Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany
Correspondence to Jens Jordan, MD, Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. E-mail: firstname.lastname@example.org
Cassandra is a tragic figure in Greek mythology. She was very good looking, intelligent, charming, her family was well off, and she was able to foresee the future. Despite all these valuable gifts, her life took a turn for the worse when she brusquely rebuffed Apollo. Greek gods do not appreciate rejections very much. Apollo got really mad and cursed Cassandra such that no one would believe her predictions anymore. Add the usual violent incidents and you will understand Cassandra's misery. The take home message for today is that the harbinger of unpleasant news is not the most popular person in town. Moreover, we tend to ignore bad news, such as the epidemic rise in obesity and associated cardiovascular disease, as much and as long as we can.
In this issue of the Journal, Tsujimoto et al. report results of an epidemiological study conducted in the Japanese Ibaraki prefecture, which is located North of Osaka. The goal of the study was to assess the risk of developing arterial hypertension associated with obesity. The authors had access to a large population of 194 333 middle-aged individuals. All had participated in health check-ups including body weight and blood pressure measurements among other cardiovascular and metabolic risk factors. Participants with arterial hypertension at baseline, incomplete data, or insufficient follow-up were excluded. In the remaining 68 205 participants, the authors determined whether BMI at baseline or BMI changes are related to development of arterial hypertension later in life.
During a mean follow-up period of 3.9 years, 45.4% of the participants exhibited arterial hypertension. Compared with BMI below 19 kg/m2, the adjusted hazard ratios for developing arterial hypertension with BMI at least 25 kg/m2 were 1.42 for men aged 40–59 years, 1.34 for men aged 60–79 years, 1.47 for women aged 40–59 years, and 1.29 for women aged 60–79 years. Participants with normal body weight at baseline and elevated body weight during follow-up, and participants with elevated body weight at both time points showed an almost identical increase in hypertension risk. The findings by Tsujimoto et al. strengthen the epidemiological association between increased adiposity and arterial hypertension. Furthermore, the study highlights the fact that obesity is an increasingly important cardiovascular risk factor throughout the world, even in countries not considered obesity hotspots. Indeed, the National Health and Nutrition Survey Japan 2006 showed that obesity prevalence in men had gradually increased over 20 years across all the age groups, whereas it had not changed in women.
The study by Tsujimoto et al. also shows that the risk for arterial hypertension in Japanese people is already substantially increased at a BMI considered normal in Western societies. The observation reminds us that the definition of overweight and obesity has to take into account ethnicity because the genetic background strongly modulates the cardiovascular and metabolic risk associated with a given increase in adiposity. According to the WHO classification, BMI values of 18.5 and 24.9 kg/m2 are considered ‘normal’, at least 25 kg/m2 ‘overweight’, and at least 30 kg/m2 ‘obese’ (http://apps.who.int/bmi/index.jsp?introPage=intro_3.html). Several WHO Expert Consultations have acknowledged that lower cut-offs may be required in Asia and in the Pacific region. The situation becomes even more complicated when abdominal adiposity – the crucial component of the metabolic syndrome – is considered . In Europe and in North America, abdominal adiposity is diagnosed with waist circumferences of at least 80 cm in women and at least 94 cm in men [International Diabetes Federation (IDF) and WHO criteria] or at least 88 cm in women and at least 102 cm in men (European and North American Cardiovascular Research Societies). Whereas IDF and WHO suggest considering at least 80 cm in women and at least 90 cm in men as waist circumference cut-off values for most Asian countries, Japanese guidelines propose cut-off values of at least 90 cm in women and at least 85 cm in men. The recommendation is based on diabetes risk estimates and represents the lowest waist circumference cut-off for men worldwide. Japan is the only country with a lower absolute waist cut-off for men than for women, which has been challenged recently [3,4].
In addition to being a risk factor for arterial hypertension, obesity can complicate the management of existing arterial hypertension. The topic has been addressed in a recent Joint Statement of the European Society of Hypertension and the European Association for the Study of Obesity . Briefly, obese hypertensive patients require more antihypertensive medications and are nevertheless less well controlled compared with lean hypertensive patients [6–8]. Moreover, obesity is an important cause of treatment-resistant arterial hypertension .
Epidemiological studies rely on correlations, which cannot prove causality, and they are more susceptible to confounding compared with randomized prospective studies. Despite these limitations, epidemiological studies have been indispensible in focusing our view on important health issues, such as the risk that the obesity epidemic may negate recent advances in cardiovascular health.
Over the past decades, cardiovascular morbidity and mortality decreased in many developed countries. An earlier study analyzed mortality data provided by the WHO for cardiovascular and all-cause mortality in Europe . Over a 30-year period ranging from 1970 to 2000, coronary artery disease mortality decreased by approximately 50% in women and in men. Similar trends have been observed in the US . More recent studies relying on more detailed data confirmed and extended these findings. Between 1986 and 2002, mortality from coronary artery disease in Sweden decreased by more than 50% regardless of sex . In Eastern European countries, an initial increase in coronary artery disease mortality was followed by a steady decline later on . Particularly striking was the steep improvement in coronary mortality in Poland in recent years . Whereas stroke mortality decreased 60% or more in Western Europe, the state of affairs was much different in Eastern European countries. For example, stroke mortality increased massively in Poland between 1991 and 2000 . Whereas cardiovascular mortality decreased in the developed parts of the world, there was a rise in cardiovascular mortality in many developing countries . From a global perspective, cardiovascular disease will be the number one cause of death for years to come.
It is tempting to speculate that improvements in cardiovascular morbidity and mortality in many countries could be explained by cardiovascular interventions and pharmacological treatments, such as antithrombotics, lipid-lowering drugs, and antihypertensives. In fact, the past decades witnessed impressive progress in the evidence base for cardiovascular treatments in the acute setting as well as in primary and secondary prevention. Yet, one half or more of the improvement in cardiovascular mortality can be attributed to population trends in major cardiovascular risk factors unrelated to medical therapy [11,13,15]. In the US, much of the improvement in coronary mortality was attributed to reductions in total cholesterol, systolic blood pressure, smoking prevalence, and physical inactivity . The remarkable trend that mean population total cholesterol decreased by as much as 1.0 mmol/l (40 mg/dl) in many developed countries has been recently reviewed . For each 1% reduction in mean population total cholesterol, cardiovascular mortality decreases approximately 2.5% . Large reductions in population cholesterol levels occurred before statins were introduced or before they were widely used in primary prevention [11,12,15,18]. Changes in diet and in physical activity are likely involved.
Given the important contribution of changes in risk factors and lifestyle to cardiovascular health, improvements in cardiovascular risk cannot be taken for granted. Moreover, people in developing countries may not enjoy the improvements in cardiovascular well being because unhealthy Western lifestyles are increasingly adopted. The large increase in the prevalence of obesity and associated cardiovascular and metabolic risk factors, particularly type 2 diabetes mellitus, is a particular matter of concern. The improvement in coronary mortality in the US was offset in part by an increase in the prevalence of obesity and type 2 diabetes mellitus . Similar observations have been reported from other developed countries . The prevalence of overweight and obesity also increases in low and middle-income countries throughout the world . According to estimates from the WHO, the worldwide prevalence of obesity has almost doubled since 1980 (http://http://www.who.int/mediacentre/factsheets/fs311/en/index.html). Indeed, in 2008 approximately 1.5 billion adults were overweight and 0.5 billion adults were obese. Fortunately, recent surveys in developed countries suggest that the prevalence of overweight and obesity in children and in adolescents may level off [20,21]. In the past few years, the obesity prevalence in the US also remained stable in adults albeit at an extremely high level . An optimistic way to interpret the data is that obesity awareness and preventive measures may have halted the progressive increase in obesity prevalence. Instead, we suggest that the adaptation to an unhealthy environment has come to an end in some countries, whereas other countries are still catching up. Let us keep our fingers crossed that an unhealthy environment does not become unhealthier.
The time lag between occurrence of a risk factor, in this case overweight or obesity, and overt cardiovascular disease ranges between years and decades. Cardiovascular mortality secondary to the obesity pandemic is likely to increase in the next and intermediate future unless we find ways to deal with the issue. Bad news that gets ignored for a long time tends to become worse. Think about poor Cassandra.
Conflicts of interest
There are no conflicts of interest.
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