Nonvascular Causes Research Articles

Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials

SummaryBackgroundLowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy.MethodsWe undertook meta-analyses of individual participant data from randomised trials involving at least 1000 participants and at least 2 years' treatment duration of more versus less intensive statin regimens (five trials; 39 612 individuals; median follow-up 5·1 years) and of statin versus control (21 trials; 129 526 individuals; median follow-up 4·8 years). For each type of trial, we calculated not only the average risk reduction, but also the average risk reduction per 1·0 mmol/L LDL cholesterol reduction at 1 year after randomisation.FindingsIn the trials of more versus less intensive statin therapy, the weighted mean further reduction in LDL cholesterol at 1 year was 0·51 mmol/L. Compared with less intensive regimens, more intensive regimens produced a highly significant 15% (95% CI 11–18; p<0·0001) further reduction in major vascular events, consisting of separately significant reductions in coronary death or non-fatal myocardial infarction of 13% (95% CI 7–19; p<0·0001), in coronary revascularisation of 19% (95% CI 15–24; p<0·0001), and in ischaemic stroke of 16% (95% CI 5–26; p=0·005). Per 1·0 mmol/L reduction in LDL cholesterol, these further reductions in risk were similar to the proportional reductions in the trials of statin versus control. When both types of trial were combined, similar proportional reductions in major vascular events per 1·0 mmol/L LDL cholesterol reduction were found in all types of patient studied (rate ratio [RR] 0·78, 95% CI 0·76–0·80; p<0·0001), including those with LDL cholesterol lower than 2 mmol/L on the less intensive or control regimen. Across all 26 trials, all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction (RR 0·90, 95% CI 0·87–0·93; p<0·0001), largely reflecting significant reductions in deaths due to coronary heart disease (RR 0·80, 99% CI 0·74–0·87; p<0·0001) and other cardiac causes (RR 0·89, 99% CI 0·81–0·98; p=0·002), with no significant effect on deaths due to stroke (RR 0·96, 95% CI 0·84–1·09; p=0·5) or other vascular causes (RR 0·98, 99% CI 0·81–1·18; p=0·8). No significant effects were observed on deaths due to cancer or other non-vascular causes (RR 0·97, 95% CI 0·92–1·03; p=0·3) or on cancer incidence (RR 1·00, 95% CI 0·96–1·04; p=0·9), even at low LDL cholesterol concentrations.InterpretationFurther reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke, with each 1·0 mmol/L reduction reducing the annual rate of these major vascular events by just over a fifth. There was no evidence of any threshold within the cholesterol range studied, suggesting that reduction of LDL cholesterol by 2–3 mmol/L would reduce risk by about 40–50%.FundingUK Medical Research Council, British Heart Foundation, European Community Biomed Programme, Australian National Health and Medical Research Council, and National Heart Foundation.

Perfusion CT in suspected ischaemic stroke: red flags that should have been blue

Perfusion CT in suspected ischaemic stroke: red flags that should have been blue

Cystatin C: an emerging marker for pre‐timely mortality

Cystatin C: an emerging marker for pre‐timely mortality

Cystatin C and risk of vascular and nonvascular mortality: a prospective cohort study of older men

To assess the relevance of cystatin C, as a marker of mild-to-moderate renal impairment, for vascular and nonvascular mortality in older people. Prospective cohort study. Re-survey in 1997 to 1998 of survivors in the 1970 Whitehall study of London civil servants. Five thousand three hundred and seventy-one men (mean age at resurvey: 77 years) who took part in the resurvey and had plasma cystatin C concentration measured. Cause-specific mortality over subsequent 11 years (1997 to 2008). Cox regression was used to estimate the associations of cystatin C with vascular and nonvascular mortality, before and after adjustment for prior disease and other risk factors (including lifetime blood pressure). During an 11.0-year follow-up period, there were 1171 deaths from vascular causes [26 per 1000 per year (py)] and 1615 deaths from nonvascular causes (36 per 1000 py). Compared with men with cystatin C in the bottom fifth of the distribution, men in the top 10th had about two-fold higher mortality rates from vascular and nonvascular mortality (fully adjusted P both <0.001) even after adjustment for prior disease and all measured confounders, including lifetime blood pressure. The fully adjusted relative risks per 50% higher cystatin C concentrations were 1.66 [95% CI 1.48 to 1.85] for vascular mortality, 1.92 [95% CI 1.66 to 2.22] for ischaemic heart disease mortality and 1.46 [95% CI 1.31 to 1.61] for nonvascular mortality. In older men, plasma concentration of cystatin C, probably as a marker of mild renal disease, is a strong independent predictor of both vascular and nonvascular mortality.

Effects of Homocysteine-Lowering With Folic Acid Plus Vitamin B12vs Placebo on Mortality and Major Morbidity in Myocardial Infarction Survivors

Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal. To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12) on vascular and nonvascular outcomes. Double-blind randomized controlled trial of 12,064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008. 2 mg folic acid plus 1 mg vitamin B(12) daily vs matching placebo. First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization. Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B(12) vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]). Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence. isrctn.org Identifier: ISRCTN74348595.

The internal thoracic artery as a transitional type of artery: a morphological and morphometric study.

Coronary artery by-pass grafting (CABG) with arterial grafts is widely accepted as the procedure of choice in the treatment of coronary ischemic disease. It brings back focus on morphological studies of arteries used as conduits in this procedure. One of the most frequently used CABG grafts is the internal thoracic artery with an excellent graft prognosis and patency rate. The aim of the study was a detailed morphological and morphometric description of the internal thoracic artery with an emphasis on its basic histological structure and its changes in aging and atherosclerosis. Therefore, 42 full-length arteries were obtained during forensic autopsies from 27 persons, aged between 20 and 81 years, who had died from non-vascular causes. The arteries were classified into three different age groups. Analysis of the serial arterial segments has shown that the internal thoracic artery is an artery of the transitional type whose media is organized into two layers: the internal, muscular layer and the external layer with spirally oriented elastic lamellae and smooth muscle cells in between. The number of elastic lamellae progressively decreases throughout the length of the examined arteries. As opposed to previous assumptions, we have proven that the grade of atherosclerosis is independent of the number of elastic lamellae in the external media. Perfectly formed elastic lamellae are not a persistent feature of the internal thoracic artery, as previously claimed. We have confirmed that the thickness of elastic lamellae decreases, while the number and the size of their fenestrations steadily increase with aging.

Chronic kidney disease and risk of major cardiovascular disease and non-vascular mortality: prospective population based cohort study

Objective To quantify associations of chronic kidney disease stages with major cardiovascular disease and non-vascular mortality in the general adult population.Design Prospective population based cohort study.Setting Reykjavik, Iceland.Participants 16 958...

Triple rule-out CT in the emergency department: protocols and spectrum of imaging findings

Triage decisions in patients suffering from acute chest pain remain a challenge. The patient's history, initial cardiac enzyme levels, or initial electrocardiograms (ECG) often do not allow selecting the patients in whom further tests are needed. Numerous vascular and non-vascular chest problems, such as pulmonary embolism (PE), aortic dissection, or acute coronary syndrome, as well as pulmonary, pleural, or osseous lesions, must be taken into account. Nowadays, contrast-enhanced multi-detector-row computed tomography (CT) has replaced previous invasive diagnostic procedures and currently represents the imaging modality of choice when the clinical suspicion of PE or acute aortic syndrome is raised. At the same time, CT is capable of detecting a multitude of non-vascular causes of acute chest pain, such as pneumonia, pericarditis, or fractures. Recent technical advances in CT technology have also shown great advantages for non-invasive imaging of the coronary arteries. In patients with acute chest pain, the optimization of triage decisions and cost-effectiveness using cardiac CT in the emergency department have been repetitively demonstrated. Triple rule-out CT denominates an ECG-gated protocol that allows for the depiction of the pulmonary arteries, thoracic aorta, and coronary arteries within a single examination. This can be accomplished through the use of a dedicated contrast media administration regimen resulting in a simultaneous attenuation of the three vessel territories. This review is intended to demonstrate CT parameters and contrast media administration protocols for performing a triple rule-out CT and discusses radiation dose issues pertinent to the protocol. Typical life-threatening and non-life-threatening diseases causing acute chest pain are illustrated.

Neurogenic orthostatic hypotension: chasing “the fall”

Orthostatic hypotension (OH) is a frequently encountered problem affecting nearly 30% of the population aged more than 60 years. It can result from neurological and non-neurological derangements which compromise the...

Capacité de marche en milieu extra-hospitalier des amputés appareillés

Purpose of the study A large body of literature has been devoted to gait analysis in amputees. Most studies have been conducted in the laboratory setting where numerous variables are analyzed: gait efficiency, energy cost, walking velocity. At the present time however, data are lacking on the real-life use of walking prostheses. Little is known about how long patients wear their prosthesis or how difficult it is for them to walk during different periods of the day. Currently, such information depends on the quality of the interview and the patient-physician relationship. A precise assessment of walking activity in amputees and use of prostheses would be a valuable source of information for therapists and would provide complimentary information to that collected from laboratory gait analysis. The purpose of this study was to study walking activity in home-dwelling prosthesis-bearing lower-limb amputees and to determine variables affecting walking performance. To our knowledge, this is the first published study on this topic. Material and methods The series included home-dwelling prosthesis-wearing lower-limb amputees (Syme amputation or more proximal) who were able to get up and go without assistance. A StepWatch3™ recorder was implanted on the prosthesis for 15 consecutive days. Variables recorded were number of steps, total walking time, and walking velocity. Variables which might affect walking in prosthesis-wearing amputees were also recorded: body mass index, use of a walking aid, level and reason for amputation, age at amputation and at recording, time between amputation and recording. Results From June 2004 to May 2005, 43 patients wore the StepWatch3™ for the scheduled 15 days during their daily activities. Mean age at amputation was 42 years (range 13-78 years) and at recording 52 years (range 25-85 years). Considered separately, gait parameters showed that all of the patients wore their prosthesis daily and that the best walking performance was significantly observed among below-knee amputees who did not use a walking aid and who underwent amputation for a non-vascular cause. Multivariate analysis revealed that above-knee amputees lost 93 minutes of walking time per day (21% loss), and that amputees who used a walking aid lost 58 minutes per day (13% loss). Daily walking time declined 2.5 minutes per year of age. Body mass index was not correlated with total daily walking time but had a direct significant effect on walking velocity.

Diabetes mellitus is associated with severe Peyronie’s disease

To evaluate the severity of penile deformity and penile blood flow variables in men with Peyronie's disease (PD) and diabetes mellitus (DM), and those with no risk factors. Men with PD and DM (59 men, group 1) and those with no risk factors (109, group 2) were compared for penile blood flow variables, severity of penile deformity, patient's age, duration of PD, the presence of pain on erection, and the degree of erectile dysfunction (ED). The men were evaluated with penile duplex Doppler ultrasonography and were categorized into specific vascular groups, using established criteria. Penile curvature was objectively measured and stratified according to the Kelâmi classification. Results were compared using Student's t-test. Men with PD and DM (group 1) were significantly older than those in group 2. The duration of disease was significantly longer in group 1 than in group 2 (median 24 vs 12 months). The mean degree of penile deformity in group 1 was significantly higher than in group 2 (45.2 degrees vs 30.2 degrees). The rate of severe penile curvature (>60 degrees ) was more frequent in group 1 (27.1% vs 5.5%). Pain on erection was significantly higher in group 2 (39.7% vs 25.5%), whereas the rate of ED was more common in group 1 (81% vs 47%). Group 1 had poorer peak-systolic velocity values and significantly higher rates of arterial insufficiency and mixed vascular disease. Nonvascular causes were twice as common in group 2 than in group 1. This comparative clinical study suggests that the presence of DM as the only risk factor significantly increases the severity of PD. Furthermore, DM as a risk factor is associated with significantly worse vascular status, as shown by penile duplex Doppler ultrasonography, in men with PD.

A comparison of magnetic resonance angiography and constructive interference in steady state-three-dimensional Fourier transformation magnetic resonance imaging in patients with hemifacial spasm

Although the decision to perform a microvascular decompression of the facial nerve is based on clinical history and assessment, preoperative imaging of the neurovascular relationships at the REZ is important to exclude a non-vascular cause or identify dolichoectatic vessels that might influence the surgical approach. We designed the current study to compare the specificity and sensitivity of gadolinium-enhanced 3D fast inflow with steady state precession (FISP) MRA with CISS. The imaging findings of 47 patients that had microvascular decompression for hemifacial spasm were retrospectively reviewed in a single blind fashion. The 47 non-symptomatic sides served as controls. Neurovascular contact could be seen in 13/47 (27.6%) in routine T2 axial scans, in 22/35 (62.8%) in high resolution T2W, in 18/34 (52.9%) in the case of MRA, and in all cases (13) when the CISS sequence was used. This study demonstrated 56.2% sensitivity and 50% specificity for MRA with gadolinium enhancement, whereas the CISS sequence can achieve a sensitivity of 100% in correctly demonstrating neurovascular compression in HFS. Overall accuracy of the two methods was 55.8 and 100% for MRA and CISS, respectively. The CISS sequence is superior in identifying neurovascular compression when compared with MRA. Preoperative knowledge of the compressing vessel has counselling implications and the higher risk of complications should be communicated to the patient. Due to cost and time implications we suggest that MR-CISS imaging replace the enhanced MRA sequence in the detailed preoperative MR assessment of hemifacial spasm

The clinical presentation of peripheral arterial disease and guidance for early recognition.

Most patients with lower extremity peripheral arterial disease (PAD) are asymptomatic. Although intermittent claudication is the classic presenting symptom in those who are symptomatic, PAD often presents atypically as a result of associated comorbidities. The differential diagnosis involves consideration of many nonvascular and nonatherosclerotic causes of exercise-associated leg pain. Weak or absent pulses are the hallmark physical finding of PAD, and the ankle-brachial index is the most efficient objective test for documenting it. PAD may progress to acute limb ischemia (acute deterioration of limb flow) or critical limb ischemia (chronic compromise in limb perfusion which resulting in rest pain and tissue loss), both of can lead to limb loss without timely treatment.

Is there a role for magnetic resonance imaging in the evaluation of non-traumatic intraparenchymal haemorrhage in children?

In contrast to adults, intraparenchymal haemorrhage (IPH) is at least as common as ischaemic stroke in children. There is often uncertainty about the most appropriate modality for imaging in the acute stage. To examine the diagnostic value of MRI and MR angiography (MRA) in the detection of underlying pathology in children with non-traumatic IPH. A retrospective review was conducted of children with IPH from January 1997 to March 2003. After exclusion of patients with traumatic IPH or previously diagnosed vascular malformation, aneurysm, or brain tumour, 50 children were identified. Case notes and imaging studies were reviewed. An underlying lesion was demonstrated with MR in two-thirds of children (25/38) with IPH. A vascular lesion was the commonest cause, followed by tumour. Three children had false-negative MR scans. MR is a valuable non-invasive imaging modality for detection of both vascular and non-vascular causes of paediatric IPH. The high rate of the latter in childhood makes incorporation of MR into paediatric IPH imaging protocols especially important. Clinical guidelines regarding the optimum sequence of investigations in non-traumatic IPH would be helpful to standardize practice and enable critical appraisal.

Incidence and Causes of Nondegenerative Nonvascular Dementia

Information on the incidence of nondegenerative and nonvascular dementia is limited. We used the records-linkage system of the Rochester Epidemiology Project to ascertain incident cases of dementia in Rochester, Minn, from January 1, 1990, through December 31, 1994. To define causes of dementia, we reviewed all diagnoses, imaging study results, laboratory test results, and clinical courses, as recorded historically in the patient dossier. We found 560 incident cases of dementia, and 60 of them (10.7%) had onset before the age of 70 years (younger-onset group). Forty-three cases (7.7%) were due to nondegenerative nonvascular causes and represented 30.0% of the total in the younger-onset group, but only 5.0% of the total in the older-onset group (aged 70-99 years). The most common nondegenerative nonvascular causes were cancer with or without brain metastases (n = 13), chronic alcoholism (n = 7), and chronic mental illness (n = 11). There were no cases of dementia due to normal-pressure hydrocephalus, subdural hematoma, hypothyroidism, vitamin B12 deficiency, or neurosyphilis. There were 2 individuals with acute confusion due to subdural hematoma and 1 with hypothyroidism whose cognition normalized with therapy. Nondegenerative nonvascular causes were more common than expected in patients with a younger onset of dementia. None of the patients with dementia reverted to normal with treatment of the putative reversible cause.

Early death following primary total hip arthroplasty: 1,727 procedures with mechanical thrombo-prophylaxis

Background The aims of this study were to quantify the risk and identify the causes of early postoperative mortality after total hip arthroplasty. This would help clinicians address preventable causes of death and help in accurate counseling and consenting of patients.Methods We determined the death rate at 90 days in an unselected consecutive series of 1,727 primary total hip arthroplasties where patients had not routinely received chemothromboprophylaxis.Results The mortality at 90 days was 17/1,727 (1%). The 90-day mortality was 0.2% in patients under 70 years of age, 1.3% in patients between 70 and 80, and 2.5% in those over 80. 7 patients died from ischemic heart disease, 4 died following cerebrovascular events, and 2 from pulmonary embolism. 4 patients died from non-vascular causes. Of the vascular deaths, ischemic heart disease outnumbered cerebrovascular events which, in turn, outnumbered pulmonary embolism (7 vs. 4 vs. 2).Interpretation Strategies aimed at reducing deaths should address all vascular causes, not just pulmonary embolism. Our findings can be used to inform patients as to the risk of early death after total hip arthroplasty.

How Computed Tomography May Be Useful in Pulsatile Tinnitus With Normal Otoscopic Findings

Pulsatile tinnitus may present a diagnostic problem, because it does not always have an easily detectable cause. It is frequently associated with a vascular condition, which can be of congenital or acquired origin. Pulsatile tinnitus that has an arterial pathogenesis is often associated with atherosclerotic carotid artery disease, especially in elderly patients, as well as with tortuous intracranial arteries and hypertension; less frequently, vascular abnormalities are characterized by arteriovenous fistulae and aneurysms. The venous form is usually associated with congenital venous abnormalities and/or intracranial hypertension of various origins. 1 The nonvascular causes of pulsatile tinnitus include palatal, stapedial, and tensor tympani muscle myoclonus, 1 as well as vascular neoplasms of the temporal bone. 2 When neoplasms involving the temporal bone or the skull base have been excluded, the diagnostic process involved in the onset of pulsatile tinnitus that is presumably caused by noncongenital phenomena requires an accurate imaging study, and it is possible that the exact pathogenesis will remain unknown.

Renal transplantation in patients with abdominal aortic aneurysm--a new surgical approach.

An increasing number of abdominal aortic aneurysms occurs in renal failure patients because of an accelerated atherosclerosis process associated with uraemia. When technically feasible, endovascular repair of an abdominal aortic lesion should be considered as the treatment of choice. If a surgical repair is suggested, there are several options to select from. Since November 1999, we performed simultaneous aortic reconstruction using fresh arterial allograft and kidney transplantation in five uraemic patients with asymptomatic abdominal aortic aneurysm. The operative and postoperative course of four patients passed without major complications. One patient had ischaemic colitis early after the operation, which required a partial resection of the colon. One patient died 6 weeks after the operation due to non-vascular causes. In conclusion, the advantage of our single-phase procedure is that both diseases are treated simultaneously during a single hospital stay. Moreover, with our procedure, the risk of vascular graft infection in patients with chronic immunosuppression is low.

Established and emerging plasma biomarkers in the prediction of first atherothrombotic events.

In the current Adult Treatment Panel guidelines for cardiovascular risk detection,1 the plasma-based markers recommended for use in global risk assessment or in the definition of the metabolic syndrome are low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. It is widely recognized, however, that more than half of all future vascular events occur in individuals without overt hyperlipidemia. For example, in a recent large-scale analysis of >27 000 healthy American women, 77% of all future events occurred in those with LDL-C levels <4.14 mmol/L (<160 mg/dL) and 45% of all events occurred in those with LDL-C values <3.36 mmol/L (<130 mg/dL).2 Although risk-scoring systems that additionally evaluate traditional risk factors such as smoking, hypertension, and diabetes greatly improve risk prediction, multiple studies demonstrate that 20% to 25% of all future events occur in individuals with only 1 of these factors.3 Moreover, the prevalence of traditional risk factors is almost as high in those without disease as in affected individuals.4 As our understanding of the pathobiology of atherothrombosis has improved, researchers have attempted to evaluate the activities of these biological processes by measuring markers in plasma or urine (ie, biomarkers). Indeed, a series of candidate biomarkers reflecting inflammation, hemostasis, thrombosis, and oxidative stress have been evaluated as potential clinical tools in an effort to improve risk prediction. To be useful in a clinical setting, the biomarker of interest must be shown in multiple prospective studies to predict future cardiovascular events. Retrospective studies are of limited value because they are prone to bias and cannot exclude the possibility that the particular biomarker is elevated as a result of, rather than a cause of, disease. To be used widely, the proposed biomarker should provide independent information on risk or prognosis beyond that available from global assessment algorithms such …

Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease.

Osteoprotegerin is a novel member of the tumor necrosis factor receptor superfamily and a soluble decoy receptor of the receptor activator of nuclear factor-kappaB ligand. Recent experimental research has implicated osteoprotegerin in atherogenesis, but epidemiological confirmation of this concept is sparse. As part of the prospective, population-based Bruneck Study, severity, initiation, and progression of atherosclerosis were assessed in carotid arteries. Cases of incident cardiovascular disease and vascular mortality were carefully recorded over a 10-year period (1990 to 2000). Osteoprotegerin levels were measured in samples obtained at baseline and during follow-up. Serum osteoprotegerin showed a strong association with numerous vascular risk factors, including age, diabetes, markers of systemic inflammation, chronic infection, and smoking. In multivariate analyses, osteoprotegerin was significantly related to severity and 10-year progression of carotid atherosclerosis. Furthermore, a high level of osteoprotegerin was an independent risk factor for incident cardiovascular disease (adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 2.2 [1.3 to 3.8]; P=0.001) and vascular mortality (adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 3.1 [1.2 to 8.2]; P=0.010) but not for mortality due to nonvascular causes. Osteoprotegerin is an independent risk factor for the progression of atherosclerosis and onset of cardiovascular disease.