scholarly journals Low-density lipoprotein cholesterol and risk of intracerebral hemorrhage

Neurology ◽  
2019 ◽  
Vol 93 (5) ◽  
pp. e445-e457 ◽  
Author(s):  
Chaoran Ma ◽  
M. Edip Gurol ◽  
Zhe Huang ◽  
Alice H. Lichtenstein ◽  
Xiuyan Wang ◽  
...  

ObjectiveTo prospectively examine the association between low-density lipoprotein (LDL) cholesterol (LDL-C) concentrations and intracerebral hemorrhage (ICH) risk.MethodsThe current cohort study included 96,043 participants (mean age 51.3 years) who were free of stroke, myocardial infarction, and cancer at baseline (2006). Serum LDL-C concentrations were assessed in 2006, 2008, 2010, and 2012. Cumulative average LDL-C concentrations were calculated from all available LDL-C data during that period. Incident ICH was confirmed by review of medical records.ResultsWe identified 753 incident ICH cases during 9 years of follow-up. The ICH risk was similar among participants with LDL concentrations of 70 to 99 mg/dL and those with LDL-C concentrations ≥100 mg/dL. In contrast, participants with LDL-C concentrations <70 mg/dL had a significantly higher risk of developing ICH than those with LDL-C concentrations of 70 to 99 mg/dL; adjusted hazard ratios were 1.65 (95% confidence interval [CI] 1.32–2.05) for LDL-C concentrations of 50 to 69 mg/dL and 2.69 (95% CI 2.03–3.57) for LDL-C concentrations <50 mg/dL.ConclusionsWe observed a significant association between lower LDL-C and higher risk of ICH when LDL-C was <70 mg/dL, and the association became nonsignificant when LDL-C ≥70 mg/dL. These data can help determination of the ideal LDL range in patients who are at increased risk of both atherosclerotic disease and hemorrhagic stroke and guide planning of future lipid-lowering studies.

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chaoran Ma ◽  
M Edip Gurol ◽  
Zhe Huang ◽  
Alice Lichtenstein ◽  
Xiuyan Wang ◽  
...  

Abstract Objectives To prospectively examine the association between low density lipoprotein cholesterol (LDL-C) concentrations and intracerebral hemorrhage (ICH) risk, and test the association in a meta-analysis combining the present data with previous studies. Methods The current cohort study included 96,043 participants (mean age 51.3 y), free of stroke, myocardial infarction, and cancer at baseline (2006). Serum LDL-C concentrations were assessed in 2006, 2008, 2010 and 2012. Cumulative average LDL-C concentrations were calculated from all available LDL-C data during that period. Incident ICH was confirmed by review of medical records. Results We identified 753 incident ICH cases during 9 years of follow-up. The ICH risk was similar among participants with LDL concentrations of 70–99 mg/dL and those with LDL-C concentrations ≥100 mg/dL. In contrast, participants with LDL-C concentrations less than 70 mg/dL had a significantly higher risk of developing ICH than those with LDL-C concentrations of 70–99 mg/dL –adjusted HR 1.65 (95%CI, 1.32 to 2.05) for LDL-C concentrations of 50–69 mg/dL and 2.69 (95%CI, 2.03 to 3.57) for LDL-C concentrations of <50 mg/dL. In the meta-analysis of 11 prospective studies, the pooled HRs of hemorrhagic stroke for per 10 mg/dL decrement in LDL-C was 1.03 (95% CI, 1.01 to 1.06). Conclusions We observed a significant association between lower LDL-C and higher risk of ICH when LDL-C concentrations <70 mg/dL, and the risk decreased to a non-significance level and stabilized when LDL-C ≥70 mg/dL. These data can help determination of ideal LDL range in patients who are at increased risk of both atherosclerotic disease and hemorrhagic stroke and also guide planning of future lipid lowering studies. Funding Sources Supported by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. Supporting Tables, Images and/or Graphs


Author(s):  
Salim S Virani ◽  
Lechauncy D Woodard ◽  
Supicha Sookanan ◽  
Cassie R Landrum ◽  
Tracy H Urech ◽  
...  

Background: Although current cholesterol performance measures define good quality as low density lipoprotein cholesterol (LDL-C) levels < 100mg/dl in cardiovascular disease (CVD) patients, they provide a snap shot at one time point and do not inform whether an appropriate action was taken to manage elevated LDL-C levels. We assessed frequency and predictors of this appropriate response (AR). Methods: We used administrative data to assess 22,902 CVD patients receiving care in a Veterans Affairs network of 7 hospitals and affiliated clinics. We determined the proportion of CVD patients at LDL-C goal <100 mg/dl, and the proportion of patients with uncontrolled LDL-C levels (>100 mg/dl) who had an AR [defined as the initiation or dosage increase of a lipid lowering medication (LLM), addition of a new LLM, receipt of maximum dosage or >1 LLM, or LDL-C reading <100 mg/dl] at 45 days follow-up. Logistic regression was performed to evaluate facility, provider and patient characteristics associated with AR. Results: LDL-C levels were at goal in 16,350 (71.4%) patients. An additional 2,110 (9.2%) had an AR at 45 days of follow-up. Controlling for clustering between facilities and patient's illness severity, history of diabetes (OR 1.18, 95% CI 1.03-1.35), hypertension (OR 1.21, 95% CI 1.02-1.44), patients showing good medication adherence (medication possession ratio > 0.8) [OR 2.29, 95% CI 1.99-2.64] were associated with AR. Older CVD patients (age >75 years) were less likely to receive AR (OR 0.60, 95% CI 0.52-0.70). Teaching vs. non-teaching facility (p=0.40), physician vs. non-physician provider (p=0.14), specialist vs. non-specialist primary care provider (p=0.12), and patient's race (p=0.12) were not predictors of AR. Conclusion: Among patients with CVD and LDL-C above guideline recommended levels, only one-third receive AR. Diabetic and hypertensive CVD patients are more likely to receive AR, whereas older Veterans with CVD receive AR less often likely reflecting providers' belief of lack of efficacy from treatment intensification in older CVD patients. Our findings are important for quality improvement and policy making initiatives as they provide more actionable information compared with isolated LDL-C goal attainment as a quality indicator.


2020 ◽  
pp. 204748732090433 ◽  
Author(s):  
Mariann I Lassenius ◽  
Iiro Toppila ◽  
Susanne Bergius ◽  
Julia Perttilä ◽  
KE Juhani Airaksinen ◽  
...  

Aims The study evaluated the quality of cardiovascular prevention in real-world clinical practice. The recurrence of up to five cardiovascular events was assessed, as data on recurrence beyond the first event and interindividual variations in event rates past the second event have been sparse. Low-density lipoprotein cholesterol concentrations and lipid-lowering therapy use were investigated. Methods This retrospective register-based study included adult patients with an incident cardiovascular event between 2004 and 2016 treated in the hospital district of southwest Finland. Patients were followed for consecutive cardiovascular events or cardiovascular death, low-density lipoprotein cholesterol and statin purchases. The timing of event recurrence was evaluated, and predictive factors were assessed. Results A wide interindividual variation in cardiovascular event recurrence was observed, each additional event caused an increased risk, the median time of recurrence decreased from 7 to one year for the second and fifth event. Event rates increased correspondingly from 12 to 43/100 patient-years and were most pronounced in the first years following the previous event. The low-density lipoprotein cholesterol goal (<1.8 mmol/l) was reached by 18% in the year after the event and statin underuse was associated with an increased risk of recurrence. Six months after the index event high intensity statins were used by only 22% of the cohort. Conclusion The study provides new perspectives on individual risk assessment showing that event rates are not stable for all patients but increase 1.2–1.9-fold per consecutive event. The underuse of statins and poor adherence support the identification of these patients for intensified multifactorial preventive measures.


2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S8-S9
Author(s):  
Nicholas E Larkey ◽  
Leslie J Donato ◽  
Allan S Jaffe ◽  
Jeffrey W Meeusen

Abstract Plasma concentrations of low-density-lipoprotein cholesterol (LDL-C) are directly associated with risk for coronary artery disease (CAD). Multisociety guidelines define LDL-C&gt;160mg/dL as a risk factor for CAD and LDL-C&gt;190mg/dL as an indication for lipid lowering medication, regardless of other clinical factors. Subfractionation of LDL according to size (LDL-s) enables differentiation between two LDL phenotypes: large-buoyant LDL and small-dense LDL. The small-dense LDL phenotype reportedly conveys increased risk for CAD. Major societies do not recommend LDL subfractions be used for clinical decision making and most payers do not cover LDL subfraction testing. Despite these restrictions, LDL subfraction is routinely requested by clinicians. Nuclear magnetic resonance (NMR) spectroscopy measures LDL-C and LDL-s. Following inquiries regarding interpretation of conflicting LDL-C and LDL-s results, we investigated associations between LDL-C and LDL-s measured by NMR in order to determine how often they provide contradicting or additive information. Verification of NMR LDL-C accuracy was confirmed by ß-quantification in a subset of patient samples (n=250). The average bias was -4.5mg/dL and the correlation coefficient was 0.92. High-risk was defined as LDL-C&gt;160mg/dL or LDL-s&lt;20.5 nm (small-dense LDL); and low-risk was defined as LDL-C&lt;70mg/dL or LDL-s&gt;20.5nm (large-buoyant LDL). In 26,710 clinical NMR analyses, the median LDL-C was 94.0mg/dL (range:5-436mg/dL) with median LDL-s of 20.8 nm (range:19.4–23.0nm). LDL-s moderately correlated with LDL-C (Ï#129;=0.51;p&lt;0.01). Small-dense-LDL was identified in only 18% (407/2,191) of patients with elevated LDL-C (&gt;160mg/dL) and was more common (73.2% of 6,093) in patients with low LDL-C (&lt;70mg/dL;p&lt;0.001). Associations with CAD were investigated among patients without cholesterol-lowering medication treatment referred for angiography (n=356). CAD (defined as stenosis &gt;50% in one or more coronary artery) was diagnosed in 14% (1/7) of subjects with low LDL-C (&lt;70mg/dL) compared to 59% (47/80) of subjects with elevated LDL-C (p=0.01). When stratifying by LDL-s, CAD was diagnosed in 50% (57/115) of subjects with small-dense LDL compared to 43% (104/241) of subjects with large-buoyant LDL (p=0.2). Small-dense LDL was identified in only 33% (26/80) of cases with elevated LDL-C. Limiting to subjects with elevated LDL-C, CAD was diagnosed in 50% (13/26) of subjects with concordant (high-risk) small-dense LDL compared to 61% (33/54) of subjects with discordant (low-risk) large-buoyant LDL (LDL-s&gt;20.5nm) (p=0.3). Our data confirm that LDL-s subfraction measured by NMR is reported discordantly in most cases when LDL-C is unequivocally high or low. Furthermore, CAD diagnosis was significantly associated with LDL-C, but not with LDL-s. Our data also show that in discrepant samples, elevated LDL-C correlates better with disease state compared to LDL-s. Therefore, LDL-s should not be used to justify treatment decisions in patients with elevated LDL-C. Laboratories should consider carefully whether or not to report LDL-s when it is known that misleading and discordant values will be reported in a majority of cases.


BMJ ◽  
2020 ◽  
pp. m4266
Author(s):  
Camilla Ditlev Lindhardt Johannesen ◽  
Anne Langsted ◽  
Martin Bødtker Mortensen ◽  
Børge Grønne Nordestgaard

Abstract Objective To determine the association between levels of low density lipoprotein cholesterol (LDL-C) and all cause mortality, and the concentration of LDL-C associated with the lowest risk of all cause mortality in the general population. Design Prospective cohort study. Setting Denmark; the Copenhagen General Population Study recruited in 2003-15 with a median follow-up of 9.4 years. Participants Individuals randomly selected from the national Danish Civil Registration System. Main outcome measures Baseline levels of LDL-C associated with risk of mortality were evaluated on a continuous scale (restricted cubic splines) and by a priori defined centile categories with Cox proportional hazards regression models. Main outcome was all cause mortality. Secondary outcomes were cause specific mortality (cardiovascular, cancer, and other mortality). Results Among 108 243 individuals aged 20-100, 11 376 (10.5%) died during the study, at a median age of 81. The association between levels of LDL-C and the risk of all cause mortality was U shaped, with low and high levels associated with an increased risk of all cause mortality. Compared with individuals with concentrations of LDL-C of 3.4-3.9 mmol/L (132-154 mg/dL; 61st-80th centiles), the multivariable adjusted hazard ratio for all cause mortality was 1.25 (95% confidence interval 1.15 to 1.36) for individuals with LDL-C concentrations of less than 1.8 mmol/L (<70 mg/dL; 1st-5th centiles) and 1.15 (1.05 to 1.27) for LDL-C concentrations of more than 4.8 mmol/L (>189 mg/dL; 96th-100th centiles). The concentration of LDL-C associated with the lowest risk of all cause mortality was 3.6 mmol/L (140 mg/dL) in the overall population and in individuals not receiving lipid lowering treatment, compared with 2.3 mmol/L (89 mg/dL) in individuals receiving lipid lowering treatment. Similar results were seen in men and women, across age groups, and for cancer and other mortality, but not for cardiovascular mortality. Any increase in LDL-C levels was associated with an increased risk of myocardial infarction. Conclusions In the general population, low and high levels of LDL-C were associated with an increased risk of all cause mortality, and the lowest risk of all cause mortality was found at an LDL-C concentration of 3.6 mmol/L (140 mg/dL).


2021 ◽  
Author(s):  
xin Su ◽  
Deqiang Zheng ◽  
Meiping Wang ◽  
Yingting Zuo ◽  
Jing Wen ◽  
...  

Abstract BackgroundPrevious studies, in which the data were collected about half a century ago, suggested that elevated low density lipoprotein cholesterol (LDL-C) is not associated with increased risk of cardiovascular disease (CVD) in patients over 70 years old. However, what is the relationship between LDL-C and CVD risk in a contemporary population aged over 70 years has not been well examined in China.MethodsThe China Health and Retirement Longitudinal Study (CHARLS) is an ongoing nationally representative study. In this analysis, participants of CHARLS who did not taking statins and did not have heart disease and stroke at 2011 were include and were followed up to 2018. The outcome of this analysis was occurrence of CVD at follow up, which include heart disease and stroke. Cox regression was used to assess the harmful effect of LDL-C on CVD occurrence. We calculated e-values to quantify the effect of unmeasured confounding on our results.ResultsOf the 9,631 participants, 15.2% (N=1,463) were aged over 70 years and 52.5% (N=5,060) were female. During the 7 years follow-up, 1,437 participants had a first CVD attack. Risk of CVD occurrence increased 8% with each 10 mg/mL elevation in LDL-C in whole participants (adjusted HR, 1.08; 95% CI, 1.06-1.10) and age groups of ≥70 years, 60-69years and <60 years. Similar results were observed in subgroup analyses, in which participants were stratified by sex, hypertension, diabetes and chronic kidney disease. According to the restricted cubic spline, we noted a U-shaped relationship between LDL-C and risk of CVD occurrence in group over 70 years old, however, we further found that in the left side of U-shape curve, LDL-C was not associated with occurrence of CVD and its attribution to CVD occurrence was only 2.1%, which indicated that lower level of LDL-C could not increase the risk of CVD occurrence as it was demonstrated by a U-shape association. E-value analysis suggested robustness to unmeasured confounding.ConclusionsIn contemporary society of China, elevated the level of LDL-C also increased the risk of CVD in participants over 70 years old as in the relatively younger participants. These results should strengthen guideline recommendations for the use of lipid lowering therapies in those elderly.


2021 ◽  
pp. 1-32
Author(s):  
Amirreza Hadaegh ◽  
Samaneh Akbarpour ◽  
Maryam Tohidi ◽  
Niloofar Barzegar ◽  
Somayeh Hosseinpour-Niazi ◽  
...  

Abstract To examine the associations of different lipid measures and related indices with incident hypertension during a median follow-up of 12.89 years. Fasting levels of total cholesterol (TC), triglycerides (TG), high and low density lipoprotein cholesterol (HDL-C and LDL-C, respectively), and related indices (TC/HDL-C and TG/HDL-C) were determined in 7335 Iranian adults (men=3270) free of hypertension, aged 39.0 [standard deviation (SD):13.2] years. Multivariate Cox proportional hazard regression was applied and lipid parameters were considered either as categorical or continuous variables. During follow-up, 2413 (men=11260) participants experienced hypertension. Using the first quartile as reference, significant trends were found between quartiles of TG, HDL-C, TC/HDL-C, and TG/HDL-C in multivariate models; moreover considering these measures as continuous variables, a 1 SD increase in each of these parameters was significantly associated with risk of incident hypertension; the corresponding hazard ratios and confidence intervals were 1.06(1.02-1.10), 0.94(0.89-0.98), 1.04(1.01-1.09), and 1.04(1.01-1.07), respectively. The association between lipid measures and incident hypertension did not change after excluding lipid lowering drug users and those with type 2 diabetes mellitus and were independent of the baseline categories of blood pressure (P for interaction > 0.08). To take into account the nutrition data, a re-analysis on a subgroup (n=1705), showed that a 1-SD increase in TG and TG/HDL-C were associated with incident hypertension, after adjusting for dietary cofounders [1.15(1.08–1.24) and 1.03(1.01–1.04), respectively]. These findings indicate that TG, TG/HDL-C, and TC/HDL-C were independently associated with higher risk while HDL-C was associated with lower risk of incident hypertension.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Connie N Hess ◽  
Christopher P Cannon ◽  
Joshua A Beckman ◽  
Philip Goodney ◽  
Manesh R Patel ◽  
...  

Introduction: Low-density lipoprotein cholesterol (LDL-C) is associated with heightened risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Strategies that lower LDL-C levels reduce this risk. Hypothesis: We hypothesized that real-world PAD patients are overall undertreated with lipid lowering therapies (LLT) but that LLT use and achieved LDL-C are improved in high risk patients with ischemic events. Methods: Patients with PAD in the MarketScan database linked to PROGNOS lab data from January 1, 2014 through December 31, 2018 were examined. Outcomes included use of LLT, defined as high intensity (HI) (high intensity statin, any statin plus ezetimibe, or any use of a PCSK9 inhibitor), low intensity (LI) (any other lipid regimen), or no therapy, and follow up LDL-C level. Goal LDL-C was defined as <70 mg/dl. Results: Among 18,747 PAD patients, 25% were on HI LLT, 43% were on LI LLT, and 32% were on no therapy at baseline (Figure A). The median LDL-C was 91 mg/dl (IQR 70, 118), and 25% of patients were at goal (Figure B). After a median follow up of 18 months, use of HI LLT increased by 4%, the median LDL-C decreased by 5 mg/dl, and an additional 3% of patients were at goal LDL-C. Greater use of HI LLT was observed among patients with a MACE (55%) or MALE (41%) event during follow up compared with patients without an ischemic event (26%) during follow up (Figure C). Follow up LDL-C levels remained above goal for most patients (post-MACE: median LDL-C 77 mg/dl, 42% patients at goal; post-MALE: median LDL-C 80 mg/dl, 36% patients at goal). Conclusions: In PAD patients, use of LLT is suboptimal, and LDL-C levels remain elevated. After an ischemic event, LLT use is intensified, with greater use of HI LLT observed after MACE than MALE. Despite this, LLT remains underutilized, with >50% of patients not at goal LDL-C. Strategies to better implement proven therapies to reduce risk in this high risk population are needed.


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