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PubMed2003

Ability of exercise testing to predict cardiovascular and all-cause death in asymptomatic women: a 20-year follow-up of the lipid research clinics prevalence study.

CONTEXT: The value of exercise testing in women has been questioned. OBJECTIVE: To determine the prognostic value of exercise testing in a population-based cohort of asymptomatic women followed up for 20 years. DESIGN AND SETTING: Near-maximal Bruce-protocol treadmill test data from the Lipid Research Clinics Prevalence Study (1972-1976) with follow-up through 1995. PARTICIPANTS: A total of 2994 asymptomatic North American women, aged 30 to 80 years, without known cardiovascular disease. MAIN OUTCOME MEASURES: Cardiovascular and all-cause mortality. RESULTS: There were 427 (14%) deaths during 20 years of follow-up, of which 147 were due to cardiovascular causes. Low exercise capacity, low heart rate recovery (HRR), and not achieving target heart rate were independently associated with increased all-cause and cardiovascular mortality. There was no increased cardiovascular death risk for exercise-induced ST-segment depression (age-adjusted hazard ratio, 1.02; 95% confidence interval [CI], 0.57-1.80; P =.96). The age-adjusted hazard ratio for cardiovascular death for every metabolic equivalent (MET) decrement in exercise capacity was 1.20 (95% CI, 1.18-1.30; P<.001); for every 10 beats per minute decrement in HRR, the hazard ratio was 1.36 (95% CI, 1.19-1.55; P<.001). After adjusting for multiple other risk factors, women who were below the median for both exercise capacity and HRR had a 3.5-fold increased risk of cardiovascular death (95% CI, 1.57-7.86; P =.002) compared with those above the median for both variables. Among women with low risk Framingham scores, those with below median levels of both exercise capacity and HRR had significantly increased risk compared with women who had above median levels of these 2 exercise variables, 44.5 and 3.5 cardiovascular deaths per 10 000 person-years, respectively (hazard ratio for cardiovascular death, 12.93; 95% CI, 5.62-29.73; P<.001). CONCLUSION: The prognostic value of exercise testing in asymptomatic women derives not from electrocardiographic ischemia but from fitness-related variables.

Adult↗
PubMed2005

N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults.

CONTEXT: B-type natriuretic peptides have been shown to predict cardiovascular disease in apparently healthy individuals but their predictive ability for mortality and future cardiovascular events compared with C-reactive protein (CRP) and urinary albumin/creatinine ratio is unknown. OBJECTIVE: To assess the prognostic value of the N-amino terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) vs CRP and urinary albumin/creatinine ratio in an older adult population. DESIGN, SETTING, AND PARTICIPANTS: A population-based prospective study of 764 participants aged 50 to 89 years from a community in Copenhagen, Denmark, in which 658 participants provided blood and urinary samples and were examined between September 1, 1998, and January 24, 2000. Of these participants, 626 without heart or renal failure were enrolled. A subgroup of 537 had no history of cardiovascular disease at baseline. During 5 years of follow-up (to December 31, 2003), 94 participants died and 65 developed a first major cardiovascular event. MAIN OUTCOME MEASURES: Risk of mortality and first major cardiovascular event by baseline levels of NT-proBNP, CRP, and urinary albumin/creatinine ratio levels. RESULTS: After adjustment for the cardiovascular risk factors of age, sex, smoking, diabetes mellitus, hypertension or ischemic heart disease, total cholesterol, and serum creatinine, the hazard ratio (HR) of mortality for values above the 80th percentile of NT-proBNP was 1.96 (95% confidence interval [CI], 1.21-3.19); for CRP, 1.46 (95% CI, 0.89-2.24); and for urinary albumin/creatinine ratio, 1.88 (95% CI, 1.18-2.98). Additional adjustment for left ventricular systolic dysfunction did not markedly attenuate the predictive value of NT-proBNP (HR, 1.82; 95% CI, 1.11-2.98). The absolute unadjusted increase in mortality risk for participants with values above the 80th percentile vs equal to or below the 80th percentile was 24.5% for NT-proBNP, 7.8% for CRP, and 19.5% for urinary albumin/creatinine ratio. The NT-proBNP levels were associated with first major cardiovascular events (nonfatal myocardial infarction, fatal coronary heart disease, unstable angina, heart failure, stroke, and transient ischemic attack) with an adjusted HR of 3.24 (95% CI, 1.80-5.79) vs 1.02 (95% CI, 0.56-1.85) for CRP and 2.32 (95% CI, 1.33-4.05) for urinary albumin/creatinine ratio when comparing participants with values above the 80th percentile with those with values equal to or below the 80th percentile. CONCLUSIONS: Measurements of NT-proBNP provide prognostic information of mortality and first major cardiovascular events beyond traditional risk factors. NT-proBNP was a stronger risk biomarker for cardiovascular disease and death than CRP was in nonhospitalized individuals aged 50 to 89 years.

Aged↗
PubMed2005

Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial.

CONTEXT: Basic research provides plausible mechanisms and observational studies suggest that apparently healthy persons, who self-select for high intakes of vitamin E through diet or supplements, have decreased risks of cardiovascular disease and cancer. Randomized trials do not generally support benefits of vitamin E, but there are few trials of long duration among initially healthy persons. OBJECTIVE: To test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women. DESIGN, SETTING, AND PARTICIPANTS: In the Women's Health Study conducted between 1992 and 2004, 39 876 apparently healthy US women aged at least 45 years were randomly assigned to receive vitamin E or placebo and aspirin or placebo, using a 2 x 2 factorial design, and were followed up for an average of 10.1 years. INTERVENTION: Administration of 600 IU of natural-source vitamin E on alternate days. MAIN OUTCOME MEASURES: Primary outcomes were a composite end point of first major cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and total invasive cancer. RESULTS: During follow-up, there were 482 major cardiovascular events in the vitamin E group and 517 in the placebo group, a nonsignificant 7% risk reduction (relative risk [RR], 0.93; 95% confidence interval [CI], 0.82-1.05; P = .26). There were no significant effects on the incidences of myocardial infarction (RR, 1.01; 95% CI, 0.82-1.23; P = .96) or stroke (RR, 0.98; 95% CI, 0.82-1.17; P = .82), as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a significant 24% reduction (RR, 0.76; 95% CI, 0.59-0.98; P = .03). There was no significant effect on the incidences of total cancer (1437 cases in the vitamin E group and 1428 in the placebo group; RR, 1.01; 95% CI, 0.94-1.08; P = .87) or breast (RR, 1.00; 95% CI, 0.90-1.12; P = .95), lung (RR, 1.09; 95% CI, 0.83-1.44; P = .52), or colon cancers (RR, 1.00; 95% CI, 0.77-1.31; P = .99). Cancer deaths also did not differ significantly between groups. There was no significant effect of vitamin E on total mortality (636 in the vitamin E group and 615 in the placebo group; RR, 1.04; 95% CI, 0.93-1.16; P = .53). CONCLUSIONS: The data from this large trial indicated that 600 IU of natural-source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer, did not affect total mortality, and decreased cardiovascular mortality in healthy women. These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women.

Aged↗
PubMed2006

Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials.

CONTEXT: Epidemiologic studies have suggested that folate intake decreases risk of cardiovascular diseases. However, the results of randomized controlled trials on dietary supplementation with folic acid to date have been inconsistent. OBJECTIVE: To evaluate the effects of folic acid supplementation on risk of cardiovascular diseases and all-cause mortality in randomized controlled trials among persons with preexisting cardiovascular or renal disease. DATA SOURCES: Studies were retrieved by searching MEDLINE (January 1966-July 2006) using the Medical Subject Headings cardiovascular disease, coronary disease, coronary thrombosis, myocardial ischemia, coronary stenosis, coronary restenosis, cerebrovascular accident, randomized controlled trial, clinical trials, homofolic acid, and folic acid, and the text words folic acid and folate. Bibliographies of all retrieved articles were also searched, and experts in the field were contacted. STUDY SELECTION: From 165 relevant retrieved reports, 12 randomized controlled trials compared folic acid supplementation with either placebo or usual care for a minimum duration of 6 months and with clinical cardiovascular disease events reported as an end point. DATA EXTRACTION: Data on study design, characteristics of participants, changes in homocysteine levels, and cardiovascular disease outcomes were independently abstracted by 2 investigators using a standardized protocol. DATA SYNTHESIS: Studies including data from 16 958 participants with preexisting vascular disease were analyzed using a random-effects model. The overall relative risks (95% confidence intervals) of outcomes for patients treated with folic acid supplementation compared with controls were 0.95 (0.88-1.03) for cardiovascular diseases, 1.04 (0.92-1.17) for coronary heart disease, 0.86 (0.71-1.04) for stroke, and 0.96 (0.88-1.04) for all-cause mortality. The relative risk was consistent among participants with preexisting cardiovascular or renal disease. CONCLUSIONS: Folic acid supplementation has not been shown to reduce risk of cardiovascular diseases or all-cause mortality among participants with prior history of vascular disease. Several ongoing trials with large sample sizes might provide a definitive answer to this important clinical and public health question.

Cardiovascular Diseases↗
PubMed2006

Validation of cardiovascular risk scores in a liver transplant population.

Increased prevalence of cardiovascular risk factors has been acknowledged in liver transplant recipients, and an increased incidence of cardiovascular events has been suspected. Individual risk determination, however, has not yet been established. Outpatient charts of 438 primary liver transplants have been reviewed, and suspected cardiovascular risk factors were correlated with cardiovascular events observed during a follow-up period of 10 yr. Receiver operation characteristics curve (ROC) analysis was performed to validate established cardiovascular risk scores. For calibration, the Hosmer-Lemeshow test was performed. A total of 303 of 438 patients were available for risk factor analysis at 6 months and demonstrated complete follow-up data (175 male, 128 female). A total of 40 of those 303 patients experienced fatal or nonfatal cardiovascular events (13.2%). In univariate analysis, age (P < 0.001), gender (P = 0.002), body mass index (P = 0.018), cholesterol (P = 0.044), creatinine (P = 0.006), diabetes mellitus (P = 0.017), glucose (0.006), and systolic blood pressure (P = 0.043), but not cyclosporine A (P = 0.743), tacrolimus (P = 0.870), or steroid medication (P = 0.991), were significantly associated with cardiovascular events. Multivariate analysis, however, identified only age, gender, and cholesterol as independent predictors. In ROC analysis, corresponding areas under the curve for Systematic Coronary Risk Evaluation Project (SCORE), Prospective Cardiovascular Münster Study (PROCAM), and Framingham risk scores (FRSs) were calculated with 0.800, 0.778, and 0.707, respectively. Calibration demonstrated an improved goodness of fit for PROCAM compared to SCORE risk calculations. In conclusion, SCORE and PROCAM proved to be valuable in discriminating our liver transplant recipients for their individual risk of cardiovascular events. Furthermore, calibrated PROCAM risk estimates are required to calculate the number of patients needed to treat in the setup of prospective intervention trials.

Adult↗
PubMed1998

Cardiovascular risk factors and diseases after renal transplantation.

UNLABELLED: Cardiovascular disease is a leading cause of death after renal transplantation (tpx), and the incidence is considerably higher than in the general population. OBJECTIVE: To evaluate the incidence of atherosclerotic cardiovascular complications after tpx, the prevalence of cardiovascular risk factors, prior to and following tpx, and the association between the risk factors and complications. PATIENTS AND METHODS: Analysis of atherosclerotic cardiovascular diseases (coronary artery disease, cerebral and peripheral vascular disease) and cardiovascular risk factors before and after transplantation in 427 renal transplant recipients between 1987 and 1992 (mean age at transplantation 45+/-12 years, 58% male, 7% diabetics) with a mean post-transplant follow-up of 29+/-20 months. RESULTS: Following tpx 11.7% developed atherosclerotic cardiovascular diseases, the majority coronary artery disease (9.8%). The comparison of risk factors 12 months before and 24 months following transplantation showed: prevalence of systemic hypertension (from 73% to 85%), diabetes mellitus (from 7% to 16%) and obesity with a body mass index >25 kg/m2 (from 26% to 48%) had increased significantly whereas the number of smokers halved to 20%. Triglycerides decreased significantly (from 235 mg/dl to 217 mg/dl). Total and HDL cholesterol rose significantly (from 232 mg/dl to 273 mg/dl and from 47 mg/dl to 56 mg/dl, respectively). LDL cholesterol increase was significant (from 180 mg/dl to 189 mg/dl). In the univariate analysis, cardiovascular diseases were significantly associated with male gender, age over 50 years, diabetes mellitus (DM), smoking, total cholesterol > or=200 mg/dl, LDL cholesterol >180 mg/dl, HDL cholesterol < or =55 mg/dl, fibrinogen > or =350 mg/dl, body mass index >25 kg/m2, serum uric acid >6.5 mg/dl and with more than two antihypertensive agents per day. The Cox proportional hazards model revealed DM with a relative risk (RR) of 4.3, age >50 years (RR=2.7), body mass index >25 kg/m2 (RR=2.6), smoking (RR=2.5), LDL cholesterol >180 mg/dl (RR=2.3) and uric acid >6.5 mg/dl as independent risk factors. CONCLUSIONS: The high incidence of cardiovascular disease following renal transplantation is mainly due to a high prevalence and accumulation of classical risk factors before and following transplantation. Future prospective studies should evaluate the success of treatment regarding reduction of cardiovascular morbidity and mortality in this high risk population.

Cardiovascular Diseases↗
PubMed1999

[Incidence of cardiovascular risk factors and complications after kidney transplantation].

BACKGROUND: Cardiovascular disease is a leading cause of death after renal transplantation (RTx), and the incidence is considerably higher than in the general population. Aim of this study was to evaluate the incidence of atherosclerotic cardiovascular complications after RTx, the prevalence of cardiovascular risk factors, prior to and following RTx, and the association between the risk factors and complications. PATIENTS AND METHODS: Analysis of atherosclerotic cardiovascular diseases (coronary artery disease, cerebral and peripheral vascular disease) and cardiovascular risk factors before and after transplantation in 427 renal transplant recipients between 1987 and 1992 (mean age at transplantation 45 +/- 12 years, 58% male, 7% diabetics) with a mean posttransplant follow-up of 28 +/- 20 months. RESULTS: Following RTx 11.7% developed atherosclerotic cardiovascular diseases, the majority coronary artery disease (9.8%). The comparison of risk factors 12 months before and 24 months following transplantation showed: The prevalence of systemic hypertension (from 67% to 86%), diabetes mellitus (from 7% to 16%) and obesity with a body mass index > 25 kg/m2 (from 26% to 48%) had increased significantly whereas the number of smokers halved to 20%. The triglycerides decreased significantly (from 235 +/- 144 mg/dl to 217 +/- 122 mg/dl). The total and HDL cholesterol rose significantly (from 232 +/- 65 mg/dl to 273 +/- 62 mg/dl and from 47 +/- 29 mg/dl to 56 +/- 21 mg/dl, respectively). The LDL cholesterol increase was insignificant (from 180 +/- 62 mg/dl to 189 +/- 53 mg/dl). In the univariate analysis, cardiovascular diseases were significantly associated with male gender, age over 50 years, diabetes mellitus (DM), smoking, total cholesterol > 200 mg/dl, LDL cholesterol > 180 mg/dl, HDL cholesterol < 55 mg/dl, fibrinogen > 350 mg/dl, body mass index > 25 kg/m2, and more than 2 antihypertensive agents per day. The Cox proportional hazards model revealed DM with a relative risk (RR) of 4.3, age > 50 years (RR = 2.7), body mass index > 25 kg/m2 (RR = 2.6), smoking (RR = 2.5), and LDL cholesterol > 180 mg/dl (RR = 2.3) as independent risk factors. CONCLUSIONS: The high incidence of cardiovascular disease following renal transplantation is mainly due to a high prevalence and accumulation of classical risk factors before and following transplantation. The treatment of the risk factors must be effective and introduced early in the course of renal failure, further, they must be continued following transplantation. Future prospective studies should evaluate the success of treatment regarding reduction of cardiovascular morbidity and mortality in this high risk population.

Age Distribution↗
PubMed2001

Risk factors for cardiovascular mortality and morbidity: the WHO Mutinational Study of Vascular Disease in Diabetes.

AIMS/HYPOTHESIS: We aimed to examine the associations between classic cardiovascular risk factors and diabetes specific factors and the incidence of fatal and non-fatal end-points in a large cohort of diabetic patients. METHODS: A cohort of 4,743 diabetic patients participating in the WHO Multinational Study of Vascular Disease in Diabetes (WHO MSVDD) has been followed up for about 12 years and the incidence of fatal and non-fatal cardiovascular disease outcomes assessed. RESULTS: The importance of blood pressure, serum cholesterol and proteinuria as predictors for cardiovascular disease mortality, fatal and non-fatal myocardial infarction and stroke is confirmed for patients with Type I (insulin-dependent) and Type II (non-insulin-dependent diabetes mellitus. Serum triglyceride was associated with cardiovascular disease death in Type II diabetes and in women with Type I diabetes and with MI incidence in Type II diabetes and stroke in Type II diabetic women. Fasting plasma glucose was associated with cardiovascular disease death, incidence of myocardial infarction and stroke in Type II diabetes only. In Type II diabetes, multivariate analysis confirmed that fasting plasma glucose was related to cardiovascular disease mortality independent of other risk factors. The independent relation of triglyceride to cardiovascular disease death was statistically significant only for Type II diabetic men. The presence of retinopathy was related to cardiovascular disease death and incidence of myocardial infarction in both types of diabetes and to stroke in Type II diabetes. CONCLUSION/INTERPRETATION: This large cohort study shows that the assessment of cardiovascular disease risk in diabetes must include 'diabetes-related' variables such as glycaemic control, proteinuria and retinopathy, as well as the classic risk factors, blood pressure, smoking and dyslipidaemia. [Diabetologia

Blood Glucose↗
PubMed2005

[Cardiovascular comorbidity in rheumatic disease. Does sex play a role?].

The importance of sex- and gender-related features of various diseases regarding the impact of different risk factors on the natural course of disease, the response to therapy and outcome have only more recently been appreciated. Studies investigating sex- and gender-related aspects in rheumatoid arthritis (RA) are scarce. Unambiguous classification of factors of potential pathogenetic relevance or with the capacity to influence clinical course and disease management into sex- or gender- related aspects is difficult (Figure 1). The majority of RA patients is female. As illustrated by Figure 2, available evidence indicates a progressive decline in the incidence of this disease over the past 40 years in both men and women. There appears to be a cyclical pattern in the annual incidence rates with peaks and troughs occurring for both sexes, but at different times, which suggests the changing exposure to environmental factors which may promote or decrease RA. Current knowledge suggests that RA is characterized by chronic local and systemic inflammation which may trigger accelerated atherogenesis. Sex hormones may also play a pathogenetic role. Androgens and estrogens may stimulate the production of inflammatory cytokines in the synovial fluid. These cytokines then may influence sex hormone metabolism thus modifying sex hormone levels (Figure 3). Compared to the general population (Figures 4 and 5), the risk of cardiovascular morbidity and mortality is significantly increased in patients with rheumatic diseases and in particular in RA. This is evidenced by a higher incidence of congestive heart failure (Figure 6), coronary artery disease and (frequently silent) myocardial infarction, as well as sudden cardiac death. Several studies have demonstrated a significantly increased standardized mortality ratio in RA and identified cardiovascular events as the most frequent cause. Compared with expected mortality rates in the normal population, women with RA have a significantly more compromised life expectancy than men (Table 1). Amongst factors with uneven distribution between sexes are traditional cardiovascular risk factors (Table 2), but also more recently recognized potential risk indicators or risk modifiers such as inflammatory markers and sex hormones. Drugs directed against RA may influence the natural course of cardiovascular disease, as, e. g., indicated by the increased rates of cardiac events and stroke associated with cyclooxygenase-(COX-)2 inhibitor treatment. In contrast, the effect of pharmacotherapy for cardiovascular diseases on the course of RA is unexplored. Prospective cohort studies aiming at early detection of cardiovascular morbidity and precise and detailed characterization of disease manifestations will be required in order to more thoroughly understand the interplay of factors and conditions determining an individuals' risk for developing cardiovascular comorbidity in autoimmune diseases. This article summarizes the available evidence for sex- and gender-related differences in the disease manifestation of rheumatic disorders as well as in cardiovascular risk factors with an emphasis on the cardiovascular comorbidity observed in RA.

Age Distribution↗
PubMed1998

Incidence of cardiovascular disease in Type 1 (insulin-dependent) diabetic subjects with and without diabetic nephropathy in Finland.

This study evaluates the impact of diabetic nephropathy on the incidence of coronary heart disease, stroke and any cardiovascular disease in the Finnish population, which has a high risk of Type 1 (insulin-dependent) diabetes mellitus and cardiovascular disease. We performed a prospective analysis of the incidence of coronary heart disease, stroke and cardiovascular disease in all Type 1 subjects in the Finnish Type I diabetes mellitus register diagnosed before the age of 18 years between 1 January 1965 and 31 December 1979 nationwide. The effect of age at onset of diabetes, attained age at the end of follow-up, sex, diabetes duration and of the presence of diabetic nephropathy on the risk for cardiovascular disease was evaluated. Cases of nephropathy, coronary heart disease, stroke and all cardiovascular diseases were ascertained from the nationwide Finnish Hospital Discharge Register and National Death Register using computer linkage with the Type I diabetes mellitus register. Of the 5148 Type 1 diabetic patients followed up, 159 had a cardiovascular event of which 58 were coronary heart diseases, 57 stroke events and 44 other heart diseases. There were virtually no cases of cardiovascular disease before 12 years diabetes duration. The cumulative incidence of cardiovascular disease by the age of 40 years was 43% in Type 1 diabetic patients with diabetic nephropathy, compared with 7% in patients without diabetic nephropathy, similarly in men and women. The relative risk for Type 1 diabetic patients with diabetic nephropathy compared with patients without diabetic nephropathy was 10.3 for coronary heart disease, 10.9 for stroke and 10.0 for any cardiovascular disease, similarly in men and women. The presence of nephropathy in Type I diabetic subjects increases not only the risk of coronary heart disease, but also of stroke by tenfold.

Adolescent↗
PubMed1999

Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study.

AIMS/HYPOTHESIS: The degree of glycaemia has been shown to be associated with all-cause and cardiovascular mortality in diabetic subjects. Whether this association also exists in the general population is still controversial. We studied the predictive value of fasting plasma glucose, 2-hour post-load glucose and HbA1c in a population-based cohort of 2363 older (50-75 years) subjects, without known diabetes. METHODS: Relative risks (RR) of all-cause and cardiovascular mortality were estimated by Cox proportional hazards model, adjusting for age and sex, and additionally for known cardiovascular risk factors. RESULTS: During 8 years of follow-up, 185 subjects died; 98 of cardiovascular causes. Fasting plasma glucose was only predictive in the diabetic range, although the risks started to increase at about 6.1 mmol/l. Post-load glucose and HbA1c values were, even within the non-diabetic range, associated with an increased risk (p for linear trend < 0.05). These increased risks were mostly, but not completely, attributable to known cardiovascular risk factors. After exclusion of subjects with newly diagnosed diabetes or with pre-existent cardiovascular disease (n = 551), a 5.8 mmol/l increase of post-load glucose (corresponding to two standard deviations of the population distribution) was associated with a higher age-adjusted and sex-adjusted risk of all-cause (RR 2.24) and cardiovascular mortality (RR 3.40) (p < 0.05). After additional adjustment for known cardiovascular risk factors, these relative risks were still statistically significant, with values of 2.20 and 3.00 respectively (p < 0.05). CONCLUSION/INTERPRETATION: High glycaemic variables, especially 2-h post-load glucose concentrations and to a lesser extent HbA1c values, indicate a risk of all-cause and cardiovascular mortality in a general population without known diabetes.

Aged↗
PubMed2005

Appropriate use of antiplatelets: is prescription in daily practice influenced by the global cardiovascular risk?

OBJECTIVE: To evaluate the appropriate prescription of antiplatelets according to patients' global cardiovascular risk level in everyday practice. METHODS: In a cross-sectional study, general practitioners (GPs) identified a random sample of 10% of patients at cardiovascular risk among all subjects coming to the surgery and collected data on cardiovascular risk factors and history of atherosclerotic cardiovascular diseases (CVD). GPs were asked to do a physical examination and record the results of laboratory tests to define the global cardiovascular risk. The use of antiplatelet drugs in patients with established CVD and in healthy subjects at high risk of developing symptomatic atherosclerotic disease was evaluated. RESULTS: A total of 162 GPs from all over Italy recruited 3,120 subjects (51% female, mean age 64 years). Of the 949 with an indication for antiplatelet treatment for secondary prevention of CVD, 442 (47%) were receiving it. Among the 2,071 without CVD, 11% were taking an antiplatelet drug. In this group, antiplatelets were prescribed in 6, 10, 16 and 23%, respectively, of patients perceived by GPs to be at mild, moderate, high and very high cardiovascular risk. CONCLUSIONS: Prescription of antiplatelets still seems to be far from what is recommended in virtually all patients with a history of CVD. In subjects with cardiovascular risk factors but without CVD antiplatelet prescription increases in relation to global cardiovascular risk but is still low in patients at high or very high risk of cardiovascular events.

Adult↗
PubMed1992

Update on fibrinogen as a cardiovascular risk factor.

Mounting data support a causal connection between high-normal fibrinogen levels and atherosclerotic cardiovascular disease. There is clearly a thrombogenic component to atherosclerosis and the onset of clinical manifestations. This offers the possibility to better identify high-risk candidates and also to protect them by reducing blood fibrinogen concentration or blocking its action. The relationship of antecedent fibrinogen to the subsequent development of cardiovascular disease is examined, based on 18 years of surveillance of a cohort of 1274 men and women aged 47 to 79 years who participated in the Framingham Study. The association with the development of peripheral arterial disease and cardiac failure is now examined in addition to previously studied relationships to coronary heart disease and stroke. In men and women, there is a significant age-adjusted relationship of fibrinogen level to coronary heart disease and to cardiovascular disease in general. In women, a significant relationship to cardiac failure and peripheral arterial disease, but not to stroke, was also found. These data on women are unique as they are not available elsewhere. Age-adjusted cardiovascular, all-cause, and coronary heart disease mortality were all related to fibrinogen in both sexes. In men, fibrinogen impact was the greatest for stroke and the least for peripheral arterial disease. For women, the impact on coronary heart disease was greatest. The absolute risk for an elevated fibrinogen level was greatest for coronary heart disease in both sexes. Average fibrinogen values are higher in women and in persons with other risk factors, including hypertension, cigarette smoking, diabetes, obesity, and elevated hematocrit. However, there is an independent contribution of fibrinogen to cardiovascular disease in general and coronary disease in particular, on adjustment for coexistent risk factors. Fibrinogen enhances the risk of cardiovascular disease in hypertensives, diabetics, and cigarette smokers. About half the cardiovascular risk of cigarette smoking appears due to the higher fibrinogen values. Now, five prospective studies document the excess incidence of cardiovascular events in persons with elevated fibrinogen levels within the "normal range." Each standard deviation increase in fibrinogen is associated with a 30% increment of coronary heart disease in men and a 40% increase in women. Fibrinogen should be added to the list of major cardiovascular risk factors. Trials of intervention to lower fibrinogen in high-risk coronary candidates are needed.

Age Factors↗
PubMed2005

Carotid artery intimal medial thickness, brachial artery flow-mediated vasodilation and cardiovascular risk factors in diabetic and non-diabetic indigenous Australians.

BACKGROUND: Indigenous Australians are at high risk for cardiovascular disease and type 2 diabetes. Carotid artery intimal medial thickness (CIMT) and brachial artery flow-mediated vasodilation (FMD) are ultrasound imaging based surrogate markers of cardiovascular risk. This study examines the relative contributions of traditional cardiovascular risk factors on CIMT and FMD in adult Indigenous Australians with and without type 2 diabetes mellitus. METHOD: One hundred and nineteen Indigenous Australians were recruited. Physical and biochemical markers of cardiovascular risk, together with CIMT and FMD were measured for all subjects. RESULTS: Fifty-three Indigenous Australians subjects (45%) had type 2 diabetes mellitus. There was a significantly greater mean CIMT in diabetic versus non-diabetic subjects (p=0.049). In the non-diabetic group with non-parametric analyses, there were significant correlations between CIMT and: age (r=0.64, p<0.001), systolic blood pressure (r=0.47, p<0.001) and non-smokers (r=-0.30, p=0.018). In the diabetic group, non-parametric analysis showed correlations between CIMT, age (r=0.36, p=0.009) and duration of diabetes (r=0.30, p=0.035) only. Adjusting for age, sex, smoking and history of cardiovascular disease, Hb(A1c) became the sole significant correlate of CIMT (r=0.35, p=0.01) in the diabetic group. In non-parametric analysis, age was the sole significant correlate of FMD (r=-0.31, p=0.013), and only in non-diabetic subjects. Linear regression analysis showed significant associations between CIMT and age (t=4.6, p<0.001), systolic blood pressure (t=2.6, p=0.010) and Hb(A1c) (t=2.6, p=0.012), smoking (t=2.1, p=0.04) and fasting LDL-cholesterol (t=2.1, p=0.04). There were no significant associations between FMD and examined cardiovascular risk factors with linear regression analysis CONCLUSIONS: CIMT appears to be a useful surrogate marker of cardiovascular risk in this sample of Indigenous Australian subjects, correlating better than FMD with established cardiovascular risk factors. A lifestyle intervention programme may alleviate the burden of cardiovascular disease in Indigenous Australians by reducing central obesity, lowering blood pressure, correcting dyslipidaemia and improving glycaemic control. CIMT may prove to be a useful tool to assess efficacy of such an intervention programme.

Adult↗
PubMedDate not supplied

Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis.

INTRODUCTION: Cardiovascular disease, the leading cause of death in much of the modern world, is the common symptomatic end stage of a number of distinct diseases and, therefore, is multifactorial and polygenetic in character. The two major underlying causes are disorders of lipid metabolism and metabolic syndrome. The ability to develop preventative and ameliorative treatments will depend on animal models that mimic human disease processes. The focus of this review is to identify suitable animal models and insights into cardiovascular disease achieved to date using such models. CRITERIA FOR ANIMAL MODELS: The ideal animal model of cardiovascular disease will mimic the human subject metabolically and pathophysiologically, will be large enough to permit physiological and metabolic studies, and will develop end-stage disease comparable to those in humans. Given the complex multifactorial nature of cardiovascular disease, no one species will be suitable for all studies. AVAILABLE MODELS: Potential larger animal models are problematic due to cost, ethical considerations, or poor pathophysiological comparability to humans. Rabbits require high-cholesterol diets to develop cardiovascular disease, and there are no rabbit models of metabolic syndrome. Spontaneous mutations in rats provide several complementary models of obesity, hyperlipidemia, insulin resistance, and type 2 diabetes, one of which spontaneously develops cardiovascular disease and ischemic lesions. The mouse, like normal rats, is characteristically resistant to cardiovascular disease, although genetically altered strains respond to cholesterol feeding with atherosclerosis, but not with end-stage ischemic lesions. CONCLUSIONS: The most useful and valid species/strains for the study of cardiovascular disease appear to be small rodents, rats, and mice. This fragmented field would benefit from a consensus on well-characterized appropriate models for the study of different aspects of cardiovascular disease and a renewed emphasis on the biology of underlying diseases.

Animals↗
PubMed2006

CRP, IL-6 and endothelin-1 levels in patients undergoing coronary artery bypass grafting. Do preoperative inflammatory parameters predict early graft occlusion and late cardiovascular events?

BACKGROUND: Inflammation is a major contributor to atherosclerotic vascular disease. Inflammatory parameters such as C-reactive protein (CRP) and Interleukin-6 (IL-6) have been shown to be strong predictors of cardiovascular events. The association between preoperative inflammatory parameters and early graft occlusion as well as cardiovascular events after coronary artery bypass grafting (CABG) has not, however, been fully elucidated. The aims of the present study were to prospectively investigate the prognostic value of the inflammatory parameters IL-6, CRP, and endothelin (ET-1) to predict early graft occlusion as well as late cardiovascular events after CABG. METHODS: In the present study 99 patients undergoing CABG because of stable angina pectoris due to significant coronary artery disease were prospectively included. Coronary angiography was repeated 3 months after CABG in 81 patients in order to evaluate early graft occlusion. Blood samples were collected before CABG in all patients. Patients were followed up for a median of 5 (3-7) years after CABG. RESULTS: Twenty-five patients (31%) had one or more occluded grafts at the 3-month control coronary angiography. The patients with occluded grafts had higher preoperative CRP and IL-6 levels in plasma [CRP 2.22 (1.11-4.47) mg/L vs. 1.23 (0.71-2.27) mg/L P=0.03] and [IL-6 2.88 (1.91-5.94) pg/mL vs. 2.15 (1.54-3.14) pg/mL P=0.006]. There were 23 late cardiovascular events among the 99 patients during the follow-up. Patients experiencing late cardiovascular events had higher preoperative IL-6 levels than those without late cardiovascular events [4.13 (1.83-5.87) pg/mL vs. 2.08 (1.53-2.29) pg/mL, P=0.002] whereas CRP levels did not differ significantly between the two groups [1.5 (0.79-4.41) mg/L vs. 1.33 (0.74-2.48) mg/L, P=0.41]. Looking at IL-6, a cut off value more than 3.8 pg/ml was associated with a significant higher risk for an early graft occlusion (P=0.04) and late cardiovascular events (P=0.00003). Preoperative endothelin-1 did not predict early graft occlusions or late cardiovascular events. CONCLUSIONS: Raised preoperative IL-6 levels are predictors of both early graft occlusion and late cardiovascular events after CABG. Elevated preoperative CRP levels can predict early graft occlusion after CABG. Endothelin did not differ between the two groups.

Aged↗
PubMed2006

Use of margarine enriched in phytosterols by patients at high cardiovascular risk and treated by hypolipidemic drugs.

BACKGROUND AND AIMS: The use of phytosterol-enriched margarines (PEM) in patients at cardiovascular risk has not been thoroughly explored. We determined the proportion of users of PEM in a population at high cardiovascular risk, and their characteristics. In addition, the correlates of using at least 25 g/d of PEM were identified. METHODS AND RESULTS: Patients with at least two cardiovascular risk factors in addition to dyslipidemia (primary prevention) or with past cardiovascular disease (secondary prevention) were recruited by general practitioners (GPs). Baseline characteristics were collected from a computerized GP database linked to a survey. GPs recorded patterns of PEM use. First, users were compared with non-users. Then, analyses were conducted to identify characteristics of patients using PEM at a recommended dose (>or=25 g/d). Among 1631 patients with documented consumption, a minority used PEM (15.2%), and only 36.4% of consumers used it at recommended level. Overall, PEM users did not differ from non-users as to general characteristics, nor as to the level of cardiovascular risk in primary prevention. However, PEM users reported significantly more cardiovascular events among their parents (OR=1.4; 95% CI=[1.0-1.9]). Consumers who used at least 25 g/d of PEM were more likely to be men (OR=3.1; 95% CI=[1.6-5.8]), to be aged 60-74 (OR=3.0; 95% CI=[1.4-6.4]), or 75 or older (OR=4.0; 95% CI=[1.5-10.6]). Again, no difference was observed regarding the level of cardiovascular risk. CONCLUSIONS: The level of use of PEM was low in this population of high cardiovascular risk patients. In addition, only a third of users consumed margarine at the recommended level. Our data suggest that pattern of use of PEM is not related to the level of cardiovascular risk.

Age Distribution↗
PubMed2006

Open-angle glaucoma and cardiovascular mortality: the Blue Mountains Eye Study.

PURPOSE: To evaluate the association between open-angle glaucoma (termed glaucoma) and 9-year mortality in an older population-based cohort. DESIGN: Population-based cohort. PARTICIPANTS: Three thousand six hundred fifty-four persons aged 49 to 97 years (82.4% of the eligible population), residents of the Blue Mountains, west of Sydney, Australia. METHODS: At baseline (1992-1994), glaucoma was diagnosed from congruous typical glaucomatous visual field changes (full-threshold fields) and optic disc cupping (stereo-optic disc photography). Demographic information from baseline participants was matched with the Australian National Death Index data (December 2001) to obtain the number and causes of deaths. Cox proportional hazards regression analysis, controlling for age, male gender, diabetes, hypertension, heart disease, stroke, use of oral beta-blockers, current smoking history, alcohol use, myopia, and nuclear cataract were performed to assess hazard ratios for cardiovascular mortality. Adjustments for all-cause mortality also included history of cancer. MAIN OUTCOME MEASURES: Cardiovascular and all-cause mortality. RESULTS: At baseline, glaucoma was diagnosed in 108 participants (3.0%). Of 873 deaths (23.9%) before January, 2002, 312 people (8.5%) died of cardiovascular events. The age-standardized all-cause mortality was 24.3% in persons with and 23.8% in those without glaucoma, whereas cardiovascular mortality was 14.6% in persons with and 8.4% in those without glaucoma. After multivariate adjustment, those with glaucoma had a nonsignificant increased risk of cardiovascular death (relative risk [RR], 1.46; 95% confidence interval [CI], 0.95-2.23). Increased cardiovascular mortality was observed mainly in glaucoma patients aged <75 years (RR, 2.78; 95% CI, 1.20-6.47). Further stratified analyses showed that cardiovascular mortality was higher among those with previously diagnosed glaucoma (RR, 1.85; 95% CI, 1.12-3.04), particularly in those also treated with topical timolol (RR, 2.14; 95% CI, 1.18-3.89). CONCLUSIONS: Findings from the Blue Mountains Eye Study demonstrate an increased cardiovascular mortality in persons with previously diagnosed glaucoma. There was a suggestion of higher cardiovascular mortality in glaucoma patients using topical timolol that merits further study.

Administration, Topical↗