Inverse Association between High-Density Lipoprotein Cholesterol and Adverse Outcomes among Acute Ischemic Stroke Patients with Diabetes Mellitus.
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ABSTRACT:
SUBMITTER: Hu G
PROVIDER: S-EPMC8698640 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and Purpose- Few studies have assessed the association of HDL (high-density lipoprotein) cholesterol with stroke risk among patients with type 2 diabetes mellitus. We aimed to investigate the association of HDL cholesterol with total and type-specific stroke risk in patients with type 2 diabetes mellitus. Methods- We performed a retrospective cohort study of 27?113 blacks and 40?431 whites with type 2 diabetes mellitus. Cox proportional hazards regression models were used to estimate the association of different levels of HDL cholesterol with stroke risk. Results- During a mean follow-up period of 3.0 years, 8496 patients developed stroke (8048 ischemic and 448 hemorrhagic). Multivariable-adjusted hazard ratios across levels of HDL at baseline (<30 [reference group], 30-39.9, 40-49.9, 50-59.9, 60-69.9, 70-79.9, and ?80 mg/dL) were 1.00, 0.86, 0.77, 0.71, 0.71, 0.77, and 0.69 ( Ptrend <0.001) for total stroke, 1.00, 0.89, 0.82, 0.75, 0.78, 0.76, and 0.75 ( Ptrend <0.001) for ischemic stroke, and 1.00, 0.89, 0.69, 0.66, 0.47, and 0.94 ( Ptrend =0.021) for hemorrhagic stroke, respectively. When we used an updated mean value of HDL cholesterol, the inverse association of HDL cholesterol with stroke risk did not change. This inverse association was consistent among patients of different ages, races, sexes, body mass index, hemoglobin A1c levels, never and past or current smokers, and patients with and without using glucose-lowering, cholesterol-lowering, or antihypertensive agents. Conclusions- The present study found consistent inverse associations between HDL cholesterol and the risk of total, ischemic and hemorrhagic stroke among patients with type 2 diabetes mellitus.
| S-EPMC6349480 | biostudies-literature
Project description:BackgroundEmerging data in the general population and those with coronary artery disease demonstrate higher risk of adverse outcomes with high (>70 mg/dL) HDL-C levels. There are limited data on the risk of adverse outcomes in women with suspected ischemic heart disease.ObjectiveTo investigate relationships between high (>70 mg/dL), average (50-70 mg/dL), and low (<50 mg/dL) HDL-C levels with major adverse cardiac events (MACE) (death, myocardial infarction, stroke, and heart failure hospitalization), and all-cause mortality in women referred for coronary angiography for suspected myocardial ischemia.MethodsA total of 607 women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) original cohort (NCT00000554) with available HDL-C values were included in this analysis. Associations between HDL-C level and outcomes were evaluated using both multivariate Cox proportional hazard regression and spline regression analysis.ResultsThe mean age was 59 ± 12 years, 62 % had 3 or more cardiac risk factors, and 66 (10.9 %) had a high HDL-C. High and low HDL-C were both associated with higher MACE risk compared to average HDL-C after adjusting for demographic and clinical characteristics (HR 1.80, CI 1.03-3.14, p = 0.038; HR 1.63, CI 1.09-2.42, p = 0.016, respectively). Similarly, high, and low HDL-C were associated with higher risk of all-cause mortality (HR 3.64, CI 1.84-7.20, p < 0.001; HR 2.81, CI 1.67-4.71, p < 0.001, respectively).ConclusionsHigh and low HDL-C levels are both independently associated with higher MACE and all-cause mortality in women with suspected ischemia undergoing coronary angiography.
| S-EPMC10946010 | biostudies-literature
Project description:BackgroundPrevious research has linked elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) with diabetes mellitus (DM). The present study aims to estimate the RC-related DM risk beyond LDL-C, and to investigate the extent to which the association of RC and DM is mediated via insulin resistance and inflammation.MethodsWe enrolled 7308 individuals without previous history of DM into the present study from the China Health and Nutrition Survey. Fasting RC was calculated as total cholesterol minus LDL-C and high-density lipoprotein cholesterol. Subjects were divided into four groups according to their LDL-C (100 mg/dL) and RC (24 mg/dL) levels to evaluate the role of LDL-C vs. RC on DM. A logistic regression analysis was then employed to evaluate the relationships between the discordant/concordant LDL-C and RC and DM. A mediation analysis was undertaken to identify potential mediators.ResultsOf all the participants, a total of 625 (8.55%) patients were newly diagnosed with DM. Compared to the high LDL-C/low RC group, the low LDL-C/high RC group was more common in DM patients. After a multivariate adjustment, elevated LDL-C and RC were associated with DM. Moreover, the low LDL-C/high RC group and the high LDL-C/low RC group manifested a 4.04-fold (95% CI 2.93-5.56) and 1.61-fold (95% CI 1.21-2.15) higher risk of DM, relative to those with low LDL-C/low RC. The subgroup analysis indicated that low LDL-C/high RC was more likely to be related to DM in females. Similar results were also shown when the sensitivity analyses were performed with different clinical cut-points of LDL-C. Insulin resistance and inflammation partially mediated the association between RC and DM.ConclusionsOur findings provided evidence for RC beyond the LDL-C associations with DM that may be mediated via insulin resistance and the pro-inflammatory state. In addition, women are more susceptible to RC exposure-related DM.
| S-EPMC9238255 | biostudies-literature
Project description:BackgroundThere are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data.MethodsUsing the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018.ResultsThe mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL.ConclusionFor primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors.
| S-EPMC9925148 | biostudies-literature
Project description:Patients undergoing maintenance hemodialysis are at high cardiovascular risk. Lowering LDL-cholesterol with statins reduces the incidence rate of cardiovascular events in patients with chronic kidney disease. In contrast, two randomized, prospective, placebo-controlled trials have been completed in hemodialysis patients that showed no significant effects of statins on cardiovascular outcomes.A post hoc analysis was conducted of the 4D (Die Deutsche Diabetes Dialyze) study to investigate whether LDL-cholesterol at baseline is predictive of cardiovascular events and whether the effect of atorvastatin on clinical outcomes depends on LDL-cholesterol at baseline.High concentrations of LDL-cholesterol by tendency increased the risks of cardiac endpoints and all-cause mortality. Concordantly, atorvastatin significantly reduced the rates of adverse outcomes in the highest quartile of LDL-cholesterol (?145 mg/dl, 3.76 mmol/L). The hazard ratios and 95% confidence intervals were 0.69 (0.48 to 1.00) for the composite primary endpoint, 0.58 (0.34 to 0.99) for cardiac death, 0.48 (0.25 to 0.94) for sudden cardiac death, 0.62 (0.33 to 1.17) for nonfatal myocardial infarction, 0.68 (0.47 to 0.98) for all cardiac events combined, and 0.72 (0.52 to 0.99) for death from all causes, respectively. No such decrease was seen in any of the other quartiles of LDL-cholesterol at baseline.In patients with type 2 diabetes mellitus undergoing hemodialysis, atorvastatin significantly reduces the risk of fatal and nonfatal cardiac events and death from any cause if pretreatment LDL-cholesterol is >145 mg/dl (3.76 mmol/L).
| S-EPMC3109927 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of ?-cell function. T2DM patients are at increased risk of micro- and macrovascular disease, and are often considered as representing an atherosclerotic coronary heart disease (CHD) risk equivalent. Interventions directed at glucose and lipid level control in T2DM patients may reduce micro- and macrovascular disease. The optimal T2DM agent is one that lowers glucose levels with limited risk for hypoglycemia, and with no clinical trial evidence of worsening CHD risk. Lipid-altering drugs should preferably reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have evidence that the mechanism of action reduces CHD risk. Statins reduce low-density lipoprotein cholesterol and apo B and have evidence of improving CHD outcomes, and are thus first-line therapy for the treatment of hypercholesterolemia. In patients who do not achieve optimal lipid levels with statin therapy, or who are intolerant to statin therapy, add-on therapy or alternative therapies may be indicated. Additional available agents to treat hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates, niacin, and ezetimibe. This review discusses the use of these alternative agents to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in combination with statin therapy.
| S-EPMC4094576 | biostudies-other
Project description:PurposeSmall dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design.MethodsWe identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis.ResultsIn univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117-1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106-1.597, P = 0.002).ConclusionsFindings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C.
| S-EPMC11317295 | biostudies-literature
Project description:AimsThe monocyte to high-density lipoprotein cholesterol ratio (MHR) has emerged as a novel inflammatory biomarker of atherosclerotic cardiovascular disease. However, it has not yet been identified whether MHR can predict the long-term prognosis of ischemic stroke. We aimed to investigate the associations of MHR levels with clinical outcomes in patients with ischemic stroke or transient ischemic attack (TIA) at 3 months and 1 year.MethodsWe derived data from the Third China National Stroke Registry (CNSR-III). Enrolled patients were divided into four groups by quartiles of MHR. Multivariable Cox regression for all-cause death and stroke recurrence and logistic regression for the poor functional outcome (modified Rankin Scale score 3-6) were used.ResultsAmong 13,865 enrolled patients, the median MHR was 0.39 (interquartile range, 0.27-0.53). After adjustment for conventional confounding factors, the MHR level in quartile 4 was associated with an increased risk of all-cause death (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.10-1.90), and poor functional outcome (odd ratio [OR], 1.47; 95% CI, 1.22-1.76), but not with stroke recurrence (HR, 1.02; 95% CI, 0.85-1.21) at 1 year follow-up, compared with MHR level in quartile 1. Similar results were observed for outcomes at 3 months. The addition of MHR to a basic model including conventional factors improved predictive ability for all-cause death and poor functional outcome validated by the C-statistic and net reclassification index (all p < 0.05).ConclusionsElevated MHR can independently predict all-cause death and poor functional outcome in patients with ischemic stroke or TIA.
| S-EPMC10324347 | biostudies-literature
Project description:BackgroundThe risk association between low-density lipoprotein (LDL) cholesterol and cancer remains controversial and largely unexplored for people not receiving statin therapy.MethodsWe examined the risk association between LDL cholesterol and cancer among patients with type 2 diabetes mellitus who were free of cancer at enrolment and whose statin use was known. We considered a variety of nonlinear relationships in our analysis.ResultsDuring a median follow-up period of 4.90 years, cancer developed in 270 (4.4%) of 6107 patients. Among the 3800 patients who did not receive statin therapy, the risk association between LDL cholesterol and cancer was represented by a V-shaped curve. Compared with patients whose LDL cholesterol was at least 2.80 mmol/L but less than 3.80 mmol/L, the risk of cancer, death from any cause or the composite outcome of cancer or death was greater among those with an LDL cholesterol level of less than 2.80 mmol/L (hazard ratio for cancer 1.74, 95% confidence interval [CI] 1.20-2.52) and those with an LDL cholesterol level of 3.80 mmol/L or greater (hazard ratio for cancer 1.87, 95% CI 1.29-2.71). Using 3.8 mmol/L as a reference point, we found that the hazard ratio for cancer for every millimole per litre absolute change in LDL cholesterol was 1.54 (95% CI 1.19-1.99) among patients not using statins; the hazard ratio was reduced to 1.24 (1.01-1.53) for the entire sample (statin users and those not using statins). These associations persisted after adjustment for covariates and exclusion of patients with less than 2.5 years of follow-up.InterpretationAmong patients with type 2 diabetes, the association between LDL cholesterol and cancer was V-shaped, whereby both low and high levels of LDL cholesterol were associated with elevated risk of cancer.
| S-EPMC2518179 | biostudies-literature
Project description:PurposeDiabetes is one of the most prevalent chronic diseases in the world, and its prevalence is expected to rise further. To help understand the utility of the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) in diabetes prevention, this large-scale longitudinal cohort study aims to explore the association of NHHR with diabetes risk and compare it as a risk predictor with conventional lipid parameters.Patients and methodsThis observational study extracted data from the NAGALA longitudinal cohort study conducted in Japan between 2004 and 2015. Multivariate Cox regression analysis was used to evaluate the association between NHHR and the risk of diabetes. The dose-response relationship was analyzed by restricted cubic spline (RCS) regression and the potential risk threshold was estimated. The receiver operator characteristic curve (ROC) was used to analyze and calculate the predictive value and optimal threshold of NHHR and other conventional lipids for new-onset diabetes.ResultsOf the 15,464 people aged 18-79, 373 (2.41%) were diagnosed with new-onset diabetes during the study period, with a median age of 46 years. The sensitivity analysis based on multivariate adjustment showed that the independent positive correlation between diabetes and NHHR was stable in different populations. RCS and ROC analysis indicated that the association between NHHR and diabetes was non-linear, and the NHHR was a better marker for predicting diabetes risk than other conventional lipid parameters; Additionally, it is worth noting that an NHHR of approximately 2.74 may be the optimal threshold for intervention in diabetes risk.ConclusionIn the general population, NHHR is a better marker for predicting diabetes risk than conventional lipid parameters, and an NHHR of about 2.74 may be the optimal threshold for assessing diabetes risk.
| S-EPMC9166911 | biostudies-literature