Any Amount of Excess Body Weight Associated With Higher Risk of Premature Death
Dr. Shilpa Bhupathiraju[/caption]
Dr. Shilpa Bhupathiraju, PhD
Harvard T.H. Chan
School of Public Health
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We wanted to investigate the association between body mass index (BMI) and mortality across major global regions. In doing so, we wanted to take into account important methodological limitations which plagued prior reports of BMI and mortality. One such limitation is reverse causality where a low body weight is the result of an underlying illness rather than the cause. Another major problem is confounding due to smoking where smokers have lower body weights than non-smokers but have much higher mortality rates.
Therefore, to obtain an unbiased association between BMI and mortality, our primary pre-specified analysis was restricted to never smokers and those who had no existing chronic diseases at the start of the study.
In this group, we found that those with a BMI of 22.5-<25 kg/m2 (considered a healthy weight range) had the lowest mortality risk during the time they were followed. The risk of mortality increased significantly with excess body weight. A BMI of 25-<27.5 kg/m2 (in the overweight range) was associated with a 7% higher risk of premature death; BMI of 27.5-<30 kg/m2 (also in the overweight range) was associated with a 20% higher risk; a BMI of 30.0-<35.0 kg/m2 was associated with a 45% higher risk; a BMI of 35.0-<40.0 kg/m2 was associated with a 94% higher risk; and a BMI of 40.0-<60.0 kg/m2 was associated with a nearly 3-fold risk. In general, we found that the association of excess body weight with mortality was greater in younger than older people and in men than women. Most importantly, the associations were broadly consistent in the major global regions we examined, including Europe, North America, Australia and New Zealand, East Asia, and South Asia.


















Dr. Audrey Chang[/caption]
MedicalResearch.com Interview with:
Dr. Audrey Chang, PhD
Kamm-Stull Lab
UT Southwestern Medical Center
AudreyN.Chang@UTSouthwestern.edu
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The heart is a singular kind of muscle that contracts and relaxes continuously over a lifetime to pump blood to the body’s organs. Contractions depend on a motor protein myosin pulling on actin filaments in specialized structures. Heart contraction is improved when myosin has a phosphate molecule attached to it (phosphorylation), and a constant amount of phosphorylation is essential for normal heart function. The amount of phosphorylation necessary for optimal cardiac performance is maintained by a balance in the activities of myosin kinase enzymes that add the phosphate and an opposing phosphatase enzyme that removes the phosphate. If the amount of phosphorylation is too low, heart failure results. Animal models with increased myosin phosphorylation have enhanced cardiac performance that resist stresses that cause heart failure.
In this recent study reported in PNAS, a new kinase that phosphorylates myosin in heart muscle, MLCK4, was discovered and its crystal structure reported, a first for any myosin kinase family member. Compared to distinct myosin kinases in other kinds of muscles (skeletal and smooth), this cardiac-specific kinase lacks a conserved regulatory segment that inhibits kinase activity consistent with biochemical studies that it is always turned on. Additionally, another related myosin kinase found only in heart muscle (MLCK3) contains a modified regulatory segment, allowing partial activity enhanced by the calcium modulator protein, calmodulin. Thus, both myosin kinases unique to cardiac muscle provide phosphate to myosin in normal beating hearts to optimize performance and prevent heart failure induced by stresses.

