Abstract
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Newsworthy…
Evidence-based guidelines for the prevention of cardiovascular disease in women
The later onset of clinical coronary disease in women, compared to men, has long obscured the fact that eventually, as many women as men die from CHD. However, women and heart disease are now very much in focus and the fact that cardiovascular disease in women is an important clinical problem is now well recognised. The American Heart Association (AHA) has released new evidence-based guidelines for the prevention of cardiovascular disease in women. The document states that the technology for identifying cardiovascular disease in its earliest stages has improved over the last decade, which has led to a blurring of the distinction between primary and secondary intervention. Instead of categorising women as either with or without CVD, the document places them as high, intermediate, lower and optimal risk, according to the Framingham risk score. The expert panel did a systematic search and summary of published data, classifying interventions by their usefulness and effectiveness, by their level of evidence but also with respect to their generality to women. Evidence-based recommendations were listed in an extensive (and very useful) table. Optimal levels of lipids in women were stated as LDL-C < 100 mg/dl (< 2.6 mmol/l), HDL-C > 50 mmol/l (> 1.3 mmol/l) and triglycerides < 150 mg/dl (< 1.7 mmol/l), which is stricter than the European recommendations, except for those with established CVD or diabetes. The guidelines also recommend that all high-risk women, even those with low-density lipoprotein cholesterol levels below 100 mg/dl, should receive cholesterol-lowering drugs, preferably statins.
Lifestyle and medical prevention measures are divided into class I—the most strongly recommended intervention—followed by class IIa and IIb, with class III indicating that an intervention is either not useful or harmful. Included in class III are now recommendations against the initiation of combined estrogen and progestin hormone therapy for CVD prevention in postmenopausal women.
Mosca L, Appel LJ, Benjamin EJ, Berra K, Chandra-Strobos N, Fabunami RP et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004;
The metabolic syndrome: An emerging health epidemic in women
Not only may the awareness of heart disease in women be increasing, it could also be that trends in CHD differ between men and women, with a decreasing ratio men/women. Some of this could be related to the obesity epidemic. The metabolic syndrome is a compilation of factors characterized by insulin resistance and the identification of 3 of the 5 criteria of abdominal obesity, elevated triglycerides, decreased high-density lipoprotein (HDL) level, elevated blood pressure, and elevated fasting plasma glucose. This syndrome is strongly related to obesity. According to a recent review paper there are 2 million more women than men in the United States categorized as being obese, with the trend of obesity and diabetes increasing. In the last decade there has been a 74% increase in obesity, mostly in women. This epidemic needs to be understood and managed to prevent further morbidity and mortality owing to diabetes and cardiovascular disease.
Steinbaum SR. The metabolic syndrome: an emerging health epidemic in women. Prog Cardiovasc Dis 2004;
A tentative explanation of the female protection from CHD
A grim way of investigating early atherosclerosis is to investigate victims of violence. In Finnish study of a total of 52 female forensic autopsy cases aged between 18 and 49 it was found that those with the central type of fat accumulation had advanced coronary plaques. Estrogen receptor expression was localized near the lipid-rich and macrophage-rich zone, perhaps suggesting a compensatory mechanism against atherosclerosis.
Kortelainen ML, Huttunen P. Expression of estrogen receptors in the coronary arteries of young and pre-menopausal women in relation to central obesity. Int J Obes Relat Metab Disord 2004;
…and a tentative explanation of the protective effect of alcohol
A U-shaped association has been reported between alcohol intake and health outcomes, particularly cardiovascular disease. Increased levels of markers of inflammation also predict CVD. To examine whether drinking alcohol could modify levels of these acute-phase reactants, the possible association between alcohol intake and three inflammatory markers—interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) was studied by an Italian team of researchers. The study included 2574 US men and women, aged 70 to 79 years, for whom complete 1-year data were available. The researchers found that levels of IL-6 and CRP were lower among men and women who drank one to seven units of alcohol each week than those who did not drink, or those who consumed more than eight drinks per week, after adjusting for confounding factors. The findings could suggest a ‘biologically plausible explanation’ for the link between moderate alcohol intake and a decreased risk of CVD.
Volpato S, Pahor M, Ferrucci L, Simonsick EM, Guralnik JM, Kritchevsky SB et al. Relationship of alcohol intake with inflammatory markers and plasminogen activator inhibitor-1 in well-functioning older adults: the Health, Aging, and Body Composition study. Circulation 2004;
Psychosocial Factors and Risk of Hypertension
Evidence on the association between psychosocial factors and risk of hypertension has been inconsistent. Yan and colleagues (see reference) analyzed data from the Coronary Artery Risk Development in Young Adults study, a population-based, prospective study of adults aged 18 to 30 years, to examine the role of 5 psychosocial factors; hostility, time urgency/impatience, achievement striving/competitiveness, depression, and anxiety-on long-term risk of hypertension. Of these factors, time urgency/impatience and hostility were associated with increased 15-year risk of hypertension.
Yan LL, Liu K, Matthews KA, Dauighs ML, Ferguson TF, Kiefe CI. Psychosocial Factors and Risk of Hypertension: The Coronary Artery Risk Development in Young Adults—CARDIA—Study. JAMA 2003;
In an editorial, Williams and coauthors (see reference) discuss biobehavioral mechanisms and gene-environment interactions that mediate the influence of psychosocial factors on the development and course of cardiovascular disease.
Williams RB, Barefoot JC, Schneiderman N. Psychosocial risk factors for cardiovascular disease: more than one culprit ar work JAMA 2003;
Relation of serial changes in childhood body-mass index to impaired glucose tolerance in young adulthood
The risk of type 2 diabetes mellitus is increased in people who have low birth weights and who subsequently become obese as adults. Whether their obesity originates in childhood and, if so, at what age is unknown. Understanding the origin of obesity may be especially important in developing countries, where type 2 diabetes is rapidly increasing yet public health messages still focus on reducing childhood ‘undernutrition.’
The Authors evaluated glucose tolerance and plasma insulin concentrations in 1492 men and women 26 to 32 years of age who had been measured at birth and at intervals of three to six months throughout infancy, childhood, and adolescence in a prospective, population-based study conducted in India.
The prevalence of impaired glucose tolerance was 10.8 percent, and that of diabetes was 4.4 percent. Subjects with impaired glucose tolerance or diabetes typically had a low body-mass index up to the age of two years, followed by an early adiposity rebound (the age after infancy when body mass starts to rise) and an accelerated increase in body-mass index until adulthood. However, despite an increase in body-mass index between the ages of 2 and 12 years, none of these subjects were obese at the age of 12 years. The odds ratio for disease associated with an increase in the body-mass index of 1 SD from 2 to 12 years of age was 1.36 (95 percent confidence interval, 1.18 to 1.57; P < 0.001).
These findings clearly indicate a strong an association between thinness in infancy and the presence of impaired glucose tolerance or diabetes in young adulthood. Crossing into higher categories of body-mass index after the age of two years is also associated with these disorders.
The young adults in this study who had impaired glucose tolerance or diabetes were, as a group, overweight. They were not, however, overweight as young children but, became overweight as a result of an accelerated gain in body mass starting in early childhood, having been thin in infancy. The ability of children to have an accelerated increase in body mass may be a recent phenomenon in India, a consequence of nutritional transition. These do not allow us to distinguish between the events that lead to increasing body-mass index and the expression of the diabetic phenotype. However, assuming that the change in body-mass index is causal rather than the result of a simple association, it is possible to speculate that the primary prevention of the epidemic of diabetes in India may require measures to prevent children from crossing into higher categories of body-mass index after the age of two years. Individual children will need to have serial measurements of body-mass index for such a growth trajectory to be identified.
Barghava SK, Sachdev HS, Fall CH, Osmond C, Lakshmy R, Barker DJ et al. Relation of serial changes in childhood-body mass index to impaired glucose tolerance in young-adulthood. N Engl J Med 2004;
Use of B-type nutriuretic peptide in the evaluation and management of acute dyspnea (BASEL study)
B-type natriuretic peptide levels are higher in patients with congestive heart failure than in patients with dyspnea from other causes.
In this prospective, randomized, controlled study 452 patients who presented to the emergency department with acute dyspnea were enrolled: 225 patients were randomly assigned to a diagnostic strategy involving the measurement of B-type natriuretic peptide levels with the use of a rapid bedside assay, and 227 were assessed in a standard manner. The time to discharge and the total cost of treatment were the primary end points.
Base-line demographic and clinical characteristics were well matched between the two groups. The use of B-type natriuretic peptide levels reduced the need for hospitalization and intensive care; 75 percent of patients in the B-type natriuretic peptide group were hospitalized, as compared with 85 percent of patients in the control group (P = 0.008), and 15 percent of those in the B-type natriuretic peptide group required intensive care, as compared with 24 percent of those in the control group (P = 0.001). The median time to discharge was 8.0 days in the B-type natriuretic peptide group and 11.0 days in the control group (P = 0.001). The mean total cost of treatment was $5,410 (95 percent confidence interval, $4,516 to $6,304) in the B-type natriuretic peptide group, as compared with $7,264 (95 percent confidence interval, $6,301 to $8,227) in the control group (P = 0.006). The respective 30-day mortality rates were 10 percent and 12 percent (P = 0.45).
In conclusion, used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide in the emergency department improved the evaluation and treatment of patients with acute dyspnea and thereby reduced the time to discharge and the total cost of treatment.
Mueller C, Scholer A, Laule-Kilian K, Martina B, Schindler C, Buser P et al. Use of B-type natrioretic peptide in the evaluation and management of acute dyspnea. N Engl J Med 2004;
Plasma natriuretic peptide levels and the risk of cardiovascular events and death
The prognostic significance of plasma natriuretic peptide levels in apparently asymptomatic persons has not been established.
The Authors prospectively studied 3346 persons without heart failure among the Framingham Offspring Study population. Using proportional-hazards regression, they examined the relations of plasma B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide to the risk of death from any cause, a first major cardiovascular event, heart failure, atrial fibrillation, Stroke or transient ischemic attack, and coronary heart disease.
During a mean follow-up of 5.2 years, 119 participants died and 79 had a first cardiovascular event. After adjustment for cardiovascular risk factors, each increment of 1 SD in log B-type natriuretic peptide levels was associated with a 27 percent increase in the risk of death (P = 0.009), a 28 percent increase in the risk of a first cardiovascular event (P = 0.03), a 77 percent increase in the risk of heart failure (P < 0.001), a 66 percent increase in the risk of atrial fibrillation (P < 0.001), and a 53 percent increase in the risk of stroke or transient ischemic attack (P = 0.002). Peptide levels were not significantly associated with the risk of coronary heart disease events. B-type natriuretic peptide values above the 80th percentile (20.0 pg per milliliter for men and 23.3 pg per milliliter for women) were associated with multivariable-adjusted hazard ratios of 1.62 for death (P = 0.02), 1.76 for a first major cardiovascular event (P = 0.03), 1.91 for atrial fibrillation (P = 0.02), 1.99 for stroke or transient ischemic attack (P = 0.02), and 3.07 for heart failure (P = 0.002). Similar results were obtained far N-terminal pro-atrial natriuretic peptide.
Therefore, in this community-based sample, plasma natriuretic peptide levels predicted the risk of death and cardiovascular events after adjustment for traditional risk factors. Excess risk was apparent at natriuretic peptide levels well below current thresholds used to diagnose heart failure.
Wang TJ, Larsson MG, Levy D, Benjamin EJ, Leip EP, Omland T et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 2004;
Taken together, the results of the BASEL Study and the Framingham Offspring Study suggest that B-type natriuretic peptide is both much less and much more than a blood test for heart failure: much less, in the sense that the diagnostic use of B-type natriuretic peptide augments but does not supersede careful clinical evaluation and reasoning, and much more, in the sense that B-type natriuretic peptide measurement may provide a very early warning signal for future cardiovascular disease in persons without symptoms.
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