31 May 2018 --- Compared to metabolically healthy women of normal weight, women who are obese and who have been metabolically healthy for decades are still at higher risk of developing cardiovascular disease. This is according to an observational study that followed over 90,000 US women for up to 30 years, published in The Lancet Diabetes & Endocrinology journal. The findings indicate that obesity is a risk factor for cardiovascular disease, regardless of whether they develop any of the common metabolic diseases such as high blood pressure or Type 2 diabetes.
“Our large cohort study confirms that metabolically healthy obesity is not a harmless condition, and even women who remain free of metabolic diseases for decades face an increased risk of cardiovascular events,” explains Professor Matthias Schulze from the German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany, who led the research.
“What's more, we observed that most healthy women are likely to develop Type 2 diabetes, high blood pressure, or high cholesterol over time, irrespective of their BMI, putting them at much higher risk for cardiovascular disease,” he says.
Obesity affects almost all of the cardiovascular disease risk factors, particularly those related to metabolic syndrome, including high blood pressure, poor blood sugar control or diabetes and abnormal blood fats. These factors can double the risk of cardiovascular disease such as heart attacks and stroke. However, some people with obesity seem to be free of these metabolic abnormalities, with estimates suggesting that as many as a third of obese people might be metabolically healthy.
Whether this so-called “metabolically healthy obesity” is associated with a higher risk of cardiovascular disease has been hotly debated for many years. It remains unclear how changes or maintenance of metabolic status may affect the development of cardiovascular disease in both normal weight and overweight/obese individuals.
To investigate this further, Schulze and colleagues examined the association between obesity and cardiovascular disease incidences in 90,257 women (initially free from cardiovascular disease) from the Nurses' Health Study – a study tracking the health of female nurses (aged 30-55 years) in the US since 1976.
Participants were divided into groups by BMI category, metabolic health (defined as the absence of three metabolic risk factors – Type 2 diabetes, high blood pressure, and high blood cholesterol), and change in metabolic health status, and followed for 30 years between 1980 and 2010. Participants were sent questionnaires every two years to update their BMI and metabolic health status, as well as to assess their lifestyle, health behavior and medical history. During an average follow-up of 24 years, 6,306 new cases of cardiovascular disease, including 3,304 heart attacks and 3,080 strokes were recorded.
Cardiovascular disease risk was especially high in all metabolically unhealthy women, regardless of their BMI. Metabolically unhealthy normal-weight women were around 2.5 times more likely to develop cardiovascular disease compared to normal weight women with no metabolic abnormalities, while those with “metabolically healthy obesity” were also at higher risk of cardiovascular disease (39 percent higher risk).
Importantly, the majority of women who were initially metabolically healthy obese (84 percent), and around two-thirds (68 percent) of normal weight metabolically healthy women, converted to unhealthy phenotypes over 20 years. Even women who maintained metabolically healthy obesity over 20 years still had a 57 percent higher risk of developing cardiovascular disease compared with normal weight metabolically healthy women.
“Long-term maintenance of metabolic health is a challenge for overweight/obese, but also for normal-weight women,” says Professor Schulze. “Our findings highlight the importance of preventing the development of metabolic diseases, and suggest that even individuals in good metabolic health may benefit from early behavioral management to improve their diet and increase physical activity in order to guard against progression to poor metabolic health.”
“Given that maintenance of metabolic health seems to be difficult for many, it would be of interest to identify determinants of long-term stable metabolic health. Also, alternative definitions of metabolic health could be explored further,” Schulze tells NutritionInsight.
Although there are some limitations, including that the study included mainly women of European descent, so the findings cannot be generalized to other ethnic groups and men; and that their definition of metabolic health (the absence of three metabolic diseases), may identify a different subgroup than in other studies. However, key strengths include the large cohort, repeated measurements and long follow up time.