BACKGROUND: The Taq/B, Msp/ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this...BACKGROUND: The Taq/B, Msp/ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this study, we investigated the associations between these 3 polymorphisms of CETP gene and variations in plasma lipid and lipoprotein levels in patients with coronary heart disease (CHD). METHODS: Genomic DNA was extracted from leukocytes of 203 CHD patients and 100 control subjects using the salting out method. Genotyping of the CETP gene was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Statistical analysis was conducted using the SPSS 10.0 software package. RESULTS: The distribution of allele and genotype frequencies of the Taq/B, MspI, and I405V polymorphisms was similar in the CHD patient group and the control group. The B1B1 genotype of the Taq/B polymorphism was associated with significantly higher TC (P=0.039) and LDL-C (P=0.044) levels than the B2B2 genotype in CHD patients, and with significantly higher LDL-C (P=0.034) levels than the B2B2 genotype in controls. Homozygotes of the I405V polymorphism exhibited significantly higher HDL-C levels than VV homozygotes among control subjects (P=0.023). In male CHD patients with unambiguously assigned haplotypes, B2-M2-V/B2-M2-I patients demonstrated significantly higher HDL-C concentrations than B1-M2-V/B1-M2-I (P=0.023) and B1-M2-V/B1-M2-V patients (P=0.047). CONCLUSIONS: Genetic variations in the CETP gene may account for a significant proportion of the differences in plasma lipid and lipoprotein concentrations among the general population. The B1B1 genotype of the Taq/B polymorphism is probably a genetic risk factor for CHD in the study population.展开更多
目的评价他汀类药物对轻度胆固醇升高的老年冠心病患者冠状动脉粥样硬化斑块的影响。方法将LDL—C为2．6～3．6mmol／I。的57例冠心病患者分为〉65岁组（I组，30例）和≤65岁组（Ⅱ组，27例）。每例患者选取一处狭窄50％～70％的斑块为...目的评价他汀类药物对轻度胆固醇升高的老年冠心病患者冠状动脉粥样硬化斑块的影响。方法将LDL—C为2．6～3．6mmol／I。的57例冠心病患者分为〉65岁组（I组，30例）和≤65岁组（Ⅱ组，27例）。每例患者选取一处狭窄50％～70％的斑块为靶病变。分别于治疗前和治疗后12个月行冠状动脉造影（CAG）和靶病变的血管内超声（IVUS），比较血管、管腔和斑块体积，并观察斑块钙化情况。结果I组和Ⅱ组患者12个月后LDI。C平均降至2．39mmol／L和2．23mmol／L，较基线下降32．1％和33．2％。两组患者血管、管腔和斑块体积在治疗前无显著差异。治疗12个月后，I组血管、管腔和斑块体积无显著变化，Ⅱ组血管体积无变化；管腔体积由（68．8±14．4）mm。增加至（83．6±22．5）mm。（P〈0．05），斑块体积由（80．1±18．6）mm。缩小至（69．9±21．7）mm。（P〈0．05）。钙化斑块比例I组明显高于Ⅱ组（56．7％ vs 25．9％，P〈0．05）。结论他汀类药物可以阻止LDLC轻度升高的老年冠心病患者冠状动脉斑块的进展。展开更多
The LDL Principle has recently been invoked to describe the observation that lowering the LDL cholesterol (by whatever means) results in a lowering of atherosclerotic cardiovascular events. The scientific basis of the...The LDL Principle has recently been invoked to describe the observation that lowering the LDL cholesterol (by whatever means) results in a lowering of atherosclerotic cardiovascular events. The scientific basis of the LDL Principle dates back to the discovery that the LDL receptor is the prime determinant of the circulating LDL-c concentration. Since that time, major advances have been made at both the basic and clinical science level in our understanding of the pathogenesis and reversal of atherosclerosis. The incorporation of atherogenic lipoproteins plus inflammatory mediators into plaque formation permits the targeted intervention into preventing plaque rupture. In addition, genetic studies identifying individuals with unique phenotypes of either abnormally high or low LDL-c concentrations have provided insight into possible therapeutic modalities that have recently provided the physician with the tools necessary to apply the LDL Principle to achieve reversal of atherosclerosis. The epidemic of atherosclerotic cardiovascular disease has resulted in numerous randomized controlled intervention trials in an attempt to identify approaches to reduce ASCD morbidity and mortality. Recently published data indicate that circulating LDL-c levels of 50 mg/dl or less are not only physiologic at birth but also effective in greatly reducing cardiovascular disease. In addition, the recent availability of two PCSK9 inhibitors provides the primary care physician with the possibility of achieving this low level of LDL-c even in statin intolerant patients. The widespread availability of the coronary artery calcium scan plus the inclusion of traditional cardiovascular risk factors in risk assessment has enabled the physician to readily identify asymptomatic individuals at high risk for cardiovascular events. Aggressively applying the LDL Principle to these individuals has the potential of greatly reducing cardiovascular mortality. This review will document the scientific basis for this principle and provide the arguments in favo展开更多
Both clinical and basic science studies during the last 30 years have emphasized the importance of cholesterol in the pathogenesis of atherosclerosis. There is a direct relationship between the level of circulating ch...Both clinical and basic science studies during the last 30 years have emphasized the importance of cholesterol in the pathogenesis of atherosclerosis. There is a direct relationship between the level of circulating cholesterol (as LDLc remnant particles) and the incidence of cardiovascular events. However, this hypothesis has not gone unchallenged, both in social media and the scientific literature. This controversy has major consequences to the health of the public,?because atherosclerosis is the number one cause of morbidity and mortality in the Western World.?The proponents of the non-importance of atherosclerosis base their argument on certain studies. We have carefully examined these studies in order to address the validity of the challenges.?Each of these studies has its own deficiencies?as pointed out in this article. Overall, the evidence that cholesterol is not the primary underlying pathogenic factor causing heart attacks and strokes is based on a flawed interpretation of study results. These studies have several serious deficiencies including lost data, inadequate power, excessive drop outs, borderline significance, and lack of a control group. The conclusion that cholesterol is essential in the pathogenesis of atherosclerosis is critical for treating and preventing atherosclerosis and reducing the prevalence of cardiovascular disease.展开更多
文摘BACKGROUND: The Taq/B, Msp/ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this study, we investigated the associations between these 3 polymorphisms of CETP gene and variations in plasma lipid and lipoprotein levels in patients with coronary heart disease (CHD). METHODS: Genomic DNA was extracted from leukocytes of 203 CHD patients and 100 control subjects using the salting out method. Genotyping of the CETP gene was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Statistical analysis was conducted using the SPSS 10.0 software package. RESULTS: The distribution of allele and genotype frequencies of the Taq/B, MspI, and I405V polymorphisms was similar in the CHD patient group and the control group. The B1B1 genotype of the Taq/B polymorphism was associated with significantly higher TC (P=0.039) and LDL-C (P=0.044) levels than the B2B2 genotype in CHD patients, and with significantly higher LDL-C (P=0.034) levels than the B2B2 genotype in controls. Homozygotes of the I405V polymorphism exhibited significantly higher HDL-C levels than VV homozygotes among control subjects (P=0.023). In male CHD patients with unambiguously assigned haplotypes, B2-M2-V/B2-M2-I patients demonstrated significantly higher HDL-C concentrations than B1-M2-V/B1-M2-I (P=0.023) and B1-M2-V/B1-M2-V patients (P=0.047). CONCLUSIONS: Genetic variations in the CETP gene may account for a significant proportion of the differences in plasma lipid and lipoprotein concentrations among the general population. The B1B1 genotype of the Taq/B polymorphism is probably a genetic risk factor for CHD in the study population.
文摘目的评价他汀类药物对轻度胆固醇升高的老年冠心病患者冠状动脉粥样硬化斑块的影响。方法将LDL—C为2．6～3．6mmol／I。的57例冠心病患者分为〉65岁组（I组，30例）和≤65岁组（Ⅱ组，27例）。每例患者选取一处狭窄50％～70％的斑块为靶病变。分别于治疗前和治疗后12个月行冠状动脉造影（CAG）和靶病变的血管内超声（IVUS），比较血管、管腔和斑块体积，并观察斑块钙化情况。结果I组和Ⅱ组患者12个月后LDI。C平均降至2．39mmol／L和2．23mmol／L，较基线下降32．1％和33．2％。两组患者血管、管腔和斑块体积在治疗前无显著差异。治疗12个月后，I组血管、管腔和斑块体积无显著变化，Ⅱ组血管体积无变化；管腔体积由（68．8±14．4）mm。增加至（83．6±22．5）mm。（P〈0．05），斑块体积由（80．1±18．6）mm。缩小至（69．9±21．7）mm。（P〈0．05）。钙化斑块比例I组明显高于Ⅱ组（56．7％ vs 25．9％，P〈0．05）。结论他汀类药物可以阻止LDLC轻度升高的老年冠心病患者冠状动脉斑块的进展。
文摘The LDL Principle has recently been invoked to describe the observation that lowering the LDL cholesterol (by whatever means) results in a lowering of atherosclerotic cardiovascular events. The scientific basis of the LDL Principle dates back to the discovery that the LDL receptor is the prime determinant of the circulating LDL-c concentration. Since that time, major advances have been made at both the basic and clinical science level in our understanding of the pathogenesis and reversal of atherosclerosis. The incorporation of atherogenic lipoproteins plus inflammatory mediators into plaque formation permits the targeted intervention into preventing plaque rupture. In addition, genetic studies identifying individuals with unique phenotypes of either abnormally high or low LDL-c concentrations have provided insight into possible therapeutic modalities that have recently provided the physician with the tools necessary to apply the LDL Principle to achieve reversal of atherosclerosis. The epidemic of atherosclerotic cardiovascular disease has resulted in numerous randomized controlled intervention trials in an attempt to identify approaches to reduce ASCD morbidity and mortality. Recently published data indicate that circulating LDL-c levels of 50 mg/dl or less are not only physiologic at birth but also effective in greatly reducing cardiovascular disease. In addition, the recent availability of two PCSK9 inhibitors provides the primary care physician with the possibility of achieving this low level of LDL-c even in statin intolerant patients. The widespread availability of the coronary artery calcium scan plus the inclusion of traditional cardiovascular risk factors in risk assessment has enabled the physician to readily identify asymptomatic individuals at high risk for cardiovascular events. Aggressively applying the LDL Principle to these individuals has the potential of greatly reducing cardiovascular mortality. This review will document the scientific basis for this principle and provide the arguments in favo
文摘Both clinical and basic science studies during the last 30 years have emphasized the importance of cholesterol in the pathogenesis of atherosclerosis. There is a direct relationship between the level of circulating cholesterol (as LDLc remnant particles) and the incidence of cardiovascular events. However, this hypothesis has not gone unchallenged, both in social media and the scientific literature. This controversy has major consequences to the health of the public,?because atherosclerosis is the number one cause of morbidity and mortality in the Western World.?The proponents of the non-importance of atherosclerosis base their argument on certain studies. We have carefully examined these studies in order to address the validity of the challenges.?Each of these studies has its own deficiencies?as pointed out in this article. Overall, the evidence that cholesterol is not the primary underlying pathogenic factor causing heart attacks and strokes is based on a flawed interpretation of study results. These studies have several serious deficiencies including lost data, inadequate power, excessive drop outs, borderline significance, and lack of a control group. The conclusion that cholesterol is essential in the pathogenesis of atherosclerosis is critical for treating and preventing atherosclerosis and reducing the prevalence of cardiovascular disease.
