Low-density lipoprotein cholesterol and mortality in older people

OBJECTIVES: To investigate the role of low-density lipoprotein cholesterol (LDL-C) as a predictor of mortality in elderly subjects. DESIGN: Population-based prospective cohort study. SETTING: Two communities in northern Italy. PARTICIPANTS: Three thousand one hundred twenty Caucasian subjects aged 65 and older recruited in for the Cardiovascular Study in the Elderly and followed up for 12 years. MEASUREMENTS: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL-C, glucose, creatinine, and body mass index. Clinical measures: medical assessment, diabetes mellitus, hypertension, stroke, coronary disease, heart failure, and smoking and drinking habits. Vital status measures: death certificates from the Registry Office and causes of death according to the International Classification of Diseases. After plotting mortality rates using quartiles of LDL-C, relative hazard rates (RHRs) were calculated using multivariate Cox regression analyses. When the trend was nonlinear, the RHRs were further calculated for the 25th, 50th, and 75th percentiles of the distribution to confirm curvilinearity. RESULTS: The distribution of risk of total mortality in women and of fatal heart failure in all subjects was curvilinear (non J-shaped), decreasing nonlinearly with LDL-C. For total mortality in men and cardiovascular mortality in both sexes, the relationship with LDL-C was J-shaped. The risk of fatal myocardial infarction was J-shaped in men, whereas it increased linearly with higher LDL-C in women. In both sexes, the association between stroke mortality and LDL-C was not significant. CONCLUSION: This study adds to the uncertainty of the role of elevated levels of LDL-C as a risk factor for mortality in old people.     

Low-density lipoprotein cholesterol goal attainment among Malaysian dyslipidemic patients

The aim of the present study was to evaluate Malaysian dyslipidemic patient treatment practices and outcomes. Factors contributing to success in reaching treatment goal were determined. A retrospective review of the records of dyslipidemic patients who attended the Universiti Sains Malaysia Hospital in 2007 was conducted. All the patients were receiving standard recommended doses of statins. Records were analysed for 890 patients. Patients were divided into three categories: 384 patients (43.1%) had coronary heart disease or coronary heart disease risk equivalents, 216 patients (24.3%) had moderate risk for coronary heart disease and 290 patients (32.6%) had low risk. Statins were the most commonly prescribed drug group (92%), of which atorvastatin was the most commonly prescribed drug (50.6%). The overall success rate for reaching goal was 64.2%. The percentages of patients achieving low-density lipoprotein cholesterol targets in the coronary heart disease and coronary heart disease risk equivalents, moderate, and low-risk groups were 50.5, 66.7, and 80.3%, respectively (p < 0.001). Multiple logistic regression showed achievement of therapeutic goal declined with increasing risk group. The baseline low-density lipoprotein cholesterol value was inversely related to therapeutic goal attainment. An inadequate proportion of dyslipidemic patients achieved the National Cholesterol Education Program therapeutic goals for low-density lipoprotein cholesterol, especially those in the coronary heart disease and coronary heart disease risk equivalent group. The achievement of this goal was dependent on baseline low-density lipoprotein cholesterol levels.     

Low-density lipoprotein cholesterol in subclinical hypothyroidism.

The significance of subclinical hypothyroidism in regard to ensuing hyperlipidemia remains unclear. Because an unfavorable lipid profile would provide a possible explanation for the reported association of coronary-heart disease with this syndrome, we have evaluated the relationship of thyrotropin (TSH) with total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides in patients with normal thyroid function (n = 4886) as well as subclinical (n = 1055) and manifest (n = 92) hypothyroidism. Serum concentrations of LDL cholesterol were similar in euthyroid persons (134+/-39 mg/dL) and in patients with subclinical hypothyroidism (137+/-40 mg/dL) but were higher (178+/-70 mg/dL, p < 0.01) in overt hypothyroidism. Within the group of subjects with subclinical hypothyroidism there was no apparent relationship between serum concentrations of TSH ranging from 4.0 to 49.0 microU/mL and concentrations of LDL cholesterol. Thus, there is no "threshold value" of TSH in these patients per se necessitating substitution therapy with thyroxine.     

Low-density lipoprotein cholesterol in high-risk asymptomatic individuals

Cardiovascular disease claims more lives each year than the other 4 leading causes of death combined. Current prevention and treatment models focus on low-density lipoprotein cholesterol (LDL-C). In 2001, the National Cholesterol Education Program/Adult Treatment Panel III established new risk categories as well as new LDL-C targets especially for high-risk individuals. Since the implementation of these new guidelines, several relevant clinical trials have been published. The results of these trials suggest that lower LDL-C levels confer a more favorable cardiovascular outcome in high-risk individuals. The idea that low levels of LDL-C are related to a halt in atherosclerosis or even plaque regression has been entertained and investigated. Recent studies conducted exclusively on individuals with known diabetes have provided an important insight on how to appropriately manage diabetic dyslipidemia.     

Low-density lipoprotein cholesterol estimation by a new formula--confirmation

Our result supports the reliability of new Anandaraja's formula for low-density lipoprotein estimation in Brazil population.     

Low-density lipoprotein cholesterol level in patients with acute myocardial infarction having percutaneous coronary intervention (the cholesterol paradox)

The relation between low-density lipoprotein (LDL) cholesterol levels and clinical outcomes after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) has not been described. A total of 9,571 eligible patients (mean age 62.6 ± 12.5 years, 6,967 men) who underwent PCI with a final diagnosis of AMI from the Korea Acute Myocardial Infarction Registry (KAMIR) were divided into 5 groups according to LDL cholesterol level: < 70, 70 to 99, 100 to 129, 130 to 159, and ≥ 160 mg/dl. Clinical outcomes in hospital and 1 and 12 months after PCI in patients with AMI were examined. Age and co-morbidities decreased as LDL cholesterol increased. Patients with higher LDL cholesterol levels had favorable hemodynamic status and laboratory findings. Lifesaving medications, including lipid-lowering drugs, were underused in patients with lower LDL cholesterol levels. Clinical outcomes in hospital and 1 and 12 months after PCI showed better results as LDL cholesterol increased, except for patients with LDL cholesterol levels ≥ 160 mg/dl. In a Cox proportional-hazards model, LDL cholesterol level was not an independent predictor of mortality at 12 months, after adjusting for clinical characteristics including demographics and biologic data. In conclusion, the cholesterol paradox in patients with AMI is related to confounding by baseline characteristics associated with survival. More intensive treatment including lipid-lowering therapy for AMI in patients with lower LDL cholesterol level may result in better clinical outcomes.     

Low-density lipoprotein cholesterol suppresses apoptosis in human multiple myeloma cells

Multiple myeloma (MM) is an incurable disease accompanied by low plasma levels of low-density lipoprotein cholesterol (LDL-c). The significance of altered cholesterol metabolism in the pathophysiology of MM remains elusive. Although it has been hypothesized that myeloma cells depend on exogenous cholesterol for its survival, the role of LDL-c on myeloma cells has not been elucidated. To evaluate the impact of exogenous LDL-c on cell viability, three human myeloma cell lines (RPMI-8226, NCI-H929, and U-266B1) were grown in the presence or absence of lipoproteins. Cell viability was markedly reduced in the absence of lipoproteins in sera. However, exogenous LDL-c improved cell viability. We showed that reduced cell viability was associated with increased levels of cleaved caspase-3, whereas proliferation rate remained unchanged. Interestingly, exogenous LDL-c counteracted apoptosis in human myeloma cell lines and primary cultures of human myeloma cells. Thus, our results demonstrated that LDL-c is an important anti-apoptotic factor for myeloma cells and begin to explain the hypocholesterolemia observed in patients with MM.     

Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio as a useful marker for early-stage carotid atherosclerosis

A higher ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) is associated with a greater risk of cardiovascular events in patients with coronary heart disease. However, the role of this lipid index during early-stage atherosclerosis has not yet been established. This study investigated relationships between LDL-C/HDL-C ratio and carotid plaque score as assessed by ultrasonography in 825 subjects from the general population (527 men, 298 women; mean age, 60.5 years). To identify factors strongly associated with plaque score, stepwise multiple regression analysis was performed using various clinical variables including conventional lipid indices. In both sexes, increased LDL-C/HDL-C ratio was associated with increased plaque score (men: β = 0.132, P = .001; women: β = 0.150, P = .012). This association was maintained in men with normal LDL-C level (<140 mg/dL). The highest quartile of LDL-C/HDL-C ratio (>2.9 in men, >2.6 in women) showed significantly increased plaque score even when adjusted by factors included in the final model of stepwise analysis (P = .007 in men, P = .033 in women). No association was seen between LDL-C and plaque score in the multivariate-adjusted model. These findings indicate that increased LDL-C/HDL-C ratio may also be associated with initiation of atherosclerosis. Assessment of this lipid ratio may thus facilitate early management of atherosclerotic risks better rather than assessment of LDL-C alone.     

Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19

Background and aimsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19).Methods and resultsWe performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th^, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19.A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14–3.31), C-reactive protein >88 mg/dl (HR 2.44; 95% CI, 1.41–4.23) and lymphopenia <1000 (HR 2.68; 95% CI, 1.91–3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up.ConclusionHypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.     

Low-density lipoprotein cholesterol levels in hypercholesterolemic rabbits with or without carbon monoxide poisoning

Low-density lipoproteins isolated by a selective precipitation procedure have been investigated in cholesterol-fed rabbits exposed or not to carbon monoxide. The main findings are a higher increase of their cholesterol content and cholesterol to phospholipid molar ratio without a modification in lecithin-cholesterol-acyltransferase activity in intoxicated animals. Thus, the aggravating effect of carbon monoxide exposure on the atherogenic properties of these lipoproteins could accelerate the development of atherosclerosis in cholesterol-fed rabbits.     

Low-density lipoprotein cholesterol estimation by a new formula in Indian population

BACKGROUND: Estimation of low-density lipoprotein cholesterol is crucial in the management of ischemic heart disease patients. Low-density lipoprotein cholesterol is routinely calculated in laboratories world over by applying Friedewald formula for logistic reasons. We derived a new formula based on multiple regression approach. METHODS: Lipid profiles were done on blood samples of 2008 patients. In initial 1000 patients, low-density lipoprotein cholesterol was estimated by a direct method and also by Friedewald formula. By applying linear regression methods on the data of direct estimation method, a new formula was obtained and the accuracy of this new formula was validated in the next 1008 patients. RESULTS: The mean low-density lipoprotein cholesterol was 116+/-41.5 mg/dl (3.02+/-1.08 mmol/l) measured by direct low-density lipoprotein cholesterol assay and that calculated by Friedewald formula was 119+/-46 mg/dl (3.09+/-1.2 mmol/l) for the initial 1000 patients. Low-density lipoprotein cholesterol measured by direct low-density lipoprotein cholesterol assay and calculated from Friedewald formula showed good correlation (r = 0.88), however, there was minimal overestimation by the Friedewald formula. The correlation improved between direct low-density lipoprotein cholesterol and calculated low-density lipoprotein cholesterol after excluding the patients with triglycerides more than 350 mg/dl (r = 0.92). The mean low-density lipoprotein cholesterol measured by the direct assay and by new formula in the next 1008 patients was 117+/-40 mg/dl (3.04+/-1.04 mmol/l) and 113.7+/-37 mg/dl (2.96+/-0.96 mmol/l), respectively with very good correlation (r = 0.97) between them. CONCLUSIONS: The new formula derived from multiple linear regression analysis appears to be more accurate than Friedewald formula in Indian population.     

Effect of hospitalization on high-density lipoprotein cholesterol in patients undergoing elective coronary angiography

The effects of time of sampling on plasma lipids and lipoprotein cholesterol concentrations were investigated in 88 patients undergoing elective coronary angiography. Patients with a myocardial infarction or major surgery within 6 weeks before catheterization were excluded. All subjects were sampled in the fasting state at the time of arteriotomy before systemic heparinization and at least 30 days after discharge from the hospital (mean 275 days) in the free living state. No statistically significant differences were noted in total cholesterol (220 +/- 51 vs 226 +/- 48 mg/dl), triglycerides (191 +/- 77 vs 191 +/- 113 mg/dl) and calculated low-density lipoprotein cholesterol levels (149 +/- 46 vs 150 +/- 43 mg/dl). High-density lipoprotein cholesterol values were significantly lower (p less than 0.0001) in subjects sampled before catheterization than in the free living state (32 +/- 10 vs 37 +/- 10 mg/dl, mean change 14%). Moreover, the frequency of high-density lipoprotein cholesterol less than 35 mg/dl was 77% before catheterization and 44% in the free living state. This effect was neither due to beta-adrenergic drugs nor to the length of time between samplings. In view of these findings, a screening lipid profile for patients with coronary artery disease should be performed in the free living state.     

Low-density lipoprotein cholesterol reduction: the end is more important than the means

Many epidemiologic studies and clinical trials have demonstrated the linear relation between elevated serum levels of low-density lipoprotein (LDL) cholesterol and the risk for coronary heart disease. Conversely, for each 1% reduction in LDL cholesterol in clinical trials, there is a corresponding 1% reduction in coronary heart disease risk. Although the degree of reduction is more important in affecting risk than the means used to lower LDL, statins are considered the most consistently effective means of lowering LDL. The National Cholesterol Education Program now recommends an optional goal of <70 mg/dl for patients at very high risk for coronary heart disease. In conclusion, on the basis of completed clinical trials, there is no evidence that achieving and maintaining such low levels of LDL cholesterol result in adverse effects. The most potent statins, rosuvastatin and atorvastatin, are capable of getting most patients to their LDL cholesterol goals, but combinations of statins with other drugs may be necessary for patients who require additional lipid lowering.     

Low-density lipoprotein and apolipoprotein B: Clinical use in patients with coronary heart disease

Managing low-density lipoprotein (LDL) is an integral part of clinical practice. What remains controversial is whether we are using the best measure of LDL quantity for this purpose. Historically, the cholesterol content of LDL particles (LDLC) has been used to express LDL quantity. However, because of variability in the cholesterol carried in LDL particles, frequent disagreement occurs between LDLC and particle measures of LDL quantity, including apolipoprotein B-100 (apo B) or nuclear magnetic resonance (NMR) LDL particle number (LDL-P). Studies consistently demonstrate apo B and LDL-P are superior predictors of coronary heart disease (CHD) risk and superior indicators of low CHD risk on lipid-lowering therapy. Recent recommendations advocate that, in addition to LDLC and non-high-density lipoprotein cholesterol, apo B (or NMR LDL-P) be used as a target of therapy. This article reviews the rationale supporting these recommendations and provides a model for integrating LDL particle measures in clinical practice.