the catheter. Four punctures were performed by each of 2 surgeons in each pig, including 1 each in the kidney, middle ureter, and right and left sides. Outcome measurements were the number of attempts and the time needed to evaluate the virtual trajectory and perform percutaneous puncture. Results: A total of 24 punctures were easily performed without complication. Surgeons required more time to evaluate the trajectory during ureteral than kidney puncture (median 15 seconds, range 14 to 18 vs 13, range 11 to 16, p ¼ 0.1). Median renal and ureteral puncture time was 19 (range 14 to 45) and 51 seconds (range 45 to 67), respectively (p ¼ 0.003). Two attempts were needed to achieve a successful ureteral puncture. The technique requires the presence of a renal stone for testing. Conclusions: The proposed electromagnetic tracking solution for renal collecting system puncture proved to be highly accurate, simple and quick. This method might represent a paradigm shift in percutaneous kidney access techniques.

Preliminary clinical trial in percutaneous nephrolithotomy using a real-time navigation system for percutaneous kidney access

Background: Precise needle puncture of renal calyces is a challenging and essential step for successful percutaneous nephrolithotomy. This work tests and evaluates, through a clinical trial, a real-time navigation system to plan and guide percutaneous kidney puncture. Methods: A novel system, entitled i3DPuncture, was developed to aid surgeons in establishing the desired puncture site and the best virtual puncture trajectory, by gathering and processing data from a tracked needle with optical passive markers. In order to navigate and superimpose the needle to a preoperative volume, the patient, 3D image data and tracker system were previously registered intraoperatively using seven points that were strategically chosen based on rigid bone structures and nearby kidney area. In addition, relevant anatomical structures for surgical navigation were automatically segmented using a multi-organ segmentation algorithm that clusters volumes based on statistical properties and minimum description length criterion. For each cluster, a rendering transfer function enhanced the visualization of different organs and surrounding tissues. Results: One puncture attempt was sufficient to achieve a successful kidney puncture. The puncture took 265 seconds, and 32 seconds were necessary to plan the puncture trajectory. The virtual puncture path was followed correctively until the needle tip reached the desired kidney calyceal. Conclusions: This new solution provided spatial information regarding the needle inside the body and the possibility to visualize surrounding organs. It may offer a promising and innovative solution for percutaneous punctures.

A-scan ultrasound system for real-time puncture safety assessment during percutaneous nephrolithotomy

Background: Kidney stone is a major universal health problem, affecting 10% of the population worldwide. Percutaneous nephrolithotomy is a first-line and established procedure for disintegration and removal of renal stones. Its surgical success depends on the precise needle puncture of renal calyces, which remains the most challenging task for surgeons. This work describes and tests a new ultrasound based system to alert the surgeon when undesirable anatomical structures are in between the puncture path defined through a tracked needle. Methods: Two circular ultrasound transducers were built with a single 3.3-MHz piezoelectric ceramic PZT SN8, 25.4 mm of radius and resin-epoxy matching and backing layers. One matching layer was designed with a concave curvature to work as an acoustic lens with long focusing. The A-scan signals were filtered and processed to automatically detect reflected echoes. Results: The transducers were mapped in water tank and tested in a study involving 45 phantoms. Each phantom mimics different needle insertion trajectories with a percutaneous path length between 80 and 150 mm. Results showed that the beam cross-sectional area oscillates around the ceramics radius and it was possible to automatically detect echo signals in phantoms with length higher than 80 mm. Conclusions: This new solution may alert the surgeon about anatomical tissues changes during needle insertion, which may decrease the need of X-Ray radiation exposure and ultrasound image evaluation during percutaneous puncture.