Effect of lipid levels and lipid-lowering therapy on restenosis after coronary artery stenting

BACKGROUND: Recent experimental and clinical data suggest that lowering serum lipid levels with statins may prevent or delay the process of restenosis. The purpose of this trial is to determine whether lipid levels relate to restenosis and/or whether statin therapy can prevent or delay the process of restenosis after intracoronary stenting. METHODS: One hundred thirty-six patients who underwent single coronary artery stenting from June 1995 to June 1997 in our institution were included in the study. All these patients were followed for at least 9 months (mean 392+/-148 days) for major adverse cardiac events (MACE). We defined as MACE the occurrence of death, myocardial infarction, or need for target lesion revascularization. From this cohort, 103 patients had at least one lipid parameter from the lipid profile evaluated within 2 months from the date of the procedure. Patients who had the stent because of an acute myocardial infarction were included in the study only if their lipid profile was evaluated before or at least 6 weeks after the event. Patients with triglyceride levels above 500 had both triglyceride and low-density lipoprotein cholesterol levels excluded from the statistical analysis. Patients were divided into two groups based on lipid levels: normal (Group I; n=31) and elevated (Group II; n=72). Patient outcomes were also analyzed by statin therapy use. RESULTS: There was no significant difference in MACE rates between the two groups when outcomes were analyzed by lipid levels (22.6% versus 20.8% P=0.8). Furthermore, outcomes were analyzed by use of statin therapy (Group III, n=53, on statin versus Group IV, n=50, on no statin). There was also no difference in MACE rates between the two groups (20.8% versus 22%; P=0.8). CONCLUSION: The process of restenosis has unique features that differentiate it from atherosclerosis. Although lipid-lowering therapy is crucial in delaying the process of atherosclerosis, its role in the prevention of restenosis is yet to be proven.     

Effects of lipid-lowering therapy with strong statin on serum polyunsaturated fatty acid levels in patients with coronary artery disease

Residual risk of cardiovascular events after treatment with stain might be explained in part because patients have low levels of n?3 polyunsaturated fatty acids (PUFA). We examined how lipid-lowering therapy with strong statin affected serum PUFA levels in patients with coronary artery disease. The study population consisted of 46 patients with coronary artery disease whose low-density lipoprotein (LDL) cholesterol was more than 100 mg/dl. Lipid-lowering therapy was performed with a strong statin including atorvastatin (n = 22), rosuvastatin (n = 9) or pitavastatin (n = 15). Serum PUFA levels were determined by gas chromatography. The treatment with strong statin decreased the sum of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) levels (195 ± 41 to 184 ± 44 μg/ml, P < 0.05) as well as the sum of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels (233 ± 71 to 200 ± 72 μg/ml, P < 0.001). These effects of strong statin resulted in a significant decrease in ratio of the sum of EPA and DHA levels to the sum of DGLA and AA levels (1.20 ± 0.27 to 1.10 ± 0.35, P < 0.05). The percent decrease in the LDL cholesterol level correlated significantly with that in the sum of EPA and DHA levels (r = 0.38, P < 0.01). In conclusion, our results showed that lipid-lowering therapy with strong statin mainly reduced n?3 PUFAs in proportion to the decrease in the LDL cholesterol level in patients with coronary artery disease.     

Prevention of positive coronary artery remodeling with statin therapy in patients with coronary artery diseases

Since positive coronary artery remodeling with large plaque burden is associated with subsequent coronary events, the authors tested their hypothesis that secondary prevention of coronary events by a statin may be associated with inhibition of the process of positive coronary artery remodeling in underlying coronary atherosclerotic lesions in patients with coronary artery diseases. They evaluated the intravascular ultrasound imaging in angiographically normal coronary lesions at baseline and after 6 months of therapy in 64 patients with coronary artery diseases. External elastic membrane area was defined as the vessel area, and the difference between the vessel and lumen area was calculated as plaque area. The relative echogenicity of coronary plaque to adventitia was evaluated as acoustic characteristics of coronary plaque. Twenty-five patients were treated with a statin and 39 patients did not receive a statin. In patients treated with a statin, plaque area decreased by 12% (p = 0.013) compared to an increase in plaque area of 13% (p = 0.023) in those who did not receive a statin. The vessel area was not enlarged in patients treated with a statin but did show positive remodeling in patients who had plaque progression without a statin. The relative echogenicity of plaque was unchanged in patients treated with a statin but significantly decreased in patients not receiving a statin. A statin may prevent positive coronary artery remodeling via inhibition of plaque progression in underlying coronary atherosclerotic lesions in patients with coronary artery diseases.     

Influence of preoperative lipid-lowering therapy on postoperative outcome in patients undergoing coronary artery bypass grafting

Statin therapy has recently been shown to decrease adverse perioperative events in patients undergoing vascular surgery. The potential beneficial effect of lipid-lowering therapy in patients undergoing coronary artery bypass grafting (CABG) is not well known. This was an observational analysis of 4,739 patients who underwent first-time isolated CABG at a single institution from 1995 to 2001. Patients were categorized into 2 groups based on treatment with a lipid-lowering agent within 30 days before surgery. Univariate and multivariate analyses were used to determine the association between lipid-lowering therapy and survival to hospital discharge. Patients in the lipid-lowering group (n = 2,334) tended to be younger (mean age 66 +/- 10 vs 68 +/- 10 years), were more likely to be diabetic (31% vs 28%), and on beta blockers (77% vs 70%) than patients in the nonlipid-lowering group (n = 2,405). In-hospital mortality was significantly lower in the lipid-lowering group than in the nonlipid-lowering therapy group (1.4% vs 2.2%, odds ratio 0.62, 95% confidence interval 0.40 to 0.96, p = 0.03). A multivariable model demonstrated a loss of statistical significance for the effect of lipid-lowering therapy on in-hospital mortality (adjusted odds ratio 0.83, 95% confidence interval 0.5 to 1.37, p = 0.46). In conclusion, preoperative use of lipid-lowering therapy in patients undergoing CABG appears safe and is associated with improved survival to hospital discharge compared with patients not receiving lipid-lowering therapy. However, patient risk factors and other cardioprotective medication use associated with the use of preoperative lipid-lowering therapy appear to explain the association with improved survival.     

A randomized pilot trial of low-dose combination lipid-lowering therapy following coronary artery bypass grafting

Vein graft atherosclerosis is a common and serious complication of coronary artery bypass grafting (CABG). There is mounting evidence that lipoprotein abnormalities play an equally important role in the development of lesions in saphenous vein grafts after CABG as in native coronary vessel disease. The potential benefit of low-dose lipid lowering combination therapy in these patients has not been investigated. In a randomized, double-blind, placebo-controlled study, we compared the efficacy and safety of a low-dose combination of colestipol 10 g and simvastatin 10 mg/day (CS) to colestipol 10 mg and bezafibrate 400 mg/day (CB) for 2 months in 33 patients with serum total cholesterol > 6.5 mmol/l and triglyceride < 4.5 mmol/l who had undergone CABG for severe coronary artery disease. In the CS group, total cholesterol decreased by 29% and low-density lipoprotein (LDL) cholesterol by 42%; similarly, CB reduced total cholesterol by 17%, LDL cholesterol by 23%, triglyceride by 19%, and increased high-density lipoprotein (HDL) cholesterol by 14%. Lipoprotein (a) and hemostatic factors were unaffected by either therapy in this study. Both combination therapies were well tolerated with no significant clinical or biochemical side effects. We conclude that low-dose combinations of colestipol and simvastatin or colestipol and bezafibrate are effective and well tolerated in the management of moderate hyperlipidemia in patients who had undergone CABG.     

降脂治疗逆转冠状动脉粥样硬化

目的通过血管内超声了解氟伐他汀和阿托伐他汀降脂治疗对冠状动脉粥样斑块退缩及其成分的影响。方法经冠状动脉造影(CAG)证实至少有一支主要冠状动脉存在20%～50%狭窄(目测)的70名患者,利用Excel表格按1∶1比例随机分为阿托伐他汀(20mg/d,35例)组和氟伐他汀(80mg/d,35例)组。通过血管内超声灰阶成像(C-IVUS)和虚拟组织学成像(VH-IVUS)脱机分析软件分别测量降脂治疗12个月前后冠状动脉粥样硬化斑块、血管、管腔体积及成分的变化。结果 56例(80%)患者完成全部随访过程,阿托伐他汀组及氟伐他汀组各28例。经过12个月的降脂治疗,阿托伐他汀组低密度脂蛋白胆固醇(LDL-C)由(3.43±0.65)mmol/L降至(2.11±0.41)mmol/L(P0.001),下降(36.9±14.7)%;氟伐他汀组LDL-C由(3.36±0.69)mmol/L降至(2.75±0.85)mmol/L(P=0.002),下降(16.1±30.3)%,两组间LDL-C下降幅度差异有统计学意义(P=0.002)。阿托伐他汀组斑块体积由(351.0±152.2)mm3减至(314.4±112.9)mm3(P=0.001),下降(8.5±12.9)%;氟伐他汀组斑块体积由(294.6±87.6)mm3增至(308.4±91.5)mm3(P=0.001),增加(4.7±9.2)%,组间斑块体积变化的百分比差异有统计学意义(P0.001)。阿托伐他汀组斑块体积下降百分比与LDL-C下降百分比呈正相关(r=0.586,P=0.001)。坏死核心(NC)比例阿托伐他汀组由(13.8±3.9)%下降至(10.8±6.9)%(P=0.023),而氟伐他汀组由(12.7±3.4)%增至(15.0±7.8)%(P=0.111),组间NC比例变化差异有统计学意义(P=0.006)。结论阿托伐他汀20mg降脂治疗可显著缩小冠状动脉粥样斑块体积,并可减少斑块坏死核心比例,斑块体积下降百分比与LDL-C下降百分比呈正相关,而氟伐他汀80mg不能阻止冠状动脉粥样硬化进展。     

Impact of a targeted intervention on lipid-lowering therapy in patients with coronary artery disease in the hospital setting

BACKGROUND: Although lipid-lowering therapy according to the National Cholesterol Education Program guidelines decreases mortality and morbidity in patients with coronary artery disease (CAD), significant undertreatment of hyperlipidemia continues to occur. This study was designed to determine the impact of an intervention targeted at improving the use of lipid-lowering therapy in patients with CAD in the hospital setting. METHODS: Cardiac case managers prompted physicians to obtain lipid profiles for patients with CAD who were not receiving lipid-lowering therapy on admission and initiate lipid-lowering therapy for patients with a low-density lipoprotein level of 130 mg/dL (3.37 mmol/L) or higher during hospitalization. The study population comprised 813 patients with CAD admitted for percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, or myocardial infarction. A retrospective chart review of lipid testing and treatment rates was conducted in 300 patients in the preintervention period, and a prospective review of rates was conducted in 513 patients during the intervention period. RESULTS: The percentage of patients with CAD not receiving lipid-lowering therapy on admission who had fractionated lipid profiles obtained during hospitalization increased from 27% preintervention to 89% during intervention (odds ratio, 18.27; 95% confidence interval, 11.61-28.74; P<.001). The percentage of patients with a low-density lipoprotein level of 130 mg/dL or higher for whom lipid-lowering therapy was initiated during hospitalization increased from 17% preintervention to 82% during intervention (odds ratio, 24.50; 95% confidence interval, 7.33-81.83; P<.001). CONCLUSIONS: The intervention provided by specialized cardiac case managers significantly increased physicians' adherence to the National Cholesterol Education Program treatment guidelines. The results of the present study suggest that intervention programs of this nature could produce a significant positive impact on cardiovascular outcomes if implemented nationally.     

动脉重塑与冠状动脉疾病

冠状动脉疾病的出现并不是动脉内膜中粥样斑块逐渐生长而导致血管腔狭窄的过程 ,直到狭窄程度达到一定的百分比之后血管腔才会减小 ,这是由于动脉重塑的存在而形成的。近年来 ,由于血管内超声成像的出现 ,使得在体内对动脉重塑进行研究成为可能。本文综述动脉重塑在冠状动脉疾病进展与消退中的作用、动脉重塑的病理生理机制和临床意义、以及动脉重塑在冠状动脉介入治疗术后再狭窄中的作用。     

Secondary prevention of coronary artery disease with lipid-lowering drugs]

Before the statins era, this was one of the most debated questions in the field of cardiology: although hypolipidemic drugs (mainly fibrates) decreased the cardiovascular morbidity and mortality, their influence on total mortality was not significant. The 4S study demonstrated the efficacy of a statin on cardiovascular morbidity and mortality and on total mortality. This was confirmed by the CARE and the LIPID trials. Statins should be prescribed to all coronary patients, whatever the type of coronary disease, the age (we do not know yet for people older than 80), the gender, the basal cholesterol level (maybe statins are not efficacious when it is<2g/l); cholesterol level has to be lowered below 2g/l. Two trials of drugs increasing the HDL cholesterol level were recently published. Unfortunately their results are contradictory. Statins should be the first level drugs. Maybe it is useful to decrease the triglycerides level and to increase the HDL cholesterol level. The association of a statin and a fibrate is reserved to specialized centers. We should not forget the usefulness of diet. We must also take the other risk factors into account.     

Effects of cardiovascular risk factors on coronary artery remodeling in patients with mild atherosclerosis

BACKGROUND: Vascular remodeling counteracts luminal encroachment during the progression of coronary artery disease (CAD) and modulates the manifestation of hemodynamically significant lesions. However, the role of cardiovascular risk factors for coronary remodeling has not been fully clarified. METHODS: Therefore, we investigated the role of local plaque burden and systemic risk factors on coronary vascular remodeling in 25 patients (49 segments) with angiographically normal or minimally diseased coronary arteries by intravascular ultrasound. In an additional 12 patients without coronary atherosclerosis, physiological vessel tapering was determined and used to calculate the extent of remodeling in diseased segments. RESULTS: An increase in local plaque burden was directly correlated with positive vascular remodeling (r = 0.54, P<0.001). However, cardiovascular risk factors like hypertension (P<0.001) and hypercholesterolemia (P = 0.03) were associated with reduced positive or even negative remodeling. Moreover, the total number of classical cardiovascular risk factors was a strong predictor for reduced positive remodeling (P for trend <0.001). In contrast, coronary flow reserve, a measure of shear stress imposed on the vessel wall, positively correlated with compensatory enlargement (r = 0.44, P = 0.002). By multivariate analysis, plaque burden (P = 0.001), hypertension (P = 0.001) and coronary flow reserve (P = 0.018) proved to be independent determinants of vascular remodeling of epicardial coronary arteries. CONCLUSIONS: Cardiovascular risk factors impair compensatory arterial enlargement and even predispose to shrinkage of epicardial arteries during the initial stage of atherosclerosis. Reduced positive vascular remodeling might contribute to the clinical manifestation of CAD by facilitating the development of flow-limiting stenoses in patients at risk.     

Impact of daily glucose fluctuations on cardiovascular outcomes after percutaneous coronary intervention for patients with stable coronary artery disease undergoing lipid-lowering therapy

Aims/IntroductionGlucose fluctuation (GF) is a residual risk factor for coronary artery disease (CAD). We investigated whether GF influenced clinical outcomes and progression of coronary stenosis in stable CAD patients.Materials and MethodsIn this prospective study, 101 consecutive lipid‐controlled stable CAD patients underwent percutaneous coronary intervention were enrolled, and GF was expressed as the mean amplitude of glycemic excursion (MAGE) obtained by continuous glucose monitoring before the procedure was evaluated. At 9 months after enrollment, culprit and non‐culprit (mild‐to‐moderate stenosis without ischemia) lesions were serially assessed by angiography. Cardiovascular events (CVE) consisting of cardiovascular death, non‐fatal myocardial infarction or ischemia‐driven revascularization during 2‐year follow up, rapid progression in non‐culprit lesions (defined as ≥10% luminal narrowing progression in lesions with stenosis ≥50%, ≥30% luminal narrowing progression in non‐culprit lesions with stenosis <50% or normal segment, or progression to total occlusion) were evaluated.ResultsCVE occurred in 25 patients, and MAGE was significantly higher in the CVE group (76.1 ± 24.8 mg/dL vs 59.3 ± 23.7 mg/dL; P = 0.003). Multivariate analysis showed that MAGE was an independent predictor of CVE (odds ratio 1.027, 95% confidence interval 1.008–1.047; P = 0.005). The optimal MAGE value to predict CVE was 70.7 mg/dL (area under the curve 0.687, 95% confidence interval 0.572–0.802; P = 0.005). Furthermore, MAGE was independently associated with rapid progression, and with the luminal narrowing progression in all non‐culprit lesions (r = 0.400, P < 0.05).ConclusionsDaily GF might influence future CVE in lipid‐controlled stable CAD patients.     

强化调脂治疗对经皮冠状动脉干预术后患者C反应蛋白的影响

目的　探讨阿托伐他汀 2 0mg/d对经皮冠状动脉干预 (percutaneouscoronaryintervention ,PCI)术后患者外周血C反应蛋白 (C reactiveprotein ,CRP)的降低能力是否强于 10mg/d。方法　连续选择因狭窄性病变行PCI的不稳定性心绞痛患者 4 8例 ,随机分为强化调脂组和常规调脂组 ,术后分别给予阿托伐他汀 2 0mg和 10mg,1次 /d。术前、术后 3d、3个月测定外周静脉血CRP、血脂等。结果　与术前比较 ,3个月后强化调脂组总胆固醇和低密度脂蛋白分别下降 2 1.6 %和 39.3% ,常规调脂组下降 11.6 %和 14 .8% ,阿托伐他汀 2 0mg/d降低总胆固醇和低密度脂蛋白的能力强于 10mg/d。强化调脂组术前 ,术后 3个月CRP中位数分别为 4 .1和 1.1mg/L ;常规调脂组为 7.1和 1.4mg/L。两组CRP的降低程度差异有显著性意义。阿托伐他汀的抗炎作用和术前的CRP水平相关 ,3个月后CRP的下降程度与血脂改变无相关性。结论　阿托伐他汀 2 0mg/d较 10mg/d能使PCI术后CRP进一步下降。     

Impact of coronary artery remodeling on clinical presentation of coronary artery disease: an intravascular ultrasound study

OBJECTIVES: We examined the association between the features of the culprit lesion in coronary artery disease (CAD) and clinical presentation as shown by intravascular ultrasound (IVUS). BACKGROUND: The association between coronary remodeling pattern and clinical presentation of CAD is unclear. METHODS: We analyzed 125 selected patients who underwent preintervention IVUS. Acute myocardial infarction (AMI) and unstable angina pectoris (UAP) were categorized as an acute coronary syndrome (ACS), and stable angina pectoris (SAP) and old myocardial infarction (OMI) as stable CAD. Coronary remodeling patterns and plaque morphology of the culprit lesion obtained by IVUS were analyzed in terms of their association with clinical presentation or angiographic morphology. RESULTS: Angiographically complex lesions were associated with ACS and OMI. In patients with a complex lesion, positive remodeling was observed more frequently than in those with a simple lesion. In AMI and UAP, positive remodeling was observed more frequently than in SAP and OMI (82% vs. 78% vs. 33% vs. 40%, respectively, p < 0.0001). The remodeling ratio was greater in AMI and UAP than in SAP and OMI (1.26 +/- 0.15 vs. 1.11 +/- 0.10 vs. 0.94 +/- 0.11 vs. 0.96 +/- 0.13, respectively, p < 0.0001). Furthermore, within ACS, the remodeling ratio was greater in AMI than in UAP (1.26 +/- 0.15 vs. 1.11 +/- 0.10, respectively, p < 0.05), whereas the frequency of positive remodeling was not different. CONCLUSIONS: Positive remodeling was more frequently observed in ACS than in stable CAD. Moreover, the degree of positive remodeling was greater in AMI than in UAP. These results may reflect the impact of remodeling types and its degree in the culprit lesion of CAD on clinical presentation.     

Successful intensive lipid-lowering therapy using atorvastatin stabilizes coronary artery plaque as assessed by multi-detector row computed tomography

A 35-year-old male was diagnosed as angina pectoris and showed severe stenosis with soft plaque in the proximal segment of the left anterior descending (LAD) coronary artery as detected by multi-detector row computed tomography (MDCT). Although percutaneous coronary stent implantation to the LAD lesion was performed, soft plaque remained in the proximal lesion of the stent. Atorvastatin increased the coronary plaque density at the 6-month follow-up MDCT examination, and the low-density lipoprotein cholesterol level fell from 141 to 63 mg/dl after 6 months. This case may indicate that assessment of the shape or composition of coronary plaque by MDCT is a useful strategy for judging the effects of intensive lipid-lowering therapy using statin.     

Effect of lipid-lowering therapy on the progression of coronary atherosclerosis assessed by scheduled repetitive coronary arteriography

We studied 42 subjects, each of whom demonstrated significant (?50%) narrowing of a non-grafted coronary artery and a baseline cholesterol level >250 mg%. All patients underwent repeat scheduled coronary arteriography after 2 years on the study. Twenty-five colestipol responders (cholesterol levels reduced at least 15% within 1 month of therapy) were compared to 17 non-responders who were given 23 months of placebo after a 1 month exposure to colestipol. Baseline risk factors and demographic characteristics were similar for the two groups. In comparison to baseline arteriography, only 3 of the 25 drug-treated patients showed progression, while 8 of 17 placebo treated patients demonstrated progression (P = 0.011). Drug-treated patients demonstrated a 20% decrease in cholesterol levels, while placebo patients did not experience a significant reduction in cholesterol levels.Our study suggests that significant reduction in serum cholesterol levels is associated with a reduced likelihood of progression of coronary atherosclerotic lesions assessed by scheduled repetitive coronary arteriography in hyperlipidemic subjects demonstrating significant coronary artery narrowing on their initial arteriograms.