1. The reproducibility of measurements of the arterial wall thickness in both the carotid and fem... more 1. The reproducibility of measurements of the arterial wall thickness in both the carotid and femoral artery was investigated by means of high-resolution B-mode ultrasonography. For this purpose, subjects with normal and increased intima-media thickness were selected. Images were stored on an optical disk and were analysed with a semi-automatic software program by two readers. Individuals were scanned twice by two independent observers. 2. Measurements were performed of the far and near wall of the common carotid artery and bulbous in 30 healthy subjects and 19 patients known to have an increased intima-media thickness. Far-wall measurements were made of the internal carotid artery on both sides and common femoral artery on the right side only. 3. In healthy subjects the mean within-observer coefficient of variation was 1.8% and 3.0% for the far wall in the common carotid artery on the right side and left side, respectively. For the near wall the mean coefficient of variation of the...
There is overwhelming evidence that statins reduce morbidity and mortality in patients with coron... more There is overwhelming evidence that statins reduce morbidity and mortality in patients with coronary disease. Statins have also been shown to reduce the risk of (recurrent) stroke. Low-density lipoprotein (LDL)-cholesterol, which plays a causal role in the development of atherosclerotic disease, is the primary lipid target in prevention, and is effectively reduced by these agents. In this review, studies are summarized addressing the issues whether statins also directly influence the atherosclerotic process in peripheral arterial disease, carotid artery stenosis, and growth of abdominal aortic aneurysms, and whether statins have an effect on perioperative outcomes in vascular surgery patients. It appears that the evidence of statins on peripheral arterial disease is scarce and its effect on perioperative outcome inconclusive. Prospective randomized trials to answer these questions cannot be performed anymore, however, because all vascular patients should receive statin treatment as secondary prevention of cardiovascular disease.
Despite reduction in low-density lipoprotein cholesterol, there is still a considerable amount of... more Despite reduction in low-density lipoprotein cholesterol, there is still a considerable amount of residual atherosclerosis-related disease. Epidemiological and pathophysiological data strongly favour increasing plasma high-density lipoprotein (HDL) cholesterol levels as antiatherogenic therapy, for example with cholesteryl ester transfer inhibition (CETP). However, negative Phase III studies on clinical end points with the CETP inhibitor torcetrapib challenge the future perspectives of other CETP inhibitors such as JTT-705. Is there potential for CETP inhibition with JTT-705 after torcetrapib's collapse? Search of articles in Pubmed citing JTT-705, torcetrapib and anacetrapib, or citing effects of pharmacological HDL-cholesterol raising or CETP inhibition. There is possibly a future for HDL-cholesterol raising therapies. Phase III clinical studies with either JTT-705 or anacetrapib will determine whether CETP inhibition is beneficial.
Hypercholesterolaemia is strongly associated with increased vessel wall thickness as measured by ... more Hypercholesterolaemia is strongly associated with increased vessel wall thickness as measured by ultrasound. The question is whether aggressive cholesterol lowering with high-dose atorvastatin can alter intima media thickening to a greater extent than conventional therapy in patients with familial hypercholesterolaemia (FH). The baseline characteristics of a double-blind, randomised trial are described to determine whether two active treatments (high-dose atorvastatin 80mg versus conventional dose simvastatin 40mg), administered over a period of 2 years, may retard the process of intima media thickening in the carotid and femoral arteries of patients with FH. 325 patients with FH were randomised. Patients entered an 8-week placebo period in which all lipid-lowering medication was discontinued. Thereafter, baseline measurements of lipoprotein parameters and intima media thickness (IMT) of carotid and femoral artery were performed. Baseline low density lipoprotein (LDL) cholesterol (±SD) levels were 8.11 ± 1.92 mmol/L (312 ± 73 mg/dl) in men and 8.22 ± 1.91 mmol/L (316 ± 73 mg/dl) in women, respectively. Mean posterior wall IMT in the left common carotid artery (CCA) was significantly greater in men (0.94 ± 0.29mm) compared with women (0.85 ± 0.20) [p < 0.05]. A similar difference was found for the internal carotid artery (ICA). In the carotid bifurcation, IMT was 1.20 ± 0.50mm in men and 1.1 ± 0.54mm in women. The IMT of the common femoral artery (CFA) was 2.03 ± 0.88mm in men with cardiovascular disease (CVD) and 1.63 ± 0.70mm in men without CVD (p < 0.05). Strikingly, plaques were present in all men and 95% of the women with CVD. The cholesterol-year score and HDL cholesterol levels partially explained the variation in IMT in the carotid bifurcation, whereas gender and smoking contributed to the variation in IMT in the CFA in this group of patients. The patients participating in the Atorvastatin and Simvastatin on Atherosclerosis Progression (ASAP) trial constitute the largest well-documented FH population exhibiting marked increases in IMT of both carotid and femoral arteries and a very high prevalence of plaques, indicating extreme CVD risk. Since lipid-lowering therapy provides the highest benefit in precisely such patients, the ASAP trial will help assess whether aggressive LDL cholesterol intervention leads to retardation of subclinical atherosclerosis progression, as estimated with ultrasonographically assessed IMT.
Cardiovascular disease as a result of accelerated atherogenesis is common in patients with end-st... more Cardiovascular disease as a result of accelerated atherogenesis is common in patients with end-stage renal disease (ESRD). Dyslipidemia may be a major contributor in this process and can be influenced by lipid-lowering drugs (statins). Moreover, statins may exhibit additional inhibitory effects on the atherogenesis, such as a modulation of the immune system as triggered by oxidatively modified LDL and a reduction of the inflammatory marker C-reactive protein (CRP). We evaluated in a single-blind randomized trial of 28 ESRD patients on hemodialysis, the dose-depending effects of both atorvastatin and simvastatin on lipids, lipoproteins, LDL particle heterogeneity, high sensitive-CRP, and markers of in vivo LDL oxidation. Both statin therapies significantly lowered total plasma cholesterol and LDL-cholesterol concentrations to the same extent, whereas reduction in the concentrations of triglyceride-rich particles was less pronounced. Furthermore, statin therapy reduced LDL cholesterol in all LDL subfractions, without altering the overall LDL particle density. After both statins plasma hs-CRP concentrations were not significantly reduced; parameters of in vivo LDL oxidation (plasma ox-LDL concentration and the oxidation level of isolated LDL), were significantly decreased. Autoantibodies against ox-LDL, however, did not change during this trial period. These results show that atorvastatin and simvastatin exhibit comparable favourable effects on lipid profiles in ESRD. Moreover, the reduction of in vivo oxidatively modified LDL as shown in this ESRD population, may indicate that these statins exhibit favourable effects on oxidative stress in vivo.
We studied the effects of the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors simva... more We studied the effects of the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors simvastatin and pravastatin on the in vitro susceptibility of low-density lipoprotein (LDL) to oxidation. Twenty-three hypercholesterolaemic patients (mean serum cholesterol 9.7 mmol l-1) were treated with increasing doses of either simvastatin or pravastatin for 18 weeks. No significant differences in effect on lipid levels between the two drugs were found. Treatment resulted in lowering of total cholesterol and LDL-cholesterol by maximally 30% and 34%, respectively. Chemical composition analysis showed that LDL particles contained relatively more protein and less free cholesterol and cholesteryl-ester after treatment. The LDL cholesterol/protein ratio decreased from 1.24 +/- 0.21 to 0.97 +/- 0.23 (n = 20). By continuous monitoring of in vitro oxidation it appeared that LDL was less susceptible to oxidation after drug treatment. Maximal rate of diene production was significantly decreased fr...
Low-density-lipoprotein (LDL) oxidation may provide the crucial link between plasma LDL and ather... more Low-density-lipoprotein (LDL) oxidation may provide the crucial link between plasma LDL and atherosclerotic-lesion formation. Oxidation can be induced in vitro by incubating LDL with cells or metal ions and can be measured by continuously monitoring conjugated-diene absorbance at 234 nm. Measurement of LDL oxidizability was improved by performing the assay with 0.05 g of LDL-protein per liter of phosphate buffer containing 1 mumol of EDTA, by initiating oxidation by adding CuCl2 (5 mumol/L) at 30 degrees C, and by using a short-run ultracentrifugation method for isolating LDL, which reduced the time needed for obtaining purified LDL and thus reduced in vitro oxidation. LDL apolipoprotein analysis and oxidizability determination showed that this method is better than the longer sequential-isolation procedure. Adding butylated hydroxytoluene (BHT) to plasma as an antioxidant unpredictably increased the LDL oxidation lag time, making BHT unsuitable as an antioxidant. Adding EDTA appear...
The purpose of this study was to understand better the factors providing oxidation resistance to ... more The purpose of this study was to understand better the factors providing oxidation resistance to human low-density lipoprotein (LDL). Therefore, the susceptibility to copper-induced in vitro oxidation of LDL from vitamin E deficient patients and normal healthy subjects was studied. Surprisingly, the LDL of vitamin E deficient patients appeared less susceptible to oxidation than control LDL. Both oxidation rate and extent of oxidation, measured as diene production, were reduced when compared to control LDL. The lag time, a measure of resistance to oxidation, was not different from the lag time of LDL from healthy subjects. No relation was found between vitamin E content and resistance against oxidation. LDL from vitamin E deficient patients contained lower amounts of vitamin E, less cholesteryl esters, and increased amounts of triglycerides. Furthermore, its oleic acid content was increased and its linoleic acid content decreased. Linear regression analyses revealed that the ratio of oleic acid content to linoleic acid content was strongly correlated with the lag time, and inversely correlated with oxidation rate and extent of oxidation. Thus, LDL rich in oleic acid and poor in linoleic acid was less easily oxidized. It is concluded that the susceptibility of LDL to oxidation is determined not only by its antioxidant content, but also by other compositional factors, and more specifically by the ratio of oleic acid content to linoleic acid content.
Enhanced induction of low density lipoprotein (LDL) oxidation may play a role in the increased ca... more Enhanced induction of low density lipoprotein (LDL) oxidation may play a role in the increased cardiovascular risk in smokers. We determined LDL oxidisability in vitro in non-smokers, smokers and in subjects after smoking cessation. Plasma lipids and copper induced LDL oxidation in vitro were measured in 31 persistent smokers, 47 smokers who tried to stop smoking and 25 non-smokers. In the smoking cessation group, blood was collected before then 1, 3, 6 and 12 months after smoking cessation, and in the persistent smoking and non-smoking groups at baseline and after 12 months. Plasma thiobarbituric acid reactive substances (TBARS) were measured 3 times (at baseline then after 1 and 3 months) in all subjects who refrained from smoking (controlled by urinary cotinine concentrations) for at least 3 months. At baseline, no differences in mean age, body mass index and lipid profiles between groups were present. Seventeen subjects of the smoking cessation group (36%) managed to quit during 12 months. Smoking cessation was associated with an increase in mean weight (P </= 0.001) and waist-hip ratio (P </= 0.001). No major differences in LDL oxidisability were found between groups. A significant transient increase in high density lipoprotein (HDL) cholesterol was seen (from 1.20 +/- 0.39 to 1.34 +/- 0.42 mmol L-1) after 1 month of smoking cessation that disappeared after 3 months. However, after 1 month of smoking cessation, plasma TBARS decreased significantly (P < 0.05). Neither the previously observed increased cardiovascular risk in smokers nor the decreased risk in those who stopped smoking seem to be mediated by permanent changes in lipid profiles or by alterations in the susceptibility to in vitro oxidation of LDL.
The present review aims to highlight the consequences for mother and child of profound hyperchole... more The present review aims to highlight the consequences for mother and child of profound hypercholesterolemia during pregnancy of women with familial hypercholesterolemia. Familial hypercholesterolemia is increasingly diagnosed in younger patients due to the existence of screening programs and more widespread cholesterol testing. Increasing numbers of young female patients with familial hypercholesterolemia raise the issue of pregnancy and its consequences for the familial hypercholesterolemia patient herself but also for her offspring. When pregnancy is considered, lipid-lowering drugs are often discontinued because of the fear for teratogenic effects. The evidence for teratogenesis associated with statin use is scant and conflicting. On the other hand, several studies do suggest that pronounced hypercholesterolemia during pregnancy has adverse effects on both fetus and mother. In fact, human and animal studies reveal an enhanced tendency toward atherosclerosis in the offspring of women who suffer from hypercholesterolemia during pregnancy. In animal studies, some evidence exists that this can be reversed by treatment with lipid-lowering and antioxidative agents. Until today, however, no human studies exist that have evaluated efficacy or safety of lipid-lowering interventions in pregnant women with familial hypercholesterolemia. Altogether, the suggested relationship between severe hypercholesterolemia and enhanced atherosclerosis in offspring and possibly the mother warrants further confirmation and, consequently, studies that focus on therapeutic strategies that can safely lower cholesterol levels during pregnancy in these women.
In order to investigate the in vivo function of hepatic lipase, cats were injected with anti-cat ... more In order to investigate the in vivo function of hepatic lipase, cats were injected with anti-cat hepatic lipase antibodies which produced a complete and specific inhibition of heparin-releasable hepatic lipase. The cat was chosen as an animal model because it displays, like man, a relative deficiency of lipoprotein lipase compared to hepatic lipase and because the possession of two subfractions of high density lipoproteins, HDL2 and HDL3. In fasted cats no changes were observed in plasma triglycerides or phospholipids. In fed animals triglycerides increased considerably, indicating that hepatic lipase may have a function in the postprandial phase. In fat-loaded cats (6 g of fat/kg) triglycerides in the d less than 1.019 g/ml fraction increased from 4 h after the blockade due to accumulation of lipoproteins with pre-beta-mobility containing the apoproteins, apo B-100, apo E and apo A-I. Apo B-48 did not accumulate consistently. Phospholipids in the HDL2-fraction and those in the HDL3-fraction of the fat-loaded cats tended to increase and decrease from 6 and 9 h after the blockade, respectively. The absolute change in HDL2 phospholipids approximated that of HDL3-phospholipids. Overall, the density of HDL particles decreased, apparently secondary to the accumulation of apo A-I in the d less than 1.019 g/ml fraction. Our findings suggest that hepatic lipase is involved in the hydrolysis of a special class of apo A-I containing triglyceride-rich lipoproteins synthesised in the postprandial phase.
1. The reproducibility of measurements of the arterial wall thickness in both the carotid and fem... more 1. The reproducibility of measurements of the arterial wall thickness in both the carotid and femoral artery was investigated by means of high-resolution B-mode ultrasonography. For this purpose, subjects with normal and increased intima-media thickness were selected. Images were stored on an optical disk and were analysed with a semi-automatic software program by two readers. Individuals were scanned twice by two independent observers. 2. Measurements were performed of the far and near wall of the common carotid artery and bulbous in 30 healthy subjects and 19 patients known to have an increased intima-media thickness. Far-wall measurements were made of the internal carotid artery on both sides and common femoral artery on the right side only. 3. In healthy subjects the mean within-observer coefficient of variation was 1.8% and 3.0% for the far wall in the common carotid artery on the right side and left side, respectively. For the near wall the mean coefficient of variation of the...
There is overwhelming evidence that statins reduce morbidity and mortality in patients with coron... more There is overwhelming evidence that statins reduce morbidity and mortality in patients with coronary disease. Statins have also been shown to reduce the risk of (recurrent) stroke. Low-density lipoprotein (LDL)-cholesterol, which plays a causal role in the development of atherosclerotic disease, is the primary lipid target in prevention, and is effectively reduced by these agents. In this review, studies are summarized addressing the issues whether statins also directly influence the atherosclerotic process in peripheral arterial disease, carotid artery stenosis, and growth of abdominal aortic aneurysms, and whether statins have an effect on perioperative outcomes in vascular surgery patients. It appears that the evidence of statins on peripheral arterial disease is scarce and its effect on perioperative outcome inconclusive. Prospective randomized trials to answer these questions cannot be performed anymore, however, because all vascular patients should receive statin treatment as secondary prevention of cardiovascular disease.
Despite reduction in low-density lipoprotein cholesterol, there is still a considerable amount of... more Despite reduction in low-density lipoprotein cholesterol, there is still a considerable amount of residual atherosclerosis-related disease. Epidemiological and pathophysiological data strongly favour increasing plasma high-density lipoprotein (HDL) cholesterol levels as antiatherogenic therapy, for example with cholesteryl ester transfer inhibition (CETP). However, negative Phase III studies on clinical end points with the CETP inhibitor torcetrapib challenge the future perspectives of other CETP inhibitors such as JTT-705. Is there potential for CETP inhibition with JTT-705 after torcetrapib's collapse? Search of articles in Pubmed citing JTT-705, torcetrapib and anacetrapib, or citing effects of pharmacological HDL-cholesterol raising or CETP inhibition. There is possibly a future for HDL-cholesterol raising therapies. Phase III clinical studies with either JTT-705 or anacetrapib will determine whether CETP inhibition is beneficial.
Hypercholesterolaemia is strongly associated with increased vessel wall thickness as measured by ... more Hypercholesterolaemia is strongly associated with increased vessel wall thickness as measured by ultrasound. The question is whether aggressive cholesterol lowering with high-dose atorvastatin can alter intima media thickening to a greater extent than conventional therapy in patients with familial hypercholesterolaemia (FH). The baseline characteristics of a double-blind, randomised trial are described to determine whether two active treatments (high-dose atorvastatin 80mg versus conventional dose simvastatin 40mg), administered over a period of 2 years, may retard the process of intima media thickening in the carotid and femoral arteries of patients with FH. 325 patients with FH were randomised. Patients entered an 8-week placebo period in which all lipid-lowering medication was discontinued. Thereafter, baseline measurements of lipoprotein parameters and intima media thickness (IMT) of carotid and femoral artery were performed. Baseline low density lipoprotein (LDL) cholesterol (±SD) levels were 8.11 ± 1.92 mmol/L (312 ± 73 mg/dl) in men and 8.22 ± 1.91 mmol/L (316 ± 73 mg/dl) in women, respectively. Mean posterior wall IMT in the left common carotid artery (CCA) was significantly greater in men (0.94 ± 0.29mm) compared with women (0.85 ± 0.20) [p < 0.05]. A similar difference was found for the internal carotid artery (ICA). In the carotid bifurcation, IMT was 1.20 ± 0.50mm in men and 1.1 ± 0.54mm in women. The IMT of the common femoral artery (CFA) was 2.03 ± 0.88mm in men with cardiovascular disease (CVD) and 1.63 ± 0.70mm in men without CVD (p < 0.05). Strikingly, plaques were present in all men and 95% of the women with CVD. The cholesterol-year score and HDL cholesterol levels partially explained the variation in IMT in the carotid bifurcation, whereas gender and smoking contributed to the variation in IMT in the CFA in this group of patients. The patients participating in the Atorvastatin and Simvastatin on Atherosclerosis Progression (ASAP) trial constitute the largest well-documented FH population exhibiting marked increases in IMT of both carotid and femoral arteries and a very high prevalence of plaques, indicating extreme CVD risk. Since lipid-lowering therapy provides the highest benefit in precisely such patients, the ASAP trial will help assess whether aggressive LDL cholesterol intervention leads to retardation of subclinical atherosclerosis progression, as estimated with ultrasonographically assessed IMT.
Cardiovascular disease as a result of accelerated atherogenesis is common in patients with end-st... more Cardiovascular disease as a result of accelerated atherogenesis is common in patients with end-stage renal disease (ESRD). Dyslipidemia may be a major contributor in this process and can be influenced by lipid-lowering drugs (statins). Moreover, statins may exhibit additional inhibitory effects on the atherogenesis, such as a modulation of the immune system as triggered by oxidatively modified LDL and a reduction of the inflammatory marker C-reactive protein (CRP). We evaluated in a single-blind randomized trial of 28 ESRD patients on hemodialysis, the dose-depending effects of both atorvastatin and simvastatin on lipids, lipoproteins, LDL particle heterogeneity, high sensitive-CRP, and markers of in vivo LDL oxidation. Both statin therapies significantly lowered total plasma cholesterol and LDL-cholesterol concentrations to the same extent, whereas reduction in the concentrations of triglyceride-rich particles was less pronounced. Furthermore, statin therapy reduced LDL cholesterol in all LDL subfractions, without altering the overall LDL particle density. After both statins plasma hs-CRP concentrations were not significantly reduced; parameters of in vivo LDL oxidation (plasma ox-LDL concentration and the oxidation level of isolated LDL), were significantly decreased. Autoantibodies against ox-LDL, however, did not change during this trial period. These results show that atorvastatin and simvastatin exhibit comparable favourable effects on lipid profiles in ESRD. Moreover, the reduction of in vivo oxidatively modified LDL as shown in this ESRD population, may indicate that these statins exhibit favourable effects on oxidative stress in vivo.
We studied the effects of the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors simva... more We studied the effects of the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors simvastatin and pravastatin on the in vitro susceptibility of low-density lipoprotein (LDL) to oxidation. Twenty-three hypercholesterolaemic patients (mean serum cholesterol 9.7 mmol l-1) were treated with increasing doses of either simvastatin or pravastatin for 18 weeks. No significant differences in effect on lipid levels between the two drugs were found. Treatment resulted in lowering of total cholesterol and LDL-cholesterol by maximally 30% and 34%, respectively. Chemical composition analysis showed that LDL particles contained relatively more protein and less free cholesterol and cholesteryl-ester after treatment. The LDL cholesterol/protein ratio decreased from 1.24 +/- 0.21 to 0.97 +/- 0.23 (n = 20). By continuous monitoring of in vitro oxidation it appeared that LDL was less susceptible to oxidation after drug treatment. Maximal rate of diene production was significantly decreased fr...
Low-density-lipoprotein (LDL) oxidation may provide the crucial link between plasma LDL and ather... more Low-density-lipoprotein (LDL) oxidation may provide the crucial link between plasma LDL and atherosclerotic-lesion formation. Oxidation can be induced in vitro by incubating LDL with cells or metal ions and can be measured by continuously monitoring conjugated-diene absorbance at 234 nm. Measurement of LDL oxidizability was improved by performing the assay with 0.05 g of LDL-protein per liter of phosphate buffer containing 1 mumol of EDTA, by initiating oxidation by adding CuCl2 (5 mumol/L) at 30 degrees C, and by using a short-run ultracentrifugation method for isolating LDL, which reduced the time needed for obtaining purified LDL and thus reduced in vitro oxidation. LDL apolipoprotein analysis and oxidizability determination showed that this method is better than the longer sequential-isolation procedure. Adding butylated hydroxytoluene (BHT) to plasma as an antioxidant unpredictably increased the LDL oxidation lag time, making BHT unsuitable as an antioxidant. Adding EDTA appear...
The purpose of this study was to understand better the factors providing oxidation resistance to ... more The purpose of this study was to understand better the factors providing oxidation resistance to human low-density lipoprotein (LDL). Therefore, the susceptibility to copper-induced in vitro oxidation of LDL from vitamin E deficient patients and normal healthy subjects was studied. Surprisingly, the LDL of vitamin E deficient patients appeared less susceptible to oxidation than control LDL. Both oxidation rate and extent of oxidation, measured as diene production, were reduced when compared to control LDL. The lag time, a measure of resistance to oxidation, was not different from the lag time of LDL from healthy subjects. No relation was found between vitamin E content and resistance against oxidation. LDL from vitamin E deficient patients contained lower amounts of vitamin E, less cholesteryl esters, and increased amounts of triglycerides. Furthermore, its oleic acid content was increased and its linoleic acid content decreased. Linear regression analyses revealed that the ratio of oleic acid content to linoleic acid content was strongly correlated with the lag time, and inversely correlated with oxidation rate and extent of oxidation. Thus, LDL rich in oleic acid and poor in linoleic acid was less easily oxidized. It is concluded that the susceptibility of LDL to oxidation is determined not only by its antioxidant content, but also by other compositional factors, and more specifically by the ratio of oleic acid content to linoleic acid content.
Enhanced induction of low density lipoprotein (LDL) oxidation may play a role in the increased ca... more Enhanced induction of low density lipoprotein (LDL) oxidation may play a role in the increased cardiovascular risk in smokers. We determined LDL oxidisability in vitro in non-smokers, smokers and in subjects after smoking cessation. Plasma lipids and copper induced LDL oxidation in vitro were measured in 31 persistent smokers, 47 smokers who tried to stop smoking and 25 non-smokers. In the smoking cessation group, blood was collected before then 1, 3, 6 and 12 months after smoking cessation, and in the persistent smoking and non-smoking groups at baseline and after 12 months. Plasma thiobarbituric acid reactive substances (TBARS) were measured 3 times (at baseline then after 1 and 3 months) in all subjects who refrained from smoking (controlled by urinary cotinine concentrations) for at least 3 months. At baseline, no differences in mean age, body mass index and lipid profiles between groups were present. Seventeen subjects of the smoking cessation group (36%) managed to quit during 12 months. Smoking cessation was associated with an increase in mean weight (P </= 0.001) and waist-hip ratio (P </= 0.001). No major differences in LDL oxidisability were found between groups. A significant transient increase in high density lipoprotein (HDL) cholesterol was seen (from 1.20 +/- 0.39 to 1.34 +/- 0.42 mmol L-1) after 1 month of smoking cessation that disappeared after 3 months. However, after 1 month of smoking cessation, plasma TBARS decreased significantly (P < 0.05). Neither the previously observed increased cardiovascular risk in smokers nor the decreased risk in those who stopped smoking seem to be mediated by permanent changes in lipid profiles or by alterations in the susceptibility to in vitro oxidation of LDL.
The present review aims to highlight the consequences for mother and child of profound hyperchole... more The present review aims to highlight the consequences for mother and child of profound hypercholesterolemia during pregnancy of women with familial hypercholesterolemia. Familial hypercholesterolemia is increasingly diagnosed in younger patients due to the existence of screening programs and more widespread cholesterol testing. Increasing numbers of young female patients with familial hypercholesterolemia raise the issue of pregnancy and its consequences for the familial hypercholesterolemia patient herself but also for her offspring. When pregnancy is considered, lipid-lowering drugs are often discontinued because of the fear for teratogenic effects. The evidence for teratogenesis associated with statin use is scant and conflicting. On the other hand, several studies do suggest that pronounced hypercholesterolemia during pregnancy has adverse effects on both fetus and mother. In fact, human and animal studies reveal an enhanced tendency toward atherosclerosis in the offspring of women who suffer from hypercholesterolemia during pregnancy. In animal studies, some evidence exists that this can be reversed by treatment with lipid-lowering and antioxidative agents. Until today, however, no human studies exist that have evaluated efficacy or safety of lipid-lowering interventions in pregnant women with familial hypercholesterolemia. Altogether, the suggested relationship between severe hypercholesterolemia and enhanced atherosclerosis in offspring and possibly the mother warrants further confirmation and, consequently, studies that focus on therapeutic strategies that can safely lower cholesterol levels during pregnancy in these women.
In order to investigate the in vivo function of hepatic lipase, cats were injected with anti-cat ... more In order to investigate the in vivo function of hepatic lipase, cats were injected with anti-cat hepatic lipase antibodies which produced a complete and specific inhibition of heparin-releasable hepatic lipase. The cat was chosen as an animal model because it displays, like man, a relative deficiency of lipoprotein lipase compared to hepatic lipase and because the possession of two subfractions of high density lipoproteins, HDL2 and HDL3. In fasted cats no changes were observed in plasma triglycerides or phospholipids. In fed animals triglycerides increased considerably, indicating that hepatic lipase may have a function in the postprandial phase. In fat-loaded cats (6 g of fat/kg) triglycerides in the d less than 1.019 g/ml fraction increased from 4 h after the blockade due to accumulation of lipoproteins with pre-beta-mobility containing the apoproteins, apo B-100, apo E and apo A-I. Apo B-48 did not accumulate consistently. Phospholipids in the HDL2-fraction and those in the HDL3-fraction of the fat-loaded cats tended to increase and decrease from 6 and 9 h after the blockade, respectively. The absolute change in HDL2 phospholipids approximated that of HDL3-phospholipids. Overall, the density of HDL particles decreased, apparently secondary to the accumulation of apo A-I in the d less than 1.019 g/ml fraction. Our findings suggest that hepatic lipase is involved in the hydrolysis of a special class of apo A-I containing triglyceride-rich lipoproteins synthesised in the postprandial phase.
Uploads