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Circulating endothelial progenitor cells and cardiovascular outcomes.

BACKGROUND: Endothelial progenitor cells derived from bone marrow are believed to support the integrity of the vascular endothelium. The number and function of endothelial progenitor cells correlate inversely with cardiovascular risk factors, but the prognostic value associated with circulating endothelial progenitor cells has not been defined. METHODS: The number of endothelial progenitor cells positive for CD34 and kinase insert domain receptor (KDR) was determined with the use of flow cytometry in 519 patients with coronary artery disease as confirmed on angiography. After 12 months, we evaluated the association between baseline levels of endothelial progenitor cells and death from cardiovascular causes, the occurrence of a first major cardiovascular event (myocardial infarction, hospitalization, revascularization, or death from cardiovascular causes), revascularization, hospitalization, and death from all causes. RESULTS: A total of 43 participants died, 23 from cardiovascular causes. A first major cardiovascular event occurred in 214 patients. The cumulative event-free survival rate increased stepwise across three increasing baseline levels of endothelial progenitor cells in an analysis of death from cardiovascular causes, a first major cardiovascular event, revascularization, and hospitalization. After adjustment for age, sex, vascular risk factors, and other relevant variables, increased levels of endothelial progenitor cells were associated with a reduced risk of death from cardiovascular causes (hazard ratio, 0.31; 95 percent confidence interval, 0.16 to 0.63; P=0.001), a first major cardiovascular event (hazard ratio, 0.74; 95 percent confidence interval, 0.62 to 0.89; P=0.002), revascularization (hazard ratio, 0.77; 95 percent confidence interval, 0.62 to 0.95; P=0.02), and hospitalization (hazard ratio, 0.76; 95 percent confidence interval, 0.63 to 0.94; P=0.01). Endothelial progenitor-cell levels were not predictive of myocardial infarction or of death from all causes. CONCLUSIONS: The level of circulating CD34+KDR+ endothelial progenitor cells predicts the occurrence of cardiovascular events and death from cardiovascular causes and may help to identify patients at increased cardiovascular risk.

Aged↗

Epidemiology of cardiovascular risk in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) patients are highly prone to cardiovascular disease for a number of reasons. At the time of starting renal replacement treatment, their cardiovascular condition is already severely compromised, suggesting that cardiovascular risk factors begin to operate very early in the progression of CKD. Moreover, those patients reaching end-stage renal disease without cardiovascular abnormalities have a high probability of developing de novo cardiovascular disease. METHODS: In this review, we analyse the prevalence of the major cardiovascular risk factors in CKD patients and their importance as contributors to the excess cardiovascular disease in this population. We also describe and discuss the main results obtained in the management of these risk factors in terms of preventing cardiovascular morbidity and mortality. RESULTS: Hypertension plays a major role in determining cardiac damage at all stages of CKD, including the dialytic phase. Anaemia is a major determinant of the development of left ventricular hypertrophy and therefore its correction can be expected to improve cardiovascular status and long-term survival, but this needs to be done before changes in cardiac structure become well established. Calcium-phosphate disorders are increasingly acknowledged to be cardiovascular risk factors in CKD, yet their medical control is still far from being satisfactory. Dyslipidaemia is particularly frequent in CKD patients, but the benefit of lipid-lowering treatments still has to be proven. Finally, CKD is associated with newly recognized risk factors for atherosclerosis, although their importance as cardiovascular risk factors is still controversial. CONCLUSIONS: Nephrologists should attempt to give optimal treatment for well-established cardiovascular risk factors, even if this generally fails to prevent the excess cardiovascular disease of CKD patients. Increasing attention is now being paid to newly recognized CKD-related risk factors for atherosclerosis, although their real importance is still under debate and, before therapeutic prescriptions can be applied to CKD patients, further studies in these new fields are needed.

Cardiovascular Diseases↗

A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients.

BACKGROUND: Cardiovascular morbidity and mortality are highly prevalent in haemodialysis (HD) patients and have been recently associated with vascular calcifications. The objective of our study was to assess the value of a simple vascular calcification score for the prediction of cardiovascular death, cardiovascular hospitalizations and fatal and non-fatal cardiovascular events in HD patients, and to correlate this score with cardiovascular disease and with other known predictors of vascular disease. METHODS: In this observational, prospective study 123 chronic HD patients (75 males and 48 females; 20% diabetic) were included, who were on low-flux HD treatment for 46.6+/-52 months (mean+/-SD). We set up a simple vascular calcification score based on plain radiographic films of pelvis and hands. Brachial pulse pressure and mean arterial pressure (MAP) were measured and cardiovascular events and hospitalization episodes were assessed. RESULTS: During an observational period of 37 months there were 17 cardiovascular deaths; 28 patients needed cardiovascular hospitalizations and 32 patients suffered fatal and non-fatal cardiovascular events. Coronary artery disease was diagnosed in 43 patients (35%), peripheral arterial disease in 33 patients (26.8%), cerebrovascular disease in 16 patients (13%) and vascular disease (coronary artery disease or peripheral arterial disease or cerebral vascular disease) in 61 patients (49.6%). By binary logistic regression, diabetes (P = 0.01), male sex (P<0.001), age (P = 0.02), HD duration (P = 0.02) and MAP (P = 0.03) were independently associated with a vascular score > or =3. This score > or =3 was independently associated with coronary artery disease (P = 0.008), peripheral arterial disease (P<0.001) and vascular disease (P = 0.001). Patients with a vascular calcification score > or =3 had a 3.9-fold higher risk of cardiovascular mortality (P = 0.03), a 2.8-fold higher risk of cardiovascular hospitalizations (P = 0.02) and a 2.3-fold higher risk of fatal or non-fatal cardiovascular events (P = 0.04). CONCLUSIONS: The present vascular calcification scoring represents a simple tool for the assessment of cardiovascular risk related with vascular calcifications in chronic HD patients.

Adult↗

Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients.

BACKGROUND: Dialysis patients have higher cardiovascular events rate than patients with normal renal function. Hyperhomocysteinemia, a risk factor for cardiovascular disease, is frequently detected in dialysis patients. Vitamin B supplementation lowers hyperhomocysteinemia, but it is unknown whether it reduces cardiovascular events rate. We planned a long-term study to analyze the effects of homocysteine-lowering vitamin B therapy on cardiovascular disease in hemodialysis patients. METHODS: We performed a single center open prospective trial. Patients, just on folate therapy at enrolment, were left out from randomization and maintained folate therapy according to study's protocol (group A). Patients, untreated with folic acid at recruitment, were randomly assigned to other 2 groups: patients submitted to folate supplementation according to study's protocol (group B), and untreated ones (group C). We instructed patients to take 5 mg oral daily folic acid or 5 mg every other day whether serum folate levels were up the normal high limit. We measured homocysteine, folate and vitamin B12 plasma levels at baseline and every 4 months. We chose the appearance of fatal and nonfatal cardiovascular events as end-points. RESULTS: We analyzed data of 114 patients for a median follow-up time of 871 days. Stepwise regression analysis demonstrated that baseline homocysteine levels were related to folate (coefficient: -1.02; F: 64.5), creatinine (coefficient: 0.98; F: 11.3), and C reactive protein (coefficient: -0.64; F: 4.3). Patients ended the study for the following reasons: cardiovascular morbidity (n = 44), death (n = 25), renal transplant (n = 9), moved away (n = 4). Cardiovascular events occurred in 58 of 114 patients (51%), in 26 of 63 (41%) treated patients (both group A and group B) and in 32 of 51 (63%; chi2 = 6.0; p = 0.05) untreated patients (group C). Kaplan-Meier survival analysis showed that cardiovascular events were less frequent in treated patients with low homocysteine levels (chi2 24.1; p < 0.0001). Cox regression analysis showed that cardiovascular events were explained by homocysteine, dialysis vintage, past cardiovascular accidents, and age. We noticed not only lower homocysteine levels, but also higher protein catabolic rate values in events-free patients as compared with patients with nonfatal cardiovascular events. After having divided patients into 4 subgroups according to high and low, split at median, Hcy and protein catabolic rate values, we observed in Kaplan-Meier survival curves for cardiovascular events by these subgroups that patients with low Hcy and high protein catabolic rate values showed a significant lower hazard rate than patients with high Hcy and low protein catabolic rate levels (chi2 = 21.7; p < 0.0001). CONCLUSIONS: This trial shows for the first time that homocysteine-lowering folate therapy decreases cardiovascular events in dialysis patients. It is necessary to perform large prospective studies to confirm our results.

Aged↗

[Cardiovascular disease after renal transplantation].

Cardiovascular disease is the leading cause of morbidity and mortality following renal transplantation. Because many renal transplant recipients die with functioning grafts, deaths resulting from cardiovascular disease have became an increasingly important cause of graft loss, particularly after the first post-transplantation year. Moreover, a contribution of some cardiovascular risk factors to renal allograft dysfunction has been demonstrated. A number of observational studies suggest that cardiovascular disease is more common in renal transplant patients than in the general population. The excessive risk for cardiovascular disease is related to a high prevalence and accumulation of atherogenic risk factors before and after transplantation. Hypertension, post-transplantation diabetes and hyperlipidemia are well-recognized risk factors for the development of cardiovascular events after renal transplantation and are strongly associated with immunosuppressive therapy. Progressive renal dysfunction may also influence the risk of cardiovascular complications after renal transplantation. The elevated risk may also be caused by non- traditional risk factors such as anaemia, adhesion molecules, hyperhomocysteinemia, microinflammatory state, abnormal coagulation and oxidative stress. To prevent post-transplantation cardiovascular disease it is crucial to define the etiological risk factors. Some risk factors can be modified, and for some of these, there is strong evidence from studies in the general population that intervention improves survival. Given the significant morbidity and mortality of cardiovascular disease in renal transplant recipients, aggressive treatment intervention for potentially modifiable factors are strongly advocated after transplantation. In addition to treatment intervention, risk management should also involve tailoring the immunosuppressive regimen to minimize both direct and indirect cardiovascular risks. In this article we attempted to review and quantify the post-transplant risk factors for cardiovascular disease as well as offer suggestions on optimizing the therapy or treatment strategies to minimize the risk of cardiovascular complications in renal transplant patients. Reduction of cardiovascular morbidity and mortality can improve not only the life expectancy and quality of life of the transplant recipients but also their graft function and survival.

Anemia↗

Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance; are they interchangeable?

AIMS: To prospectively compare the agreement of left ventricular volumes and ejection fraction by M-mode echocardiography (echo), 2D echo, radionuclide ventriculography and cardiovascular magnetic resonance performed in patients with chronic stable heart failure. It is important to know whether the results of each technique are interchangable, and thereby how the results of large studies in heart failure utilizing one technique can be applied using another. Some studies have compared cardiovascular magnetic resonance with echo or radionuclude ventriculography but few contain patients with heart failure and none have compared these techniques with the current fast breath-hold acquisition cardiovascular magnetic resonance. METHODS AND RESULTS: Fifty two patients with chronic stable heart failure taking part in the CHRISTMAS Study, underwent M-mode echo, 2D echo, radionuclude ventriculography and cardiovascular magnetic resonance within 4 weeks. The scans were analysed independently in blinded fashion by a single investigator at three core laboratories. Of the echocardiograms, 86% had sufficient image quality to obtain left ventricular ejection fraction by M-mode method, but only 69% by 2D Simpson's biplane analysis. All 52 patients tolerated the radionuclude ventriculography and cardiovascular magnetic resonance, and all these scans were analysable. The mean left ventricular ejection fraction by M-mode cube method was 39+/-16% and 29+/-15% by Teichholz M-mode method. The mean left ventricular ejection fraction by 2D echo Simpson's biplane was 31+/-10%, by radionuclude ventriculography was 24+/-9% and by cardiovascular magnetic resonance was 30+/-11. All the mean left ventricular ejection fractions by each technique were significantly different from all other techniques (P<0.001), except for cardiovascular magnetic resonance ejection fraction and 2D echo ejection fraction by Simpson's rule (P=0.23). The Bland-Altman limits of agreement encompassing four standard deviations was widest for both cardiovascular magnetic resonance vs cube M-mode echo and cardiovascular magnetic resonance vs Teichholz M-mode echo at 66% each, and was 58% for radionuclude ventriculography vs cube M-mode echo, 44% for cardiovascular magnetic resonance vs Simpson's 2D echo, 39% for radionuclide ventriculography vs Simpson's 2D echo, and smallest at 31% for cardiovascular magnetic resonance-radionuclide ventriculography. Similarly, the end-diastolic volume and end-systolic volume by 2D echo and cardiovascular magnetic resonance revealed wide limits of agreement (52 ml to 216 ml and 11 ml to 188 ml, respectively). CONCLUSION: These results suggest that ejection fraction measurements by various techniques are not interchangeable. The conclusions and recommendations of research studies in heart failure should therefore be interpreted in the context of locally available techniques. In addition, there are very wide variances in volumes and ejection fraction between techniques, which are most marked in comparisons using echocardiography. This suggests that cardiovascular magnetic resonance is the preferred technique for volume and ejection fraction estimation in heart failure patients, because of its 3D approach for non-symmetric ventricles and superior image quality.

Echocardiography↗

[Cardiovascular hyperactivity in patients with family history of high blood pressure].

BACKGROUND AND OBJECTIVE: The association between family history of essential high blood pressure (FH of HBP) and the cardiovascular hyperactivity to the isometric exercise is not well known; that is why the aim of this study was to describe this relation and to determine whether it is independent of the presence of cardiovascular risk factors. PATIENTS AND METHOD: We carried out a correlational descriptive study with a sample of 1855 people of both sexes between 18 and 70 years of age. The cardiovascular hyperactivity, expression of the cardiovascular response to the activity of the sympathetic nervous system (SNS), was determined by means of the test of the sustained weight (TSW). Comparisons of the values of cardiovascular reactivity were developed between individuals with and without FH of HBP and a model of logistical regression. The level of statistical significance was 95%. RESULTS: The arterial blood pressure at the end of the TSW was higher in individuals with FH of HBP independently of the age group. The cardiovascular hyperactivity, measured by means of they systolic index of cardiovascular reactivity, was also significantly higher in subjects with FH of HBP. Finally, individuals with FH of HBP showed a higher risk (more than 5 times) of having cardiovascular hyperactivity (OR = 5.16; CI 95%, 3.51-7.59), this association being independent of other cardiovascular factors of risk. CONCLUSIONS: The FH of HBP is independently related to the cardiovascular hyperactivity, to the isometric exercise, of other cardiovascular risks factors. These elements help explain the relationship between cardiovascular hyperactivity, the activity of SNS and essential high blood pressure, at least in an important group of people.

Adolescent↗

Pharmacokinetic-pharmacodynamic modelling of the cardiovascular effects of drugs - method development and application to magnesium in sheep.

BACKGROUND: There have been few reports of pharmacokinetic models that have been linked to models of the cardiovascular system. Such models could predict the cardiovascular effects of a drug under a variety of circumstances. Limiting factors may be the lack of a suitably simple cardiovascular model, the difficulty in managing extensive cardiovascular data sets, and the lack of physiologically based pharmacokinetic models that can account for blood flow changes that may be caused by a drug. An approach for addressing these limitations is proposed, and illustrated using data on the cardiovascular effects of magnesium given intravenously to sheep. The cardiovascular model was based on compartments for venous and arterial blood. Blood flowed from arterial to venous compartments via a passive flow through a systemic vascular resistance. Blood flowed from venous to arterial via a pump (the heart-lung system), the pumping rate was governed by the venous pressure (Frank-Starling mechanism). Heart rate was controlled via the difference between arterial blood pressure and a set point (Baroreceptor control). Constraints were made to pressure-volume relationships, pressure-stroke volume relationships, and physical limits were imposed to produce plausible cardiac function curves and baseline cardiovascular variables. "Cardiovascular radar plots" were developed for concisely displaying the cardiovascular status. A recirculatory kinetic model of magnesium was developed that could account for the large changes in cardiac output caused by this drug. Arterial concentrations predicted by the kinetic model were linked to the systemic vascular resistance and venous compliance terms of the cardiovascular model. The kinetic-dynamic model based on a training data set (30 mmol over 2 min) was used to predict the results for a separate validation data set (30 mmol over 5 min). RESULTS: The kinetic-dynamic model was able to describe the training data set. A recirculatory kinetic model was a good description of the acute kinetics of magnesium in sheep. The volume of distribution of magnesium in the lungs was 0.89 L, and in the body was 4.02 L. A permeability term (0.59 L min-1) described the distribution of magnesium into a deeper (probably intracellular) compartment. The final kinetic-dynamic model was able to predict the validation data set. The mean prediction error for the arterial magnesium concentrations, cardiac output and mean arterial blood pressure for the validation data set were 0.02, 3.0 and 6.1%, respectively. CONCLUSION: The combination of a recirculatory model and a simple two-compartment cardiovascular model was able to describe and predict the kinetics and cardiovascular effects of magnesium in sheep.

Animals↗

Hyperinsulinemia and the risk of cardiovascular death and acute coronary and cerebrovascular events in men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND: The role of hyperinsulinemia as a cardiovascular risk factor is controversial. We studied whether hyperinsulinemia is independently associated with increased cardiovascular morbidity and mortality. METHODS: Fasting serum insulin level and other cardiovascular risk factors were determined in 1521 men in eastern Finland aged 42 to 60 years with neither cardiovascular disease nor diabetes at baseline. Forty-five cardiovascular deaths, 110 acute coronary events, 48 strokes, and 163 any cardiovascular events occurred during an average follow-up of 9.5 years. A total of 163 cardiovascular events (45 cardiovascular deaths, 110 acute coronary events, and 48 strokes) occurred during an average follow-up of 9.5 years. RESULTS: In Cox regression analysis adjusting for age and examination years, fasting serum insulin level as a continuous variable was directly associated with the risk of cardiovascular death (P = .006), acute coronary events (P = .04), and stroke (P = .02). Men with insulin levels of 52 to 66 pmol/L, 67 to 89 pmol/L, and 90 pmol/L or more (3 highest quartiles) had 1.4-fold (95% confidence interval, 0.5-3.7), 1.4-fold (95% confidence interval, 0.5-3.7), and 2.5-fold (95% confidence interval, 1.0-5.9; P = .05) cardiovascular mortality, respectively, compared with men with insulin levels of less than 52 pmol/L (lowest quartile) (P = .04 for linear trend). Adjustment for serum lipid levels, blood pressure, and obesity reduced the excess cardiovascular mortality in the highest insulin quartile by 7%, 33%, and 67%, respectively. There were no statistically significant differences in the incidence of acute coronary events and stroke between the insulin quartiles. CONCLUSIONS: Hyperinsulinemia had a modest association with increased cardiovascular mortality in middle-aged men. This relationship was largely explained by obesity, hypertension, and dyslipidemia. Hyperinsulinemia had even weaker associations with the risk of acute coronary event and stroke.

Acute Disease↗

Unfavorable cardiovascular risk profiles in untreated and treated psoriasis patients.

Psoriasis is a chronic inflammatory skin disease that is associated with an increased cardiovascular risk profile. The systemic inflammation present in psoriasis, various systemic treatments for psoriasis and an increased prevalence of unhealthy life style factors may all contribute to this unfavorable risk profile. The purpose of this article is to provide an overview of what is known about these risk factors in psoriasis, the way they influence the cardiovascular risk of psoriasis patients, and what can be done to reduce this risk. Genetic studies demonstrate that psoriasis and cardiovascular disease share common pathogenic features in which, for example inflammatory cytokines like TNF-alpha and IL-1 play an important role. The chronic inflammation in psoriasis has an unfavorable effect on the cardiovascular risk profile. Multiple cardiovascular risk factors seem to be influenced; the blood pressure, oxidative stress, dyslipidemia, endothelial cell dysfunction, homocysteine levels and blood platelet adhesion. Moreover, classic cardiovascular risk factors like smoking and obesity that have an increased prevalence among patients with psoriasis, indirectly also worsen the cardiovascular risk profile by stimulating the psoriasis activity. Systemic treatments in psoriasis reduce the cardiovascular risk by diminishing the inflammation, but it should be taken into account that most therapies also have adverse cardiovascular effects like dyslipidemia, hyperhomocysteinemia and hypertension. As a consequence preventive measures may be indicated at least during long-term treatments. Prospective research is warranted to accurately estimate the increased cardiovascular risk in psoriasis, to determine the underlying processes and to consider preventive measures according to the absolute risk of cardiovascular disease. The present overview provides data to advice health care providers to pay more attention to the cardiovascular risk profile in psoriasis patients.

Cardiovascular Diseases↗

Cardiovascular disease in rheumatoid arthritis: single-center hospital-based cohort study in France.

INTRODUCTION: Rheumatoid arthritis (RA) was independently associated with cardiovascular events in several studies, most of which were conducted in the US. OBJECTIVES: To estimate the risk of cardiovascular events in a cohort of RA patients recruited at a hospital in France, to identify cardiovascular risk factors, and to measure the severity of cardiovascular events. METHODS: Two hundred and thirty-nine patients admitted between January 1, 1998, and March 31, 1999, for RA meeting American College of Rheumatology criteria, with a negative history for cardiovascular events, were sent a questionnaire in 2004 to evaluate the occurrence of myocardial infarction, stroke, or cardiovascular death. RESULTS: During the mean follow-up of 5.4+/-1.8 years, there were 10 cases of myocardial infarction (0.8%/year), 3 cases of stroke (0.2%/year), and 9 cardiovascular deaths (0.7%/year). Of the 10 patients who experienced myocardial infarction, 5 had clinical symptoms of heart failure and 4 died from cardiovascular causes. Independent risk factors for cardiovascular events were older age (relative risk [RR], 2.5/10 years; 95% confidence interval [95%CI], 1.4-4.2), male gender (RR, 5.1; 95%CI, 1.8-14.6), treated hypertension (RR, 4.3; 95%CI, 1.4-13.2), and treated hypercholesterolemia (RR, 6.0; 95%CI, 1.8-20.7). CONCLUSION: Our data suggest a higher risk of cardiovascular events in patients with RA compared to the general population in France (0.1-0.5%/year for myocardial infarction and 0.07%/year for stroke in the age group covered by our cohort). Cardiovascular events in the patients with RA seemed unusually severe. Patients with RA should be carefully screened for conventional cardiovascular risk factors.

Age Distribution↗

Blood pressure and cardiovascular morbidity and mortality rates in the elderly.

The influence of blood pressure on the development of cardiovascular disease and mortality rate beyond 75 years of age has been uncertain. A reported inverse relation to mortality rate noted in the very old could reflect poor cardiovascular health. This report examines the impact of blood pressure on cardiovascular morbidity and mortality rates and all-cause mortality rate in those aged 75 to 94 years. For this analysis the data were the Framingham study subjects found free of cardiovascular disease and a second sample of those with cardiovascular disease present on the biennial examinations. Investigation of the relation of systolic and diastolic blood pressures to all causes and cardiovascular morbidity and mortality rates within each 2-year interval for those aged 75 to 94 years was carried out. Over the period of 38 years of follow-up there were increasing cardiovascular morbidity and mortality rates with increasing blood pressure levels for both men and women in the sample free of cardiovascular disease. In those with cardiovascular disease at the biennial examination there was a distinct U-shaped curve of cardiovascular mortality rate in relation to systolic blood pressure in men with a substantial increase in mortality rate below systolic pressures of 120 mm Hg for both men and women. Excess mortality rate reported in elderly persons with low blood pressure appears to be a result of poor cardiovascular health and not from the low pressure itself. The excess mortality rate reported for low blood pressure levels in persons older than 75 years derives from the inclusion of the substantial proportion of this age group who have cardiovascular disease.

Aged↗

Discordance of influence of hypertension on mortality and cardiovascular risk in hemodialysis patients.

BACKGROUND: Hemodialysis patients are at significantly increased risk for both morbidity and mortality from cardiovascular disease. However, most recent reports have indicated elevated mortality risk associated with low blood pressure, rather than high blood pressure. We added nonfatal cardiovascular events as an outcome in addition to cardiovascular and all-cause mortality to analyze the risk of hypertension. METHODS: One hundred sixty-four patients receiving regular hemodialysis between January and December 1998 were examined and prospectively followed up until the end of 2003. The primary end point was hospital admission or death from cardiovascular disease. Secondary end points were cardiovascular and all-cause mortality. RESULTS: During the 5-year follow-up period, 52 patients experienced cardiovascular events and 45 patients died (18 patients, from cardiovascular disease). Based on Cox analysis, high systolic blood pressure (relative risk [RR], 1.23; 95% confidence interval [CI], 1.07 to 1.43; P = 0.004) and older age were independently associated with cardiovascular events. Elevated systolic blood pressure (RR, 1.25; 95% CI, 0.99 to 1.59; P = 0.063) was a marginal predictor for cardiovascular mortality. Age, serum albumin level, malignant neoplasm, and diabetes were independent risk factors for all-cause mortality, whereas there was no association between blood pressure and all-cause mortality. The hazard ratio for cardiovascular events after adjustment for age, sex, and diabetes was lowest in patients with systolic blood pressure of 140.1 mm Hg or less and progressively increased with the increase in systolic blood pressure. CONCLUSION: Hypertension is a potent risk factor for cardiovascular disease in hemodialysis patients, as in the general population, whereas there is no association of hypertension with mortality. Active reduction in systolic blood pressure is important to minimize the occurrence of cardiovascular events.

Cardiovascular Diseases↗

Carotid intima-media thickness, arterial stiffness and risk of cardiovascular disease: current evidence.

AIMS: Over recent decades the interest in cardiovascular epidemiology has broadened from studies on causes and consequences of elevated cardiovascular risk factors to include research on causes and consequences of atherosclerosis and associated arterial wall abnormalities. One of the underlying reasons was that established cardiovascular risk factors were insufficiently accurate in identifying those individuals who will suffer from cardiovascular disease in the future and measures of subclinical atherosclerosis may enhance the precision of these predictions and thus enable better-tailored medical care to be provided. The usefulness of measuring subclinical atherosclerosis is conditional on evidence that presence of subclinical atherosclerosis confers an increased risk of cardiovascular disease and that favourable changes in subclinical atherosclerosis parallel reductions in risk. We aimed at providing an overview of epidemiological data on carotid intima-media thickness (CIMT) and arterial stiffness measurements and their relation to risk of cardiovascular disease. METHODS: We reviewed the published epidemiological data. RESULTS AND CONCLUSION: CIMT is a good indicator of cardiovascular risk and provides a graded measure of vascular damage: no clear CIMT level above which the cardiovascular risk appears to increase considerably The evidence for arterial stiffness, assessed as carotid distensibility or aortic pulse wave velocity, as an indicator for risk of cardiovascular disease is restricted to subjects with either hypertension or end-stage renal disease or based on small studies in renal transplant patients and elderly. Evidence to indicate that information on carotid intima-media thickness or arterial stiffness, additional to established cardiovascular risk factors, helps to distinguish subjects into those with a high and those with a low absolute risk of cardiovascular disease is limited, but needed. Also, information on the direct comparison of both arterial stiffness measures in their ability to predict cardiovascular disease is needed.

Cardiovascular Diseases↗

Long-term cardiovascular morbidity and mortality in autosomal dominant polycystic kidney disease patients after renal transplantation.

Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased incidence of hypertension and cardiovascular abnormalities. In this long-term follow-up study (5.88 years on average), we evaluated cardiovascular disease and patient and graft survival in 101 ADPKD patients and 692 nondiabetic control patients receiving cadaveric renal transplants between March 1967 and April 1991 at the Leiden University Hospital. Graft and patient survival was not different between patient groups, using the same immunosuppressive therapy. However, death with functioning graft, mainly due to cardiovascular disease, was significantly more frequent in the ADPKD patients than in controls using AZA (P < 0.01). Multivariate analysis of pretransplant data showed that ADPKD patients on AZA therapy demonstrated an elevated age-adjusted relative risk of 2.07 (95% confidence interval [95% CI]: 1.12-3.80) for cardiovascular events and 2.88 (95% CI: 1.41-5.90) for cardiovascular mortality alone. After adjustment for age, gender, and other cardiovascular risk factors, a relative risk of 2.39 (95% CI: 1.06-5.40) was found. This was 2.87 (95% CI: 1.04-7.93) when cardiovascular mortality was the dependent variable. With posttransplant data, the age-adjusted relative risk for cardiovascular morbidity and mortality in ADPKD patients using AZA was 2.16 (95% CI: 1.12-4.15) and 2.97 (95% CI: 1.40-6.27), with only cardiovascular mortality as the dependent variable. After adjustment for age, gender, and other cardiovascular risk factors, this was 1.59 (95% CI: 0.64-3.91) and 2.28 (95% CI: 0.79-6.53), respectively. With CsA treatment, an elevated risk for cardiovascular morbidity and mortality in ADPKD patients was present, but the corresponding 95% CI were wide and include unity, due to the shorter period of follow-up (CsA: 3.81 +/- 2.50 years vs. AZA: 7.28 +/- 6.74 years). Survival of ADPKD patients using AZA was less in those patients without pretransplant nephrectomy as compared with control patients, but the morbidity and mortality of pretransplant nephrectomies should be taken into account. We conclude that ADPKD patients show a similar graft and patient survival after renal transplantation as control patients, but they are especially at risk for cardiovascular disease after renal transplantation.

Adult↗

Prehypertension and cardiovascular morbidity.

PURPOSE: The Seventh Report of the Joint National Commission (JNC 7) on High Blood Pressure established prehypertension (120 to 139 mm Hg systolic or 80 to 89 mm Hg diastolic) as a new risk category. We aim to determine the risk of major cardiovascular events associated with blood pressure in the prehypertensive range in a longitudinal, population-based cohort. METHODS: Analyses were conducted on participants in the National Health and Nutrition Examination Survey I (1971-1975) observed for 18 years for major cardiovascular disease events. Cox proportional hazard ratios were calculated to assess relative risk of cardiovascular disease, including stroke, myocardial infarction, and heart failure, in participants with prehypertension and normal blood pressure (<120/80 mm Hg). RESULTS: Prehypertension was associated with increased risk for cardiovascular disease (1.79 [95% confidence interval (CI) 1.40-2.24]) in unadjusted analysis. After adjustment for cardiovascular risk factors, the relationship of prehypertension to cardiovascular disease was diminished but persisted (1.32 [95% CI 1.05-1.65]). Ninety-three percent of prehypertensive individuals had at least 1 cardiovascular risk factor. Low prehypertension (120-129/80-84 mm Hg) was associated with increased cardiovascular disease in unadjusted analyses (1.56 [95% CI 1.23-1.98]) but was not statistically significant in adjusted analyses (1.24 [95% CI 0.96-1.59]). High-normal blood pressure (130-139/85-89 mm Hg) remained a predictor of cardiovascular disease in unadjusted (2.13 [95% CI 1.64-2.76]) and adjusted (1.42 [95% CI 1.09-1.84]) analyses. CONCLUSIONS: In a longitudinal, population-based, US cohort, prehypertension was associated with increased risk of major cardiovascular events independently of other cardiovascular risk factors. These findings, along with the presence of cardiovascular risk factors in the majority of participant sample with prehypertension, support recommendations for physicians to actively target lifestyle modifications and multiple risk reduction in their prehypertensive patients.

Adult↗

Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial.

OBJECTIVE: We investigated in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: The Primary Prevention Project (PPP) is a randomized, open trial with a two-by-two factorial design aimed to investigate low-dose aspirin (100 mg/day) and vitamin E (300 mg/day) in the prevention of cardiovascular events in patients with one or more cardiovascular risk factors. The primary end point was a composite end point of cardiovascular death, stroke, or myocardial infarction. A total of 1,031 people with diabetes in the PPP, aged >/=50 years, without a previous cardiovascular event were enrolled by 316 general practitioners and 14 diabetes outpatient clinics. RESULTS: The PPP trial was prematurely stopped (after a median of 3.7 years) by the independent data safety and monitoring board because of a consistent benefit of aspirin compared with the control group in a population of 4,495 patients with one or more major cardiovascular risk factors. In diabetic patients, aspirin treatment was associated with a nonsignificant reduction in the main end point (relative risk [RR] = 0.90, 95% CI 0.50-1.62) and in total cardiovascular events (0.89, 0.62-1.26) and with a nonsignificant increase in cardiovascular deaths (1.23, 0.69-2.19). In nondiabetic subjects, RRs for the main end point, total cardiovascular events, and cardiovascular deaths were 0.59 (0.37-0.94), 0.69 (0.53-0.90), and 0.32 (0.14-0.72), respectively. No significant reduction in any of the end points considered could be found with vitamin E in either diabetic or nondiabetic subjects. CONCLUSIONS: Our data suggest a lower effect of primary prevention of cardiovascular disease (CVD) with low-dose aspirin in diabetic patients as opposed to subjects with other cardiovascular risk factors. If confirmed, these findings might indicate that the antiplatelet effects of aspirin in diabetic patients are overwhelmed by aspirin-insensitive mechanisms of platelet activation and thrombus formation, thus making the balance between benefits and harms of aspirin treatment unfavorable. Further large-scale trials investigating the role of aspirin in the primary prevention of CVD in diabetic patients are urgently needed.

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Self-reported adherence with medication and cardiovascular disease outcomes in the Second Australian National Blood Pressure Study (ANBP2).

OBJECTIVE: To investigate whether responses to a previously validated four-item medication adherence questionnaire were associated with adverse cardiovascular events. DESIGN: Survey conducted among a cohort of participants in the Second Australian National Blood Pressure Study. SETTING: Australian general practice. PARTICIPANTS: 4039 older people with hypertension. MAIN OUTCOME MEASURES: All major cardiovascular events or death; first specific cardiovascular event. RESULTS: Subjects who adhered to their medication regimen (compared with non-adherent subjects) were significantly less likely to experience a first cardiovascular event or a first non-fatal cardiovascular event (hazard ratio [HR] for both, 0.81; 95% CI, 0.67-0.98; P = 0.03); a fatal other cardiovascular event (HR, 0.68; 95% CI, 0.48-0.99; P = 0.04); or a first occurrence of heart failure (HR, 0.58; 95% CI, 0.37-0.90; P = 0.02). Those who answered yes to "Did you ever forget to take your medication?" were significantly more likely to experience a cardiovascular event or death (HR, 1.28; 95% CI, 1.04-1.57; P = 0.02); a first cardiovascular event or death (HR, 1.31; 95% CI, 1.07-1.60; P = 0.01); a first cardiovascular event (HR, 1.34; 95% CI, 1.09-1.65; P = 0.01); or a first non-fatal cardiovascular event (HR, 1.35; 95% CI, 1.09-1.66; P = 0.01). Those who answered yes to "Sometimes, if you felt worse when you took your medicine, did you stop taking it?" were significantly more likely to experience a first occurrence of heart failure (HR, 2.06; 95% CI, 1.16-3.64; P = 0.01). CONCLUSIONS: Subjects who adhered to their medication regimen were less likely to experience major cardiovascular events or death. The question relating to forgetting to take medication identified non-adherent subjects likely to experience a cardiovascular event or death. Clinicians could use this question to identify patients with hypertension who are likely to benefit from medication adherence strategies.

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