scholarly journals Association between low density lipoprotein and all cause and cause specific mortality in Denmark: prospective cohort study

BMJ ◽  
2020 ◽  
pp. m4266
Author(s):  
Camilla Ditlev Lindhardt Johannesen ◽  
Anne Langsted ◽  
Martin Bødtker Mortensen ◽  
Børge Grønne Nordestgaard
Keyword(s):  
Cohort Study ◽  
General Population ◽  
Prospective Cohort ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Specific Mortality

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).

scholarly journals Effects of Weight Gain after 20 Years of Age and Incidence of Hyper-Low-Density Lipoprotein Cholesterolemia: The Iki Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD)

2021 ◽  
Vol 10 (14) ◽  
pp. 3098
Author(s):  
Shota Okutsu ◽  
Yoshifumi Kato ◽  
Shunsuke Funakoshi ◽  
Toshiki Maeda ◽  
Chikara Yoshimura ◽  
...  
Keyword(s):  
Weight Gain ◽  
General Population ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Population Based ◽  
Lipid Lowering ◽  
Low Density ◽  
Obesity Hypertension ◽  
Old Men

The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of Japanese people. Methods: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. Results: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of <10 kg (41.8/1000 person-years). This association remained statistically significant even after adjustment for age, sex, smoking, daily drinking, exercise, obesity, hypertension, and diabetes (multivariable hazard ratio 1.31, 95% confidence interval 1.08–1.58, p = 0.006). Conclusion: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese.

Cardiovascular event rates increase after each recurrence and associate with poor statin adherence

2020 ◽  
pp. 204748732090433 ◽  
Author(s):  
Mariann I Lassenius ◽  
Iiro Toppila ◽  
Susanne Bergius ◽  
Julia Perttilä ◽  
KE Juhani Airaksinen ◽  
...  
Keyword(s):  
Cardiovascular Event ◽  
Cardiovascular Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Increased Risk ◽  
Event Rates

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.

Low-Density Lipoprotein Subfractionation: What Is the Role of the Lab When Reporting Discrepant Results?

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S8-S9
Author(s):  
Nicholas E Larkey ◽  
Leslie J Donato ◽  
Allan S Jaffe ◽  
Jeffrey W Meeusen
Keyword(s):  
Coronary Artery ◽  
High Risk ◽  
Clinical Decision Making ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Risk ◽  
Lipid Lowering ◽  
Low Density ◽  
Small Dense Ldl ◽  
Increased Risk

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.

scholarly journals HDL-C is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response fashion: a pooled analysis of 37 prospective cohort studies

2020 ◽  
Vol 27 (11) ◽  
pp. 1187-1203 ◽  
Author(s):  
Guo-Chao Zhong ◽  
Su-Qun Huang ◽  
Yang Peng ◽  
Lun Wan ◽  
You-Qi-Le Wu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
General Population ◽  
Cohort Studies ◽  
Dose Response ◽  
Prospective Cohort ◽  
Density Lipoprotein ◽  
Prospective Cohort Studies ◽  
Hazard Ratios ◽  
Increased Risk ◽  
All Cause Mortality

Objective The association between high-density lipoprotein cholesterol (HDL-C) levels and mortality remains controversial. We aimed to investigate the potential dose–response associations between HDL-C levels and mortality from all causes, cardiovascular disease and cancer in the general population. Methods PubMed and Embase were searched through April 2019. Prospective cohort studies reporting risk estimates of HDL-C levels and mortality were included. Linear and non-linear dose–response analyses were conducted. A random-effects model was employed to calculate pooled hazard ratio. Results Thirty-seven studies, involving 3,524,505 participants and more than 612,027 deaths, were included. HDL-C level was found to be associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose–response pattern, with the lowest risk observed at HDL-C levels of 54–58 mg/dL, 68–71 mg/dL and 64–68 mg/dL, respectively. Compared with HDL-C level of 56 mg/dL, the pooled hazard ratios for all-cause mortality were 1.03 (95% confidence interval (CI) 1.01, 1.05) and 1.10 (95% CI 1.09, 1.12) for each 10-mg/dL increase and decrease in HDL-C levels, respectively; furthermore, compared with the reference category, the pooled hazard ratios for all-cause mortality were 1.21 (95% CI 1.09, 1.36) and 1.36 (95% CI 1.21, 1.53) for the highest and the lowest categories of HDL-C levels, respectively. Similar results were obtained for cardiovascular and cancer mortality. Conclusions In the general population, HDL-C level is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose–response manner; both extremely high and low HDL-C levels are associated with an increased risk of mortality.

scholarly journals Low Levels of Low-Density Lipoprotein Cholesterol and Mortality Outcomes in Non-Statin Users

2019 ◽  
Vol 8 (10) ◽  
pp. 1571 ◽  
Author(s):  
Sung ◽  
Huh ◽  
Ryu ◽  
Lee ◽  
Scorletti ◽  
...  
Keyword(s):  
Reference Group ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
All Cause Mortality ◽  
Low Levels

We aimed to test the association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD), cancer, and all-cause mortality in non-statin users. A total of 347,971 subjects in Kangbuk Samsung Health Study (KSHS.57.4% men, mean follow up: 5.64 ± 3.27 years) were tested. To validate these associations, we analyzed data from another cohort (Korean genome and epidemiology study, KoGES, 182,943 subjects). All subjects treated with any lipid-lowering therapy and who died during the first 3 years of follow up were excluded. Five groups were defined according to baseline LDL-C concentration (<70, 70–99, 100–129, 130–159, ≥160 mg/dL). A total of 2028 deaths occurred during follow-up in KSHS. The lowest LDL-C group (LDL < 70 mg/dL) had a higher risk of all-cause mortality (HR 1.95, 1.55–2.47), CVD mortality (HR 2.02, 1.11–3.64), and cancer mortality (HR 2.06, 1.46–2.90) compared to the reference group (LDL 120–139 mg/dL). In the validation cohort, 2338 deaths occurred during follow-up. The lowest LDL-C group (LDL < 70 mg/dL) had a higher risk of all-cause mortality (HR 1.81, 1.44–2.28) compared to the reference group. Low levels of LDL-C concentration are strongly and independently associated with increased risk of cancer, CVD, and all-cause mortality. These findings suggest that more attention is needed for subjects with no statin-induced decrease in LDL-C concentrations.

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 ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density ◽  
Hazard Ratios ◽  
Increased Risk ◽  
The Ideal

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.

scholarly journals Low-density Lipoprotein Cholesterol and Risk of Intracerebral Hemorrhage: A Prospective Study, Systematic Review, and Meta-analysis (P18-029-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chaoran Ma ◽  
M Edip Gurol ◽  
Zhe Huang ◽  
Alice Lichtenstein ◽  
Xiuyan Wang ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Hemorrhagic Stroke ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Increased Risk

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

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