Arterial calcification at multiple sites: sex-specific cardiovascular risk profiles and mortality risk-the Rotterdam Study.

BACKGROUND: Evidence has pointed towards differences in the burden of arteriosclerosis according to its location and sex. Yet there is a scarcity of population-based data on aggregated sex-specific cardiovascular risk profiles, instead of single risk factors, and mortality risk according to the location of arteriosclerosis. We assessed sex-specific cardiovascular risk profiles and mortality risk associated with arteriosclerosis. METHODS: From the population-based Rotterdam Study, 2357 participants (mean age 69 years, 53% women) underwent non-contrast computed tomography to quantify calcification, as a proxy for arteriosclerosis, in the coronary arteries (CAC), aortic arch (AAC), extracranial (ECAC) and intracranial carotid arteries (ICAC), vertebrobasilar arteries (VBAC), and aortic valve (AVC). Principal component analysis (PCA) of eight distinct cardiovascular risk factors was performed, separately for women and men, to derive risk profiles based on the shared variance between factors. We used sex-stratified multivariable logistic regression to examine the associations between PCA-derived risk profiles and severe calcification at different locations. We investigated the associations of severe calcification with mortality risk using sex-stratified multivariable Cox regression. RESULTS: PCA identified three cardiovascular risk profiles in both sexes: (1) anthropometry, glucose, and HDL cholesterol; (2) blood pressure; and (3) smoking and total cholesterol. In women, the strongest associations were found for profile 2 with severe ECAC and ICAC (adjusted OR [95% CI] 1.32 [1.14-1.53]) and for profile 3 with severe at all locations, except AVC. In men, the strongest associations were found for profile 2 with VBAC (1.31 [1.12-1.52]) and profile 3 with severe AAC (1.28 [1.09-1.51]). ECAC and AVC in women and CAC in men showed the strongest, independent associations with cardiovascular mortality (HR [95% CI] 2.11 [1.22-3.66], 2.05 [1.21-3.49], 2.24 [1.21-3.78], respectively). CONCLUSIONS: Our findings further underline the existence of sex- and location-specific differences in the etiology and consequences of arteriosclerosis. Future research should unravel which distinct pathological processes underlie differences in risk profiles for arteriosclerosis.

Chelation therapy for atherosclerotic cardiovascular disease.

BACKGROUND: Chelation therapy is promoted and practiced around the world as a form of alternative medicine in the treatment of atherosclerotic cardiovascular disease. It has been suggested as a safe, relatively inexpensive, non-surgical method of restoring blood flow in atherosclerotic vessels. However, there is currently limited high-quality, adequately-powered research informing evidence-based medicine on the topic, specifically regarding clinical outcomes. Due to this limited evidence, the benefit of chelation therapy remains controversial at present. This is an update of a review first published in 2002. OBJECTIVES: To assess the effects of ethylene diamine tetra-acetic acid (EDTA) chelation therapy versus placebo or no treatment on clinical outcomes among people with atherosclerotic cardiovascular disease. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 6 August 2019. We searched the bibliographies of the studies retrieved by the literature searches for further trials. SELECTION CRITERIA: We included studies if they were randomised controlled trials of EDTA chelation therapy versus placebo or no treatment in participants with atherosclerotic cardiovascular disease. The main outcome measures we considered include all-cause or cause-specific mortality, non-fatal cardiovascular events, direct or indirect measurement of disease severity, and subjective measures of improvement or adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality using standard Cochrane procedures. A third author considered any unresolved issues, and we discussed any discrepancies until a consensus was reached. We contacted study authors for additional information. MAIN RESULTS: We included five studies with a total of 1993 randomised participants. Three studies enrolled participants with peripheral vascular disease and two studies included participants with coronary artery disease, one of which specifically recruited people who had had a myocardial infarction. The number of participants in each study varied widely (from 10 to 1708 participants), but all studies compared EDTA chelation to a placebo. Risk of bias for the included studies was generally moderate to low, but one study had high risk of bias because the study investigators broke their randomisation code halfway through the study and rolled the placebo participants over to active treatment. Certainty of the evidence, as assessed by GRADE, was generally low to very low, which was mostly due to a paucity of data in each outcome's meta-analysis. This limited our ability to draw any strong conclusions. We also had concerns about one study's risk of bias regarding blinding and outcome assessment that may have biased the results. Two studies with coronary artery disease participants reported no evidence of a difference in all-cause mortality between chelation therapy and placebo (risk ratio (RR) 0.97, 95% CI 0.73 to 1.28; 1792 participants; low-certainty). One study with coronary artery disease participants reported no evidence of a difference in coronary heart disease deaths between chelation therapy and placebo (RR 1.02, 95% CI 0.70 to 1.48; 1708 participants; very low-certainty). Two studies with coronary artery disease participants reported no evidence of a difference in myocardial infarction (RR 0.81, 95% CI 0.57 to 1.14; 1792 participants; moderate-certainty), angina (RR 0.95, 95% CI 0.55 to 1.67; 1792 participants; very low-certainty), and coronary revascularisation (RR 0.46, 95% CI 0.07 to 3.25; 1792 participants). Two studies (one with coronary artery disease participants and one with peripheral vascular disease participants) reported no evidence of a difference in stroke (RR 0.88, 95% CI 0.40 to 1.92; 1867 participants; low-certainty). Ankle-brachial pressure index (ABPI; also known as ankle brachial index) was measured in three studies, all including participants with peripheral vascular disease; two studies found no evidence of a difference in the treatment groups after three months after treatment (mean difference (MD) 0.02, 95% CI -0.03 to 0.06; 181 participants; low-certainty). A third study reported an improvement in ABPI in the EDTA chelation group, but this study was at high risk of bias. Meta-analysis of maximum and pain-free walking distances three months after treatment included participants with peripheral vascular disease and showed no evidence of a difference between the treatment groups (MD -31.46, 95% CI -87.63 to 24.71; 165 participants; 2 studies; low-certainty). Quality of life outcomes were reported by two studies that included participants with coronary artery disease, but we were unable to pool the data due to different methods of reporting and varied criteria. However, there did not appear to be any major differences between the treatment groups. None of the included studies reported on vascular deaths. Overall, there was no evidence of major or minor adverse events associated with EDTA chelation treatment. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the effectiveness or ineffectiveness of chelation therapy in improving clinical outcomes of people with atherosclerotic cardiovascular disease. More high-quality, randomised controlled trials are needed that assess the effects of chelation therapy on longevity and quality of life among people with atherosclerotic cardiovascular disease.

Interaction between Albuminuria and Treatment Group Outcomes for Patients with Renal Artery Stenosis: The NITER Study.

PURPOSE: To perform a post-hoc analysis of the Nephropathy Ischemic Therapy (NITER) trial, which enrolled patients with atherosclerotic renal artery stenosis, to evaluate whether medical therapy plus stent placement is superior to medical therapy alone in patients without elevated albuminuria. MATERIALS AND METHODS: Data from 51 patients were analyzed and stratified into 2 cohorts by median urinary albumin (UAlb) levels: cohort 1 ("low albuminuria," UAlb ≤0.04 g/24h) and cohort 2 ("high albuminuria," UAlb >0.04g/24h). Interaction effect between treatment arms and UAlb cohorts was calculated using Cox regression analysis. Survival analysis was followed by test for effect size, power analysis, and construction of a Kaplan-Meier survival table. RESULTS: At study completion, 13 patients had an outcome event: 6 (23%) from cohort 1 and 7 (28%) from cohort 2. Patients in cohort 1 had event-free survival of 83% at 3.9 ± 0.3 years from the primary endpoints of all-cause mortality, dialysis, and cardiovascular events when treated with interventional therapy, compared to 45% when treated with medical therapy alone (P = .501), which showed a 62% treatment effect for stent placement. In cohort 2, event-free survival rates were 64% for medical therapy versus 52% for medical plus interventional therapy (P = .64). Using Cox regression analysis, the interaction effect between treatment arms and UAlb cohorts was not significant (P = .32). The power of the study to detect an interaction effect, if one existed, was only 15%. CONCLUSIONS: Inference cannot be drawn for similar populations because of inadequate sample size, but, in this sample, patients treated with stent placement who had low albuminuria had better outcomes than patients treated with medical therapy alone.

APC resistance due to Factor V Leiden is not related to baseline inflammatory mediators or survival up to 10 years in patients with critical limb ischemia.

To prospectively evaluate the potential influence of resistance to activated protein C (APC-resistance) on the initial inflammatory response, amputation rate and survival during 10 years of follow-up in patients with critical limb ischemia (CLI). Two hundred and fifty-six consecutive CLI patients were analyzed for APC-ratio, the Factor V Leiden mutation and inflammatory mediators and then prospectively followed for 10 years. Inflammatory mediators, amputation rate, morbidity and mortality were compared between patients with and without APC resistance. Of the 256 CLI patients, 35 (14 %) were heterozygotes and 2 (1 %) homozygotes for the Factor V gene mutation, whereas 219 (86 %) patients were non-APC resistant. No significant differences were found between APC resistant and non-APC resistant patients regarding inflammatory mediators. Non-APC resistant patients more often had infrainguinal atherosclerosis (172 [79 %] vs 22 [59 %]; p = 0.017). Amputation rate at 1 year did not differ. Furthermore, there were no significant differences between groups regarding 1-, 3-, 5-, or 10-year survival. APC resistance in patients with CLI was not related to inflammatory activity, and had no impact on limb salvage or rate of amputation or long-term mortality. APC-resistant CLI-patients less frequently had infrainguinal arteriosclerosis, however.

Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial.

BACKGROUND: Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease. The impact of lowering total homocysteine levels in kidney transplant recipients is unknown. METHODS AND RESULTS: In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome (myocardial infarction, stroke, cardiovascular disease death, resuscitated sudden death, coronary artery or renal artery revascularization, lower-extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high-dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n=547 total events; hazards ratio [95 confidence interval]=0.99 [0.84 to 1.17]), secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86 to 1.26]), or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93 to 1.43]) compared to the low-dose multivitamin. CONCLUSIONS: Treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level.

Soluble P-selectin levels are associated with cardiovascular mortality and sudden cardiac death in male dialysis patients.

BACKGROUND/AIMS: P-selectin is released by activated platelets and endothelium contributing to inflammation and thrombosis. We evaluated the association between soluble P-selectin and atherosclerotic cardiovascular disease (ASCVD) in dialysis patients. METHODS: We measured soluble P-selectin in serum from 824 incident dialysis patients. Using Cox proportional hazards models, we modeled the association of P-selectin levels with ASCVD events, cardiovascular mortality and sudden cardiac death. RESULTS: After adjustment for demographics, comorbidity and traditional cardiovascular risk factors, higher P-selectin levels were associated with increased risk of ASCVD and cardiovascular mortality among males (p = 0.02 and p = 0.01, respectively), but not females (p = 0.52 and p = 0.31, respectively; p interaction = 0.003), over a median of 38.2 months. Higher P-selectin was associated with a greater risk of sudden cardiac death among males (p = 0.05). The associations between increasing P-selectin and cardiovascular mortality as well as sudden cardiac death in males persisted after adjustment for C-reactive protein, interleukin-6, serum albumin and platelet count (p = 0.01 and p = 0.03, respectively). The risk for sudden cardiac death was more than 3 times greater for males in the highest tertile of soluble P-selectin compared with the lowest tertile after adjustment (HR: 3.19; 95% CI: 1.18 - 8.62; p = 0.02). CONCLUSION: P-selectin is associated with ASCVD, cardiovascular mortality and sudden cardiac death among male dialysis patients.

Republished paper: Arterial stiffness in chronic kidney disease: causes and consequences.

Chronic kidney disease is associated with elevated cardiovascular risk, and heart failure and arrhythmias are the biggest causes of cardiovascular death in this population. Increased arterial stiffness is a hallmark of chronic kidney disease and is associated with adverse alterations in cardiac structure and function that may predispose to an increased risk of cardiovascular death. These changes are already apparent in early kidney disease, which is highly prevalent in the developed world. The mechanisms underlying increased arterial stiffness in chronic kidney disease are undoubtedly complex, but an understanding is paramount to enable the development of novel therapeutic strategies to prevent or reverse this pathophysiology and therefore reduce the cardiovascular disease burden in this high-risk cohort.

Higher long-term adherence to statins in rural patients at high atherosclerotic risk.

BACKGROUND: Rural patients with atherosclerotic cardiovascular disease (ASCVD) experience greater cardiovascular morbidity and mortality than their urban counterparts. Statin therapy is a key component of ASCVD treatment. The extent to which there may be regional differences in long-term adherence to statins is unknown. OBJECTIVE: To assess long-term rates of adherence to statins in a high-risk ASCVD cohort, and whether regional differences exist between rural and urban patients. METHODS: Follow-up was conducted in patients who underwent coronary angiography at a single tertiary center between 2009 and 2013. Adherence was defined as consumption of prescribed statin ≥6 days per week. Patients were divided into remoteness areas (RAs), classified as RA1 (major city), RA2 (inner regional), and RA3 (outer regional) based on the Australian Standard Geographical Classification. RESULTS: Five hundred twenty-five patients (69% male, mean age 64 ± 11 years) were followed-up after a median of 5.3 years. Baseline characteristics were similar between RAs. Overall adherence was 83%; however, rural patients were significantly more adherent to their statin therapy (80% in RA1, 83% in RA2, and 93% in RA3, P = .04). Living in RA3 independently predicted greater statin adherence than living in RA1 (odds ratio: 2.75, 95% CI: 1.1-7.8, P = .03). All-cause mortality was significantly higher in RA3 than other regional areas (6% RA1, 12% RA2, and 18% RA3, P = .01). CONCLUSIONS: Despite higher all-cause mortality, rural patients with ASCVD demonstrate significantly greater long-term adherence to statins than urban patients. Other factors, such as reduced access to health care and delayed diagnosis may explain the gap in outcomes between rural and urban patients.

Biomarker analysis by fluorokine multianalyte profiling distinguishes patients requiring intervention from patients with long-term quiescent coronary artery disease: a potential approach to identify atherosclerotic disease progression.

BACKGROUND: The study rationale was to compare the biomarker profile of metalloproteinases (MMPs) and inflammation markers (IMs) in patients requiring revascularization with that of patients with long-term, clinically quiescent coronary artery disease (CAD). METHODS: Seventy-eight patients with symptomatic CAD (S-CAD) (7 patients with myocardial infarction and 71 patients with stable angina) and 67 patients with asymptomatic CAD (A-CAD) were enrolled. Plasma samples were analyzed for MMPs, MMP inhibitors (MMPIs), IMs, coagulation factors, and apolipoproteins by use of the fluorokine multianalyte profiling assay. RESULTS: Patients with S-CAD had markedly elevated levels of specific MMPs (MMP-2, MMP-9), MMPIs (alpha2-macroglobulin, tissue inhibitor of MMP 1), IMs (C-reactive protein; interleukin [IL] 8; IL-10, regulated upon activation, normal T-cell expressed and secreted [RANTES], endothelin, plasminogen activator inhibitor 1, and apolipoprotein C-III compared with patients with A-CAD (P < .005 for all measurements), whereas patients with A-CAD had significantly greater levels of MMP-3 and IL-1alpha compared with patients with S-CAD (P < or = .02 for both measurements). CONCLUSIONS: A specific profile of MMPs, IMs, and other biomarkers distinguishes the patient with progressive coronary atherosclerosis culminating in either elective or emergent percutaneous coronary intervention from the patient with quiescent disease. The early implementation of a biomarker analysis may identify the patient at risk for plaque progression and refine the definition of "stable" angina.

[Screening in cardiovascular diseases]. / Screening bei Herz- und Gefässkrankheiten.

Cardiovascular disease still ranks number one in the mortality statistics in the industrialized world. In Germany the five most common causes of death are all associated with arteriosclerotic changes of the arterial vasculature. As the treatment often extends over long periods and it can be impossible for patients to work, peripheral arterial occlusive disease (PAOD) constitutes a not inconsiderable economic factor. Thus, screening for arteriosclerotic disease seems to be reasonable, because the potential for influencing arteriosclerotic changes is known to be higher in an early stage of the disease even before symptoms become apparent. Not every case can be cured, but progression can frequently be slowed down. The need for invasive procedures, some of them associated with ionizing radiation, limited the use of imaging of the arterial vasculature for a long time. Noninvasive clinical examinations such as the "ankle brachial index" (ABI) can indicate the presence of PAOD, though exact localization of the pathologic changes is not possible except with imaging methods. In contrast to these, MRI is a noninvasive imaging modality that does not involve ionizing radiation but offers high spatial resolution arterial imaging.

Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury.

Dehydroepiandrosterone (DHEA) is an endogenous steroid that blocks carcinogenesis, retards aging, and exerts antiproliferative properties. In vitro, it is a potent inhibitor of glucose-6-phosphate dehydrogenase, the first committed step of the pentose phosphate pathway. In man, serum levels of DHEA and its sulfate peak in early adulthood and drop markedly with age. Epidemiologic evidence indicates that low levels of DHEA or its sulfate conjugate are linked to an increased risk of developing cancer or of death from cardiovascular disease. Like cancer, atherosclerosis is a proliferative process characterized by both initiation and promotion phases. This similarity provided a framework in which to study the antiatherogenic effects of DHEA. Rabbits were randomly assigned to four groups. Two groups of rabbits received aortic endothelial injury by balloon catheter and were fed a 2% cholesterol diet for 12 wk. DHEA, 0.5%, was incorporated into the diet of one group receiving the 2% cholesterol diet and endothelial injury and also into the diet of one of the control groups. Animals were killed after 12 wk and aortas, hearts, and livers were studied. Plasma samples were analyzed for total cholesterol, VLDL, LDL, HDL, triglycerides, DHEA, and DHEA-sulfate levels. The atherogenic insult resulted in severe atherosclerosis in animals not treated with DHEA. In those receiving DHEA there was an almost 50% reduction in plaque size (P = 0.006), inversely related to the serum level of DHEA attained. Fatty infiltration of the heart and liver were also markedly reduced. These beneficial actions were not attributable to differences in body weight gain, food intake, total plasma cholesterol or distribution of cholesterol among the VLDL, LDL, or HDL fractions. The results show that high levels of plasma DHEA inhibit the development of atherosclerosis and they provide an important experimental link to the epidemiologic studies correlating low DHEA-sulfate plasma levels with an enhanced risk of cardiovascular mortality.

Ischaemic stroke--impact of renal dysfunction on in-hospital mortality.

Renal dysfunction predicts mortality in patients with myocardial infarction but less is known about the impact of renal dysfunction on in-hospital mortality after ischaemic stroke. All 361 patients (185 men, 176 women; mean age 72.1 years) with ischaemic stroke and glomerular filtration rate (GFR) <90 ml/min/1.73 m2 were followed-up. GFR was calculated according to abbreviated modification of diet in renal disease (MDRD) formula. Stroke severity was determined by National Institutes of Health Stroke Scale (NIHSS). The mean GFR was 61.5 +/- 16.6 ml/min/1.73 m2. There were 49 (13.6%) in-hospital deaths. Patients who died had higher NIHSS (P = 0.0001), were older (P = 0.024), had lower GFR (P = 0.028), higher hs-C-reactive protein (P = 0.001) and lower albumin (P = 0.048). No differences in presence of diabetes and hypertension, cholesterol (total, HDL and LDL), triglycerides and BMI between patients who died or survived were found. With univariate analysis association between in-hospital mortality and NIHSS (P = 0.0001), GFR (P = 0.041), total cholesterol (P = 0.021) and LDL cholesterol (P = 0.034) was found. With Cox multivariable regression analysis of risk factors, NIHSS (P = 0.0001), GFR (P = 0.018), total cholesterol (P = 0.008) and LDL cholesterol (P = 0.011) were only predictors of in-hospital mortality. In patients with ischaemic stroke, decreased GFR was associated with higher in-hospital mortality.

[Gender differences in vascular medicine]. / Geschlechtsunterschiede in der Gefässmedizin.

In vascular medicine only a few studies concerning gender differences in vascular diseases, course of the disease and therapy exist. Risk factors are allocated differently between men and women with different influences on cardiovascular diseases. Diabetic women do have a particular high risk. The proportion of women smokers with a risk for aggravation of the other risk factors is increased. In young female smokers the hypoplastic aortoiliac syndrome is a special course of peripheral arterial disease associated with a bad prognosis. The benefit of hormone replacement therapy in vascular diseases of postmenopausal women has not yet been demonstrated. On the other hand testosterone seems to have a favourable effect on vascular diameter and endothelium of coronaries. Women with peripheral arterial disease represent high risk patients with a particular risk for cardiovascular letality. Periprocedural complications of the analysed operations or interventions are found more frequent in women. Furthermore the disease is in an advanced stage when treated. Especially men with asymptomatic high grade carotid stenosis benefit more from an operation than women because of the higher risk for ischemic stroke. Unfortunately the benefit of the operation in women is neutralized by the higher rate of periprocedural complications. Some studies demonstrate the gender bias in treatment: women seldom receive revascularisation and guideline therapy as frequently as men. The same is true with thromboembolic prophylaxis concerning in hospital patients. In pharmacotherapy women have in result of metabolism more side effects. Additionally women are underrepresented in drug admission studies compared to their percentage of population and gender prevalence of diseases. Further studies concerning gender differences in vascular medicine are definitely needed.

Pre-existing arterial pathologic changes affecting arteriovenous fistula patency and cardiovascular mortality in hemodialysis patients.

The radiocephalic arteriovenous fistula (AVF) provides optimal vascular access for hemodialysis; it has a higher long-term patency rate and fewer complications than other vascular access methods. However, the AVF has a high primary failure rate. The presence of small-diameter vessels at anastomosis sites is an important risk factor for AVF failure. However, in a recent study, despite selecting an adequate artery and vein for creating an AVF by routine preoperative vascular mapping, AVF maturation and primary failure occurred. Thus, pre-existing arteriosclerosis at AVF anastomosis sites likely contributes to AVF failure. In this review, we discuss the relationship between pathologic changes and AVF patency in hemodialysis patients. Because arteriosclerosis of the major arteries such as the coronary and carotid arteries is associated with cardiovascular mortality, we also review the impact of arteriosclerosis of upper arm arteries at AVF anastomosis sites on cardiovascular mortality in hemodialysis patients.

Comparability between ICD-9 and ICD-10 for the leading causes of death in Spain.

BACKGROUND: Implementation of a new Revision of the International Classification of Diseases can create discontinuity in mortality statistics. Revisions are nevertheless essential to ensure international comparability of health statistics. The purpose of this work was to describe the effects of the 10th Revision on mortality statistics by sex and age for leading causes of death in Spain. METHODS: A cross-sectional study of leading causes of death was carried out when the underlying cause of death was coded using both the 9th and 10th Revisions of the International Classification of Diseases in 88,044 death certificates completed in five Autonomous Communities of Spain (Andalusia, Cantabria, Murcia, Navarra, the Basque Country), and the city of Barcelona during the year 1999. Changes introduced by the 10th Revision were described by simple correspondence, percentage of change, Kappa index and comparability ratios between the 10th and the 9th Revision along with their 95% confidence intervals by sex and five-year age group, for the leading causes of death. RESULTS: Under the 10th Revision, AIDS deaths rose by 3.6% (comparability ratio (CR): 1.036; 95% confidence interval (CI):1.015-1.058), arteriosclerosis by 7.1% (CR: 1.071; 95% CI: 1.052-1.090), and drug overdose by 5.2% (CR: 1.052; 95% CI: 0.964-1.140). Mortality due to vascular and senile dementia and non specific dementia declined by 3.2% under the 10th (CR: 0.969; 95% CI: 0.950-0.988). In all the other causes of death the percentage of change regardless of direction was less than 2%. CONCLUSION: The present study found good agreement between ICD-9 and ICD-10 on the leading causes of death and premature mortality in Spain. Causes of death which present differences between Revisions were AIDS, arteriosclerosis, drug overdose and senile dementia. For these causes, the comparability ratios must be taken into account when interpreting mortality statistics.

[Burden of mortality associated to physical inactivity in Bogota, Colombia]. / Carga de mortalidad asociada a la inactividad física en Bogotá.

UNLABELLED: Estimates of the burden of mortality associated to physical inactivity (PI) have not been quantified for large urban centers located in developing countries. OBJECTIVES: To estimate the burden of mortality due to six chronic diseases (CDZ) associated to PI and the number of potentially preventable deaths associated to reductions in the prevalence of PI. METHODS: PI exposure prevalence obtained via population surveys was linked to mortality data registered during 2002 among adult (> 45 y) Bogotá residents. The strength of association between PI and disease-specific mortality was obtained from the literature. Population attributable risk (PAR) was used to calculate the CDZ mortality attributable to PI and to estimate the number of potentially preventable deaths associated to a 30 % reduction in the prevalence of PI. RESULTS: A 53,2 % PI exposure prevalence was associated to a PAR of 19,3 % for coronary artery disease, 24,2 % for stroke, 13,8 % for arterial hypertension, 21 % for Diabetes Mellitus, 17,9 % for colon cancer and 14,2 % for breast cancer. An estimated 7,6 % of all-cause mortality and 20,1 % of CDZ mortality could be attributed to PI. An estimated 5% of the CDZ mortality could be prevented if PI prevalence is reduced by 30 %. CONCLUSION: Conservative estimates indicate that a considerable proportion of deaths due to highly prevalent CDZ could be attributed to PI. Strategies to reduce the prevalence of PI in Bogotá could lead to progressive reductions in the burden of CDZ mortality.

[Effects of ethanol on circulatory system]. / Wplyw alkoholu etylowego na uklad krazenia.

Moderate alcohol consumption decreases the risk of coronary heart disease (CHD). Epidemiological studies indicate that consumption of alcohol at the level 20-30 g per day can reduce risk of CHD by at least 20-25%. The mechanism of this protection has been associated with an increase in the level of HDL-cholesterol. Second of the proposed mechanisms of the protective effect of moderate alcohol intake is its beneficial effect on homeostasis.

Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis : clinical significance determined in a follow-up study.

BACKGROUND: Previous work has proved that increased titers of antibodies against heat-shock protein (hsp) 65 are associated with atherosclerotic lesions independently of other established risk factors. The present follow-up study was designed to further scrutinize the association of hsp antibodies and atherosclerosis and evaluate the possible predictive value of these antibodies for the development and/or progression of lesions in the same population. METHODS AND RESULTS: A total of 750 subjects 45 to 74 years old were recruited, and the rate of participation was 93.6%; 58 subjects died between 1990 and 1995. All participants were subjected to determination of serum antibodies against hsp65 and sonography to assess carotid atherosclerotic lesions and evaluate other risk factors, ie, age, sex, body mass index, blood cholesterol, apolipoprotein B, apolipoprotein A, triglycerides, lipoprotein(a), fibrinogen, leukocyte number, antithrombin III, ESR, ferritin, hypertension, smoking, and diabetes mellitus. Our data show that hsp65 antibody titers in the population emerged as highly consistent over a 5-year observation period (r=0.78, P<0.0001). Titers were significantly elevated in subjects with progressive carotid atherosclerosis and correlated with intima/media thickness. Multiple linear regression analysis documented these associations to be independent of age, sex, and other risk factors. Subanalyses revealed a preferential association of hsp65 antibody titers with advanced lesions (odds ratio, 1.42; 95% CI, 1.02 to 1.98; P=0.039). Other risk factors neither confounded nor modified this association. Finally, hsp65 antibody titers significantly predicted the 5-year mortality (hazard ratio, 1.52; 95% CI, 1.14 to 2.03; P<0.001). CONCLUSIONS: These findings indicate a sustained existence of anti-hsp65 antibodies in subjects with severe atherosclerosis, which is predictive for mortality.

Impact of infectious burden on extent and long-term prognosis of atherosclerosis.

BACKGROUND: Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. In hypothesizing an association between infectious agents and the development of atherosclerosis, we would expect a correlation to the extent of atherosclerosis. Moreover, this effect could be multiplied by the number of pathogens to which an individual had been exposed. METHODS AND RESULTS: In 572 patients, IgG or IgA antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, Hemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori were measured. The extent of atherosclerosis was determined by coronary angiography, carotid duplex sonography, and evaluation of the ankle-arm index. Elevated IgA antibodies against C pneumoniae (P<0.04) and IgG antibodies against H pylori (P<0.02), cytomegalovirus (P<0.05), and herpes simplex virus 2 (P<0.01) were associated with advanced atherosclerosis (> or =2 vascular regions), adjusted for age, sex, cardiovascular risk factors, and highly sensitive C-reactive protein. Infectious burden divided into 0 to 3, 4 to 5, and 6 to 8 seropositivities was significantly associated with advanced atherosclerosis, with an odds ratio (95% CI) of 1.8 (1.2 to 2.6) for 4 to 5 (P<0.01) and 2.5 (1.2 to 5.1) for 6 to 8 seropositivities (P<0.02) (adjusted). After a mean follow-up of 3.2 years, cardiovascular mortality rate was 7.0% in patients with advanced atherosclerosis and seropositive for 0 to 3 pathogens compared with 20.0% in those seropositive for 6 to 8 pathogens. CONCLUSIONS: Our results support the hypothesis that infectious agents are involved in the development of atherosclerosis. We showed a significant association between infectious burden and the extent of atherosclerosis. Moreover, the risk for future death was increased by the number of infectious pathogens, especially in patients with advanced atherosclerosis.