A substantial contribution to the knowledge on the evolution of major chronic diseases in women has come from the Nurses' Health Study (NHS). With a new analysis of the data of over 90,000 female candidates during a 30-year timespan, researchers of the NHS aimed at examining cardiovascular disease risk in women with metabolic health, i.e. absence of diagnosed diabetes, hypertension and hypercholesterolemia, across different body mass index (BMI) categories [1]. Moreover, they verified the effect of the onset of metabolic disorders on cardiovascular risk in women who were healthy upon inclusion in the study [1]. BMI was defined as normal (18.5–24.9 kg/m²), overweight (BMI 25.0–29.9 kg/m²), and obese (BMI ≥ 30 kg/m²). Health status was assessed every 2 years based on questionnaires. Investigated outcomes were fatal and non-fatal myocardial infarction and stroke, as well as their combination as total cardiovascular disease. Results of the analysis showed that the risk of total cardiovascular disease was higher in women who were metabolically healthy overweight (hazard ratio (HR) 1.20) or obese (HR 1.39) than in women with metabolically healthy normal weight, but lower than that of women with pre-existing metabolic conditions across all BMI groups (HR 2.43 for normal weight, HR 2.61 for overweight, HR 3.15 for obese women). Metabolic health proved to be transient for most women as only 6% of obese, 7.9% of overweight and 15.4% of normal-weight subjects remained healthy over a 30-year follow-up. Women who converted to a metabolically unhealthy phenotype, especially those who developed diabetes (HR 1.29 for normal weight, HR 1.93 for overweight, HR 2.17 for obese women) or hypertension (HR 1.92 for normal weight, HR 1.87 for overweight, HR 2.03 for obese women), had a risk between that of women with stable metabolic health and that of women with pre-existing metabolic conditions; the risk was higher if these were long-standing. Incident hypercholesterolemia had a very slight effect on cardiovascular risk. In conclusion, the presence of metabolic disorders, especially hypertension and diabetes, confers the highest cardiovascular risk across all categories, which is proportional to BMI but also to their duration. Obesity, even in the absence of metabolic conditions, determines a cardiovascular risk which is higher than that for normal weight.

Comment

In clinical practice, it is important to convey the message that the absence of metabolic disorders in an obese individual is not a reliable marker of the risk for cardiovascular disease. Obese patients may harbor conditions such as pre-hypertension and pre-diabetes that are, per se, associated with cardiovascular risk [2, 3] and that, in time, will convert almost always to established hypertension and diabetes [2, 3]. Aging may contribute to this, as metabolically healthy obesity seems to be more prevalent in subjects of younger age than in elderly ones [4]. The authors of the NHS study [1] suggested that a healthier distribution of fat mass, with more subcutaneous, less visceral fat mass, may characterize obese subjects that manage to stay healthy. Interestingly, ethnicity may have some influence [4]. Unfortunately, the NHS study reported no data on physical fitness in relation to metabolic health [1], although it is recognized to benefit cardiovascular health. In a very recent report, highly active/obese women, although more likely to report risk factors (hypertension, high cholesterol, and diabetes) than inactive/normal-weight women, did not have increased rates of cardiovascular disease [5]. Physical activity has proven an efficient measure to reduce the risk of progression to type 2 diabetes in people diagnosed with prediabetes [6] and reduce the risk of cardiovascular complications in women with established diabetes [7]. Similarly, studies show beneficial effects on individuals with pre-hypertension and hypertension [8]. These findings should promote more large-scale investigations on early lifestyle intervention to prevent conversion from a metabolically healthy to a metabolically unhealthy status, especially in women with a modifiable risk such as obesity.

Dr Patrizia Monteleone

References

1. Eckel N, Li Y, Kuxhaus O, Stefan N, Hu FB, Schulze MB. Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses' Health Study): 30 year follow-up from a prospective cohort study. Lancet Diabetes Endocrinol 2018;6:714-24
   http://www.ncbi.nlm.nih.gov/pubmed/29859908
2. Booth JN 3rd, Li J, Zhang L, Chen L, Muntner P, Egan B. Trends in prehypertension and hypertension risk factors in US adults: 1999-2012. Hypertension 2017;70:275-84
   http://www.ncbi.nlm.nih.gov/pubmed/28607131
3. Tabak AG, Herder C, Rathmann W, Brunner EJ, Kivimaki M. Prediabetes: a high-risk state for diabetes development. Lancet 2012;379:2279–90
   http://www.ncbi.nlm.nih.gov/pubmed/22683128
4. Lin H, Zhang L, Zheng R, Zheng Y. The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: a systematic review and meta-analysis: A PRISMA-compliant article. Medicine (Baltimore) 2017;96:e8838
   http://www.ncbi.nlm.nih.gov/pubmed/29381992
5. Pharr JR, Coughenour CA, Bungum TJ. An assessment of the relationship of physical activity, obesity, and chronic diseases/conditions between active/obese and sedentary/normal weight American women in a national sample. Public Health 2018;156:117-23
   http://www.ncbi.nlm.nih.gov/pubmed/29427767
6. Glechner A, Keuchel L, Affengruber L, et al. Effects of lifestyle changes on adults with prediabetes: a systematic review and meta-analysis. Prim Care Diabetes 2018;12:393–408
   http://www.ncbi.nlm.nih.gov/pubmed/30076075
7. Gregg EW, Lin J, Bardenheier B, et al.; Look AHEAD Study Group. Impact of intensive lifestyle intervention on disability-free life expectancy: The Look AHEAD Study. Diabetes Care 2018;41:1040-8
   http://www.ncbi.nlm.nih.gov/pubmed/29545462
8. Cornelissen VA, Smart NA. Exercise training for blood pressure: a systematic review and meta-analysis. J Am Heart Assoc 2013;2:e004473
   http://www.ncbi.nlm.nih.gov/pubmed/23525435

Prof Susan Davis, IMS President, is delighted to introduce all members to the new Scientific Editor for Menopause Live and Our Menopause World, Dr Patrizia Monteleone. She comments, ‘Dr Monteleone is based in Pisa, Italy, and has a unique combination of clinical experience, medical writing and editing which makes her ideal for this role. Dr Monteleone joined the IMS on 1st October and will be focusing on delivering a high standard of research reviews and commentaries which we know you all consider one of the most useful and valued electronic services. Please welcome her to our Society and, if anyone feels they would like to write a commentary for Menopause Live on any new research, guidelines or recommendations, please feel free to contact her via the IMS secretariat’.

Content updated 16 Octber 2018