Value Of Low-density Lipoprotein Cholesterol Research Articles

Characteristics of plaque progression detected by serial coronary computed tomography angiography

We previously reported that serial coronary computed tomography angiography (CTA) had a potential to evaluate the interval change of plaque morphology of coronary arteries. The aim of this study was to evaluate variables associated with the plaque progression by serial CTA. We included 148 patients (age 66.3 ± 9.8 years, male 81.1 %, median scan interval 12 months) with coronary artery disease undergoing serial CTA. Each coronary artery was compared visually between baseline and follow-up CTA to detect plaque progression. Baseline characteristics between progression and nonprogression patients did not demonstrate any significant differences. Logistic analysis revealed that only low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dl at follow-up was associated with plaque progression (odds ratio 2.59, 95 % confidence interval 1.12-6.34, P = 0.0263). Cutoff value of LDL-C for plaque progression at follow-up was 103.0 mg/dl based on receiver-operator characteristic curves analyses. Of the 36 progressive lesions in 32 patients, plaque composition at baseline included 13 lesions (36.1 %) of noncalcified plaque, 1 lesion (2.8 %) of calcified plaque, 12 lesions (33.3 %) of partially calcified plaque, and the remaining 10 lesions (27.8 %) had no plaque at baseline and revealed de novo plaques at follow-up. There were 9 lesions (25 %) with high-risk plaque (HRP) characteristics at baseline and 18 lesions (50 %) with HRP at follow-up. Plaque progression of coronary arteries by serial CTA was associated with LDL-C ≥100 mg/dl at follow-up regardless of baseline LDL-C level. There was no specific finding to predict plaque progression on the baseline plaque characteristics.

Non-high-density lipoprotein cholesterol vs low-density lipoprotein cholesterol as a risk factor for ischemic stroke: a result from the Kailuan study

Objectives: To compare the predictive value of serum low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol levels for ischemic stroke in the Chinese population.Methods: We performed a four-year cohort study of 95 778 men and women, aged 18–98 years, selected from the Kailuan study (2006–2007). Baseline LDL cholesterol levels were estimated using direct test method. Total cholesterol levels were estimated using endpoint test method. The predictive values of LDL cholesterol and non-HDL cholesterol for ischemic stroke were compared.Results: During the follow-up period, there were 1153 incident cases of ischemic stroke. The hazard ratio (HR) for ischemic stroke in the top quintile of LDL cholesterol was the highest among five quintiles (HR: 1·25; 95% confidence interval (CI), 1·01–1·53). The HR in the top quintile of non-HDL cholesterol for ischemic stroke was also the highest among five quintiles (HR: 1·53; 95% CI, 1·24–1·88). Analysis of trends showed a significant positive relationship between ischemic stroke incidence and serum LDL cholesterol level, and non-HDL cholesterol level, respectively (both P < 0·05). The area under the curve of LDL cholesterol and non-HDL cholesterol for ischemic stroke was 0·51 and 0·56, respectively (P < 0·05 for the difference).Conclusions: Serum Non-HDL cholesterol level is a stronger predictor for the risk of ischemic stroke than serum LDL cholesterol level in the Chinese population.

Evaluation of nitric oxide and superoxide dismutase in different stages of chronic kidney disease

Objective The aim of this work was to evaluate nitric oxide (NO) and superoxide dismutase (SOD) as parameters of oxidative stress in different stages of chronic kidney disease (CKD) and their correlation with the lipid profile. Background CKD is a debilitating disease that leads to many complications, the most common being cardiovascular. Hence, this study was carried out to evaluate the oxidative stress that predisposes to cardiovascular diseases in these patients. Methods This study included 60 patients with CKD. In addition, 12 apparently healthy age-matched and sex-matched individuals were included as a control group. Patients were classified into five groups according to estimated glomerular filtration rate (eGFR) calculated using the CKD-EPI formula. We estimated serum creatinine, urea, lipid profile [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c)], serum NO, and SOD levels. Results There was a progressive increase in the mean value of TC, TG, and LDL-c from group I to group V, whereas HDL-c decreased progressively from group I to group V. There was a highly significant progressive decrease in the mean value of NO and SOD from group I to group V when compared with the controls and on comparison of groups with each other. There was no significant correlation between NO and SOD with other parameters in group I, group II, and group III. However, there was a significant positive correlation between NO and SOD with eGFR, HDL-c and a significant negative correlation between NO and SOD with urea, creatinine, TC, TG, and LDL-c in group IV and group V. Conclusion This study suggests that the progressive decline in kidney function could lead to decreased antioxidants levels along with disturbance in the lipid profile.

Effect of HMGCR Variant Alleles on Low‐Density Lipoprotein Cholesterol—Lowering Response to Atorvastatin in Healthy Korean Subjects

The investigators quantified the relationship between the genetic polymorphism of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) and the low-density lipoprotein cholesterol (LDL-C)-lowering effects of atorvastatin in a prospective clinical study. Twenty-four healthy participants were grouped into HMGCR rs3846662 GG (n = 13) and AA (n = 11) genotypes and given atorvastatin (20 mg/d) for 14 days. Serum levels of LDL-C, high-density lipoprotein cholesterol, total cholesterol, triglycerides, and creatinine kinase (CK) were measured before (day 1) and 7, 13, 14, 15, 16, 21, and 28 days after dosing initiation. Blood samples for pharmacokinetics were taken on days 14 through 16. The levels of LDL-C in the GG group were significantly higher than in the AA group at all observation times, with mean differences of 18% to 33% (P < .05). The area under the LDL-C-time curve and the minimum value of LDL-C in the GG group were 24% and 23% higher than in the AA group, respectively (P < .01). There was no significant difference in other lipids, CK, and pharmacokinetic parameters. The HMGCR rs3846662 GG genotype was quantitatively documented to be a significant determinant for higher LDL-C level in basal state and possibly in response to atorvastatin.

Low Density Lipoprotein Cholesterol Target Goal Attainment Rate in Korean Patients with Diabetes

Hypertension, dyslipidemia, and smoking are all factors that increase the risk of cardiovascular disease in patients with type 2 diabetes [1]. Among them, one of the most important risk factors is dyslipidemia. Among lipoproteins, low density lipoprotein cholesterol (LDL-C) level is the most important predicting factors for cardiovascular disease, and many large-scale studies have been ongoing for many years to determine the target value for LDL-C treatment [2]. Since the risk of cardiovascular disease in type 2 diabetes patients is higher than that in healthy, the target LDL-C value in diabetes patients has been emphasized as being even more important than other metrics [3]. When the recommended LDL-C treatment goals of the 2003 Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program (NCEP) and the 2008 American Diabetes Association (ADA) released consensus with the American College of Cardiology (ACC) [4] and the dyslipidemia treatment goal guidelines in accordance with the 2011 European Society of Cardiology (ESC) and the European Society of Arteriosclerosis (ESA) were examined, recent trends generally call for more aggressive LDL-C reduction than what has been seen in previous guidelines particularly in the patient group with the highest risk, where an LDL-C target value less than 70 mg/dL is encouraged [5]. Based on the ESC and the ESA guidelines, cardiovascular disease, severe chronic kidney disease, and target organ damage are all included in the highest risk factors for the diabetes group. Even when diabetes is the only risk factor, the target value for LDL-C is recommended to be less than 70 mg/dL [5]. The LDL-C treatment target values have gradually been getting more aggressive all over the world. Although the changes in these values are aggressive, there is no set guideline for LDL-C treatment target values in Koreans, specifically Koreans who have diabetes. There are also very few studies that show the actual level of success of dyslipidemia treatment according to this guideline or how effectively the treatment target value is achieved (achievement rate). Hwang et al. [6] performed a study on diabetes patients over 18 years of age who were receiving treatment for hyperlipidemia. Research was conducted on the difference between the achievement rate of actual treatment target value of LDL-C and recognition rate of target values by medical personnel (expected achievement rate). Among the patients who had received treatment, 35.9% (approximately 1/3 of the total participants) reached the actual LDL-C target value, while that the expected achievement rate was reported in 70.6% of the total participants. In addition, even when lipid levels did not reach the target value, 65.3% of patients were receiving the same statin dosage as when the treatment was started. The authors felt that these results were due to a lack of recognition of the target lipid values by the medical personnel. So, in order to decrease the risk of cardiovascular disease in Korean diabetes patients and in order for LDL-C treatment goals to be reached, they proposed that the recognition standards of the medical personnel be changed [6]. A limitation to this study is that they did not consider whether participants performed any sort of diet or exercise, and drug compliance was also not considered. In actual clinical practice, it could easily be seen that lipid levels did not reach the target values, and clinicians were able to provide adequate care. In particular, in diabetes patients at relatively high risk for cardiovascular disease, statin dosage is increased, being able to reach the target value is the most feasible basis. In the future, even when patients receive treatment, prospective studies regarding the difficulty to reach the lipid target value (due to the low success rate) are required. In addition, during dyslipidemia treatment, statin drug therapy is not the only treatment method used; diet management and exercise are often combined with the treatment process. Additional studies on other positive effects, the need for education, and effectiveness of these treatments will be very helpful in the treatment of dyslipidemia.

Treatment with HELP‐apheresis in patients suffering from sudden sensorineural hearing loss: A prospective, randomized, controlled study

This study's aim was to verify whether, in patients affected by sudden sensorineural hearing loss (SSHL) with high plasmatic levels of low-density-lipoprotein (LDL) cholesterol and/or fibrinogen, the therapeutic approach with a single selective plasmapheresis (HELP-apheresis) followed by 10 days of standard treatment (glycerol and dexamethazone) is more effective than 10 days of standard treatment. Randomized, superiority study (difference >or=30%). One hundred thirty-two patients were admitted to the trial and randomly allocated to two different arms; 60 were given standard treatment and 72 were treated with HELP-apheresis plus standard treatment. Patients showed a value of LDL cholesterol >120 mg/dL and/or fibrinogen >320 mg/dL. In the HELP-apheresis plus standard therapy group, we observed a hearing recovery in 75% of the patients 24 hours after treatment and in 76.4% of the patients 10 days after treatment. Only 25% of the patients after 24 hours and 23.6% of the patients after 10 days showed no change. In the standard therapy group, the percentage of patients with hearing recovery was 41.7% after 24 hours and 45% after 10 days, whereas 58.3% after 24 hours and 55% after 10 days had no change. The analysis enabled us to consider HELP-apheresis as the element that makes a difference in hearing recovery. In a specific group of patients, with alterations in cholesterol and/or fibrinogen, the HELP-apheresis treatment is a further option available in SSHL therapy.

Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol and the incidence of cardiovascular disease in an urban Japanese cohort study: The Suita study

Objective Only a small number of population-based cohort studies have directly compared the predictive value of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDLC) for coronary artery disease in Asian populations, such as Japan. Methods We performed an 11.9-year cohort study of 4694 men and women, aged 30–74 years, selected randomly from an urban general population in Japan. Baseline LDL-C levels were estimated using the Friedewald formula. The predictive values of LDL-C and non-HDLC for myocardial infarction (MI) and stroke were compared. Results and conclusion During the follow-up period, there were 80 incident cases of MI and 139 of stoke, comprised of 23 intracerebral hemorrhages, 85 cerebral infarctions and 31 other types of stroke. The Hazard ratio (HR) for MI was highest in the top quintile of LDL-C (HR: 3.03, 95% CI, 1.32–6.96) when male and female data were combined. The HR for MI was also highest in the top quintile of non-HDLC (HR: 2.97, 95% CI, 1.26–6.97). Analysis of trends showed a significant positive relationship between MI incidence and serum LDL-C and non-HDLC levels (both P = 0.02). However, there was no relationship between the incidence of any subtype of stroke and either LDL-C or non-HDLC. The predictive value of LDL-C and non-HDLC for MI, assessed by calculating the differences in the −2 logarithm likelihood (−2 ln [L]) and area under the curve (AUC), were almost similar.

Achieving Vascular Risk Factor Targets: A Survey of a London General Practice

We assessed lipid goal achievement in patients at high risk for vascular events from a general practice (London, United Kingdom). Patients were identified as those with a prescription for hypolipidaemic medication, a significant (>20%) Framingham risk, and from the myocardial infarction register. Two hundred forty-five patients were currently taking a statin (average dose, 23.1 mg/day). Cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides changed significantly following statin treatment. Of 285 patients who had taken statins at some time point, 11 (3.9%) were intolerant, 5 of which subsequently tolerated another statin. Approximately 10.1% of patients discontinued statin treatment for unclear reasons. Only 64 patients (29.1% of 220) reached the Joint British Societies' Guidelines on Prevention of Cardiovascular Disease target of a total cholesterol of <4.0 mmol/L; 50 patients (38.8% of 129) reached the low-density lipoprotein-cholesterol target of <2.0 mmol/L. This value of low-density lipoprotein-cholesterol is similar to that recommended by the American Heart Association/American College of Cardiology. With regard to the General Medical Services guidelines target for total cholesterol, 162 (73.6% of 220) patients reached <or=5.0 mmol/L. The group that best achieved target cholesterol (Joint British Societies' Guidelines and General Medical Services) were those with comorbidities. In conclusion, while reaching General Medical Services targets was satisfactory, the percentage of patients reaching Joint British Societies' Guidelines targets was not. This discrepancy may reflect the presence of multiple guidelines. The current stricter lipid targets are difficult to achieve; possible methods that may be used to improve lipids further could involve using combination therapy, statin dose titration, and better education.

The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer

Coronary artery calcification is more prevalent in dialysis patients than in patients without kidney disease and this is associated with high serum phosphorus. In this study, we evaluate the effect of calcium carbonate or sevelamer treatments on the progression of calcification in 90 predialysis patients. Inclusion criteria were stable serum calcium, phosphorus, parathyroid hormone, and a similar baseline total calcium score (TCS). These patients were not treated by phosphate binder, vitamin D, or statin. They were given low-phosphorus diets without or with daily calcium carbonate or sevelamer throughout the study that averaged 2 years. Baseline demographic or clinical characteristics along with biochemical parameters were not different among the three groups. The TCS significantly increased in patients on the low-phosphorus diet alone, to a lesser extent in calcium carbonate-treated patients, and not at all in sevelamer-treated patients. The progression of coronary calcification paralleled that of the calcium score. Our study shows that sevelamer treatment should not be restricted to dialysis patients; however, a larger study should be undertaken to confirm these results.

Usefulness of Follow-Up Low-Density Lipoprotein Cholesterol Level as an Independent Predictor of Changes of Coronary Atherosclerotic Plaque Size as Determined by Intravascular Ultrasound Analysis After Statin ( Atorvastatin or Simvastatin) Therapy

Using serial intravascular ultrasound (IVUS), we identified independent predictors of changes in coronary plaque size in relation to serum lipid levels. One hundred three patients with nonstenotic coronary plaques underwent baseline and 12-month follow-up IVUS studies; 54 patients (52%) were treated with statins. Standard IVUS analyses were performed. Baseline IVUS study showed no statistical differences in mean external elastic membrane, lumen, and plaque/media (P&M) area between statin-treated and nonstatin-treated patients. Although there was an increase in mean P&M cross-sectional area in nonstatin-treated patients, mean P&M cross-sectional area decreased in statin-treated patients (0.11 +/- 0.24 vs -0.20 +/- 0.30 mm(2), p <0.001). There was a positive relation between changes in mean P&M area and follow-up low-density lipoprotein (LDL) cholesterol level (r = 0.430, p <0.001), follow-up total cholesterol level (r = 0.365, p <0.001), changes in LDL cholesterol level (r = 0.312, p = 0.002), and changes in total cholesterol level (r = 0.252, p = 0.012). In multivariate linear regression analysis, the only independent predictor of changes in mean P&M area was follow-up LDL cholesterol level (r = 0.469, p <0.001, 95% confidence interval 0.003 to 0.006). The cut-off value of follow-up LDL cholesterol for no change or a decrease in mean P&M area was <100 mg/dl at regression analysis. In conclusion, the present 12-month follow-up IVUS study showed that follow-up LDL cholesterol level was the only independent predictor of changes in coronary plaque size. When patients achieved a follow-up LDL cholesterol level <100 mg/dl, regression or no progression of coronary plaque was expected. Aggressive lipid-lowering treatments with statins to decrease the follow-up LDL cholesterol level to <100 mg/dl are recommended.

Diagnostic, clinical, and therapeutic aspects of familial hypercholesterolemia in children.

The clinical diagnosis of familial hypercholesterolemia (FH) in children is based on family history and laboratory findings. The best available value of low-density lipoprotein cholesterol (LDL-C) for the diagnosis of FH in children is >3.50 mmol/L (>135 mg/dL) when FH runs in the family. Levels below this concentration were only found in 4.3% of children that had a mutation in the LDL-receptor gene. In contrast, children with LDL-C equal to or above 3.50 mmol/L had 0.98 posttest probability of FH. Untreated FH carries a substantial burden of morbidity and mortality if left untreated or if inadequately treated. The guidelines of the American National Cholesterol Education Program suggested that drug treatment should be considered from the age of 10 years if LDL-C levels are greater than or equal to 4.9 mmol/L (190 mg/dL) or greater than or equal to 4.1 mmol/L (158 mg/dL) in the presence of other cardiovascular risk factors, including a positive family history of premature cardiovascular disease. Impaired flow mediated dilatation was more pronounced in FH children with a positive family history of premature cardiovascular disease. The currently prescribed diet is sometimes considered to be monotonous and can lead to problems with compliance. A reduction of the total intake fat and saturated fatty acids is important. Plant sterolesters should be evaluated in young FH children and can supplement drug and diet therapy, with an additional reduction of 10 to 15% of LDL-C. The use of resins leads to poor compliance, and statins are recommended for FH children and adolescents when drug treatment is indicated. Pravastatin, simvastatin, and atorvastatin decrease LDL-C 30 to 40% without serious adverse events and have a high degree of compliance.

Association of cholesterol levels and occurrence of angiographically detectable endothelial disruption during coronary angioplasty.

Disruption of the atherosclerotic plaque is a common feature of both acute coronary syndromes and balloon dilatation of coronary artery stenoses. The study was undertaken to evaluate whether the known association of cholesterol levels and acute coronary syndromes also exists for the occurrence of angiographically detectable endothelial disruption (ED) following coronary angioplasty. For this purpose, we examined 79 consecutive patients (men/women 58/21; mean age: 62 +/- 11 years), with a noncalcified, de novo, significant stenosis in a single native coronary artery, undergoing elective coronary intervention because of stable effort angina. Coronary angioplasty was performed using regular balloon catheters, aiming for a balloon/ artery ratio of 1, with stent implantation allowed only provisionally. Following balloon dilatation, patients were divided into two groups according to the presence or absence of angiographically detectable ED. Endothelial disruption occurred in 28 patients (35%). The two groups with and without ED were comparable with respect to clinical, angiographic, and procedural parameters. A history of hypercholesterolemia was significantly more frequent in patients with ED (93 vs. 2%; p < 0.001). Total and low-density lipoprotein (LDL) cholesterol levels were significantly higher in the group with ED (230.1 +/- 46.5 vs. 204.4 +/- 30.2 mg/dl, p < 0.05; and 150.6 +/- 39.2 vs. 125.8 +/- 26 mg/dl, p < 0.03, respectively). A cut-off value of LDL cholesterol > or = 135 mg/dl identified patients at higher risk of developing ED. High cholesterol levels appear to favor the occurrence of ED during coronary angioplasty. Aggressive lipid-lowering therapy and a more careful procedural approach may be warranted in patients with hypercholesterolemia undergoing coronary interventions in order to decrease the occurrence of ED and the associated clinical (acute ischemia) and procedural (stent implantation) consequences.