Failure to achieve recommended LDL cholesterol levels by suboptimal statin therapy relates to elevated cardiac event rates

OBJECTIVES: The majority of patients with myocardial infarction (MI) and hypercholesterolaemia does not achieve guideline recommended low-density lipoprotein cholesterol (LDL) levels. Suboptimal dosages of statins explain this dilemma in most patients. DESIGN AND SETTING: We evaluated the relationship between statin treatment quality (optimal: LDL<115 mg/dl, suboptimal: LDL>/=115 mg/dl, no statin therapy despite hypercholesterolaemia) and the subsequent incidence of coronary events (coronary death, nonfatal MI, bypass surgery) over a 30 months follow-up in a large cohort of post MI patients with hypercholesterolaemia (n=2045). Analysis was performed in a nested case-control manner comparing 173 cases with a coronary event and 346 matched controls. RESULTS: Patients who developed a coronary event were treated optimally in 11.0%, suboptimally in 43.4% (p<0.05 vs. optimal treatment) and were untreated in 45.7% (p<0.001 vs. optimal treatment). Respective numbers in event-free patients were 21.4%, 47.7%, and 30.9%. After adjustment for most potential confounders, including all cardiovascular risk factors and medication, the relative risk of future non-fatal MI and coronary death associated with a suboptimal statin treatment was 2.02 (95% CI 1.04 to 4.18) compared to optimal statin treatment. Moreover, the statin equivalent dose in optimally treated individuals was significantly higher than in suboptimally treated individuals (0.85+/-0.03 vs. 0.78+/-0.02, p<0.05). CONCLUSION: In this community-based study, a lipid lowering therapy with statins into the recommended target range of LDL levels may be associated with decreased cardiovascular risk compared to a statin therapy without titrating the LDL level below 115 mg/dl. Thus, the quality of statin treatment was identified as an independent predictor of coronary events in post MI patients.     

Marked low-density lipoprotein cholesterol reduction below current national cholesterol education program targets provides the greatest reduction in carotid atherosclerosis

BACKGROUND: Current National Cholesterol Education Program (NCEP) guidelines recognize low-density lipoprotein cholesterol (LDL-C) below 100 mg/dl as an optimal level. Evidence supporting this is scant. Both LDL-C and C reactive protein (CRP) are known correlates of atherosclerosis progression. HYPOTHESIS: We examined the effect of final LDL-C and CRP obtained with statin therapy on carotid intima-media thickness (CIMT), a valid surrogate for clinical benefit of lipid-lowering therapies. METHODS: In a randomized, single-center trial, 161 patients were assigned to statin therapy of different potencies (pravastatin 40 mg, n = 82; atorvastatin 80 mg, n = 79). The effects on CIMT were assessed in relationship to LDL-C and CRP levels obtained after 12 months of therapy. RESULTS: Changes in CIMT were directly related to the final LDL-C level obtained on statin therapy after 12 months (R = 0.219, p = 0.015). Carotid intima-media thickness regression was seen in 61% of the subjects in the lowest quartile of final LDL-C (< 70 mg/dl) versus 29% of the subjects with the highest quartile of final LDL-C (> or = 114 mg/dl, p = 0.008). No threshold value was seen, with more favorable effects on absolute change in CIMT with lower values of LDL-C (decrease in CIMT of 0.06 +/- 0.17 mm in the lowest quartile compared with an increase of 0.06 +/- 0.09 in the highest quartile of LDL-C, p = 0.008). On-treatment LDL and CRP concentrations both below the group median values were associated with the greatest likelihood of CIMT regression. CONCLUSIONS: Regression of carotid atherosclerosis is directly related to the absolute LDL-C level on statin therapy. The greatest regression was obtained with an LDL-C < 70 mg/dl, supporting marked LDL-C reduction to levels below current NCEP guidelines.     

Usefulness of lowering low-density lipoprotein cholesterol to <70 mg/dl and usefulness of C-reactive protein in patient selection

C-reactive protein levels may identify patients likely to benefit from lowering low-density lipoprotein (LDL) cholesterol to ultra-low levels. We find that above-average C-reactive protein with statin therapy predicts failure of carotid intima-media thickness regression in those with currently defined optimal LDL cholesterol (<100 mg/dl) but not if LDL cholesterol is <70 mg/dl.     

C-reactive protein and risk of cardiovascular disease: Evidence and clinical application

Prospective epidemiologic data consistently show that elevated C-reactive protein (CRP) levels are associated with an increased risk of subsequent cardiovascular events in apparently healthy populations, and accumulating laboratory research is uncovering possible mechanisms by which CRP may influence the development of atherothrombotic disease. CRP is a stronger predictor of cardiovascular disease than is low-density lipoprotein (LDL) cholesterol. CRP adds prognostic information at all levels of the calculated Framingham risk score and at all levels of severity of the metabolic syndrome. Commercially available high-sensitivity assays suitable for use in clinical settings allow for the routine assessment of CRP as a useful adjunct in cardiovascular risk screening. When such assays are used, CRP levels of less than 1, 1 to 3, and greater than 3 mg/L differentiate patients at low, moderate, and high risk, respectively, for future cardiovascular events. Persons with high CRP but normal LDL cholesterol comprise a high-risk group frequently overlooked in clinical practice. Knowledge of their high-risk status may improve these patients’ compliance with recommended lifestyle changes that are likely to improve prognosis. Preliminary data suggest that individuals with elevated CRP but low LDL cholesterol may benefit from pharmacologic interventions, including statin therapy. Large-scale trials are underway to assess the net efficacy and public health impact of this approach to the primary prevention of myocardial infarction and stroke.     

Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles

Given that combination therapy with statin plus fibrate confers a risk of myopathy, it is worthwhile to determine whether statin or fibrate monotherapy is associated with greater clinical benefit in individuals with combined hyperlipidemia. In this randomized double-blind study, we compared the efficacy of simvastatin and fenofibrate on indexes of endothelial function (flow-mediated dilation (FMD) of the brachial artery) and inflammatory markers (plasma high-sensitivity C-reactive protein (CRP), interleukin-1β (IL-1β), soluble CD40, and soluble CD40 ligand (sCD40L) levels), as surrogate indicators of future coronary heart disease (CHD), in patients with combined hyperlipidemia. A total of 70 patients with plasma triglyceride levels between 200 and 500 mg/dl and total cholesterol levels of >200 mg/dl were randomly assigned to receive either simvastatin (20 mg/day) (n=35) or micronized fenofibrate (200 mg/day) (n=35) for 8 weeks. Treatment with simvastatin was associated with significantly greater reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), while the decrease in triglycerides was significantly greater in patients receiving fenofibrate. Both fenofibrate and simvastatin markedly reduced plasma levels of high-sensitivity CRP, IL-1β, and sCD40L, and improved endothelium-dependent FMD without mutual differences. The changes in plasma inflammatory markers did not correlate with baseline clinical characteristics in both groups. However, the improvement in FMD with fenofibrate treatment correlated inversely with baseline high-density lipoprotein cholesterol (HDL-C) levels, whereas the improvement in FMD with simvastatin treatment was positively related to HDL-C levels. Accordingly, in the subgroup with a baseline HDL-C of ≤40 mg/dl, only fenofibrate significantly improved the endothelium-dependent FMD. On the other hand, in the subgroup with HDL-C >40 mg/dl, only treatment with simvastatin achieved significant improvement in FMD. The data here indicate that in patients with combined hyperlipidemia, both fenofibrate and simvastatin have comparative beneficial effects on various inflammatory markers and differential beneficial effects on endothelial function according to baseline HDL-C levels. These findings should be validated by additional prospective studies, in which patients are stratified by baseline HDL-C prior to randomization.     

Baseline characteristics of participants in the JUPITER trial, a randomized placebo-controlled primary prevention trial of statin therapy among individuals with low low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein

The Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) is a randomized, double-blind, placebo-controlled primary prevention trial of statin therapy among persons with average to low levels of low-density lipoprotein (LDL) cholesterol who are at increased cardiovascular risk due to elevated plasma concentrations of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP). A total of 17,802 persons with LDL cholesterol<130 mg/dl (3.36 mmol/L) and hs-CRP>or=2 mg/L were recruited from 26 countries and randomly allocated to 20 mg/day rosuvastatin or placebo. In contrast to previous studies of statin therapy in primary prevention, JUPITER is evaluating a group with modest plasma concentrations of LDL cholesterol (median 108 mg/dl, interquartile range 94 to 119). Further, the trial includes 6,801 women (38.2%) and 5,577 participants with metabolic syndrome (32.1%). Thus, in addition to broadening our understanding of statin therapy and inflammation, the JUPITER trial will provide important and clinically relevant information on primary prevention among patients who do not currently qualify for lipid-lowering therapy. In conclusion, as 20 mg of rosuvastatin can reduce LDL cholesterol by up to 50%, JUPITER will also provide crucial safety data for several thousand patients who should achieve LDL cholesterol levels<50 mg/dl on a long-term basis.     

Lipid management with statins. The lower the better?

The primary and not yet accomplished goal remains to treat all patients with coronary heart disease to the LDL cholesterol target < 100 mg/dl. To date there is no conclusive evidence for a recommendation of a LDL cholesterol goal lower than 100 mg/dl for all patients. Patients with high vascular risk benefit from statin therapy irrespective of cholesterol levels, underlining the importance of the assessment of global vascular risk as the basis of modern lipid therapy.     

Effects of simvastatin on C-reactive protein in mixed hyperlipidemic and hypertriglyceridemic patients

This study examined the effects of simvastatin on C-reactive protein (CRP) and other inflammatory markers in study subjects with significant elevations in triglyceride (TG) blood levels. CRP, vascular cellular adhesion molecule (VCAM), serum amyloid A (SAA), and interleukin 6 (IL-6) were measured in archived plasma samples from 2 multicenter, randomized, double-blind, placebo-controlled studies designed to examine the lipid-altering efficacy of simvastatin in study subjects with elevated TGs. In the first study, 130 study subjects with mixed hyperlipidemia (low-density lipoprotein [LDL] cholesterol > or =130 mg/dl; TGs 300 to 700 mg/dl) received placebo or simvastatin 40 or 80 mg once daily for three 6-week periods in a complete-block crossover design. In the second study, 195 study subjects with hypertriglyceridemia (TGs 300 to 900 mg/dl) received daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks. Significant but weak correlations were observed between baseline CRP values and baseline levels of LDL cholesterol and high-density lipoprotein (HDL) cholesterol, but not with TGs. CRP was also correlated with body mass index and fasting levels of glucose and insulin. Treatment with simvastatin 20, 40, and 80 mg led to significant reductions in CRP plasma levels versus placebo (p <0.05). Although CRP change was weakly correlated with changes in LDL cholesterol, TGs, and HDL cholesterol, results of regression analyses showed that only baseline CRP and treatment allocation were significant predictors of CRP response after 6 weeks of study drug administration. Simvastatin had no effect on VCAM, SAA, or IL-6. In summary, simvastatin significantly reduced CRP in patients with mixed hyperlipidemia and hypertriglyceridemia.     

Statin therapy, lipid levels, C-reactive protein and the survival of patients with angiographically severe coronary artery disease

OBJECTIVES: The joint predictive value of lipid and C-reactive protein (CRP) levels, as well as a possible interaction between statin therapy and CRP, were evaluated for survival after angiographic diagnosis of coronary artery disease (CAD). BACKGROUND: Hyperlipidemia increases risk of CAD and myocardial infarction. For first myocardial infarction, the combination of lipid and CRP levels may be prognostically more powerful. Although lipid levels are often measured at angiography to guide therapy, their prognostic value is unclear. METHODS: Blood samples were collected from a prospective cohort of 985 patients diagnosed angiographically with severe CAD (stenosis > or =70%) and tested for total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and CRP levels. Key risk factors, including initiation of statin therapy, were recorded, and subjects were followed for an average of 3.0 years (range: 1.8 to 4.3 years) to assess survival. RESULTS: Mortality was confirmed for 109 subjects (11%). In multiple variable Cox regression, levels of TC, LDL, HDL and the TC:HDL ratio did not predict survival, but statin therapy was protective (adjusted hazard ratio [HR] = 0.49, p = 0.04). C-reactive protein levels, age, left ventricular ejection fraction and diabetes were also independently predictive. Statins primarily benefited subjects with elevated CRP by eliminating the increased mortality across increasing CRP tertiles (statins: HR = 0.97 per tertile, p-trend = 0.94; no statins: HR = 1.8 per tertile, p-trend < 0.0001). CONCLUSIONS: Lipid levels drawn at angiography were not predictive of survival in this population, but initiation of statin therapy was associated with improved survival regardless of the lipid levels. The benefit of statin therapy occurred primarily in patients with elevated CRP.     

Elevated preprocedural high-sensitivity C-reactive protein levels are associated with neointimal hyperplasia and restenosis development after successful coronary artery stenting.

BACKGROUND: Recent data indicate that an elevated serum level of high-sensitivity C-reactive protein (hs-CRP) predicts the risk of recurrent coronary events, and that statin therapy decreases the risk of coronary events. This study assessed the relationship between the pre-procedural hs-CRP level and in-stent neointimal hyperplasia (NIH) after stenting and the effects of statins on the relationship between restenosis after stenting and the serum hs-CRP levels of patients with coronary artery disease. METHODS AND RESULTS: This study included 100 patients who underwent stent implantation for angiographically significant stenosis. Patients were divided into a normal C-reactive protein (CRP) group (<0.5 mg/dl, n=59) and elevated CRP group (>or=0.5 mg/dl, n=41). All patients underwent angiographic and intravascular ultrasound follow-up at 6 months. The baseline CRP level was 0.29+/-0.08 mg/dl in the normal CRP group and 2.90+/-2.31 mg/dl in the elevated CRP group. The NIH cross-sectional area (CSA) in the minimal lumen CSA at follow-up was significantly larger in the elevated CRP group compared with the normal CRP group (1.9+/-1.3 mm2 vs 3.0+/-1.5 mm2, p=0.001). A significant positive correlation was found between pre-interventional CRP level and NIH area (r=0.52, p<0.001). In patients with normal CRP, an association between statin therapy and restenosis was not observed. However, when the analysis was confined to patients with elevated CRP, statin therapy significantly reduced the restenosis rate (20% vs 37.5%, p=0.031). In the normal CRP group, the intra-stent neointimal area at 6 months was not different between the non-statin and statin groups (2.2+/-1.4 mm2 vs 1.8+/-1.1 mm2). However, in the elevated CRP group, statin therapy significantly decreased the neointimal area at 6-month follow-up (3.6+/-1.7 mm2 vs 2.4+/-1.3 mm2, p<0.001). CONCLUSION: Measuring the pre-interventional hs-CRP level may help predict the development of restenosis after stenting and statin therapy will significantly reduce the restenosis rate in patients with an elevated hs-CRP.     

To statin or to non-statin in coronary disease--considering absolute risk is the answer

The newest guidelines for treating people with coronary artery disease (CAD) suggest benefit from statin-induced LDL cholesterol lowering regardless of baseline LDL cholesterol level. These guidelines were based on recent clinical trials that showed statistically significant statin-induced relative risk reductions (RRR) in cardiovascular events. However, there are proven "non-statin" anti-atherosclerotic treatments. This analysis was designed to allow the physician to decide which patients benefit from the various anti-atherosclerotic treatments available. Analysis is presented as absolute risk reduction (ARR) because ARR takes baseline risk into account. There was a large benefit from statin therapy in stable CAD when LDL cholesterol levels were high. There were diminishing returns, despite statistically significance, with statin treatment of people with chronic CAD and lower LDL cholesterol levels. People with chronic CAD and lower LDL cholesterol levels had at least as much and possibly twice the ARR when treated with niacin or gemfibrozil as that would occur with statin treatment. For the first year after the acute coronary syndrome, risk was higher than in stable CAD, and trials showed a benefit especially with a Mediterranean diet and also with statin therapy that reduced LDL cholesterol levels to approximately 80 mg dl(-1). The Mediterranean diet was also beneficial in chronic CAD. These results suggest that both statin and non-statin therapy are important for reducing the sequelae of atherosclerosis.     

Atorvastatin monotherapy vs. combination therapy in the management of patients with combined hyperlipidemia

BACKGROUND: Mixed hyperlipidemia is a common disorder characterized by elevated VLDL and LDL levels. Patients with this syndrome usually are in need of combination therapy, comprising a fibric acid derivate with a statin drug in order to achieve LDL and triglyceride target values. Atorvastatin is a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor demonstrated to be effective in reducing both cholesterol (CHOL) and triglyceride (TG) levels in humans. We examined the efficacy of atorvastatin as monotherapy in achieving a better or the same lipid profile in patients with mixed hyperlipidemia treated with combination therapy. DESIGN: We compared atorvastatin with a combination of a fibric acid derivate and a statin drug (other than atorvastatin) in a 24-week, prospective randomized, open-label study of 27 patients with mixed hyperlipidemia. METHODS: All 27 patients had been treated with statin-fibrate therapy in different regimens for at least a year. Atorvastatin at a daily dose of 20 mg was substituted for statin-fibrate therapy. Lipid and safety profiles were assessed. RESULTS: Atorvastatin significantly reduced total cholesterol, LDL-C, and HDL-C compared to statin-fibrate therapy. In contrast, TG and glucose levels were significantly elevated with atorvastatin. Target LDL-C and TG was achieved in 10 patients with the single therapy of atorvastatin vs. 6 patients under statin-fibrate. In 16 patients, atorvastatin was at least as effective as, or better than, the combination therapy, and was recommended for continuation of treatment. CONCLUSION: Atorvastatin is an adequate monotherapy for many mixed hyperlipidemia patients. We recommend atorvastatin be considered for every patient suffering from mixed hyperlipidemia.     

Rapid effects of simvastatin on lipid profile and C-reactive protein in patients with hypercholesterolemia

BACKGROUND: Rapid lowering of low-density lipoprotein (LDL) cholesterol levels as well as C-reactive protein (CRP) by administration of drugs may produce early benefit to the coronary endothelium in patients with coronary heart disease and reduce angina and coronary events after revascularization. Limited information has been available in evaluating a potentially effective first 2-week therapeutic approach for the treatment of patients with hypercholesterolemia using a statin. HYPOTHESIS: The study was undertaken to investigate whether a rapid LDL cholesterol and CRP reduction can be achieved by 2-week simvastatin therapy using a common lipid-lowering protocol in patients with hypercholesterolemia. METHODS: Forty-two patients were randomly assigned to 20 or 40 mg/day of simvastatin. Blood samples were drawn at Day 0 and at Day 14 for measuring lipid profile, CRP levels, and hepatic enzymes in all patients. RESULTS: The results showed that both doses of simvastatin (20 and 40 mg) induced significant reductions in total cholesterol (TC, 25 and 38%) and LDL cholesterol (31 and 46%) compared with baseline. However, the highest dose of simvastatin (40 mg) resulted in significantly greater reductions in TC and LDL cholesterol (p = 0.04, p = 0.02, respectively) compared with the group receiving 20 mg (p < 0.04, p < 0.02, respectively). A less significant reduction was observed in mean triglycerides (TG) level (16 and 25%) compared with TC and LDL cholesterol. There was no significant difference in mean high-density lipoprotein (HDL) cholesterol levels compared with baseline in either group. In addition, both doses of simvastatin induced significant reductions in mean CRP levels on Day 14 (22.3 and 23.1%) in a non dose-dependent manner (p < 0.001, respectively. CONCLUSIONS: Our data suggest that a common daily dose of simvastatin, especially 40 mg, is an effective 2-week therapy for patients with hypercholesterolemia, and benefit to the vascular endothelium can be derived quickly by reduction of CRP levels.     

Cholesterol, C-reactive protein, and cerebrovascular events following intensive and moderate statin therapy

Background: While statins have been shown to reduce cerebrovascular events (CVE), the relationship between cholesterol, C-reactive protein (CRP), and CVE in patients treated with different statin strategies is still being explored. Methods: PROVE IT-TIMI 22 was a randomized trial of intensive (atorvastatin 80 mg/day) and moderate (pravastatin 40 mg/day) statin therapy in 4,162 patients with acute coronary syndromes followed for an average of 24 months; serial biomarkers allowed for an assessment of the lipid and non-lipid effects of statins as they relate to CVE. Results: In this study, 45 patients on intensive statin therapy and 40 patients on moderate statin therapy had a CVE during the study period (2.1% v. 1.9%, P = 0.62). While the lipid profiles of patients with and without CVE were similar, those with CVE had higher CRP levels at 30 days and 4 months (2.7 v. 1.9, 2.4 v. 1.7 mg/L; P = 0.012, P = 0.005). Day 30 CRP remained an independent predictor of CVE after adjusting for age, development of atrial fibrillation, diabetes, and prior CVE. Patients with low density lipoprotein (LDL) levels < 70 mg/dL and ≥ 70 mg/dL had similar rates of CVE, while patients with CRP < 2 mg/L tended to have lower event rates when compared to those with higher levels. The lowest rates of CVE were seen in patients who had LDL < 70 mg/dL and CRP < 2 mg/L. Conclusion: In PROVE IT - TIMI 22, achieved LDL levels did not appear to independently impact the rate of CVE. In contrast, patients with elevated CRP levels were at higher risk of stroke or transient ischemic attack, reinforcing the link between inflammation and CVE. Condensed abstract The goal of this PROVE IT-TIMI 22 sub-study was to examine the relationship between cholesterol, CRP, and CVE in patients on intensive and moderate statin therapy. The achieved lipid levels were similar in patients with and without a CVE; however, the achieved levels of CRP were higher in patients who subsequently developed a stroke or TIA. These findings further support the relationship between inflammation and CVE.     

Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial)

Patients with combined hyperlipidemia (elevated triglyceride [TG] levels, elevated low-density lipoprotein [LDL] cholesterol, and multiple lipoprotein abnormalities) are at increased risk for coronary heart disease. We conducted a multicenter (in the United States), randomized, double-blind, active-controlled, 18-week study to determine if combination therapy with simvastatin plus fenofibrate is more effective in reducing elevated TG levels, thus improving the lipoprotein pattern in patients with combined hyperlipidemia compared with simvastatin monotherapy, and to evaluate safety and tolerability. Patients (aged 21 to 68 years) with a diagnosis of combined hyperlipidemia (fasting TG levels >/=150 and 130 mg/dl) received simvastatin monotherapy (20 mg/day, n = 207) or simvastatin 20 mg plus fenofibrate (160 mg/day) combination therapy (n = 411) for 12 weeks following a 6-week diet and placebo run-in period. From baseline to week 12, median TG levels decreased 43.0% (combination therapy) and 20.1% (simvastatin monotherapy [treatment difference -23.6%, p <0.001]). Mean LDL cholesterol levels decreased 31.2% and 25.8% (treatment difference -5.4%, p <0.001), and high-density lipoprotein cholesterol levels increased 18.6% and 9.7% (treatment difference 8.8%, p <0.001) in the combination therapy versus monotherapy groups, respectively. No drug-related serious adverse experiences were observed. No patient experienced clinical myopathy or severe abnormalities in liver function. Combination therapy with simvastatin 20 mg and fenofibrate 160 mg in patients with combined hyperlipidemia resulted in additional improvement in all lipoprotein parameters measured compared with simvastatin 20 mg monotherapy and was well tolerated. Thus, this combination therapy is a beneficial therapeutic option for managing combined hyperlipidemia.     

Clinical significance of plasma lipid levels

Epidemiologic studies have established that elevated low-density lipoprotein (LDL) cholesterol values and decreased levels of high-density lipoprotein (HDL) cholesterol are risk factors for coronary artery disease (CAD). Results from clinical trials indicate that reduction in LDL cholesterol decreases the incidence of and reduces the risk of CAD. The National Cholesterol Education Program recently developed guidelines for the evaluation of plasma cholesterol in adults. Initial classification is categorized and based on the following values: less than 200 mg/dl is "desirable" blood cholesterol; from 200 through 239 mg/dl is classified as "moderate-high" blood cholesterol; and greater than or equal to 240 mg/dl is "high" blood cholesterol. Decision-making regarding therapeutic intervention is influenced by the presence of other lipoprotein risk factors, such as reduced HDL cholesterol and elevated lipoprotein (a), and nonlipid factors, including age, sex, hypertension, obesity, smoking, diabetes mellitus, and family or patient history of CAD. Persons with borderline-high blood cholesterol and established CAD or 2 other risk factors as well as those with high blood cholesterol should undergo lipoprotein analysis. LDL cholesterol is the primary lipoprotein to consider when determining treatment goals. Patients with LDL cholesterol levels greater than 160 mg/dl without CAD or 2 other risk factors and those patients with LDL cholesterol greater than 130 mg/dl with CAD or 2 other risk factors are initially managed with dietary therapy. The goal of treatment of hyperlipidemia is to reduce LDL cholesterol to less than 160 mg/dl or to less than 130 mg/dl in patients with established CAD or with 2 other risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein cholesterol

Objectives. Do the benefits of intensive lipid-lowering therapy extend to patients with only borderline or moderately elevated levels of low density lipoprotein (LDL) cholesterol?Background. The merits of the present LDL cholesterol treatment goal of ≤100 mg/dl need to be clarified for patients without high levels of LDL cholesterol, particularly for those patients previously classified as having only borderline high (130 to 159 mg/dl) or desirable (101 to 130 mg/dl) levels.Methods. Disease change and clinical events were examined in LDL cholesterol subgroups in the Familial Atherosclerosis Treatment Study (FATS) trial, a randomized, blinded, quantitative arteriographie comparison of one conventional and two intensive lipid-lowering strategies in men with coronary artery disease, a positive family history and apolipoprotein B ≥125 mg/dl. The primary end point, disease change per patient, was measured as the mean change in severity of stenosis (Δ%S_Prox) among nine standard proximal segments.Results. Of the 120 patients completing the 30-month protocol, 60 had a baseline LDL cholesterol <90th percentile (mean LDL cholesterol 152 mg/dl) and 60 >90th percentile (mean LDL cholesterol 221 mg/dl). Thirty-one patients had levels <160 mg/dl (mean LDL cholesterol 134 mg/dl) and 89 >160 mg/dl (mean LDL cholesterol 205 mg/dl). Patients with LDL cholesterol <90th percentile benefited angiographically from therapy (Δ%S_Prox= −1.5% diameter stenosis [regression] during intensive therapy vs. 4-2.3% diameter stenosis [progression] during conventional therapy, p < 0.01), as did patients with LDL cholesterol <160 mg/dl (Δ%S_Prox= −4.2% vs. +3.3% diameter stenosis, p = 0.0001). By comparison, angiographie benefit was less pronounced among those entdring with very high LDL cholesterol (Δ%S^Prox= −0.2% vs. +1.9% diameter stenosis, p = 0.07) or with LDL cholesterol ≥160 mg/dl (Δ%S_Prox= +0.2% vs. +1.6% diameter stenosis, p = 0.13). Intensive therapy resulted in a statistically significant reduction in clinical events only in the subgroup with baseline LDL cholesterol < 90th percentile (2 of 42 vs. 8 of 29 patients initially enrolled, p = 0.01) and a trend toward fewer events in patients with LDL cholesterol < 160 mg/dl (2 of 20 vs. 6 of 15 patients, p = 0.05). No such difference was seen in the higher LDL cholesterol subgroups.Conclusions. Treatment benefit in the FATS trial was not confined to patients with very high levels of LDL cholesterol and was in fact particularly evident in those patients with levels < 160 mg/dl. Such patients should be considered more likely, not less, to benefit from intensive lipid-lowering therapy.     

Effect of levothyroxine on total lipid profiles as assessed by analytical capillary isotachophoresis in a patient with hypothyroidism

The patient was a 51-year-old Japanese female who had been diagnosed with hyperlipidemia. At the first medical examination, her serum levels of total cholesterol (TC) and triglyceride (TG) were 482 and 205 mg/dl, respectively. Since hyperlipidemia was not improved by pravastatin, atorvastatin or niceritrol, and since the levels of thyroid-stimulating hormone (TSH) and free T4 were 730 IU/ml and 0.3 ng/dl, respectively, the patient was diagnosed as secondary hyperlipidemia with hypothyroidism. A method for the charge isolation of lipoproteins using capillary isotachophoresis (cITP) is proposed as a clinical application because it allows us to quantitatively measure electronegative low-density lipoprotein cholesterol (LDL-C), a potent marker of coronary heart disease. After 5 months of treatment with levothyroxine, Serum TC and LDL-C levels drastically decreased without statin treatment and high-density lipoprotein cholesterol (HDL-C) increased. In the lipoprotein profiles as assessed by cITP after treatment with levothyroxin, all HDL-C subfractions were increased and fast-migrating LDL/electronegative LDL appeared to be greatly reduced after treatment, while the area under the non-modified LDL peak was increased. The cITP analysis was able to obtain more information about coronary risk factors and may be clinically useful for evaluating the effect of treatment with levothyroxine in patients with hypothyroidism and secondary hyperlipidemia.     

Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy

This study compares the effect of plant stanol ester spread with a placebo spread on cholesterol in patients taking statin therapy, but who still had elevated low-density lipoprotein (LDL) cholesterol. This was a randomized, double-blind, placebo-controlled clinical trial, with 67 women and 100 men with LDL cholesterol >/=130 mg/dl and triglycerides 相似文献