Arterial stiffness for the early prediction of pre-eclampsia compared with blood pressure, uterine artery Doppler and angiogenic biomarkers: a prospective cohort study.

OBJECTIVE: Our aim was to evaluate the ability of arterial stiffness parameters to predict pre-eclampsia early compared with peripheral blood pressure, uterine artery Doppler and established angiogenic biomarkers. DESIGN: Prospective cohort study. SETTING: Tertiary care antenatal clinics in Montreal, Canada. POPULATION: Women with singleton high-risk pregnancies. METHODS: In the first trimester, arterial stiffness was measured by applanation tonometry, along with peripheral blood pressure and serum/plasma angiogenic biomarkers; uterine artery Doppler was measured in the second trimester. The predictive ability of different metrics was assessed through multivariate logistic regression. MAIN OUTCOME MEASURES: Arterial stiffness (carotid-femoral pulse wave velocity, carotid-radial pulse wave velocity) and wave reflection (augmentation index, reflected wave start time), peripheral blood pressure, ultrasound indices of velocimetry and circulating angiogenic biomarker concentrations. RESULTS: In this prospective study, among 191 high-risk pregnant women, 14 (7.3%) developed pre-eclampsia. A first-trimester 1 m/s increase in carotid-femoral pulse wave velocity was associated with 64% increased odds (P < 0.05), and a 1-millisecond increase in time to wave reflection with 11% decreased odds for pre-eclampsia (P < 0.01). The area under the curve of arterial stiffness, blood pressure, ultrasound indices and angiogenic biomarkers was 0.83 (95% confidence interval [CI] 0.74-0.92), 0.71 (95% CI 0.57-0.86), 0.58 (95% CI 0.39-0.77), and 0.64 (95% CI 0.44-0.83), respectively. With a 5% false-positive rate, blood pressure had a sensitivity of 14% for pre-eclampsia and arterial stiffness a sensitivity of 36%. CONCLUSIONS: Arterial stiffness predicted pre-eclampsia earlier and with greater ability than blood pressure, ultrasound indices or angiogenic biomarkers.

Blood pressure variability within a single visit and all-cause mortality.

BACKGROUND: Within-visit variability of repeated sequential readings of blood pressure (BP) is an important phenomenon that may affect precision of BP measurement and thus decision making concerning BP-related risk and hypertension management. However, limited data exist concerning predictive ability of within-visit BP variability for clinical outcomes. Therefore, we aimed to investigate the association between the variability of three repeated office BP measurements and the risk of all-cause mortality, independent of BP levels. METHODS: Data collected through the National Health and Nutrition Examination Survey (NHANES) were analysed. NHANES is a program of studies designed to assess health and nutritional status of adults and children in the United States. A complete set of three sequential BP measurements, together with survival status, were available for 24969 individuals (age 46.8±;19.3 years, 49% males). Multivariable logistic regression models were used to determine the prognostic ability of the examined demographic, clinical, and haemodynamic indices. RESULTS: Among various examined indices of variability of systolic (SBP) and diastolic (DBP) blood pressure measurements, the standard deviation of DBP (DBPSD) was the stronger independent predictor of mortality (odds ratio 1.064, 95% Confidence Interval: 1.011-1.12) after adjustment for age, sex, body mass index, smoking, SBP, heart rate, history of hypertension, diabetes mellitus, hypercholesterolaemia, and cardiovascular events. CONCLUSION: Within-visit variability of three sequential office DBP readings may allow for the identification of high-risk patients better than mean SBP and DBP levels. The predictive value of within-visit BP variability and methods to improve its clinical application are worthy of further research.

Cholesterol efflux capacity, carotid atherosclerosis, and cerebrovascular symptomatology.

OBJECTIVE: To investigate the association of cholesterol efflux capacity with carotid atherosclerosis and cerebrovascular disease. APPROACH AND RESULTS: Patients with high-grade carotid stenosis (n=154) were recruited from Vascular Surgery clinics and 9 healthy controls from the McGill University Health Network, Montreal, Canada. Cerebrovascular symptomatology history was obtained. Stenosis was assessed by carotid ultrasound. Fasting blood samples were collected and depleted of apolipoprotein B particles by polyethylene glycol precipitation from serum. Cholesterol efflux was determined by incubating apolipoprotein B-depleted serum in cAMP-stimulated J774 cells for 6 hours. Carotid specimens were classified by 2 vascular pathologists using the American Heart Association atheromatous plaque classification. Differences in efflux were assessed according to (1) stenosis, (2) American Heart Association classification, and (3) cerebrovascular symptomatology. Normalized efflux was significantly lower in patients with carotid atherosclerosis compared with controls (0.97±0.16 versus 1.5±0.46; P<0.0001). Efflux was inversely associated with stenosis; the odds ratio for 80% to 99% versus 50% to 79% stenosis of tertile 1 (lowest) versus tertile 3 (highest) of efflux was 3.78 (95% confidence interval, 1.18-12.06) after adjusting for age, sex, low-density lipoprotein, and high-density lipoprotein. There were significant differences in cholesterol efflux between American Heart Association fibroatheroma (Va, 0.91±0.13), mainly calcific (Vb, 0.97±0.15), and mainly fibrotic (Vc, 1.03±0.21; P=0.05). There were no significant differences in efflux according to symptomatology. CONCLUSIONS: Cholesterol efflux capacity is inversely associated with increasing carotid stenosis and is associated with more advanced carotid plaque morphology, suggesting that cholesterol efflux capacity may be a biomarker for severity of carotid atherosclerotic burden. Whether therapies targeting high-density lipoprotein quality could be useful for stabilizing carotid atherosclerosis needs to be assessed.

Association of ultrasonic texture and echodensity features between sides in patients with bilateral carotid atherosclerosis.

OBJECTIVES: Our objective was to estimate the correlation of echodensity and textural features, using ultrasound and digital image analysis, between plaques in patients with bilateral carotid stenosis. DESIGN: Cross-sectional observational study. METHODS: Patients undergoing carotid endarterectomy were recruited from Vascular Surgery at the Royal Victoria and Jewish General hospitals in Montreal, Canada. Bilateral pre-operative carotid ultrasound and digital image analysis was performed to extract echodensity and textural features using a commercially available Plaque Texture Analysis software (LifeQMedical Ltd). Principal component analysis (PCA) was performed. Partial correlation coefficients for PCA and individual imaging variables between surgical and contralateral plaques were calculated with adjustment for age, sex, contralateral stenosis, and statin use. RESULTS: In the whole group (n = 104), the six identified PCA variables and 42/50 individual imaging variables were moderately correlated (r = .211-.641). Correlations between sides were increased in patients with ≥50% contralateral stenosis and symptomatic patients. CONCLUSION: Textural and echodensity features of carotid plaques were similar between two sides in patients with bilateral stenosis, supporting the notion that plaque instability is determined by systemic factors. Patients with unstable features of one plaque should perhaps be monitored more closely or treated more aggressively for their contralateral stenosis, particularly if this is hemodynamically significant.

Carotid endarterectomy improves peripheral but not central arterial stiffness.

OBJECTIVE: Carotid endarterectomy (CEA) reduces the risk of cerebrovascular events due to the presence of atherosclerotic plaque in the internal carotid artery. Arterial stiffness is an indicator of cardiovascular risk and strongly associates with the development of atherosclerosis. This study aims to assess the short-term effect of CEA on arterial stiffness and haemodynamics. DESIGN: Prospective observational study. METHODS: Measurements of arterial stiffness and haemodynamics, including carotid-femoral pulse wave velocity (cfPWV), carotid-radial PWV (crPWV), augmentation pressure, augmentation index, subendocardial viability ratio, central pressures and pulse pressure amplification, were performed pre- and 6 weeks post-CEA on both surgical and non-surgical sides. RESULTS: Fifty-nine patients completed the study (n = 46 men, age 68.9 ± 10.1 years). crPWV was decreased after CEA on the surgical (P = 0.01) and non-surgical side (P = 0.0008), AIx75 tended to decrease only on the surgical side (P = 0.06). cfPWV did not change significantly on either side. CONCLUSION: We assessed, for the first time, the short-term effect of CEA on arterial stiffness and haemodynamics. CEA improved peripheral but not central arterial stiffness. This study provides evidence for significant changes in certain arterial stiffness and haemodynamic parameters. Longer-term follow-up will assess whether these changes are sustained and whether CEA is associated with further haemodynamic benefits.

Sex differences in young patients with acute myocardial infarction.

AIMS: To identify sex differences in risk factors, presenting symptoms and outcomes of young patients with acute myocardial infarction. METHODS: We adopted a comprehensive approach and performed two parallel studies: (1) using provincial administrative databases from Quebec, Canada from 2000 to 2007, we identified baseline characteristics and post-acute myocardial infarction survival of patients aged < 50 years (n = 10,619); (2) to overcome the lack of clinical data in the administrative databases, a medical chart review was performed on 215 patients < 50 years of age with an acute myocardial infarction between April 2000 and August 2006 from our institution. RESULTS: Administrative cohort: fewer women than men sought medical attention for retrosternal chest pain 1-month pre-acute myocardial infarction (P = 0.035). Diabetes and hypertension were more prevalent in women, and patients equally received interventional procedures post-infarction. Diabetes significantly reduced post-infarction survival in men and women [HR = 2.02 (95% CI 1.21-3.36) and HR = 2.25 (95% CI 1.06-4.80), respectively]. However, young women had greater post-infarction mortality in-hospital and up to 1 year after discharge (4.23% vs. 2.21%, respectively; P = 0.005). Medical chart review: diabetes and hypertension were more prevalent in women, while men were more obese. There were no significant sex differences in typical presenting symptoms, or in interventional procedures post-infarction. CONCLUSIONS: Young men and women with acute myocardial infarctions equally presented with retrosternal chest pain, although fewer women sought medical attention for retrosternal chest pain before admission. Diabetes and hypertension were more prevalent in young women, and mortality was higher in young female patients. Our results highlight the continued need for diabetes prevention and control in young patients, especially women.

Lipid management and peripheral arterial disease.

Peripheral arterial disease (PAD) is a common disorder usually associated with silent or symptomatic arterial disease elsewhere in the circulation and a "cluster" of cardiovascular risk factors (e.g. smoking, dyslipidemia, hypertension, and insulin resistance/diabetes mellitus). The medical management of PAD should focus on both the relief of symptoms and prevention of secondary cardiovascular complications. This approach must include smoking cessation, optimal cholesterol levels, blood pressure and glycemic control as well as prescribing antiplatelet therapy. This review focuses on the evidence supporting the use of lipid-lowering drugs in PAD. Several trials indicate that getting low density lipoprotein-cholesterol levels to target (<2.6 mmol/l; 100 mg/dl), or even lower, is associated with improvement of symptoms and a reduction in vascular events in patients with PAD.

Tangier disease four decades of research: a reflection of the importance of HDL.

Reduced circulating levels of high density lipoprotein cholesterol (HDL-C) are a frequent lipoprotein disorder in coronary heart disease patients and can be caused by either genetic and/or environmental factors (sedentary lifestyle, diabetes mellitus, smoking, obesity or a diet enriched in carbohydrates). Extremely low serum HDL-C levels occur in patients with Tangier disease (TD), which is caused by mutations in the adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1). Clinical manifestations are related to the storage of cholesteryl esters in reticuloendothelial tissues and to peripheral neuropathy. This review focuses on the genetic and lipid abnormalities of TD, the consequence of these on clinical outcome and the possible treatment options. These abnormalities reflect the importance of HDL in the pathogenesis of vascular disease.

Effect on serum uric acid levels of drugs prescribed for indications other than treating hyperuricaemia.

Beyond allopurinol and the well-established uricosuric drugs, several other agents can decrease serum uric acid (SUA) levels, such as losartan, fenofibrate and some non-steroidal anti-inflammatory drugs (NSAIDs). Some of these drugs increase renal urate excretion. Hyperuricaemia and gout are common problems (at least 1% of Western men are affected by gout). Raised SUA levels increase the incidence of acute gout and renal calculi. Hyperuricaemia may also predict an increased risk of vascular events. Therefore, lowering SUA levels is of clinical relevance. In this review we consider the effect on SUA levels of drugs that are prescribed for indications other than treating hyperuricaemia. These drugs may obviate the need for specific treatment (e.g. allopurinol) aimed at lowering SUA levels. Furthermore, because hyperuricaemic patients may already be on several drugs (e.g. due to associated dyslipidaemia, hypertension and/or arthritis) compliance may be improved by avoiding additional medication. The potential for adverse effects associated with polypharmacy would also be decreased.

The predictive value of lipid markers in vascular disease.

Lipid markers are well established predictors of vascular disease. The most frequently measured lipid variables are total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides. In this review we consider the predictive value of these variables and other more specialised related tests. We also discuss the effect of lipid altering drugs on these markers. The interaction of other vascular risk factors and the lipid effects of non-lipid altering drugs (e.g. blood pressure lowering agents) are also briefly described. Similarly, we discuss the effects of lipid lowering drugs on non-lipid vascular risk factors. Finally, we briefly consider the effect of altering the lipid profile on surrogate markers and events associated with atherosclerosis.

The use of ezetimibe in achieving low density lipoprotein lowering goals in clinical practice: position statement of a United Kingdom consensus panel.

There is no doubt that lowering serum cholesterol levels reduces the risk of major coronary events. This evidence has led treatment guidelines to set progressively lower targets for low density lipoprotein cholesterol (LDL-C). However, despite widespread use of statins, substantial numbers of patients do not achieve the LDL-C goals. Using higher doses of statins in an attempt to achieve these targets may increase the risk of serious adverse effects. Furthermore, the use of combination therapy with agents such as bile acid sequestrants, niacin and fibrates has been limited by increased potential for side effects, drug interactions and poor compliance. Ezetimibe, a selective cholesterol transport inhibitor, reduces the intestinal uptake of cholesterol without affecting absorption of triglycerides or fat-soluble vitamins. In clinical studies, ezetimibe 10 mg, in combination with statins or as monotherapy, was well tolerated and reduced LDL-C by 34-53% and 17-18%, respectively. The available evidence for ezetimibe is reviewed. The role of ezetimibe in increasing the proportion of patients attaining LDL-C treatment goals is discussed.

Long-term treatment of deep venous thrombosis with a low molecular weight heparin (tinzaparin): a prospective randomized trial.

OBJECTIVES: Evaluation of the effectiveness and safety of the low molecular weight heparin (LMWH) tinzaparin versus unfractionated heparin (UFH) followed by acenocoumarol in proximal deep venous thrombosis (DVT). DESIGN: Prospective, randomized clinical trial. MATERIAL AND METHODS: Consecutive patients (n=108) with acute leg DVT, confirmed by duplex, were randomized to either tinzaparin alone or UFH and acenocoumarol for 6 months. Patients were evaluated ultrasonographically at entry, 1, 3, 6 and 12 months. Thrombus regression, reflux distribution and the incidence of complications were studied. A cost-analysis, comparing the two treatments, was performed. RESULTS: The overall incidence of major events (mortality, DVT recurrence, pulmonary embolism, major bleeding, heparin-induced thrombocytopenia) was significantly different (p=0.035) in favor of tinzaparin (7 versus 17 events). The ultrasonographic clot volume score (an index of recanalization) decreased significantly in both treatment groups. However, tinzaparin produced significantly more extended overall recanalization from 3 months onwards (p<0.02). Thrombus regression was equivalent or in favor of tinzaparin in the different DVT subgroups and venous segments, but the statistical significance varied. Reflux showed non-significant differences overall or in subgroups. A cost-analysis resulted in favor of LMWH. CONCLUSIONS: A fixed daily dose of tinzaparin for 6 months was at least as effective and safe as UFH and acenocoumarol. Regarding major events and recanalization, there was a significant benefit in favor of tinzaparin. Long-term DVT treatment with tinzaparin could represent an alternative to conventional treatment.

Prevention and treatment of the metabolic syndrome.

The prevalence of the metabolic syndrome is increasing owing to lifestyle changes leading to obesity. This syndrome is a complex association of several interrelated abnormalities that increase the risk for cardiovascular disease and progression to diabetes mellitus (DM). Insulin resistance is the key factor for the clustering of risk factors characterizing the metabolic syndrome. The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III defined the criteria for the diagnosis of the metabolic syndrome and established the basic principles for its management. According to these guidelines, treatment involves the improvement of the underlying insulin resistance through lifestyle modification (eg, weight reduction and increased physical activity) and possibly by drugs. The coexistent risk factors (mainly dyslipidemia and hypertension) should also be addressed. Since the main goal of lipid-lowering treatment is to achieve the NCEP low-density lipoprotein cholesterol (LDL-C) target, statins are a good option. However, fibrates (as monotherapy or in combination with statins) are useful for the treatment of the metabolic syndrome that is commonly associated with hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) levels. The blood pressure target is < 140/90 mm Hg. The effect on carbohydrate homeostasis should possibly be taken into account in selecting an antihypertensive drug. Patients with the metabolic syndrome commonly have other less well-defined metabolic abnormalities (eg, hyperuricemia and raised C-reactive protein levels) that may also be associated with an increased cardiovascular risk. It seems appropriate to manage these abnormalities. Drugs that beneficially affect carbohydrate metabolism and delay or even prevent the onset of DM (eg, thiazolidinediones or acarbose) could be useful in patients with the metabolic syndrome. Furthermore, among the more speculative benefits of treatment are improved liver function in nonalcoholic fatty liver disease and a reduction in the risk of acute gout.

Uric acid levels and vascular disease.

There is evidence showing that serum uric acid (SUA) levels predict the risk for vascular events. For example, up to 29% of the reduction in the primary composite endpoint seen in the LIFE trial (favouring losartan versus atenolol) can be attributed to a fall in SUA levels. We also discuss the findings of the GREACE study (treating to target with atorvastatin versus 'usual' care) in relation to SUA levels. In this brief comment we extend this argument to consider the SUA-lowering effect of other drugs commonly prescribed in patients with vascular disease (e.g. statins, fibrates and antihypertensive agents). A judicious use of drugs (alone or in combination) will result in small reductions in SUA levels. These changes may translate into a substantial reduction in the risk of vascular events. Results retrieved from completed trials together with new prospective findings will support or refute the proposed association between lowering SUA levels and reducing vascular morbidity and mortality.

Stroke: epidemiology, clinical picture, and risk factors--Part I of III.

The aim of this review is to present the current knowledge regarding stroke. It will appear in three parts (in part II the pathogenesis, investigations, and prognosis will be presented, while part III will consist of the management and rehabilitation). In the current part (I) the definitions of the clinical picture are presented. These include: amaurosis fugax, vertebrobasilar transient ischemic attack, and stroke (with good recovery, in evolution and complete). The role of the following risk factors is discussed in detail: age, gender, ethnicity, heredity, hypertension, cigarette smoking, hyperlipidemia, diabetes mellitus, obesity, fibrinogen and clotting factors, oral contraceptives, erythrocytosis and hematocrit level, prior cerebrovascular and other diseases, physical inactivity, diet and alcohol consumption, illicit drug use, and genetic predisposition. In particular, regarding the carotid arteries, the following characteristics are analyzed: atheroma, carotid plaque echomorphology, carotid stenosis, presence of ulcer, local variations in surface deformability, pathological characteristics, and dissection. Finally the significance of the cerebral collateral circulation and the conditions predisposing to cardioembolism and to cerebral hemorrhage are presented.

The efficacy of the new SCD response compression system in the prevention of venous stasis.

OBJECTIVE: The current commercially available sequential intermittent pneumatic compression device used for the prevention of deep venous thrombosis has a constant cycle of 11 seconds' compression and 60 seconds' deflation. This deflation period ensures that the veins are filled before the subsequent cycle begins. It has been suggested that in some positions (eg, semirecumbent or sitting) and with different patients (eg, those with venous reflux), refilling of the veins may occur much earlier than 60 seconds, and thus a more frequent cycle may be more effective in expelling blood proximally. The aim of the study was to test the effectiveness of a new sequential compression system (the SCD Response Compression System), which has the ability to detect the change in the venous volume and to respond by initiating the subsequent cycle when the veins are substantially full. METHODS: In an open controlled trial at an academic vascular laboratory, the SCD Response Compression System was tested against the existing SCD Sequel Compression System in 12 healthy volunteers who were in supine, semirecumbent, and sitting positions. The refilling time sensed by the device was compared with that determined from recordings of femoral vein flow velocity by the use of duplex ultrasound scan. The total volume of blood expelled per hour during compression was compared with that produced by the existing SCD system in the same volunteers and positions. RESULTS: The refilling time determined automatically by the SCD Response Compression System varied from 24 to 60 seconds in the subjects tested, demonstrating individual patient variation. The refilling time (mean +/- SD) in the sitting position was 40.6 +/- 10. 0 seconds, which was significantly longer (P <.001) than that measured in the supine and semirecumbent positions, 33.8 +/- 4.1 and 35.6 +/- 4.9 seconds, respectively. There was a linear relationship between the duplex scan-derived refill time (mean of 6 readings per leg) and the SCD Response device-derived refill time (r = 0.85, P <. 001). The total volume of blood (mean +/- SD) expelled per hour by the existing SCD Sequel device in the supine, semirecumbent, and sitting positions was 2.23 +/- 0.90 L/h, 2.47 +/- 0.86 L/h, and 3.28 +/- 1.24 L/h, respectively. The SCD Response device increased the volume expelled to 3.92 +/- 1.60 L/h or a 76% increase (P =.001) in the supine position, to 3.93 +/- 1.55 L/h or a 59% increase (P =. 001) in the semirecumbent position, and to 3.97 +/- 1.42 L/h or a 21% increase (P =.026) in the sitting position. CONCLUSIONS: By achieving more appropriately timed compression cycles over time, the new SCD Response System is effective in preventing venous stasis by means of a new method that improves on the clinically documented effectiveness of the existing SCD system. Further studies testing its potential for improved efficacy in preventing deep venous thrombosis are justified.