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PubMed2005

[Incidence of cardiovascular events in giant cell arteritis: preliminary results of a prospective double cohort study (GRACG)].

UNLABELLED: Giant cell arteritis is the most frequent vasculitis. Cardiovascular events such as cerebrovascular accident or ischemic heart disease may occur in patients with giant cell arteritis. However, their real incidence, as well as their relative risk compared to the general population, remains unknown. PURPOSE: To assess in a prospective, double cohort study, the incidence of cardiovascular events in giant cell arteritis patients compared to controls, after controlling for cardiovascular risk factors. PATIENTS AND METHODS: We included on predefined criteria 432 newly diagnosed patients with giant cell arteritis, each assigned to sex- and age-matched controls randomly selected from the general population. Cardiovascular risk factors (high-blood pressure, diabetes, smoking, hypercholesterolemia and preexisting peripheral vascular disease) were collected at inclusion. During the 24-month follow-up, all cardiovascular events were collected. After stratification for cardiovascular risk factors, a log-rank test was performed to compare cases and controls. A parametric survival model was used for multivariate analysis. RESULTS: Cardiovascular events all combined were significantly increased in patients with giant cell arteritis (RR = 2.15 [1.21-3.81], P = 0.009), and were mainly associated with age (P = 0.0001), past history of cardiovascular disease (P = 0.023) but also with giant cell arteritis (P = 0.009). However, each subset of cerebrovascular accident (RR = 2.42 [0.84-7]) or ischemic heart disease (RR = 1.67 [0.72-3.89]) increased but did not significantly. CONCLUSION: Cardiovascular events incidence is increased in patients with giant cell arteritis, and prescription of preventive antiagregant treatment may be discussed.

Aged↗
PubMed2006

Incidence of cardiovascular risk factors and complications before and after kidney transplantation.

BACKGROUND: Cardiovascular disease is a leading cause of death after renal transplantation with an incidence considerably higher than that in the general population. The aim of this study was to evaluate the association of atherosclerotic cardiovascular complications and the prevalence of cardiovascular risk factors prior to and following transplantation. PATIENTS AND METHODS: Atherosclerotic cardiovascular diseases including coronary artery disease, as well as cerebral and peripheral vascular disease, and cardiovascular risk factors pre- and posttransplantation were analyzed in 500 renal transplant recipients between 1988 and 1992. The mean recipient age at transplantation was 45 +/- 12 years, with 58% men and 7% diabetics. RESULTS: Following transplantation 11.7% developed atherosclerotic cardiovascular diseases, the majority being coronary artery disease (9.8%). Comparison of the risk factors before and after transplantation showed the increased prevalence of systemic hypertension to be 67% to 86%, of diabetes mellitus, 7% to 16%, and obesity, with a body mass index > 25 kg/m2 from 26% to 48%, whereas the number of smokers was halved to 20%. The triglycerides decreased significantly (from 235 +/- 144 mg/dL to 217 +/- 122 mg/dL) but the total and high-density lipoprotein (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 low-density lipoprotein (LDL) cholesterol increase was insignificant (from 180 +/- 62 mg/dL to 189 +/- 53 mg/dL). Upon 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 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); 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 risk factors must be introduced early in the course of renal failure and continued following transplantation. Future prospective studies should evaluate the success of treatment regarding reduction of cardiovascular morbidity and mortality in this high-risk population.

Body Mass Index↗
PubMed2000

Effect of lovastatin on cardiovascular resource utilization and costs in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). AFCAPS/TexCAPS Research Group.

This cost-consequences analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study compares the costs of lovastatin treatment with the costs of cardiovascular hospitalizations and procedures. The cost of lovastatin treatment was defined as the average retail price and the cost of drug safety monitoring and adverse experiences. Costs were determined by actual rates of hospitalizations and procedures. Within a trial, lovastatin treatment cost approximately $4,654/patient. Lovastatin treatment significantly reduced the cumulative rate of cardiovascular hospitalizations and procedures (p = 0.002). Over the duration of the study, the cumulative number of cardiovascular hospitalizations and related therapeutic procedures was significantly reduced by 29%. The time to first cardiovascular-related hospitalization or procedure was significantly extended by lovastatin (p = 0.002). Lovastatin reduced the frequency of cardiovascular hospitalization (28%), and cardiovascular therapeutic (32%) and diagnostic procedures (23%). Among therapeutic procedures, treatment reduced coronary artery bypass graft surgery by 19% and percutaneous transluminal coronary angioplasty by 37%. Total cardiovascular-related hospital days were reduced by 26% (p = 0.025). The between-group offset in direct medical costs was $524, which resulted in a 11% cost offset of lovastatin therapy over the mean study duration of 5.2 years. Lovastatin provides meaningful reductions in cardiovascular-related resource utilization and reductions in direct cardiovascular-related costs associated with the onset of coronary disease.

Aged↗
PubMed2002

Comparison of cardiovascular thrombotic events in patients with osteoarthritis treated with rofecoxib versus nonselective nonsteroidal anti-inflammatory drugs (ibuprofen, diclofenac, and nabumetone).

Aspirin, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), and specific cyclooxygenase-2 (COX-2) inhibitors each have distinctive effects on COX-1-mediated thromboxane biosynthesis, the major determinant of platelet aggregation. It is unclear whether these effects are associated with differences in thrombogenic risks. To compare the risk for thrombotic cardiovascular events among patients receiving rofecoxib, nonselective NSAIDs, and placebo, cardiovascular safety was assessed in 5,435 participants in 8 phase IIB/III osteoarthritis trials. The median treatment exposure was 31/2 months. The primary end point assessed was the risk of any arterial or venous thrombotic cardiovascular adverse event (AE). A second analysis assessed differences in the Anti-Platelet Trialists' Collaboration (APTC) events, a cluster end point that consists of the combined incidence of (1) cardiovascular, hemorrhagic, and unknown death; (2) myocardial infarction; and (3) cerebrovascular accident. Similar rates of thrombotic cardiovascular AEs were reported with rofecoxib, placebo, and comparator nonselective NSAIDs (ibuprofen, diclofenac, or nabumetone). In trials that compared rofecoxib with NSAIDs, the incidence of thrombotic cardiovascular AEs was 1.93/100 patient-years in the rofecoxib treatment group compared with 2.27/100 patient-years in the combined nonselective NSAID group. In trials that compared rofecoxib with placebo, the incidence of thrombotic cardiovascular AEs was 2.71/100 patient-years in the rofecoxib group compared with 2.57/100 patient-years in the placebo group. Consistent with the risks of cardiovascular AEs, similar rates of APTC events were reported with rofecoxib, placebo, and comparator nonselective NSAIDs. Thus, in the rofecoxib osteoarthritis development program, there was no difference between rofecoxib, comparator nonselective NSAIDs, and placebo in the risks of cardiovascular thrombotic events.

Adult↗
PubMed2003

Management of diabetes mellitus and insulin resistance in patients with cardiovascular disease.

Patients with diabetes have a greatly increased relative risk of developing cardiovascular disease when compared with patients without diabetes. Much of this risk is related to insulin resistance and is associated with both traditional and nontraditional cardiovascular risk factors. Therapy for diabetes must address these risk factors in an attempt to prevent and adequately treat cardiovascular disease. Pharmacologic therapy directed toward dyslipidemia and hypertension has a beneficial effect on risk factors and has been shown to decrease cardiovascular events. The effects of insulin and oral hypoglycemic agents on insulin resistance are variable, and their direct effect on cardiovascular disease is less clear. Metformin is the only oral hypoglycemic agent shown to decrease cardiovascular events independent of glycemia. The thiazolidinediones directly improve insulin resistance, decrease plasma insulin concentration, and have the potential to decrease the risk of cardiovascular disease in patients with diabetes. A number of studies have demonstrated that the thiazolidinediones produce changes in several cardiovascular risk factors associated with the insulin resistance syndrome, including lowering blood pressure, correcting diabetic dyslipidemia, improving fibrinolysis, and decreasing carotid artery intima-medial thickness. These agents bind a newly described class of receptors, peroxisome proliferator-activated receptors, which may have implications for atherosclerosis. Although these drugs increase low-density lipoprotein (LDL) cholesterol, they induce a favorable change in the LDL particle size and susceptibility to oxidation. Long-term clinical trials are being conducted to determine the effect that thiazolidinediones have on cardiovascular events in individuals with type 2 diabetes.

Cardiovascular Diseases↗
PubMed1997

Usefulness of microalbuminuria in predicting cardiovascular mortality in treated hypertensive men with and without diabetes mellitus. Risk Factor Intervention Study Group.

In the present study we report on the predictive power of microalbuminuria for total and cardiovascular mortality in a prospective study (mean follow up 6.3 years) of treated hypertensive men, aged 50 to 72 years, with (n = 94) and without (n = 345) maturity onset diabetes mellitus. Thirty-three (35.1%) of the hypertensive patients with diabetes mellitus died during the follow-up period compared with 57 patients (16.5%) in the hypertensive group without diabetes mellitus (p <0.0002). In those with diabetes mellitus and hypertension, a log-rank test revealed a lower cardiovascular mortality in the normoalbuminuric group compared with both the microalbuminuric (p = 0.035) and the macroalbuminuric group (p = 0.002). The logarithm of urinary albumin excretion was a predictor of both total (p = 0.009) and cardiovascular (p = 0.001) mortality during the follow-up period using Cox regression analysis. This relation remained significant even after adjustment for other risk factors. HbA1c was also an independent predictor of total and cardiovascular mortality. In patients without diabetes mellitus, the small group of patients with macroalbuminuria had a markedly increased cardiovascular mortality compared with both the microalbuminuric (p <0.0001) and the normoalbuminuric groups (p <0.0001). No difference was observed between the normoalbuminuric and the microalbuminuric groups. Smoking at entry and concomitant cardiovascular disease at entry were independent predictors of cardiovascular mortality in these patients. We conclude that microalbuminuria was an independent predictor for cardiovascular mortality in treated hypertensive men with maturity onset diabetes mellitus. Macroalbuminuria, but not microalbuminuria, predicted cardiovascular mortality in nondiabetic treated hypertensive men.

Aged↗
PubMed1998

Type 2 diabetes care: the role of insulin-sensitizing agents and practical implications for cardiovascular disease prevention.

Millions of Americans are at risk for cardiovascular morbidity and mortality related to disorders of glucose intolerance--particularly type 2 diabetes and prediabetic conditions, including the insulin resistance, or "cardiovascular dysmetabolic," syndrome. The latter is apparently more intricately associated with macrovascular disease--myocardial infarction, stroke, and peripheral vascular disease. In some situations the risk of cardiovascular disease might be reduced by the prevention of diabetes and also by prevention or treatment of the cardiovascular dysmetabolic syndrome. Studies have shown that intensive glycemic control can delay the development of microvascular complications in type 1, and possibly type 2, diabetes. Several longitudinal observational studies have demonstrated a relationship between glycemic control and the development of cardiovascular disease. Prospective clinical intervention trials to address this issue are underway. Insulin may have a role in atherogenesis, both directly and by promoting development of such risk factors as hypertension and dyslipidemia. Genetic factors and mechanisms promoting or discouraging development of glucose intolerance are also under investigation. Lifestyle changes--dietary and exercise modification, weight loss, and smoking cessation--have been shown to have a positive effect on cardiovascular disease risk. Clinical trials suggest that oral antidiabetic agents--particularly the new noninsulin secretagogues (including troglitazone and metformin, which act on the liver and on skeletal muscle)--may be useful in delaying or preventing development of type 2 diabetes and the cardiovascular dysmetabolic syndrome, as well as in their treatment, when present. Both agents, acting primarily by different mechanisms of action, have also demonstrated potential beneficial effects on serum lipid profiles and other cardiovascular risk factors and may be useful in patients with cardiovascular dysmetabolic syndrome who do not yet meet the criteria for diabetes.

Administration, Oral↗
PubMed2001

Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project.

BACKGROUND: In addition to the treatment of specific cardiovascular risk factors, intervention which interferes with the general mechanisms of atherosclerosis could further reduce the incidence of cardiovascular events. We aimed to investigate in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with one or more major cardiovascular risk factors. METHODS: We did a randomised controlled open 2x2 factorial trial to investigate low-dose aspirin (100 mg/day) and vitamin E (300 mg/day) in the prevention of cardiovascular events, in people with one or more of the following: hypertension, hypercholesterolaemia, diabetes, obesity, family history of premature myocardial infarction, or individuals who were elderly. FINDINGS: 4495 people (2583 female, mean age 64.4 years) were included in the trial. After a mean follow-up of 3.6 years the trial was prematurely stopped on ethical grounds when newly available evidence from other trials on the benefit of aspirin in primary prevention was strictly consistent with the results of the second planned interim analysis. Aspirin lowered the frequency of all the endpoints, being significant for cardiovascular death (from 1.4 to 0.8%; relative risk 0.56 [95% CI 0.31-0.99]) and total cardiovascular events (from 8.2 to 6.3%; 0.77 [0.62-0.95]). Severe bleedings were more frequent in the aspirin group than the no-aspirin group (1.1% vs 0.3%; p<0.0008). Vitamin E showed no effect on any prespecified endpoint. Analyses were by intention-to-treat. INTERPRETATION: In women and men at risk of having a cardiovascular event because of the presence of at least one major risk factor, low-dose aspirin given in addition to treatment of specific risk factors contributes an additional preventive effect, with an acceptable safety profile. The results on vitamin E's cardiovascular primary preventive efficacy are not conclusive per se, although our results are consistent with the negative results of other large published trials on secondary prevention.

Aged↗
PubMed1996

Age at menopause as a risk factor for cardiovascular mortality.

BACKGROUND: Although an association of occurrence of menopause and subsequent oestrogen deficiency with increased cardiovascular disease has been postulated, studies on this association have not shown convincing results. We investigated whether age at menopause is associated with cardiovascular mortality risk. METHODS: We studied a cohort of 12115 postmenopausal women living in Utrecht, Netherlands, aged 50-65 years at enrolment in a breast cancer screening project. During follow-up of up to 20 years the women attended screening rounds at which we asked questions on menopausal status, age of menopause, medication use, cardiovascular risk factors, and ovarian function. Deaths were ascertained from the patient's family physicians. Life-table analysis and Cox regression analysis were used to investigate the association between aga at menopause and cardiovascular mortality. All analyses were adjusted for biological age. FINDINGS: 824 women died of cardiovascular causes. 1459 women had left the study area. The risk of cardiovascular mortality was higher for women with early menopauses than for those with late menopauses. The age-adjusted hazard ratio of age at menopause was 0.982 (95% CI 0-968-0-996, p=0.01)_ie, for each year's delay in the menopause the cardiovascular mortality risk decreased by 2%. The extra risk of early menopause seemed to decrease with biological age (p for interaction 0.07); at biological age 60 the reduction of the annual hazard was 3%, but at age 80 there was no reduction. Adjustment for known cardiovascular risk factors and indicators of ovarian function did not significantly alter the risk estimate. INTERPRETATION: These results support the hypothesis that longer exposure to endogenous oestrogens protects against cardiovascular diseases. The effect of an early menopause may be more important at younger biological ages.

Age Factors↗
PubMed1997

Sodium sensitivity and cardiovascular events in patients with essential hypertension.

BACKGROUND: In patients with sodium-sensitive hypertension, glomerular pressure is increased and microalbuminuria, a marker of glomerular hypertension, is a predictor of cardiovascular events. Similarly, the lack of a nocturnal decrease in blood pressure in these patients is also associated with an increased risk of cardiovascular events. We hypothesised that sodium sensitivity may be the common factor and carried out a retrospective study of cardiovascular events in patients with essential hypertension who had had sodium sensitivity measured in our clinic. METHODS: Sodium sensitivity was assessed in about 350 patients with essential hypertension during the initial investigation of their disorder. The definition of sodium sensitivity was a 10% or greater difference in blood pressure on low-sodium or high-sodium diets. By alphabetical order, the records of 201 patients were obtained and 156 patients without pre-existing disorders were followed up. The records of patients who had a cardiovascular event or died were reviewed without knowledge of the patient's sodium-sensitivity status. FINDINGS: 62 patients were deemed sodium sensitive and 94 non-sodium sensitive. Left-ventricular hypertrophy was found more frequently in the sodium-sensitive group than in the non-sodium-sensitive group (38 vs 16%; p < 0.01), whereas significantly fewer patients in this group smoked (23 vs 42%; p < 0.05). There were 17 cardiovascular events in the sodium-sensitive group and 14 in the non-sodium-sensitive group. The rate of total, non-fatal and fatal cardiovascular events, was 2.0 per 100 patient-years in the non-sodium-sensitive group and 4.3 per 100 patient-years in the sodium-sensitive group. Cox's proportional-hazards model identified sodium sensitivity (p < 0.01), mean arterial pressure (p < 0.01), and smoking (p < 0.01) as independent cardiovascular risk factors. INTERPRETATION: Cardiovascular events occurred more frequently in patients with sodium-sensitive hypertension. Sodium sensitivity is an independent cardiovascular risk factor in Japanese patients with essential hypertension.

Adult↗
PubMed1999

Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria.

BACKGROUND: The new fasting American Diabetes Association (ADA) criteria for the diagnosis of diabetes mellitus rely mainly on fasting blood glucose concentrations and use a lower cut-off value for diagnosis than the WHO criteria. We aimed to assess the sensitivity of these criteria for the detection of cardiovascular disease, the main complication of diabetes mellitus in the elderly. METHODS: We did a cross-sectional and prospective analysis of 4515 participants of the Cardiovascular Health Study, an 8 year longitudinal study designed to identify factors related to the onset and course of cardiovascular disease in adults aged at least 65 years. We calculated the prevalence and incidence of cardiovascular disease for the ADA and WHO criteria. FINDINGS: There was a higher prevalence of cardiovascular disease among individuals with impaired glucose or newly diagnosed diabetes by both criteria than among those with normal glucose concentrations. However, because fewer individuals had abnormal glucose states by the fasting ADA criteria (22.3%) than by the WHO criteria (46.8%), the number of cases of cardiovascular disease attributable to abnormal glucose states was a third of that attributable by the WHO criteria (53 vs 159 cases per 10,000). For the two sets of criteria, the relative risk for incident cardiovascular disease (mean follow-up 5.9 years) was higher in individuals with impaired glucose and newly diagnosed diabetes than in those with normal glucose. Individuals classified as normal by the fasting ADA criteria had a higher absolute number of incident events (455 of 581 events) than those classified as normal by the WHO criteria (269 of 581 events). Fasting ADA criteria were therefore less sensitive than the WHO criteria for predicting cardiovascular disease among individuals with abnormal glucose (sensitivity, 28% vs 54%). INTERPRETATION: The new fasting ADA criteria seem to be less predictive than the WHO criteria for the burden of cardiovascular disease associated with abnormal glucose in the elderly.

Age Factors↗
PubMed2006

Validity of an alternative anthropometric trait as cardiovascular diseases risk factor: example from individuals with traumatic lower extremity amputation.

BACKGROUND: Published studies reveal that individuals with lower extremity amputation are vulnerable to cardiovascular diseases (CVD) because of poor physical activity level. Many cardiovascular risk assessment studies have utilized anthropometric traits (primarily body mass index and waist circumference) as cardiovascular risk factor. However, some studies emphasized the technical limitations of measuring waist circumference for studying cardiovascular risk, and so it is difficult to obtain correct measurement from the individuals with lower extremity amputation. OBJECTIVES: The objectives of the present article are to study the prevalence of CVD risk factors among the individuals with traumatic lower extremity amputation and to test the validity of upper arm circumference (UAC) as an alternative anthropometric measurement for screening the CVD risk condition. SUBJECTS AND SETTING: Anthropometric data and other cardiovascular traits data have been collected from unilateral traumatic lower extremity amputated adult males (n = 85) residing in Calcutta and adjoining areas. RESULTS: Results show higher prevalence of cardiovascular risk factor among individuals with above-knee amputation than below-knee amputation. The receiver operating characteristics curve analysis shows significant ability of upper arm circumference to diagnose cardiovascular risk condition. The cutoff value of UAC > 26.6 cm show maximum sensitivity and specificity for the diagnosis of cardiovascular risk condition. Although, binomial tests for equality of proportion does not show any significant difference, however, agreement statistics reveal better diagnostic ability of cutoff value of UAC than the existing cutoff value of waist circumference. CONCLUSIONS: Therefore, UAC provides a better assessment of cardiovascular risk condition than does waist circumference especially for individuals with lower extremity amputation. SPONSORSHIP: Indian Statistical Institute, Kolkata.

Adult↗
PubMed2003

White coat hypertension is a cardiovascular risk factor: a 10-year follow-up study.

The objective of this paper was to evaluate the cardiovascular risk in white coat hypertension (WCH). WCH is a well-known clinical entity defined by persistently elevated blood pressure (BP) in the doctor's office, whereas BP in other conditions is normal. The prognosis of WCH is unsettled, although two prospective studies that include normal control groups imply that the condition is benign. This study is a 10-year follow-up study on 420 patients with grade I-II hypertension newly diagnosed by their general practitioner and 146 normal controls (NTs). Ambulatory blood pressure (ABP) monitoring was performed at baseline. With our protocollated cutoff value of daytime-ABP <135/90 mmHg, 76 (18.1%) of the 420 hypertensives were white coat hypertensives (WCHs) and 344 were established hypertensives (EHs). With a lower cutoff of 135/85 mmHg, 40 (9.5%) were WCHs. Complete follow-up data were obtained for all 566 subjects. The mean duration of follow-up was 10.2 years (range 9.0-12.5). In the WCH group, 14 first events were recorded (18.4%) consisting of two cardiovascular deaths and 12 nonfatal cardiovascular events. In the EH group, the corresponding number of events were 56 first events (16.3%), 12 cardiovascular deaths and 44 nonfatal cardiovascular events, and in the NT group 10 first events (6.8%), two cardiovascular deaths and eight nonfatal cardiovascular events. The event rate was similar in the WCH group and the EH group and significantly lower in the NT group (P<0.05). When corrected for daytime-ABP, age and other confounders, the difference remained statistically significant. When using the lower cutoff of 135/85 mmHg, WCH was still associated with a significantly higher cardiovascular event rate. In conclusion, the main finding of this 10-year follow-up study is an increased cardiovascular risk in WCH compared to normotensive controls.

Adult↗
PubMed1999

Inflammation enhances cardiovascular risk and mortality in hemodialysis patients.

BACKGROUND: Atherosclerosis, a major problem in patients on chronic hemodialysis, has been characterized as an inflammatory disease. C-reactive protein (CRP), the prototypical acute phase protein in humans, is a predictor of cardiovascular mortality in the general population. We hypothesize that several of the classic, as well as nontraditional, cardiovascular risk factors may respond to acute phase reactions. An activated acute phase response may influence or predict cardiovascular risk. METHODS: In 280 stable hemodialysis patients, serum lipids, apolipoproteins (apo) A-I and B, lipoprotein(a) [Lp(a)], fibrinogen, and serum albumin (Salb) were determined in relation to CRP and serum amyloid A (SAA), two sensitive markers of an acute phase response. Mortality was monitored prospectively over a two year period. RESULTS: Serum CRP and SAA were found to be elevated (more than 8 and more than 10 mg/liter, respectively) in 46% and 47% of the patients in the absence of clinically apparent infection. Patients with elevated CRP or SAA had significantly higher serum levels of Lp(a), higher plasma fibrinogen, and lower serum levels of high-density lipoprotein cholesterol, apo A-I, and Salb than patients with normal CRP or SAA. The rise in Lp(a) concentration was restricted to patients exhibiting high molecular weight apo(a) isoforms. During follow-up, 72 patients (25.7%) had died, mostly due to cardiovascular events (58%). Overall mortality and cardiovascular mortality were significantly higher in patients with elevated CRP (31% vs. 16%, P < 0.0001, and 23% vs. 5%, P < 0.0001, respectively) or SAA (29% vs. 19%, P = 0.004, and 20 vs. 10%, P = 0.008, respectively) and were also higher in patients with Salb of lower than 40 g/liter (44% vs. 14%, P < 0.0001, and 34% vs. 6%, P < 0.0001, respectively). Univariate Cox regression analysis demonstrated that age, diabetes, pre-existing cardiovascular disease, body mass index, CRP, SAA, Salb, fibrinogen, apo A-I, and Lp(a) were significantly associated with the risk of all-cause and cardiovascular mortality. During multivariate regression analysis, SAA, fibrinogen, apo A-I, and Lp(a) lost their predictive values, but age and CRP remained powerful independent predictors of both overall death and cardiovascular death. CONCLUSION: These results suggest that a considerable number of hemodialysis patients exhibit an activated acute phase response, which is closely related to high levels of atherogenic vascular risk factors and cardiovascular death. The mechanisms of activated acute phase reaction in patients on chronic hemodialysis remain to be identified. A successful treatment of the inflammatory condition may improve long-term survival in these patients.

Acute-Phase Reaction↗
PubMed2001

Paradox of risk factors for cardiovascular mortality in uremia: is a higher cholesterol level better for atherosclerosis in uremia?

Patients with chronic uremia have a substantially elevated risk of death from cardiovascular disease than do the general population. Although uremic and nonuremic groups share some of the risk factors for cardiovascular mortality, such as older age, diabetes, and inflammation, other factors appear to affect cardiovascular mortality in the opposite direction. For example, being overweight and having hyperlipidemia are established risk factors in the general population, whereas lower body mass index and lower plasma cholesterol have been shown to be risk factors for cardiovascular mortality in end-stage renal disease (ESRD). This paradoxical phenomenon is explained by two facts: (1) that malnutrition is a strong predictor of cardiovascular mortality in ESRD and (2) that plasma lipid levels are lowered in malnutrition. However, it is not known whether atherosclerosis is promoted by malnutrition or by low cholesterol level. Because the cardiovascular mortality rate is theoretically the product of event rate and fatality rate after an event, risk factors for cardiovascular mortality could fall into two categories: those raising the event rate and those affecting the fatality rate. Some factors could work both ways. Patients with ESRD show a significant increase in both event rate and fatality rate. Dyslipidemia is an independent factor affecting atherosclerotic arterial wall changes and cardiovascular events in ESRD. Other factors affecting the cardiovascular event rate in ESRD include diabetes and an elevated homocysteine level. In contrast, factors associated with poor survival after an event include diabetes and anemia. Malnutrition could be a factor causing the fatality rate to rise, although there is no direct evidence supporting this possibility. Further studies are needed to show the differential effects of a risk factor on event rate and fatality rate. Patients with ESRD would have a better chance of living longer by better management of the two categories of risk factors.

Arteriosclerosis↗
PubMed2002

High serum insulin-like growth factor binding protein-1 is associated with increased cardiovascular mortality in elderly men.

Insulin-like growth factor binding protein-1 (IGFBP-1) has been implicated in the development of cardiovascular disease, but it is not known whether IGFBP-1 is related to cardiovascular mortality. We examined the relation of circulating IGFBP-1 to death from coronary heart disease, cardiovascular disease, and all causes in a cohort study consisting of 622 men aged 65 - 84 years, at baseline in 1984. Fasting serum IGFBP-1 and other risk factors were measured in 1984 and 1989. Cardiovascular events for those who died between 1984 and 1995 were analyzed, and cardiovascular diagnoses were coded centrally according to standardized procedures. Of the 622 men, 358 died between 1984 and 1995; 160 deaths were due to cardiovascular causes, 113 of which were coronary deaths. High fasting serum IGFBP-1 concentration (> 75 percentile) in 1984 was associated with increased five-year total mortality (OR 2.05, 95 % CI 1.41 - 2.99; p < 0.0002), cardiovascular mortality (OR 2.20, 95 % CI 1.37 - 3.50; p < 0.0009) and coronary heart disease mortality (OR 2.29, 95 % CI 1.35 - 3.88; p < 0.002). After adjustment for age, high serum IGFBP-1 concentrations still carried an increased risk of total mortality due to (OR 1.73, 95 % CI 1.16 - 2.59; p < 0.007), cardiovascular (OR 1.91 95 % CI 1.18 - 3.09; p < 0.008) and coronary heart disease (OR 2.02. 95 % CI 1.18 - 3.47; p < 0.01). In conclusion, high fasting serum IGFBP-1 is related to increased five-year total and cardiovascular mortality in elderly men.

Age Factors↗
PubMed1993

Serum cholesterol in young men and subsequent cardiovascular disease.

BACKGROUND: The increased risk of cardiovascular disease associated with higher serum cholesterol levels in middle-aged persons has been clearly established, but there have been few opportunities to examine a potential link between serum cholesterol levels measured in young men and clinically evident premature cardiovascular disease later in life. METHODS: We performed a prospective study of 1017 young men (mean age, 22 years) followed for 27 to 42 years to quantify the risk of cardiovascular disease and total mortality associated with serum cholesterol levels during early adult life. The mean serum cholesterol level at entry was 192 mg per deciliter (5.0 mmol per liter). RESULTS: During a median follow-up of 30.5 years, there were 125 cardiovascular-disease events, 97 of which were due to coronary heart disease. The serum cholesterol level at base line was strongly associated with the incidence of events related to coronary heart disease and cardiovascular disease, as well as to total mortality and mortality due to cardiovascular disease. The risks were similar whether the events occurred before or after the age of 50. In a proportional-hazards analysis adjusted for age, body-mass index (the weight in kilograms divided by the square of the height in meters), the level of physical activity, coffee intake, change in smoking status, and the incidence of diabetes and hypertension during follow-up, a difference in the serum cholesterol level at base line of 36 mg per deciliter (0.9 mmol per liter)--the difference between the 25th and 75th percentiles of cholesterol level in the study population at base line--was associated with an increased risk of cardiovascular disease (relative risk, 1.72; 95 percent confidence interval, 1.39 to 2.14), coronary heart disease (relative risk, 2.01; 95 percent confidence interval, 1.59 to 2.53), and mortality due to cardiovascular disease (relative risk, 2.02; 95 percent confidence interval, 1.23 to 3.32). A difference in the base-line serum cholesterol level of 36 mg per deciliter was significantly associated with an increased risk of death before the age of 50 (relative risk, 1.64; 95 percent confidence interval, 1.03 to 2.61), but not with the overall risk of death (relative risk, 1.21; 95 percent confidence interval, 0.93 to 1.58). CONCLUSIONS: These findings indicate a strong association between the serum cholesterol level measured early in adult life in men and cardiovascular disease in midlife.

Adult↗
PubMed2005

Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention.

BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors have come under scrutiny because of reports suggesting an increased cardiovascular risk associated with their use. Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern. METHODS: We reviewed all potentially serious cardiovascular events among 2035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for the prevention of colorectal adenomas. All deaths were categorized as cardiovascular or noncardiovascular, and nonfatal cardiovascular events were categorized in a blinded fashion according to a prespecified scheme. RESULTS: For all patients except those who died, 2.8 to 3.1 years of follow-up data were available. A composite cardiovascular end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure was reached in 7 of 679 patients in the placebo group (1.0 percent), as compared with 16 of 685 patients receiving 200 mg of celecoxib twice daily (2.3 percent; hazard ratio, 2.3; 95 percent confidence interval, 0.9 to 5.5) and with 23 of 671 patients receiving 400 mg of celecoxib twice daily (3.4 percent; hazard ratio, 3.4; 95 percent confidence interval, 1.4 to 7.8). Similar trends were observed for other composite end points. On the basis of these observations, the data and safety monitoring board recommended early discontinuation of the study drug. CONCLUSIONS: Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure. In light of recent reports of cardiovascular harm associated with treatment with other agents in this class, these data provide further evidence that the use of COX-2 inhibitors may increase the risk of serious cardiovascular events.

Adenomatous Polyps↗