Triglycerides Paradox Among the Oldest Old: “The Lower the Better?”

Abstract

OBJECTIVES Currently, most treatment guidelines suggest lowering hypertriglyceridemia of any severity, even in elderly individuals. However associations of serum triglycerides (TGs) with adverse health and mortality risk decrease with age, it remains unclear among the oldest old (aged 80 years and older). The study was to investigate the relationship of serum TG concentrations with cognitive function, activities of daily living (ADLs), frailty, and mortality among the oldest old in a prospective cohort study. DESIGN Longitudinal prospective cohort study. SETTING Community‐based setting in longevity areas in China. PARTICIPANTS A total of 930 (mean age = 94.0 years) Chinese oldest old. MEASUREMENTS The TG concentrations were measured at baseline survey in 2009. Cognitive function, ADLs, frailty, and mortality were determined over 5 years of follow‐up. Cox proportional hazards models and competing risk models were performed to explore the association, adjusting for potential confounders. RESULTS Each 1‐mmol/L increase in TGs was associated with a nearly 20% lower risk of cognitive decline, ADL decline, and frailty aggravation during the 5 years of follow‐up. Consistently, higher TGs (each 1 mmol/L) was associated with lower 5‐year all‐cause mortality after fully adjustment (hazard ratio [HR] = 0.79; 95% confidence interval [CI] = 0.69‐0.89). Nonelevated TG concentrations (less than 2.26 mmol/L) were associated with higher mortality risk (HR = 1.72; 95% CI = 1.22‐2.44), relative to TGs of 2.26 mmol/L or more. We observed similar results regarding TG concentrations and mortality in 1‐year lag analysis and when excluding participants with identified chronic disease. CONCLUSION In the oldest old, a higher concentration of TGs was associated with a lower risk of cognitive decline, ADL decline, frailty aggravation, and mortality. This paradox suggests the clinical importance of revisiting the concept of “the lower the better” for the oldest old. J Am Geriatr Soc 67:741–748, 2019.

PVRL2 rs6859 Modifies the Effect of Triglyceride on Progression of Mild Cognitive Impairment: The Shanghai Aging Study

“…For example, Power, M.C found that elevated TG at midlife were associated with cognitive decline over the follow-up of 20 years in non-dementia subjects of the Atherosclerosis Risk in American population [10]. To the contrary, Lv Y.B et al found that each 1-mmol/L increase of TG was associated with a nearly 20% lower risk of cognitive decline during the 5 follow-up years in 930 Chinese oldest (mean age: 94.0 years) [7]. Moreover, Sabrina found that higher baseline TG concentrations were associated with mixed dementia while it disappeared after adjusting for vascular risk factors in the Three-City (3C) study of European population (mean age = 76.3 years) with up to 13 years of followup [8].…”

“…To our knowledge, this is the rst prospective cohort study to report the interactive effect of TG and PVRL2 rs6859 on MCI-AD progression in Chinese elderly population. Previous studies largely focused on the relationship between TG and AD risk irrespective of AD risk-related SNPs, and there was no uni ed conclusion [7][8][9][10][11][12][13][14][15][16]. For example, Power, M.C found that elevated TG at midlife were associated with cognitive decline over the follow-up of 20 years in non-dementia subjects of the Atherosclerosis Risk in American population [10].…”

“…Unlike cholesterol measurements, the effect of TG on cognitive function in the elderly has not garnered enough attention in recent years [7]. Additionally, previous epidemiological studies regarding the impact of TG on cognitive function in elderly populations have not reached a consensus, including associations of adverse TG with an increased AD risk [8][9][10], absence of an association [11][12][13][14][15], or even inverse associations [7,16]. Gina et al found that two AD-risk SNPs had interaction with midlife TG level on AD risk (rs11218343 and APOE ε4) in the Framingham Heart Study [17], which indicated that genetic factor might be one of the reasons for inconsistent results of TG-AD relationship.…”

The Association between Allostatic Load and Mortality among Chinese Older Adults: The Chinese Longitudinal Health and Longevity Study

“…To be in line with previous studies [6,8,24,25], we used the highest quartile for heart rate, SBP, DBP, glucose, and CRP and the lowest quartile for HDL cholesterol to de ne high-risk group (coded 1). Because BMI, total cholesterol, and triglyceride were inversely associated with mortality among older adults, especially the oldest old [19,29,30], we used the lowest quartile to de ne high-risk group for these three biomarkers. For participants who self-reported having been diagnosed with hypertension and heart disease, we classi ed their SBP, DBP, and glucose into the high-risk category.…”

U-shaped association between low-density lipid cholesterol and diabetes mellitus in patients with hypertension

“…[6, 7] The relationship between statins and DM is also subject to “reverse epidemiology” or the “risk factor paradox” observed in obese or geriatric populations [8, 9]. In China, low LDL-C levels appeared to associate with an increased risk of intracerebral hemorrhage [10], while high triglycerides (TG) associated with a decreased risk of cognitive decline and daily activity, as well as an increased risk of frailty and mortality in elderly [11]. Meanwhile, data from representative cross-sectional studies in the USA and Spain indicated an positive association between LDL-C levels and body mass index (BMI) only in lean individuals [12].…”