This study examines the associations between objectively measured sedentary time and breaks in sedentary time with cardio-metabolic and inflammatory biomarkers in US adults. Using data from the National Health and Nutrition Examination Survey (NHANES) 2003–06, the study found that prolonged sedentary time was linearly and detrimentally associated with several biomarkers, including waist circumference, HDL-cholesterol, C-reactive protein, triglycerides, insulin, and HOMA-β and HOMA-γ. In contrast, breaks in sedentary time were beneficially associated with waist circumference and C-reactive protein. These associations were consistent across sex, age, and race/ethnicity, with some notable exceptions. For example, sedentary time was detrimental to waist circumference in non-Hispanic whites but not in Mexican Americans or non-Hispanic blacks. The study also found that breaks in sedentary time were beneficially associated with HDL-cholesterol in non-Hispanic whites but not in Mexican Americans or non-Hispanic blacks. The findings suggest that reducing and breaking up sedentary time may be beneficial for cardiovascular disease risk. The study is the first to examine these associations in a large, representative sample of US adults, and it highlights the importance of considering prolonged sedentary time as a distinct health risk behavior. The study also found that sedentary time was detrimentally associated with C-reactive protein, while breaks were beneficially associated. These findings have implications for public health guidelines and interventions aimed at reducing sedentary behavior. The study used accelerometers to measure sedentary time and breaks, and found that the associations were independent of other potential confounders. The study also found that the associations were consistent across different subgroups, including sex, age, and race/ethnicity. The study's findings suggest that reducing sedentary time could have a significant impact on cardiovascular disease prevention. The study also found that the associations were consistent across different subgroups, including sex, age, and race/ethnicity. The study's findings suggest that reducing sedentary time could have a significant impact on cardiovascular disease prevention.This study examines the associations between objectively measured sedentary time and breaks in sedentary time with cardio-metabolic and inflammatory biomarkers in US adults. Using data from the National Health and Nutrition Examination Survey (NHANES) 2003–06, the study found that prolonged sedentary time was linearly and detrimentally associated with several biomarkers, including waist circumference, HDL-cholesterol, C-reactive protein, triglycerides, insulin, and HOMA-β and HOMA-γ. In contrast, breaks in sedentary time were beneficially associated with waist circumference and C-reactive protein. These associations were consistent across sex, age, and race/ethnicity, with some notable exceptions. For example, sedentary time was detrimental to waist circumference in non-Hispanic whites but not in Mexican Americans or non-Hispanic blacks. The study also found that breaks in sedentary time were beneficially associated with HDL-cholesterol in non-Hispanic whites but not in Mexican Americans or non-Hispanic blacks. The findings suggest that reducing and breaking up sedentary time may be beneficial for cardiovascular disease risk. The study is the first to examine these associations in a large, representative sample of US adults, and it highlights the importance of considering prolonged sedentary time as a distinct health risk behavior. The study also found that sedentary time was detrimentally associated with C-reactive protein, while breaks were beneficially associated. These findings have implications for public health guidelines and interventions aimed at reducing sedentary behavior. The study used accelerometers to measure sedentary time and breaks, and found that the associations were independent of other potential confounders. The study also found that the associations were consistent across different subgroups, including sex, age, and race/ethnicity. The study's findings suggest that reducing sedentary time could have a significant impact on cardiovascular disease prevention. The study also found that the associations were consistent across different subgroups, including sex, age, and race/ethnicity. The study's findings suggest that reducing sedentary time could have a significant impact on cardiovascular disease prevention.