Impact of major cardiovascular disease risk factors, particularly in combination, on 22-year mortality in women and men

BACKGROUND: The appropriateness of current cardiovascular disease (CVD) risk factor guidelines in women continues to be debated. OBJECTIVE: To present new data on the appropriateness of current CVD risk factor guidelines, for women and men, from long-term follow-up of a large population sample. METHODS: Cardiovascular disease risk factor status according to current clinical guidelines and long-term impact on mortality were determined in 8686 women and 10503 men aged 40 to 64 years at baseline from the Chicago Heart Association Detection Project in Industry; average follow-up was 22 years. RESULTS: At baseline, only 6.6% of women and 4.8% of men had desirable levels for all 3 major risk factors (cholesterol level, <5.20 mmol/L [<200 mg/dL]; systolic and diastolic blood pressure, <120 and <80 mm Hg, respectively; and nonsmoking). With control for age, race, and other risk factors, each major risk factor considered separately was associated with increased risk of death for women and men. In analyses of combinations of major risk factors, risk increased with number of risk factors. Relative risks (RRs) associated with any 2 or all 3 risk factors were similar: for coronary heart disease mortality in women, RR= 5.72 (95% confidence interval [CI], 2.35-13.93), and in men, RR = 5.51 (95% CI, 3.10-9.77); for CVD mortality in women, RR = 4.54 (95% CI, 2.33-8.84), and in men, RR = 4.12 (95% CI, 2.56-6.37); and for all-cause mortality in women, RR = 2.34 (95% CI, 1.73-3.15), and in men, RR = 3.20 (95% CI, 2.47-4.14). Absolute excess risks were high in women and men with any 2 or all 3 major risk factors. CONCLUSIONS: Combinations of major CVD risk factors place women and men at high relative, absolute, and absolute excess risk of coronary heart disease, CVD, and all-cause mortality. These findings support the value of (1) measurement of major CVD risk factors, especially in combination, for assessing long-term mortality risk and (2) current advice to match treatment intensity to the level of CVD risk in both women and men.     

Do changes in cardiovascular risk factors explain the increasing socioeconomic difference in mortality from ischaemic heart disease in Finland?

STUDY OBJECTIVE: To estimate the extent to which changes in blood pressure, smoking, and serum cholesterol concentration explain the observed increase in socioeconomic differences in mortality from ischaemic heart disease (IHD) in Finland during the past 20 years. DESIGN: Predicted changes in mortality from IHD were calculated using logistic regression models with the risk factor levels assessed by cross sectional population surveys conducted in 1972, 1977, 1982, and 1987. The subjects included white collar and blue collar workers and farmers. The predicted changes were compared with the observed mortality changes in the same socioeconomic groups in the total population of the same geographical area. SETTING: North Karelia and Kuopio provinces, eastern Finland. PARTICIPANTS: 16,741 men and 16,389 women aged 30-59 randomly drawn from the population registers of the study areas. Mortality data were obtained from the total population in the same areas. MAIN RESULTS: In men, the changes in diastolic blood pressure, total serum cholesterol, and smoking predicted a 28% decline in the mortality from IHD among white collar workers, a 30% decline among blue collar workers, and a 33% decline in farmers. Observed declines in the same socioeconomic groups were 61%, 40%, and 37%, respectively. In women, the predicted decline was 41% among white collar workers, 35% among blue collar workers, and 39% among farmers. The respective observed declines were 57%, 43%, and 20%. CONCLUSIONS: Less than half of the decline in IHD mortality among white collar men was explained by the risk factor changes, while they explained 75% of the decline among blue collar men and 89% of the decline among male farmers. Changes in risk factors did not explain the increasing difference in IHD mortality between the socioeconomic groups, especially among men.     

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.     

Reducing risk for cardiovascular disease.

The focus of this review article is to examine the importance of psychological and social factors in the development and maintenance of cardiovascular diseases, primarily coronary heart and artery disease, and to provide an overview of the effectiveness of psychosocial risk reduction interventions. First we summarize the prevalence and economic burden of cardiovascular disease, as well as the role of psychosocial factors in disease development and progression. We then examine the primary modifiable risk factors and evaluate the role of psychotherapists in the treatment of heart disease. Finally, we assess the effectiveness of risk factor modification and rehabilitation interventions, describe the potential costs and benefits of these programs, and discuss the role of primary prevention programs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mastery is associated with cardiovascular disease mortality in men and women at apparently low risk.

Objective: We examine the prospective relationship between mastery, where limited mastery is defined as the inability to control negative emotions (and perceiving stressful experiences as beyond personal control), and cardiovascular disease (CVD) mortality particularly among individuals at apparently low CVD risk. Design: Prospective population-based study of 19,067 men and women, aged 41–80 years with no previous heart disease or stroke at baseline assessment. Main Outcome Measures: Primary outcome measure CVD mortality. Results: A total of 791 CVD deaths were recorded up to June 2009 during a median 11.3 person-years of follow-up. Limited perceived mastery over life circumstances was associated with an increased risk of CVD mortality, independently of biological, lifestyle, and socioeconomic risk factors (hazard ratio 1.11 per SD decrease in mastery score, 95% confidence interval 1.01–1.21). This association was more pronounced among those participants apparently at low CVD risk (p = .01 for test of interaction according to the number of CVD risk factors at baseline). Conclusions: Limited perceived control over life circumstances is associated with an increased risk of CVD mortality, independently of classical cardiovascular risk factors, and particularly among those at apparently low risk. Future attention should be given to this potentially modifiable personal characteristic, through the design of preliminary intervention studies, to reduce cardiovascular risk. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A risk factor index predicting adolescent cigarette smoking: A 7-year longitudinal study.

The authors used longitudinal data to develop a risk factor index (RFI) for the prediction of smoking behavior in youth. Students were followed yearly from 6th through 12th grades in a prospective longitudinal study. Ten risk factors were identified and combined into an RFI. Data were analyzed with a generalized estimating equations approach. The RFI predicted both concurrent smoking and use of cigarette in the succeeding year. It further predicted whether a youth would smoke at any point during his or her school career. Prediction was better for boys than for girls. Furthermore, the RFI better predicted heavy smoking than any use of cigarettes. The RFI could be useful in selecting youth for intensive prevention and early intervention efforts. Results also suggest the importance of further examination of gender differences in smoking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Isolated systolic hypertension: an important cardiovascular risk factor

BACKGROUND: The rising number of vancomycin-resistant enterococci (VREs) is a major concern to modern medicine because vancomycin is currently the 'last resort' drug for life-threatening infections. The D-alanyl-D-X ligases (where X is an hydroxy or amino acid) of bacteria catalyze a critical step in bacterial cell-wall peptidoglycan assembly. In bacteria that produce glycopeptide antibiotics and in opportunistic pathogens, including VREs, D-, D-ligases serve as switches that confer antibiotic resistance on the bacteria themselves. Peptidoglycans in vancomycin-sensitive bacteria end in D-alanyl-D-alanine, whereas in vancomycin-resistant bacteria they end in D-alanyl-D-lactate or D-alanyl-D-serine. RESULTS: We demonstrate that the selective utilization of D-serine by the Enterococcus casseliflavus VanC2 ligase can be altered by mutagenesis of one of two residues identified by homology to the X-ray structure of the Escherichia coli D-alanyl-Dalanine ligase (DdlB). The Arg322-->Met (R322M) and Phe250-->Tyr (F250Y) ligase mutants show a 36-44-fold decrease in the use of D-serine, as well as broadened specificity for utilization of other D-amino acids in place of D-serine. The F250Y R322M double mutant is effectively disabled as a D-alanyl-D-serine ligase and retains 10% of the catalytic activity of wild-type D-alanyl-D-alanine ligases, reflecting a 6,000-fold switch to the D-alanyl-D-alanine peptide. Correspondingly, the Leu282-->Arg mutant of the wild-type E. coli DdlB produced a 560-fold switch towards D-alanyl-D-serine formation. CONCLUSIONS: Single-residue changes in the active-site regions of D-, D-ligases can cause substantial changes in recognition and activation of hydroxy or amino acids that have consequences for glycopeptide antibiotic efficacy. The observations reported here should provide an approach for combatting antibiotic-resistant bacteria.     

Increased cardiovascular disease mortality rates in traumatic lower limb amputees

We evaluated the 24-year mortality rates of male traumatic lower limb amputees (n = 201) of the Israeli army, wounded between 1948 and 1974 compared with a cohort sample representing the general population (n = 1,832). Mortality rates were significantly higher (21.9% vs 12.1%, p <0.001) in amputees than in controls. Cardiovascular disease (CVD) mortality was the main cause for this difference. The prevalence of selected risk factors for CVD was determined in 101 surviving amputees (aged 50 to 65 years) and a sample of the controls (n = 96) matched by age and ethnic origin. Amputees had higher plasma insulin levels (during fasting and in response to oral glucose loading) and increased blood coagulation activity. No differences were found in rates of current symptoms of ischemic heart disease or of cerebrovascular disease, obesity, hypertension, altered plasma lipoprotein profile, impaired physical activity, smoking, or nutritional habits. Traumatic lower limb amputees had increased mortality rates due to CVD. Surviving amputees had hyperinsulinemia, increased coagulability, and increased sympathetic and parasympathetic responses (described previously). These established CVD risk factors may explain the excess mortality due to CVD in traumatic amputees.     

Beer binging and mortality: results from the Kuopio ischaemic heart disease risk factor study, a prospective population based study

OBJECTIVE: To examine the association between beer binging (regular sessions of heavy beer drinking) and mortality. DESIGN: Prospective population based study with the baseline assessment of level of alcohol intake (dose), by type of drink and drinking pattern, previous and existing diseases, socioeconomic background, occupational status, involvement in organisations during leisure time, physical activity in leisure time, body mass index, blood pressure, serum lipids and plasma fibrinogen concentration, during an average of 7.7 years' follow up of mortality. SETTING: Finland. SUBJECTS: A population sample of 1641 men who consumed beer who were aged 42, 48, 54, or 60 years at baseline. MAIN OUTCOME MEASURES: All cause mortality, cardiovascular mortality, death due to external causes, fatal myocardial infarctions. RESULTS: The risk of death was substantially increased in men whose usual dose of beer was 6 or more bottles per session compared with men who usually consumed less than 3 bottles, after adjustment for age and total alcohol consumption (relative risk 3.01 (95% confidence interval 1.54 to 5.90) for all deaths; 7.10 (2.01 to 25.12) for external deaths; and 6.50 (2.05 to 20.61) for fatal myocardial infarction). The association changed only slightly when smoking, occupational status, previous diseases, systolic blood pressure, low density lipoprotein and high density lipoprotein cholesterol concentration, plasma fibrinogen concentration, body mass index, marital status, leisure time physical activity, and involvement in organisations were controlled for. CONCLUSION: The pattern of beer binging is associated with increased risk of death, independently of the total average consumption of alcoholic drinks. The relation is not explained by known behavioural, psychosocial, or biological risk factors. Death due to injuries and other external causes is overrepresented among beer bingers, but a strong association with fatal myocardial infarction suggests that the pathway may also involve other acute triggers of severe health events.     

Soy protein, isoflavones and cardiovascular disease risk

Since the early 1940s, scientists have examined the effect of soy protein on blood cholesterol concentrations. Although studies in animals have suggested that soy protein lowers blood cholesterol concentrations, similar studies in humans have yielded less consistent results. The presence or absence of the soybean isoflavone fraction may be a confounding factor. This fraction, consisting primarily of genistein, daidzein and glycetein, has been shown to have a hypocholesterolemic effect in animals and humans. Potential mechanisms by which soy protein and/or isoflavones induce lowering of blood cholesterol concentrations include thyroid status, bile acid balance and the estrogenic effects of genistein and daidzein. Some studies have suggested that isoflavones exhibit antioxidant properties and have favorable effects on arterial compliance. In addition to the aforementioned potential beneficial effects, the increased consumption of products containing soy protein may displace foods relatively high in saturated fat and cholesterol from the diet and hence have an indirect blood cholesterol-lowering effect.     

Magnetic field exposure and cardiovascular disease mortality among electric utility workers

Glial cell line-derived neurotrophic factor (GDNF) was identified as a consequence of the hypothesis that glia secrete factors that influence growth and differentiation of specific classes of neurons. Glia are a likely source of additional neurotrophic factors; however, this strategy has not been applied extensively. The discovery of GDNF in 1993 led to an abundance of studies that within only a few years qualified GDNF as a bona fide neurotrophic factor. Of particular interest are studies demonstrating the effectiveness of GDNF protein in ameliorating neurodegeneration in animal models of Parkinson's disease and amyotrophic lateral sclerosis (ALS). It remains to be determined whether GDNF will be an effective therapy in humans with these diseases. However, since these diseases are slowly progressive and the CNS relatively inaccessible, the delivery of GDNF as a therapeutic molecule to the CNS in a chronic manner is problematic. Studies addressing this problem are applying viral vector mediated transfer of the GDNF gene to the CNS in order to deliver biosynthesized GDNF to a specific location in a chronic manner. Recent studies suggest that these GDNF gene therapy approaches are effective in rat models of Parkinson's disease. These studies are reviewed in the context of what developments will be needed in order to apply GDNF gene therapy to the clinic.     

Heart protection: controlling risk factors for cardiovascular disease

Cardiovascular disease is the leading cause of illness and death in the United States. Clinical data continue to support primary prevention through the aggressive treatment of well-defined cardiovascular risk factors. Three risk factors that can be modified to lower the risk of cardiovascular disease and death are hypercholesterolemia, hypertension, and cigarette smoking. Even patients with asymptomatic cardiovascular disease have been shown to benefit from aggressive cholesterol-lowering therapy. New JNC-VI guidelines for managing hypertensive disease recommend that treatment decisions be based on level of blood pressure plus presence or absence of target organ damage or other risk factors. The risk of myocardial infarction in former smokers approaches that of nonsmokers after 3 years.     

Renal and cardiovascular predictors of 9-year total and sudden cardiac mortality in non-insulin-dependent diabetic subjects

BACKGROUND: The objective was to evaluate the impact of urinary albumin excretion rate (UAER), glomerular filtration rate (GFR) and subclinical autonomic neuropathy (SANP) on 9-year total (TM) and sudden cardiac mortality (SCM) in recently diagnosed (< 1 year; RD; n = 150) and known (mean duration 11 years; KD; n = 146) NIDDM subjects. METHODS: The study was prospective and controlled (n = 150). Mortality predictors were analysed by logistic regression analysis. The dependent variables were TM and SCM, the predictors were UAER, GFR, SANP, age, gender, BMI, mean arterial pressure (MAP), fasting serum cholesterol, HDL-cholesterol, triglycerides, insulin, haemoglobin A1c, diabetes duration, QTc-interval (ECG), coronary heart disease (CHD), peripheral vascular disease (PVD), cerebrovascular disease (CVD), congestive heart failure (CHF), antihypertensive therapy, and smoking habits. RESULTS: CHD predicted TM and SCM in both RD (P = 0.041 and 0.029) and KD (P = 0.034 and 0.006). PVD predicted TM and SCM in KD only (P = 0.001 and 0.003). CVD predicted TM and SCM in RD only (P = 0.001 and 0.017). In RD male gender (P = 0.049), fasting serum cholesterol (P = 0.007) and CHF (P = 0.001) predicted TM and in kDa haemoglobin A1c (P = 0.004), age (P = 0.001) and MAP (P = 0.014) predicted TM. Serum triglycerides predicted SCM in both RD and kDa (P = 0.001 and 0.003). SANP predicted TM (P = 0.009) and SCM (P = 0.044) in KD only. GFR (inverse value) predicted TM and SCM (P = 0.04 and 0.027) in kDa only. The UAER did not predict mortality in the diabetic subjects. CONCLUSION: SANP and a slightly reduced GFR still in the normal range predicted mortality in KD. Microalbuminuria (30 < UAER < 300 mg/24 h) did not independently predict 9-year mortality in the NIDDM subjects studied.     

Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid

Elevated plasma homocysteine, an independent risk factor for cardiovascular disease (CVD) can be lowered by administration of pharmacological doses of folic acid. The effect of lower doses in apparently normal subjects is currently unknown but is highly relevant to the question of food fortification. Healthy male volunteers (n = 30) participated in a chronic intervention study (26 weeks). Folic acid supplements were administered daily at doses increasing from 100 micrograms (6 weeks), to 200 micrograms (6 weeks), to 400 micrograms (14 weeks). Fasting blood samples collected before, during and 10 weeks post intervention were analysed for plasma homocysteine, serum and red-cell folate levels. Results, expressed as tertiles of baseline plasma homocysteine concentration, showed significant (p < or = 0.001) homocysteine lowering in the top (10.90 +/- 0.83 mumol/l) and middle (9.11 +/- 0.49 mumol/l) tertiles only. In the low tertile, where the mean baseline homocysteine level was 7.07 +/- 0.84 mumol/l, no significant response was observed. Of the three folic acid doses, 200 micrograms appeared to be as effective as 400 micrograms, while 100 micrograms was clearly not optimal. There is thus a minimal level of plasma homocysteine below which folic acid has no further lowering effect, probably because an optimal folate status has been reached. A dose as low as 200 micrograms/day of folic acid is effective in lowering plasma homocysteine concentrations in apparently normal subjects. Any public health programme for lowering homocysteine levels, with the goal of diminishing CVD risk, should not be based on unnecessarily high doses of folic acid.     

Decrease in cardiovascular disease mortality in the Czech Republic from 1984 to 1993 and its possible causes

BACKGROUND: The objective of the investigation was to evaluate the ten-year development of the cardiovascular mortality rate in two population groups in the age bracket from 25 to 64 years, i.e. in subjects living in six districts which participated in the international WHO project MONICA and in the population of the whole Czech Republic. METHODS AND RESULTS: Data on the mortality rate in 1984-1993 for the age group from 25-64 years were provided by the Institute of Health Information and Statistics, information on the prevalence of risk factors was obtained in three cross-sectional studies implemented in six districts as part of the MONICA project in 1985, 1988 and 1992. In the mortality rate per 100,000 population in the six districts the following changes were revealed (in parentheses the values for 1984 and 1993 are given): men - a statistically significant declining trend in the from all caused mortality (849.3-742.5; p < 0.001) and cardiovascular mortality (367.2-280.4; p < 0.001) and cerebrovascular mortality (69.7-44.8; p < 0.001). In the mortality from ischaemic heart disease (215.7-170.6; ns) a declining trend was not recorded. In women aged 25-64 years in the six districts there was a statistically significant decline of the mortality from all caused (359.5-322.1; p < 0.001), the cardiovascular mortality (115.6-100.6; p < 0.001) and cerebrovascular mortality (31.1-23.6; p < 0.001). The mortality from ischaemic heart disease did not change (49.2-48.8; ns). In the population of the Czech Republic in men the following were detected: a drop of the from all caused mortality (907.1-784.8; P < 0.001), the cardiovascular mortality (383.5-308.4; p < 0.001) and cerebrovascular mortality (76.5-55.3; p < 0.001). Also in women of the Czech Republic a decline of the mortality from all caused was recorded (390.1-328.5; p < 0.001), the cardiovascular mortality (135.3-103.8; p < 0.001), ischaemic heart disease (58.0-48.6; p < 0.001) and cerebrovascular mortality (43.5-27.4; p < 0.001). In 1990 an increased cardiovascular mortality was recorded in men different from the trend during 1984-1993, statistically significant in the Czech Republic (p < 0.05) and in the six districts (p < 0.05). The reasons of this trend are not clear. The role of health services in the mortality drop is not clear, although available data indicate their improvement. Favourable changes were found in risk factors: during the period from 1985-1992 the prevalence of hypercholesterolaemia declined significantly in men and women, the prevalence of hypertension in women and the prevalence of smoking in men declined in the six districts. From nationwide data ensues that after 1989 significant changes occurred in the diet of the Czech population. The meat consumption declined by 1993 by 13%, the milk and dairy product consumption by 26.8% the butter consumption by 43.6% the consumption of vegetable fats increased by 16%, of vegetables by 8%, tropical fruit by 43.2%. These changes probably had an impact on the cholesterol level and BMI of the Czech population. CONCLUSIONS: In the declining cardiovascular mortality trend during 1984-1993 the following may have participated: improved medical care, dietary changes, improvement of the risk profile and other, in particular socioeconomic factors. With regard to the close temporal association of the investigated changes it may be assumed that this development is at least partly associated with changes of the political and economic position in the Czech Republic after 1989.     

A 35-year follow-up study on burnout among Finnish employees.

This three-wave 35-year prospective study used the Job Demands-Resources model and life course epidemiology to examine how life conditions in adolescence (1961–1963) through achieved educational level and working conditions in early adulthood (1985) may be indirectly related to job burnout 35 years later (1998). We used data (N = 511) from the Finnish Healthy Child study (1961–1963) to investigate the hypothesized relationships by employing structural equation modeling analyses. The results supported the hypothesized model in which both socioeconomic status and cognitive ability in adolescence (1961–1963) were positively associated with educational level (measured in 1985), which in turn was related to working conditions in early adulthood (1985). Furthermore, working conditions (1985) were associated with job burnout (1998) 13 years later. Moreover, adult education (1985) and skill variety (1985) mediated the associations between original socioeconomic status and cognitive ability, and burnout over a 35-year time period. The results suggest that socioeconomic, individual, and work-related resources may accumulate over the life course and may protect employees from job burnout. (PsycINFO Database Record (c) 2011 APA, all rights reserved)