Abstract
The News and notices section is published in every issue of the European Journal of Cardiovascular Prevention and Rehabilitation. It provides readers with details of current affairs, the best of what is being published in other journals and upcoming events for your diaries. Readers are invited to submit material, upcoming events and training opportunities to the News Editors.
Professor Pantaleo Giannuzzi Salvatore Maugeri Foundation IRCCS, Cardiology Department Medical Centre of Veruno Via Revislate 13 I-28010 Veruno, Italy Tel: +39 0322 884711 Fax: 32 0322 884816 E-mail:
Professor Annika Rosengren The Cardiovascular Institute Gr för kardiovascular forskn Medicin, plan 2 CK SU/Östra 416 85 Göteborg, Sweden Tel: +46 31 343 4086 Fax: +46 31 259 254 E-mail:
Newsworthy…
Heart disease research wins award in the UK
A change of diet could reduce the 125 000 UK deaths from heart problems by a quarter, according to award-winning researchers who have won the 2003 BUPA Foundation award for epidemiology.
Researchers at the Royal Free & University College Medical School, led by Jonathan Emberson, statistician at the Department of Primary Care and Population Sciences at the Royal Free & University College Medical School in London found that long-term changes in risk factors are more effective than drugs at reducing the number of new cases of coronary heart disease (CHD) in the United Kingdom. Working in collaboration with researchers at St George's Hospital Medical School in London and Bristol University, the British Regional Heart Study team examined how changes in cholesterol and blood pressure, two of the most important risk factors for CHD, compared with drug treatment. The research was carried out on behalf of the British Heart Foundation and used a sample of approximately 6000 middle-aged men with no signs of CHD from 24 different towns, monitored for CHD over 10 years.
The team examined the benefits of population-wide reductions in risk factors, which have often been underestimated in previous studies. They found that when average cholesterol and blood pressure levels in the population fell by just 5%, the number of CHD cases dropped by almost one-quarter. In contrast, the number of CHD cases fell by only half as much when expensive blood pressure and cholesterol-lowering drugs were prescribed, the usual approach to prevention. While drugs are important for those who already have clinically manifest cardiovascular disease, for those with particularly high levels of single risk factors, and for diabetics, the most effective way of reducing the development of CHD in those who are healthy is to reduce the key risk factors, such as cholesterol and blood pressure, throughout the population. The means to do that is through lifestyle changes, including no smoking, less saturated f at, more fruit and vegetables, and increased physical activity.
In a recent paper published in the European Heart Journal the same team of authors found that four out of five major CHD events in these initially healthy middle-aged men can be attributed to high serum cholesterol, high diastolic blood pressure or smoking. The population attributable risk fraction (PARF) was predicted for a range of risk factor thresholds before and after adjustment for regression dilution of serum total cholesterol and blood pressure. Defining ‘low-risk’ individuals as being in the bottom tenth of the population distributions of serum total cholesterol (< 5.2 mmol/l) and diastolic blood pressure (< 70 mmHg) and a non-cigarette smoker, the population attributable risk fraction (PARF) was 75%, increasing to 86% after adjustment for regression dilution. Regardless of the threshold criteria chosen, the PARF was substantially greater than 65% before adjustment for regression dilution and greater than 75% after adjustment. However, exactly how lifestyle translates into risk factor pattern remains to be determined.
Emberson JR, et al. Re-assessing the contribution of serum total cholesterol, blood pressure and cigarette smoking to the aetiology of coronary heart disease: impact of regression dilution bias. Eur Heart J 2003;
New research links hypertension and inflammation
A multitude of studies have demonstrated that people with hypertension have increased risk of cardiovascular disease, yet comparatively few have investigated risk factors for developing hypertension. A prospective cohort study that began in 1992 of 20 525 female US health professionals aged 45 years or older with initially normal levels of blood pressure [systolic blood pressure (BP) < 140 mmHg and diastolic BP < 90 mmHg], without medication were followed up for a median of 7.8 years for the development of incident hypertension. Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected. During follow-up, a quarter of the women developed incident hypertension. Those with the highest baseline levels of C-reactive protein levels were 2.5 times more likely to develop hypertension than those with the lowest levels. This estimate dropped to 1.5 after full adjustment for coronary risk factors but a strong correlation between CRP and hypertension still persisted. These data provide evidence that inflammation may be an important mechanism through which hypertension develops, suggesting that hypertension is in part an inflammatory disorder, similar to the development of atherosclerosis.
Sesso HD, et al. C-reactive protein and the risk of developing hypertension. JAMA 2003;
…and inflammation is also linked with dementia…
Risk of dementia increases dramatically with age and affects almost one in three in people who survive to age 85. Still, the development of dementia is not necessarily a natural phenomenon in old people. Post-mortem analyses suggest that atherosclerosis more often contributes to late-onset dementia than hitherto expected. Several studies have shown that risk factors commonly associated with coronary disease, stroke and other vascular disorders also predict dementia, and accordingly some dementia processes may be preventable.
Two reports from the Leiden 85-plus Study have investigated cross-sectional relations between dementia and cardiovascular disease, including inflammation. In one analysis the atherosclerotic burden was assessed by counting the number of cardiovascular pathologies in the medical histories of 599 men and women aged 85 years (response 87%). All subjects completed the Mini-Mental State Examination (MMSE). There was a highly significant dose-response relationship between the number of cardiovascular pathologies and cognitive impairment for both men and women, indicating that in old age atherosclerosis significantly contributes to cognitive impairment.
van Exel E, et al. Atherosclerosis and cognitive impairment are linked in the elderly. The Leiden 85-plus Study. Atherosclerosis 2002;
In a more recent publication the researchers went on to test the hypothesis that a proinflammatory response would be associated with cognitive impairment. Production of the proinflammatory cytokine tumor necrosis factor-α and the anti-inflammatory cytokine interleukin-10 were assessed using a liposaccharide stimulus in a whole-blood assay. These measures were compared with global cognitive function. Of the 553 study participants, more than half (63%) had signs or symptoms of cardiovascular disease. In this group, median global cognitive functioning was significantly lower in those showing a proinflammatory response compared with those with an anti-inflammatory response (P = 0.02). Similar associations were also seen for the neuropsychological tests and when assessing for the presence of dementia. Associations remained unaltered after adjusting for possible confounders, and they were seen regardless of whether or not the person had suffered from a stroke. In contrast, neither the outcome for the cognitive tests nor the presence of dementia was affected by inflammatory response among individuals without cardiovascular disease.
van Exel E, et al. Interaction of atherosclerosis and inflammation in elderly subjects with poor cognitive function. Neurology 2003;
Previous research have found links between several of the cardiovascular risk factors, including hypertension, hy-percholesterolemia, and obesity, and future development of dementia. With decreasing death rates from coronary heart disease and increasing life expectancy in many European countries, perhaps dementia should also be targeted for prevention, alongside coronary heart disease, stroke and peripheral vascular disease.
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.
Psychosocial Factors and Risk of Hypertension: The Coronary Artery Risk Development in Young Adults – CARDIA – Study.
Lijing L. Yan, et al. 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.
Redford B. Williams. JAMA 2003;
Prolonged oxygen uptake kinetics during low-intensity exercise are related to poor prognosis in patients with mild-to-moderate congestive heart failure
This study investigated the prognostic value of VO2 kinetics during low-intensity, constant-workload exercise in a relatively large population of patients with chronic heart failure. It shows that the mean response time of VO2 (MRT) [i.e., the time constant of VO2] is a good predictor of prognosis in patients with congestive heart failure.
Its predictive value was at least as good as a variety of parameters that are known to be predictive of prognosis. In particular, it was a better predictor of prognosis than body weight-adjusted VO2 peak, which is widely used in selecting patients for cardiac transplantation. Thus, VO2 kinetics during low-intensity exercise may add important information for risk stratification in heart failure patients.
Furthermore, it may serve as a substitute for VO2 peak in patients who are unable to exercise maximally for reasons other than chronic heart failure.
The interest in using submaximal exercise testing for the assessment of heart failure patients is increasing. Parameters of submaximal exercise may better reflect cardiac limitations during daily life than maximal exercise testing.
MRT, which is a measure of VO2 kinetics at the onset of constant low-intensity exercise, is a significant predictor of outcome in patients with congestive heart failure. Our results suggest that VO2 kinetics are independent from and may be even superior to VO2 peak in the assessment of prognosis. Since it has several additional advantages over peak exercise testing (e.g., less time-consuming, less demanding for the patients, less dependent on motivation, and feasible to perform in patients with limited exercise capacity due to reasons other than congestive heart failure), it has the potential to become an essential test for the assessment of prognosis in heart failure patients. Still, further studies are required to confirm these results.
Schalcher C, et al. Chest 2003;
Leptin and the ventilatory response to exercise in heart failure
Leptin is a 167-amino-acid product of the ob gene, which is produced primarily by adipocytes. Although originally associated with the central regulation of safety and energy metabolism, there is now increasing evidence that leptin may be an important mediator in cardiovascular patho-physiology. In addition, recent studies in animals suggest that leptin may play an important role in the regulation of respiration, particularly the ventilatory responses to CO2, and may act both as a neurohumoral modulator of respiratory control mechanisms as well as by producing changes in respiratory mechanics.
However, the pathophysiologic role of circulating leptin in chronic heart failure (CHF) remains unknown.
In the present study the authors tested the hypothesis that leptin is involved in the regulation of ventilatory responses to exercise in subjects with CHF.
They studied 50 patients with stable CHF without cachexia. All subjects underwent anthropometric measurements, resting echocardiography, pulmonary functions tests, and a cardiopulmonary exercise test. The ventilatory response to exercise was assessed by calculating the VE/VCO2 and VE/VO2 slopes (VE = ventilation per unit time, VCO2 = carbon dioxide production, VO2 = oxygen consumption).
Using a multiple regression model, leptin was significantly and positively correlated with both VE/VCO2 slope (regression coefficient = 0.87, F= 39,32, P < 0.001). This correlation was independent of age, gender, body mass index, body fat, ejection fraction, New York Heart Association functional class, pulmonary function, plasma norepinephrine, angiotensin II, brain nutriuretic peptide levels, and medication. Also, the greatest VE/VCO2 slope was seen in subjects in the highest tertile of leptin.
Therefore, leptin is an independent predictor of VE/VCO2 slope in heart failure, and may be a link between metabolic, cardiovascular, and respiratory abnormalities in CHF.
Wolk R, et al. J Am Coll Cardiol 2003;
Arachidonate 5-Lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis
Leukotrienes are inflammatory mediators generated from arachidonic acid (polyunsaturated n-6 fatty acid) by the enzyme 5-lipoxygenase. Since atherosclerosis involves arterial inflammation, we hypothesized that a polymorphism in the 5-lipoxygenase gene promoter could relate to atherosclerosis in humans and that this effect could interact with the dietary intake of competing 5-lipoxy-genase substrates.
The 5-lipoxygenase genotypes, carotid-artery intima-media thickness, and markers of inflammation were determined in a randomly sampled cohort of 470 healthy, middle-aged women and men from the Los Angeles Atherosclerosis Study. Dietary arachidonic acid and marine n-3 fatty acids (including a competing 5-lipoxygenase substrate that reduces the production of inflammatory leukotrienes) were measured with the use of six 24-h recalls of food intake.
Variant 5-lipoxygenase genotypes (lacking the common allele) were found in 6.0% of the cohort. Mean (± SE) intima-media thickness adjusted for age, sex, height, and racial or ethnic group was increased by 80 ± 19 μm (95% confidence interval, 43 to 116; P < 0.001) among carriers of two variant alleles, as compared with carriers of the common (wild-type) allele. In multivariate analysis, the increase in intima-media thickness among carriers of two variant alleles (62 μm, P < 0.001) was similar in this cohort to that associated with diabetes (64 μm, P = 0.01), the strongest common cardiovascular risk factor. Increased dietary arachidonic acid significantly enhanced the apparent atherogenic effect of genotype, whereas increased dietary intake of n-3 fatty acids blunted the effect. Finally, the plasma level of C-reactive protein, a marker of inflammation, was increased by a factor of 2 among carriers of two variant alleles as compared with that among carriers of the common allele.
Variant 5-lipoxygenase genotypes identify a subpopulation with increased atherosclerosis. The observed diet-gene interactions further suggest that dietary n-6 polyunsaturated fatty acids promote, whereas marine n-3 fatty acids inhibit, leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation. If confirmed, these findings would constitute clear evidence that genetic variation in an inflammatory pathway, and the leukotriene pathway in particular, can trigger atherogenesis in humans. These findings could lead also to new dietary and targeted molecular approaches to the prevention and treatment of cardiovascular disease according to genotype.
James H, et al. N Engl J Med 2004;
Upcoming events
The 8th World Congress of Cardiac Rehabilitation and Secondary Prevention will take place in Dublin, Ireland May 23-26, 2004. Scientific Programme details available at www.iccconcepts.com.
The plans for the upcoming Elsinore meeting of the ESC Working Group on Epidemiology and Prevention are now being finalized. The date for the meeting is June 9-12, 2004. The meeting will be organized by the following Societies and institutions in collaboration:
Danish Society of Cardiology
Danish Society of Public Health
Danish Epidemiological Society
The Danish Heart Foundation
Research Centre for Prevention and Health
The meeting will be held at Marienlyst Conference Centre in Elsinore right at the seaside facing Sweden. The Conference Centre overlooks the old Kronborg Castle where Shakespeare's Hamlet is set centuries ago. All abstract submissions must be done electronically through: www.2004-wg13.dk. The deadline for submitting abstracts is March 1, 2004. The deadline for registration is June 1, 2004. To guarantee full room and board at the conference centre registration before April 9 is needed. Please check for further details through the homepage: www.2004-wg13.dk.