Prolonged or Transition to Metabolically Unhealthy Status, Regardless of Obesity Status, Is Associated with Higher Risk of Cardiovascular Disease Incidence and Mortality in Koreans

Abstract

The risk of chronic disease and mortality may differ by metabolic health and obesity status and its transition. We investigated the risk of cardiovascular disease (CVD) and cancer incidence and mortality according to metabolic health and obesity status and their transition using the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) and the Ansan-Ansung (ASAS) cohort of the Korean Genome and Epidemiology Study. Participants that agreed to mortality linkage (n = 28,468 in KNHANES and n = 7530 adults in ASAS) were analyzed (mean follow-up: 8.2 and 17.4 years, respectively). Adults with no metabolic risk factors and BMI <25 or ≥25 kg/m2 were categorized as metabolically healthy non-obese (MHN) or metabolically healthy obese (MHO), respectively. Metabolically unhealthy non-obese (MUN) and metabolically unhealthy obese (MUO) adults had ≥1 metabolic risk factor and a BMI < or ≥25 kg/m2, respectively. In KNHANES participants, MUN, and MUO had higher risks for cardiovascular mortality, but not cancer mortality, compared with MHN adults. MHO had 47% and 35% lower risks of cancer mortality and all-cause mortality, respectively, compared to MHN. Similar results were observed in the ASAS participants. Compared to those persistently MHN, the risk of CVD was greater when continuously MUN or MUO. Transitioning from a metabolically healthy state to MUO also increased the risk of CVD. Few associations were found for cancer incidence. Using a nationally representative cohort and an 18-year follow-up cohort, we observed that the risk of CVD incidence and mortality and all-cause mortality, but not cancer incidence or mortality, increases with a continuous or a transition to an unhealthy metabolic status in Koreans.

Metabolic health and adiposity transitions and risks of type 2 diabetes and cardiovascular diseases: a systematic review and meta-analysis

“…Assessment of metabolic health and obesity varied across studies. Six studies considered five components for determination of metabolic health, including blood pressure, plasma glucose, HDL-cholesterol, triacylglycerols, and waist circumference [ 27 , 28 , 30 , 32 , 34 , 35 , 37 ]; eight studies considered four components, including blood pressure, plasma glucose, HDL-cholesterol, and triacylglycerols [ 25 , 26 , 29 , 31 , 32 , 38 – 40 ]; one study examined four components, including blood pressure, plasma glucose, triacylglycerols, and waist circumference [ 33 ]; the remaining two studies examined three components [ 9 , 36 ]. Overweight/obesity was defined as BMI ≥ 24 kg/m 2 in five studies [ 25 , 28 , 30 , 31 , 33 ], ≥ 30 kg/m 2 in two studies [ 29 , 39 ], and ≥ 25 kg/m 2 in the remaining studies.…”

“…Overweight/obesity was defined as BMI ≥ 24 kg/m 2 in five studies [ 25 , 28 , 30 , 31 , 33 ], ≥ 30 kg/m 2 in two studies [ 29 , 39 ], and ≥ 25 kg/m 2 in the remaining studies. Five studies examined transition of metabolic health and adiposity status prior to initiation of follow-up [ 9 , 26 , 32 , 37 , 40 ], five studies examined transition during the early phase of follow-up (mainly within the first 3–8 years) [ 27 , 29 , 33 , 34 , 36 ], and seven studies examined transition over the entire follow-up period from baseline to the end of follow-up [ 25 , 28 , 30 , 31 , 35 , 38 , 39 ].…”

Risk of Death Associated With Reversion From Prediabetes to Normoglycemia and the Role of Modifiable Risk Factors

“…Moreover, our study revealed that BMI was an important risk factor associated with changes in prediabetes status. Previous studies 25,26 suggested that the transition to metabolic unhealthiness (such as the onset of type 2 diabetes) substantially increases the risk of death among individuals with obesity. Because several other metabolic health factors, such as hypertension and hyperlipidemia, might confound the association between changes in prediabetes status and risk of death, we further adjusted for hypertension and total cholesterol level and found no substantial differences in the results.…”

Association of Metabolically Healthy Obesity and Risk of Cardiovascular Disease Among Adults in China: A Retrospective Cohort Study

“…The primary reason for this discrepancy lies in the definition of “metabolic health”, which demands no metabolic syndrome manifestations presented according to their diagnostic criteria, while most international standards require less than 2. 6 , 25 , 26 …”

“…The primary reason for this discrepancy lies in the definition of "metabolic health", which demands no metabolic syndrome manifestations presented according to their diagnostic criteria, while most international standards require less than 2. 6,25,26 More recently, the China Kadoorie Biobank and the China XinJiang cohort study, including 458,246 and 5,059 Chinese adults, respectively, showed that MHO individuals were at an increased risk of CVD (HR 1.54, 95% CI 1.49-1.60 and HR 2.60, 95% CI 1.93-3.49) than their MHNW counterparts. 3,27 On the basis of these studies, the strength of our study was that the cohort was well characterized, the laboratory data were complete at baseline and follow-up and the uniform definition was defined according to the Joint Interim Statement (JIS).…”