The relationship of low-density lipoprotein cholesterol and all-cause or cardiovascular mortality in patients with type 2 diabetes: a retrospective study

Abstract

Background The optimal levels of low-density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes (T2D) are not currently clear. In this study, we determined the relationship between various mean LDL-C and all-cause or cardiovascular mortality risks in patients with T2D, stratifying by albumin level, age, sex, and antilipid medication use. We also evaluated the association of LDL-C standard deviation (LDL-C-SD) and all-cause and cardiovascular mortality by type of antilipid medication use. Methods A total of 46,675 T2D patients with a prescription for antidiabetic agents >6 months from outpatient visits (2003–2018) were linked to Taiwan’s National Death Registry to identify all-cause and cardiovascular mortality. The Poisson assumption was used to estimate mortality rates, and the Cox proportional hazard regression model was used to assess the relative hazards of respective mortality in relation to mean LDL-C in patient cohorts by albumin level, age, sex, and antilipid use adjusting for medications, comorbidities, and laboratory results. We also determined the overall, and anti-lipid-specific mortality rates and relative hazards of all-cause and cardiovascular mortality associated with LDL-C-SD using the Poisson assumption and Cox proportional hazard regression model, respectively. Results All-cause and cardiovascular mortality rates were the lowest in T2D patients with a mean LDL-C > 90-103.59 mg/dL in the normal albumin group (≥ 3.5 g/dL). Compared to T2D patients with a mean LDL-C > 90–103.59 mg/dL, those with a mean LDL-C ≤ 77 mg/dL had an elevated risk of all-cause mortality in both the normal and lower albumin groups. T2D patients with a mean LDL-C ≤ 90 and > 103.59–119 mg/dL had relatively higher risk of cardiovascular mortality in the normal albumin group, but in the lower albumin group (<3.5 g/dL), any level of mean LDL-C ≤ 119 mg/dL was not significantly associated with cardiovascular mortality. Increased risks of all-cause and cardiovascular mortality were observed in patients with a mean LDL-C ≤ 77 mg/dL in both sexes and in all age groups except in those aged <50 years, a lower mean LDL-C was not associated with cardiovascular mortality. Similarly, patients with an LDL-C-SD <10th and > 90th percentiles were associated with significant risks of all-cause and cardiovascular mortality. In statin users, but not fibrate users, lower and higher levels of mean LDL-C and LDL-C-SD were both associated with elevated risks of all-cause and cardiovascular mortality. Conclusions The optimal level of LDL-C was found to be >90–103.59 mg/dL in T2D patients. Lower and higher levels of mean LDL-C and LDL-C-SD were associated with all-cause and cardiovascular mortality, revealing U-shaped associations. Further studies are necessary to validate the relationship between optimal LDL-C levels and all-cause and cardiovascular mortality in patients with diabetes.

A Non-Linear Association of Low-density lipoprotein cholesterol with All-Cause and Cardiovascular Mortality Among Patients with Hypertension

“…Zhen Z et al reported there was a U-shaped relationship between untreated LDL-C level and all-cause mortality 34 and Tikhonoff V et al found LDL-C concentration is a multifaceted risk factor in older adults 35 . Chang C-H et al demonstrated both lower and higher levels of mean LDL-C were associated with increased all-cause and cardiovascular mortality in type 2 diabetes patients through 36 . Also, multiple studies in general population had got the similar result 17,[37][38][39] .…”

Assessing the impact of type 2 diabetes on mortality and life expectancy according to the number of risk factor targets achieved: an observational study

“…A detailed definition of risk factors can be found in Additional file 1 : Table S2. We did not consider low-density lipoprotein (LDL) cholesterol as a risk factor because evident evidence has shown that low LDL cholesterol levels are associated with increased mortality risk in the general population and patients with T2D [ 10 , 20 – 22 ]. In a recent study of the UK Biobank, a significant U-shaped relationship was also observed between LDL cholesterol and all-cause mortality [ 23 ].…”

Different levels of hypoglycemia in patients with type 2 diabetes, their achieved mean HbA1c vs. all-cause and cardiovascular mortality

“…FEMH, a tertiary medical center, has set up its electronic medical database of out-patient and emergency visits since 2001 and 2008, respectively. The details of our out-patient electronic database have been described in previous studies [12][13][14]. In this study, we extended our database to emergency visits electronic records.…”

“…From the out-patient medical records, the information of oral hypoglycemic agents, insulin, antihypertensive and antilipid medications were collected during the study period as stated in our previous studies [12][13][14]. We also explored each study participant's comorbidities and complications as described in S1 Table [15].…”