Association Between Serum Cholesterol And Risk Of Mortality:A Cohort Study

Backgrounds and ObjectiveOver the past years,blood lipid level in the Chinese population has increased gradually and the incidence of dyslipidemia has also been increasing significantly.As an important component of blood lipids,serum cholesterol has been of interest for its relationship with healthy outcomes for many years.Although serum cholesterol,especially high LDL-C level,was regarded as an established risk factor for atherosclerotic cardiovascular disease,results for the associations between serum cholesterol and risk of mortality remain inconsistent,indicating either positive linear,inverse,U-curve or L-curve associations.In addition,some recent large-scale prospective cohort studies have reported that extremely high levels of HDL were paradoxically associated with all-cause and CVD mortality.However,few studies have evaluated the association between serum cholesterol and the risk of mortality among the general Chinese population.Therefore,this study evaluated the relationship of TC,LDL-C and HDL-C with the risk of all-cause and cause-specific mortality using data from health information system in Ningbo city,with the aim to provide epidemiology evidence for lipids control and health promoting.Materials and MethodsIn this study,the electronic health records of residents established from 2010 to 2014 on the health information system of Yinzhou District(YHIS)of Ningbo City were used.We recruited subjects aged over 40 years who underwent routine health examinations from 2010 to 2014.Persons with the history of cancer or cardiovascular events(heart attack and stroke)or with missing information at baseline were excluded.Overall,a total of 76107 subjects were included and were followed until December 31,2018 through the local Resident Death Register System.We used ICD-10(international classification of diseases,10threvision)to assess participants’ underlying cause of death from cardiovascular disease(codes I00-I99)or cancer(C00-C99).To examine the non-linear or irregular shape of the relationship between cholesterol and mortality,we used Cox models with penalized splines.Results were expressed in terms of hazard ratio curves,and a minimal value in the HR curve was considered as a reference.We further divided TC levels into 7 groups(<4.14,4.14～,4.66～[reference],5.18～,5.70～,6.22～ and ≥6.73 mmol/L),LDL-C levels into 7 groups(<2.07,2.07～,2.59～[reference],3.11～,3.63～,4.14～and ≥4.66 mmol/L),HDL-C levels into 5 groups(<1.04[reference],1.04～,1.56～,2.07～ and≥2.33 mmol/L)respectively to estimate hazard ratios(HRs)and 95% confidence intervals(CIs)using multivariable Cox proportional hazards model.Potential covariates were as follows: age at baseline,sex,BMI,systolic blood pressure,tobacco smoking,alcohol drinking,physical activity,diabetes,the use of lipid-lowering medication.Fine-Gray competing risks regression models were used when assessing the associations between cholesterol and causespecific mortality.We also performed stratified and sensitive analyses.ResultsDuring the mean follow-up of 6.67 years,3643deaths(including 1239 from cardiovascular disease and 1136 from cancer)occurred.The mortality density was 7.19 death per 1000 person years.Cox models with penalized splines revealed a U-shaped relationship of TC with all-cause,cardiovascular disease and cancer mortality and the minimum mortality reached at around 5.49,5.12 and 6.14mmol/L,respectively.U-shaped relationships were also observed for LDL-C and all-cause and cancer mortality and more likely “J”-shape for cardiovascular disease mortality,with the nadir at round 3.37,3.82 and 2.89 mmol/L respectively.The relationships of HDL-C with all-cause,cardiovascular disease and cancer mortality were similar to “L”-curve,indicating that HDL-C was inversely associated with mortality in the range of 0～1.5mmol/L.Compared with participants with TC of 4.66～5.17mmol/L,multivariable adjusted hazard ratios(95% CIs)were 1.38(1.25-1.52),1.12(1.01-1.23),1.45(1.21-1.74)for all-cause mortality in those with TC<4.14,4.14～4.65 and ≥6.73mmol/L,respectively,and multivariable adjusted hazard ratios(95% CIs)were 1.43(1.20-1.71)and 2.13(1.61-2.82)for cardiovascular disease mortality in those with TC<4.14mmol/L and ≥6.73mmol/L when considered competing risk.Compared with participants with LDLC2.59～3.10mmol/L,multivariable adjusted hazard ratios(95% CIs)were 1.32(1.17-1.49),1.11(1.00-1.22),1.88(1.45-2.45)for all-cause mortality in those with LDL-C<2.07,2.07～2.58 and ≥4.66mmol/L,respectively,and multivariable adjusted hazard ratios(95% CIs)were 1.38(1.09-1.76),1.48(1.02-2.13)and 2.72(1.79-4.13)for cardiovascular disease mortality in those with LDL-C of 3.63～4.13,4.14～4.65 and ≥4.66mmol/L respectively when considered competing risks.Compared with participants with HDLC<1.04mmol/L,those with HDL-C of 1.04～1.55 and1.55～2.06mmol/L had significant lower risk of death from all-cause,cardiovascular disease and cancer and subjects with HDL-C of 2.07～2.32mmol/L had also significant lower risk of cardiovascular disease mortality.However,the hazard ratios were not statistically significant for death from all-cause or cardiovascular disease when HDL-C≥2.07mmol/L or≥2.33mmol/L.Stratified analyses showed that stronger associations for low TC or LDL-C levels and the risk of mortality was observed in women or people aged over 60 years.Sensitive analyses excluding subjects who were followed less than 2 years or with a BMI of less than18.5 did not materially change our results.ConclusionIn this general population,either too low or too high TC level was associated with higher risk of mortality and high LDL-C level was associated with much higher risk of cardiovascular disease mortality.Low HDL-C level was associated with higher risk of all-cause mortality.Cautions should be taken in health management and disease prevention among people who have high LDL-C and low HDL-C levels.Moreover,too low TC level may not predict good survival outcomes,especially in the elderly.