White blood cell count and risk of all-cause and cardiovascular mortality in nationwide sample of Japanese--results from the NIPPON DATA90.

BACKGROUND: The association of white blood cell (WBC) count with all-cause and cardiovascular disease (CVD) mortality were examined in the National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged (NIPPON DATA) 90. METHODS AND RESULTS: A total of 6,756 Japanese residents (2,773 men and 3,983 women) throughout Japan without a history of CVD were followed for 9.6 years. A Cox proportional hazards regression model was used to estimate the relative risk (RR) and 95% confidence interval (CI). We documented 576 deaths with 161 deaths from CVD. Overall, after adjusting for several confounders including age, sex, body mass index at baseline, smoking status, alcohol consumption, regular exercise, diastlic blood pressure, total cholesterol, high-density lipoprotein-cholesterol and hemoglobin A1c, a graded association between WBC count and higher risk of all-cause mortality was observed (WBC of 9,000-10,000 cells/mm(3) vs WBC of 4,000-4,900: RR =1.61, 95% CI: 1.07-2.40, p for trend =0.02). Elevated WBC count was almost significantly associated with high risk of CVD mortality (WBC of 9,000-10,000 vs WBC of 4,000-4,900: RR =1.79, 95% CI: 0.97-3.71). These associations strengthened among women. Stratified by smoking status, never-smokers with WBC counts of 9,000-10,000 had a 3.2 fold elevated risk for CVD death compared with those with WBC counts of 4,000-4,900. CONCLUSIONS: The WBC count may have potential as a predictor for all-cause mortality, particularly CVD mortality.     

Coronary heart disease mortality,plasma homocysteine,and B-vitamins: a prospective study

The results of prospective studies on the relations between the plasma concentration of total homocysteine (tHcy) and B-vitamins, on the one hand, and coronary heart disease (CHD) mortality, on the other hand, are inconclusive and scarce considering the relation with B-vitamins. We prospectively determined these relations in a case-cohort study. The full-cohort existed in approximately 36,000 Dutch adults aged 20-59 years at baseline. The statistical analyses were done with a random sample from the cohort (n=630) complemented with all subjects who died of CHD (n=102) during a mean follow-up of 10.3 years. All subjects reported the absence of cardiovascular diseases (CVDs) at baseline. The plasma concentrations of tHcy, folate, PLP, and vitamin B12 were determined in samples obtained at baseline. Men with a tHcy concentration in the highest tertile (T3) compared with men in the lowest tertile (T1) had a relative risk (RR) of 1.14 for CHD (95% confidence interval (CI): 0.50, 2.61) after adjusting for age, study center, hypertension, HDL and total cholesterol, smoking, and creatinine. For women, this RR was 2.04 (95% CI: 0.48, 8.62). For each 5 micromol/l increase in tHcy, the RR of CHD was 1.03 (95% CI: 0.83-1.29) for men and women combined. In women only, high folate levels were associated with a statistically significant protection of fatal CHD (T3 versus T1; RR: 0.22, 95% CI: 0.06, 0.87). Plasma PLP (B6) and vitamin B12 concentrations were not associated with CHD risk. We conclude that elevated tHcy concentrations do not seem to be a risk factor for CHD mortality in these relatively young healthy Dutch subjects free of baseline CVD. Higher folate concentrations may be protective of CHD, but this needs confirmation.     

Homocysteine as a risk factor for CVD mortality in men with other CVD risk factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study

OBJECTIVE: Based on case-control and prospective studies elevated blood total homocysteine (tHcy) has been suggested to be an independent risk factor for cardiovascular diseases (CVD). The purpose of the study was to explore the joint effect of increased serum tHcy concentration and other risk factors on the risk of CVD mortality in middle-aged men without a history of heart disease or stroke. DESIGN: A prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. SETTING: Eastern Finland. Subjects. A total of 802 men aged 46-64 years, examined in 1991-93. MAIN OUTCOME MEASURES: CVD mortality event. RESULTS: The mean serum tHcy concentration was 10.8 micromol L(-1) (SD 3.3). During the average follow-up time of 10.8 years 50 men experienced a CVD death. The hazard rate ratio for CVD mortality was 1.80 (95% confidence interval: 1.02-3.19) in men in the highest serum tHcy third versus lower thirds after adjustment for cardiovascular risk factors. Furthermore, elevated serum tHcy concentration appeared to increase the risk of CVD death in men who smoke or who have high circulating concentrations of serum total or LDL cholesterol, apo-B apolipoprotein or plasma fibrinogen. CONCLUSION: We conclude that homocysteine may increase the risk of CVD mortality in middle-aged men from Eastern Finland, and it may especially increase the risk when present with other risk factors for CVD.     

Plasma homocysteine and microvascular and macrovascular complications in type 1 diabetes: a cross-sectional nested case-control study

OBJECTIVES. To examine the independent relationship between plasma total homocysteine (tHcy) and microvascular and macrovascular complications. DESIGN. We performed a cross-sectional nested case-control study from the EURODIAB Prospective Complications Study. SETTING. A hospital-based multicentre study at 24 centres in 13 European countries. SUBJECTS. A total of 533 type 1 diabetic patients, diagnosed at <36 years of age. Cases (n=359) were defined as those with one or more complications of diabetes and control subjects (n=174) were all those with no evidence of any complication. Main outcome measures. Retinopathy, albumin excretion rate (AER), glomerular filtration rate (GFR) estimated by Cockcroft-Gault formula, hypertension and cardiovascular disease (CVD) were assessed. RESULTS. In unadjusted models, tHcy (per 5 micromol L(-1)) was significantly associated with nonproliferative retinopathy (OR=1.45, 95% CI: 1.10-1.91), proliferative retinopathy (OR=1.74, 95% CI: 1.34-2.27), macroalbuminuria (OR=1.90, 95% CI: 1.49-2.42), hypertension (OR=2.23, 95% CI: 1.69-2.93) and CVD (OR=1.59, 95% CI: 1.18-2.14). In multivariate models, tHcy was significantly related to macroalbuminuria (OR=1.66, 95% CI: 1.24-2.24) and hypertension (OR=1.57, 95% CI: 1.19-2.07), independent of age, sex, diabetes duration, GFR, microvascular and macrovascular complications and cardiovascular risk factors. There was a significant relationship between tHcy and decreased GFR, independent of established risk factors. The relationship between tHcy and retinopathy was not independent of albuminuria or GFR. The initial positive relationship with CVD was explained by cardiovascular risk factors. CONCLUSION. In this large study of European type 1 diabetic subjects, increased concentrations of tHcy were independently related to macroalbuminuria, renal function and hypertension, which suggests that tHcy might play an important role in the pathogenesis of vascular complications in type 1 diabetes.     

Associations of Metabolic Syndrome and its Components With Mortality in the Elderly: A Cohort Study of 73,547 Taiwanese Adults

Available evidence shows that metabolic syndrome (Mets) has clear adverse effects for middle-aged and pre-elderly adults; however, the effect of Mets on mortality among elderly adults remains unclear. In addition, the comparative utility of Mets and its component for predicting mortality among the elderly has not been clearly established. Using data from a large Taiwanese cohort, we evaluated the effect of Mets and its components on subsequent all-cause and cause-specific mortality overtime among the elderly.A total of 73,547 elders (age ≥65 years) participated in the Taipei Elderly Health Examination Program from 2007 to 2010. Mets was diagnosed using the adult treatment panel III criteria, and mortality was ascertained by using national death records. Time-dependent analysis was used to evaluate associations of Mets and its components with all-cause mortality, cardiovascular disease (CVD) mortality, and expanded CVD mortality.This retrospective cohort study found that 42.6% of elders had Mets. During 194,057 person-years of follow-up, 2944 deaths were observed. After adjusting for sociodemographic characteristics and comorbidities, Mets was associated with increased risk of expanded CVD mortality (hazard ratio [HR], 1.27; 95% CI, 1.10–1.46) but not all-cause or CVD mortality. Among Mets components, decreased high-density lipoprotein cholesterol (HDL-C, HR 1.25, 95% CI 1.13–1.37) and hyperglycemia (HR 1.21, 95% CI 1.12–1.31) were associated with a significant increase in all-cause mortality. Hypertension and low HDL-C were predictors of CVD mortality and expanded CVD mortality, and, as compared with Mets, were associated with a higher risk of expanded CVD mortality.The present findings indicate that, in elderly adults, individual components of Mets are better predictors of all-cause and cause-specific mortality than is Mets as a whole. Our results suggest that future efforts should focus on preventing and managing individual risk factors (particularly hypertension, low HDL-C, and hyperglycemia) rather than on “diagnosing” Mets in elders.     

Nonfasting plasma total homocysteine levels and stroke incidence in elderly persons: the Framingham Study.

BACKGROUND: Total homocysteine levels are associated with arteriosclerotic outcomes. OBJECTIVE: To determine whether total homocysteine levels predict incident stroke in elderly persons. DESIGN: Prospective population-based cohort study with 9.9 years of follow-up. SETTING: Framingham, Massachusetts. PATIENTS: 1947 Framingham Study participants (1158 women and 789 men; mean age +/- SD, 70 +/- 7 years). MEASUREMENTS: Baseline total homocysteine levels and 9.9-year stroke incidence. RESULTS: The quartiles of nonfasting total homocysteine levels were as follows: quartile 1, 4.13 to 9.25 micromol/L; quartile 2, 9.26 to 11.43 micromol/L; quartile 3, 11.44 to 14.23 micromol/L; quartile 4, 14.24 to 219.84 micromol/L. During follow-up, 165 incident strokes occurred. In proportional hazards models adjusted for age, sex, systolic blood pressure, diabetes, smoking, and history of atrial fibrillation and coronary heart disease, relative risk (RR) estimates comparing quartile 1 with the other three quartiles were as follows: quartile 2 compared with quartile 1--RR, 1.32 (95% CI, 0.81 to 2.14); quartile 3 compared with quartile 1--RR, 1.44 (CI, 0.89 to 2.34); quartile 4 compared with quartile 1--RR, 1.82 (CI, 1.14 to 2.91). The linear trend across the quartiles was significant (P < 0.001). CONCLUSION: Nonfasting total homocysteine levels are an independent risk factor for incident stroke in elderly persons.     

Serum cholesterol concentrations and all-cause mortality in older people

OBJECTIVE: To study the impact of serum cholesterol concentrations on the total risk of mortality in older people. DESIGN: Retrospective cohort study with a follow-up of 8-10 years. SUBJECTS: A total of 989 subjects (367 men and 622 women) aged 65 and over, living in the Marshfield Epidemiologic Study Area at the time of their first complete serum lipid assessment. METHODS: We calculated sex-specific mean levels of serum total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides, and the ratio of total cholesterol to high-density lipoprotein, for subjects who died of all causes and for those who survived to the end of follow-up, with adjustment for relevant covariates. We obtained estimates of the risk factor-adjusted sex-specific relative risk for all-cause mortality with approximate quartiles of serum cholesterol concentrations by proportional hazards regression models. We also evaluated the possible combined effects of age, sex and cholesterol on all-cause mortality. RESULTS: A high level of high-density lipoprotein was significantly associated with a low total risk of mortality in older men. Conversely, an elevated ratio of total cholesterol to high-density lipoprotein was directly related to an increased total risk of mortality in older men. Age and high-density lipoprotein level had a significant synergistic effect on all-cause mortality for the elderly men. We found little or no association in women between all-cause mortality and any of the lipid measures studied. CONCLUSIONS: An increased ratio of total cholesterol to high-density lipoprotein appears to be associated with an increase in risk for all-cause mortality in men aged 65 and over, while an elevated level of high-density lipoprotein, considered alone, seems to be protective against mortality from all causes in men aged 65-74 years, but this effect diminishes over the age of 75.     

Elevated levels of plasma homocysteine are associated with neurotoxicity

OBJECTIVE: The aim of the present study is to investigate whether increased plasma homocysteine (tHcy) has an effect on the cerebral metabolic concentrations, reflecting neurotoxicity, measured with Magnetic Resonance Spectroscopy (MRS). METHODS: One hundred and thirteen patients had a MRS investigation of the brain and the concentration of N-acetyl-aspartate (NAA), choline and creatine was measured and fasting plasma tHcy was assessed. We used linear regression models to investigate the association between tHcy and cerebral metabolic concentrations. RESULTS: We found that tHcy is associated with cerebral NAA (B = -0.09 mmol/l (95% CI, -0.17 to -0.00)) and with creatine (B = -0.09 mmol/l (95% CI, -0.16 to -0.02)) per 1 micromol/l increase tHcy. Patients with a tHcy >/=14 micromol/l had a lower concentration cerebral of NAA (P < 0.05) and creatine (P < 0.01) compared with patients with a tHcy <14 micromol/l. No significant association was found for the cerebral choline. CONCLUSION: Elevated levels of tHcy were associated with low concentrations of cerebral NAA and creatine, independent of renal function or the presence of atherosclerotic disease. These preliminary results suggest that tHcy has a neurotoxic effect in vivo.     

A Body Shape Index is positively associated with all-cause and cardiovascular disease mortality in the Chinese population with normal weight: A prospective cohort study

Background and aimA body shape index (ABSI) is a valuable predictor of mortality in the Western population, but similar evidence in the general Chinese population is limited. This study aims to evaluate the association between the ABSI and all-cause and cardiovascular disease (CVD) mortality in the Chinese population with normal weight.Methods and results9046 participants with normal BMI (18.5–24.9 kg/m²) from the China Hypertension Survey were enrolled. The baseline ABSI was calculated as waist circumference/(BMI^2/3height^1/2). Cox proportional hazards regression was performed to evaluate the association of the ABSI with all-cause and CVD mortality. Over an average follow-up of 5.4 years, 686 all-cause and 215 CVD deaths occurred. A 0.01-unit increment in the ABSI was associated with a 31% greater risk of all-cause mortality (hazard ratio [HR], 1.31; 95% CI: 1.12, 1.48) and CVD mortality (HR, 1.30; 95% CI: 1.08, 1.58). Compared with quartile 1 of the ABSI, the adjusted HRs of all-cause mortality for quartiles 2–4 were, respectively, 1.25 (95% CI: 0.98, 1.59), 1.28 (95% CI: 0.99, 1.67), and 1.54 (95% CI: 1.17, 2.03) (P_trend = 0.004), and those of CVD mortality for quartiles 2–4 were, respectively, 1.28 (95% CI: 0.88, 1.83), 1.42 (95% CI: 0.97, 2.08), and 1.45 (95% CI: 0.98, 2.170) (P_trend = 0.043). The dose–response analysis showed a linear positive association of the ABSI with all-cause (P_nonlinearity = 0.158) and CVD mortality (P_nonlinearity = 0.213).ConclusionThe ABSI was positively associated with all-cause and CVD mortality among the general Chinese population with normal BMI. The data suggest that the ABSI may be an effective tool for central fatness for mortality risk assessment.     

Plasma total homocysteine and hospitalizations for cardiovascular disease: the Hordaland Homocysteine Study

BACKGROUND: Elevated total plasma homocysteine (tHcy) level is a risk factor for occlusive disease in the coronary, cerebral, and peripheral vessels and is related to several lifestyle factors associated with cardiovascular disease (CVD). OBJECTIVE: To examine the association of a single tHcy measurement on subsequent hospitalizations due to CVD. METHODS: A population-based prospective cohort study was conducted from April 1, 1992, to May 31, 1998 (mean follow-up, 5.3 years) in western Norway. The study included 17 361 individuals aged 40 to 42 or 65 to 67 years at baseline. Main outcome measure was CVD as the main hospital discharge diagnosis or coronary revascularization procedures (denoted "CVD hospitalizations") during follow-up (n = 1275). RESULTS: At baseline, participants with preexisting CVD had higher mean tHcy values than individuals without CVD. Risk of CVD hospitalizations increased significantly with increasing baseline tHcy only in the oldest age group. Here, multiple risk factor-adjusted hospitalization rate ratios in 5 tHcy categories (<9, 9-11.9, 12-14.9, 15-19.9, and >or=20 micromol/L [to convert tHcy to milligrams per liter, divide by 7.397]) were as follows: 1 (reference level), 1.00, 1.34, 1.67, and 1.94, respectively (P for trend <.001). The relation between tHcy level and CVD hospitalizations was significantly stronger among individuals with preexisting CVD than those without (hospitalization rate ratio per 5-micromol/L tHcy increment, 1.29 vs 1.10; P for interaction,.02). CONCLUSIONS: Plasma tHcy level is a strong predictor of CVD hospitalizations only in elderly individuals, and especially among those with preexisting CVD. Our findings are compatible with the theory that tHcy interacts with conventional CVD risk factors to provoke the acute event of CVD.     

Influence of methionine synthase (A2756G) and methionine synthase reductase (A66G) polymorphisms on plasma homocysteine levels and relation to risk of coronary artery disease

BACKGROUND: Elevated plasma total homocysteine (tHcy) is increasingly being recognized as a risk factor for coronary artery disease (CAD) and other defects. Recent genetic studies have characterized molecular determinants contributing to altered homocysteine metabolism. Our objectives were therefore to confirm the relationship of tHcy with CAD and to examine the importance of genetic influence on tHcy in the coronary angiograms and conventional cardiovascular risk factors recorded in 230 subjects. We also determined the genotype frequencies distribution of the A2756G transition of the B12-dependent methionine synthase (MTR) gene and the A66G mutation of the methionine synthase reductase (MTRR) gene. RESULTS: Patients with CAD (n=151) had significantly higher tHcy concentrations than control subjects (15.49 +/- 2.75 micromol/l vs. 11.21 +/- 3.54 micromol/l, P < 0.001). Hyperhomocysteinaemia (tHcy > or =15 micromol/l) was a risk factor for CAD [RR = 4.07, 95% CI: 2.21 - 7.47, P < 0.001]. The homocysteine concentrations were significantly different between smokers and non-smokers, at 15.63 +/- 3.10 vs. 12.45 +/- 3.84 micromol/l, P < 0.05. In addition, smokers with hyperhomocysteinaemia demonstrated a markedly increased risk of CAD (OR = 2.50, 95% CI: 1.67 - 3.32, P < 0.05) compared with non-smokers with normal homocysteine.The 2756G and the 66G allele contribute to a moderate increase in homocysteine levels (P = 0.008 and P = 0.007, respectively), but not to CAD (P > 0.05). Combined MTR and MTRR polymorphisms, the 2756AG + 66AG and the 2756AG + 66GG were the combined genotypes that were a significant risk factor for having hyperhomocysteinaemia (14.4 +/- 2.8 micromol/l, OR = 2.75, IC 95% = 1.21 - 6.24, P=0.016 and 17.9 +/- 4.1 micromol/l, OR = 6.28, IC 95% = 1.46 - 12.1, P = 0.021, respectively). Statistic analysis using the UniANOVA test shows that these two polymorphisms have an interactive effect circulating homocysteine levels (P < 0.05). CONCLUSION: Our data suggest that moderately elevated tHcy levels are prevalent in our population and are associated with an increased risk for CAD. This study provides evidence that the MTR A2756G and MTRR A66G polymorphisms significantly influence the circulating homocysteine concentration. In addition, the MTR and MTRR genes may interact to increase the risk for having hyperhomocysteinaemia.     

Hypertension, concurrent cardiovascular risk factors and mortality: the Singapore Cardiovascular Cohort Study

The current hypertension (HTN) guidelines recommend the assessment of other cardiovascular disease (CVD) risk factors in individuals with HTN for further management. Few studies in Asian populations have been published to identify the outcome of individuals with HTN and other CVD risk factors. This study aims to assess the effect of HTN alone, and in combination with other CVD risk factors on all-cause and CVD mortality. Three cross-sectional studies carried out in Singapore (baseline 1982--1995) consisting of 5830 persons were grouped by the absence or presence of HTN and CVD risk factors. They were followed-up (mean 14.1 years) by linkage with the National Death Register. Cox's proportional hazards model was used to obtain adjusted hazard ratios (HRs) for risk of mortality. HTN individuals with either <2 CVD risk factors (adjusted HR 1.4; 95% confidence interval (CI) 1.0-1.8) or > or =2 CVD risk factors (adjusted HR 2.3; 95% CI 1.9-3.0) were at increased risk of all-cause mortality compared to normotensive individuals. The findings were similar for CVD mortality. HTN individuals who also smoked or had diabetes were at highest risk of all-cause mortality, whereas those with elevated total cholesterol/high-density lipoprotein cholesterol, smoked or diabetes had the highest risk for CVD mortality. These findings show that in HTN individuals it is important to assess the presence of other CVD risk factors and manage accordingly.     

Plasma Carboxymethyl-Lysine, an Advanced Glycation End Product, and All-Cause and Cardiovascular Disease Mortality in Older Community-Dwelling Adults

OBJECTIVES: To determine whether older adults with high plasma carboxymethyl-lysine (CML), an advanced glycation end product, are at higher risk of all-cause and cardiovascular disease (CVD) mortality.
DESIGN: Prospective cohort study.
SETTING: Population-based sample of adults aged 65 and older residing in Tuscany, Italy.
PARTICIPANTS: One thousand thirteen adults participating in the Invecchiare in Chianti study.
MEASUREMENTS: Anthropometric measures, plasma CML, fasting plasma total, high-density and low-density lipoprotein cholesterol, triglycerides, glucose, creatinine. Clinical measures: medical assessment, diabetes mellitus, hypertension, coronary heart disease, heart failure, stroke, cancer. Vital status measures: death certificates and causes of death according to the International Classification of Diseases . Survival methods were used to examine the relationship between plasma CML and all-cause and CVD mortality, adjusting for potential confounders.
RESULTS: During 6 years of follow-up, 227 (22.4%) adults died, of whom 105 died with CVD. Adults with plasma CML in the highest tertile had greater all-cause (hazard ratio (HR)=1.84, 95% confidence interval) CI)=1.30–2.60, P <.001) and CVD (HR=2.11, 95% CI=1.27–3.49, P =.003) mortality than those in the lower two tertiles after adjusting for potential confounders. In adults without diabetes mellitus, those with plasma CML in the highest tertile had greater all-cause (HR=1.68, 95% CI=1.15–2.44, P =.006) and CVD (HR=1.74, 95% CI=1.00–3.01, P =.05) mortality than those in the lower two tertiles after adjusting for potential confounders.
CONCLUSION: Older adults with high plasma CML are at higher risk of all-cause and CVD mortality.     

Circulating levels of tumor necrosis factor receptors are highly predictive of mortality in patients with rheumatoid arthritis

OBJECTIVE: To investigate whether circulating levels of soluble tumor necrosis factor receptors (sTNFR) are predictive of mortality in rheumatoid arthritis (RA). METHODS: Levels of sTNFRI and sTNFRII at study entry were quantified using enzyme-linked immunosorbent assays in sera from 401 white patients with RA followed up for 13 years. Patients were tracked via the National Health Service Central Register, and the relationship between sTNFR levels and mortality was analyzed using a Cox proportional hazards regression model. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: At the end of the followup period, 132 (32.9%) of 401 patients had died. Of these, 64 (48.5%) died of cardiovascular disease (CVD). Significant associations between all-cause mortality and baseline levels of sTNFRI and sTNFRII were identified in men (HR 1.7 [95% CI 1.2-2.4] and HR 1.18 [95% CI 1.05-1.32], respectively) and women (HR 1.33 [95% CI 0.99-1.8] and HR 1.14 [95% CI 1.02-1.28], respectively). Analysis including levels of both sTNFRI and sTNFRII indicated that the sTNFRII level was the best overall predictor of mortality. Multivariate analysis also revealed that the sTNFRII level was a predictor of all-cause and CVD mortality independently of age, sex, disease duration, C-reactive protein level, erythrocyte sedimentation rate, rheumatoid factor, nodular disease, modified Health Assessment Questionnaire score, taking CVD drugs, and smoking. CONCLUSION: Our data indicate that serum levels of sTNFR are powerful predictors of mortality in RA. Elevated levels are particularly associated with mortality due to CVD and may be useful for identifying patients at increased risk of premature death.     

Sex differences in the effect of heart rate on mortality in the elderly

OBJECTIVES: To examine the association between heart rate and mortality risk in the elderly. DESIGN: Longitudinal cohort. SETTING: Outpatient. PARTICIPANTS: Four hundred twenty-two people, aged 70 upon entry, were surveyed and followed for 6 years. MEASUREMENTS: Pulse rate was measured manually, while sitting and standing, and heart rate was measured from electrocardiogram recordings. The population was divided into quartiles of heart rate, with the top quartile comprising those with heart rate greater than 77 beats per minute (bpm) and the bottom quartile those with heart rate less than 60 bpm. RESULTS: After controlling for possible confounders, there was a clear correlation (r) between heart rate and all-cause mortality in elderly women (r=0.25, P=.0003). The correlation in women was observed using the three different methods for measuring heart rate. Heart rate was associated with all-cause and cardiovascular mortality. There was no relationship between heart rate and level of exercise or smoking status. In multiple regression analysis, the increased risk of death in the women was independent of previous cardiovascular or cerebrovascular disease, hypertension, anemia, congestive heart failure, smoking, and level of exercise or activities of daily living (relative odds ratio (ROR)=3.37, 95% confidence interval (CI)=0.96-11.8). When women using beta-blockers were excluded, this relationship became even stronger (ROR=8.5, 95% CI=1.19-60.1). CONCLUSION: Elevated heart rate is related to increased mortality in elderly women, thus representing a simple index of general health status in this population. Elevated heart rate did not predict mortality in elderly men.     

The association between circulating white blood cell count, triglyceride level and cardiovascular and all-cause mortality: population-based cohort study

OBJECTIVES: To examine the individual and combined relationship between elevated white blood cell count (WBC), triglyceride level and cardiovascular and all-cause mortality among older Australians. DESIGN: Prospective population-based cohort study. SETTING: Community in Blue Mountains region, Australia. PARTICIPANTS: 2904 individuals, aged 49-84 years, free of cardiovascular disease and cancer at the baseline examination. MAIN OUTCOME MEASURES: Cardiovascular (n=242) and all-cause mortality (n=575). RESULTS: Elevated WBC count and triglyceride level were found to be associated with cardiovascular and all-cause mortality, independent of several important confounders. Multivariable relative risk [RR] (95% confidence interval [CI]) comparing fourth (6.8 x 10(9) cells/L and above) versus first quartile (4.8 x 10(9) cells/L and below) of WBC count was 2.01 (1.40-2.90) for cardiovascular mortality and 1.68 (1.35-2.09) for all-cause mortality. Multivariable RR (95% CI) comparing fourth (1.98 mmol/L and above) versus first quartile (0.95 mmol/L and below) of triglyceride level was 1.58 (1.08-2.30) for cardiovascular mortality and 1.40 (1.11-1.77) for all-cause mortality. Furthermore, a combined exposure to the fourth quartiles of both WBC count and triglyceride level was found to be related to more than three-fold risk of cardiovascular mortality (RR [95% CI]: 3.15 [2.17-4.57], p-interaction=0.01), independent of traditional risk factors. CONCLUSIONS: Elevated WBC count and triglyceride level were associated with cardiovascular and all-cause mortality among older Australians. These data provide new epidemiological evidence regarding cardiovascular risk stratification using simple, inexpensive, and routinely available measures, suggesting that a combined exposure to both high WBC count and triglyceride level is related to more than three-fold risk of cardiovascular mortality, independent of traditional risk factors.     

静息心率对老年人群心脑血管事件及全因死亡的影响

目的探讨老年人群(≥60岁)静息心率(RHR)水平对心脑血管事件及全因死亡的影响。方法本前瞻性队列研究于2006年和2007年进行,参加者为101 010名开滦集团的员工,选择其中年龄≥60岁、无心律失常、无心脑血管病史、未服用β受体阻滞剂的18 924例职工为研究对象。按RHR四分位数值分为以下4组:<67次/min、68~71次/min、72~79次/min、≥80次/min。随访期间收集心脑血管疾病及全因死亡事件,应用Cox比例风险模型评估RHR与全因死亡及CVD的风险。结果 (1)中位随访11.18年,4组发生心脑血管事件例数和累积发病率分别为[536(11.32%)、479(12.38%)、686(12.53%)、618(12.76%)],差异无统计学意义(P>0.05);4组发生全因死亡例数和累积全因死亡率分别为1 086(22.93%)、940(24.30%)、1 330(24.28%)、1 462(30.19%)例,差异有统计学意义(P<0.01)。(2)校正传统心血管疾病危险因素后多因素分析显示,与RHR最低四分位数组相比,最高四分位组发生心脑血管事件及全因死亡的HR值分别为1.06(95%CI 0.93~1.20)、1.07(95%CI 0.95~1.20)、1.07(95%CI 0.94~1.21);1.14(95%CI 1.04~1.25)、1.12(95%CI 1.03~1.22)、1.37(95%CI 1.26~1.49)。结论 RHR升高是开滦研究老年人群全因死亡的危险因素。     

Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

BACKGROUND: Homocysteine and folate have been suggested to have opposite effects on the risk of stroke, although the results are controversial. DESIGN AND METHODS: The purpose of this study was to assess the effects of serum total homocysteine (tHcy) and serum folate levels on the risk of stroke in a prospective cohort study. The subjects were 1015 men aged 46-64 years and free of prior stroke, examined in 1991-1993 in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. RESULTS: At baseline the mean serum tHcy concentration was 10.9 micromol/l (SD 3.4). During an average follow-up time of 9.6 years, 49 men experienced a stroke, of which 34 were ischaemic. In Cox proportional hazards models, men in the highest tHcy third had a risk factor-adjusted hazard rate ratio (RR) of 2.77 [95% confidence interval (CI): 1.23-6.24] for any stroke and 2.61 (95% CI: 1.02-6.71) for ischaemic stroke, compared with men in the lowest third. The mean baseline serum folate concentration was 10.4 nmol/l (SD 4.1). Men in the highest third of serum folate (>11.2 nmol/l) had an adjusted RR for any stroke of 0.35 (95% CI: 0.14-0.87) and for ischaemic stroke of 0.40 (95% CI: 0.15-1.09), compared with men in the lowest third. CONCLUSION: Elevated serum tHcy is associated with increased risk of all strokes and ischaemic strokes in middle-aged eastern Finnish men free of prior stroke. On the other hand, high serum folate concentration may protect against stroke.     

Usefulness of serum bilirubin and cardiorespiratory fitness as predictors of mortality in men

Elevated serum bilirubin has been suggested to reduce the risk for mortality. Cardiorespiratory fitness (CRF) has also been reported to have inverse association with all-cause and cardiovascular disease (CVD) mortality. The association between serum bilirubin, all-cause and CVD mortality, and the effect of CRF on the observed association was investigated. A total of 1,279 men aged 30 to 82 years underwent baseline medical examinations from 1974 to 1997 at the Cooper Clinic in Dallas, Texas. During an average of 17 years of follow-up, 698 men died, with 253 deaths due to CVD (36%). Men in the highest bilirubin quartiles had significantly lower risk for all-cause mortality compared to men in the lowest quartiles (p for trend = 0.0043), after adjusting for age and examination year. This inverse association remained significant after further adjustment for known confounders (p for trend = 0.0018). Additional adjustment for treadmill time attenuated the association (p for trend = 0.0090). Similar patterns of association were observed between serum bilirubin quartiles and CVD mortality. CRF was inversely associated with all-cause mortality (p for trend <0.0001) after adjusting for age and examination year. This inverse association also was observed after further adjusting for known confounders (p for trend = 0.0004). After additional adjustment for serum bilirubin, the association between CRF and all-cause mortality remained significant (p for trend = 0.0012). All-cause mortality and CVD mortality were significantly lower in men in the moderate- to high-fitness quartiles in the low- and high-bilirubin groups. In conclusion, serum bilirubin level and CRF level were strongly and independently associated with all-cause and CVD mortality.     

Chronic kidney disease and risk of incident myocardial infarction and all-cause and cardiovascular disease mortality in middle-aged men and women from the general population.

AIMS: Chronic kidney disease (CKD) was found to be an independent risk factor for all-cause mortality as well as adverse cardiovascular disease (CVD) events in high-risk populations. Findings from population-based studies are scarce and inconsistent. We investigated the gender-specific association of CKD with all-cause mortality, cardiovascular mortality, and incident myocardial infarction (MI) in a population-based cohort. METHODS AND RESULTS: The study was based on 3860 men and 3674 women (aged 45-74 years) who participated in one of the three MONICA Augsburg surveys between 1984 and 1995. CKD was defined by an estimated glomerular filtration rate between 15 and 59 mL/min/1.73 m(2). Hazard ratios (HRs) were estimated from Cox proportional hazard models. In this study, 890 total deaths, 400 CVD deaths, and 321 incident MIs occurred in men up to 31 December 2002; the corresponding numbers in women were 442, 187, and 102. In multivariable analyses, the HR for women with CKD compared to women with preserved renal function was significant for incident MI [HR 1.67; 95% confidence interval (CI) 1.07-2.61] and CVD mortality (HR 1.60; 95% CI 1.17-2.18). In men, CKD was also significantly associated with incident MI (HR 1.51; 95% CI 1.09-2.10) and CVD mortality (HR 1.48; 95% CI 1.15-1.92) after adjustment for common CVD risk factors. In contrast, men and women with CKD had no significant increased risk of all-cause mortality. CONCLUSION: CKD was strongly associated with an increased risk of incident MI and CVD mortality independent from common cardiovascular risk factors in men and women from the general population.