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PubMed1990

The epidemiological relationship of hypercholesterolemia, hypertension, diabetes mellitus and obesity to coronary heart disease and atherogenesis.

Coronary heart disease (CHD) is an imprecise, inappropriate monitor of atherosclerosis severity and by inapplicable extrapolation CHD risk factors are incorrectly assumed to be causes of atherosclerosis. Taking into account (1) the misuse and substantial diagnostic error of CHD, (2) errors in determining the prevalence of risk factors, (3) the use of a young non-representative minority of sufferers of CHD, (4) bias posed by inclusion of familial hypercholesterolemia (FH) in clinical studies and (5) mutual inter-relationships, genetic influence and age dependence of hypercholesterolemia, hypertension, diabetes mellitus and body mass or obesity, it is unlikely that multivariate statistical analyses can adequately differentiate between their effects. These factors are age dependent and so are CHD and atherosclerosis. The importance of hypercholesterolemia in atherogenesis is suspect particularly since the vascular pathology of familial hypercholesterolemia and of cholesterol-fed animals has been misrepresented and does not provide support for the role of hypercholesterolemia in atherogenesis.

Age Factors↗
PubMed1995

Spontaneously hypertensive rats are resistant to the development of hypercholesterolemia.

The arterioles of young spontaneously hypertensive rats (SHR) are purported to have an enhanced sensitivity to nitric oxide (NO)-dependent vasodilators, relative to normotensive animals, while NO-related arteriolar responses are diminished in both mature SHR as well as hypercholesterolemic normotensive rats. Because endothelial production of NO relaxes vascular smooth muscle and inhibits platelet adhesion and aggregation, hypercholesterolemia may synergistically affect the development of genetic hypertension. The NO-mediated baseline vascular tone, acetylcholine-induced dilation, and inhibition of platelet thrombus formation were studied over time (10 weeks) in SHR and hypercholesterolemic SHR (HC-SHR). The in vivo microcirculation of the cremaster muscle was used to quantitate all observations. The HC-SHR became significantly hypercholesterolemic after 1 week on the cholesterol-supplemented diet, with serum cholesterol concentrations remaining elevated for the 10 weeks studied. However, the serum cholesterol concentrations of HC-SHR were significantly less than those of Sprague-Dawley and Wistar-Kyoto rats fed the same diet. Dietary hypercholesterolemia did not exacerbate the development of genetic hypertension. Second- and third-order arterioles of SHR and age-matched HC-SHR constricted to the same extent when the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was applied. The third order arterioles of both groups also dilated the same amount to acetylcholine and sodium nitroprusside. Platelet thrombus formation induced by light/dye photochemistry was not different between the SHR and HC-SHR groups either at 1 or 10 weeks of diet, and L-NAME decreased the time to thrombus occlusion of blood flow equally in both groups. This is in marked contrast to the previously reported hypercholesterolemia-induced decreases in vascular reactivity in Sprague-Dawley rats. These current findings demonstrate that SHR are resistant to the development of hypercholesterolemia and that NO-mediated vascular responses in SHR are not attenuated by hypercholesterolemia.

Acetylcholine↗
PubMed2004

Association of gene polymorphisms with coronary artery disease in individuals with or without nonfamilial hypercholesterolemia.

A substantial proportion of individuals with coronary artery disease (CAD) has concomitant hypercholesterolemia. A large-scale association study was performed to identify separately genes that confer susceptibility to CAD in the absence or presence of nonfamilial hypercholesterolemia. The study population comprised 5248 unrelated Japanese individuals, including 3085 subjects with CAD (2350 men, 735 women) and 2163 controls (1329 men, 834 women). Among all study subjects, 2541 individuals (1688 men, 853 women) had nonfamilial hypercholesterolemia, and 2707 individuals (1991 men, 716 women) did not have this condition. The genotypes for 33 polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hyperuricemia revealed that three polymorphisms [994G --> T (Val279Phe) in the platelet-activating factor acetylhydrolase gene, 242C --> T (His72Tyr) in the NADH/NADPH oxidase p22 phox gene, and 1100C --> T in the apolipoprotein C-III gene] were significantly associated with CAD in men with hypercholesterolemia. Genotyping of these three polymorphisms may prove informative for prediction of the genetic risk for CAD in men with nonfamilial hypercholesterolemia.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2004

Influences of hypercholesterolemia on red cell indices and erythrocyte sedimentation rate in elderly persons.

BACKGROUND: We investigated whether hypercholesterolemia influenced the values of mean corpuscular volume (MCV) and erythrocyte sedimentation rate (ESR). METHODS: A total of 463 nonanemic elderly persons were evaluated regarding red cell indices, ESR, and ESR-related parameters, such as fibrinogen, albumin, and C-reactive protein (CRP). RESULTS: There were no significant differences in MCV between elderly men with and without hypercholesterolemia (>/=240 mg/dl) nor between the subjects with a marked increase of serum cholesterol concentrations (>/=260 mg/dl) and with severely lowered cholesterol concentrations (<155 mg/dl). ESR in elderly men with hypercholesterolemia averaged 12.3+/-6.8 mm/h, which were significantly higher than in those without hypercholesterolemia (6.0+/-4.7 mm/h, p<0.01). ESR averaged threefold higher in the elderly men with serum cholesterol concentration >/=260 mg/dl versus those with serum cholesterol concentrations <155 mg/dl, although no significant differences were observed in fibrinogen, albumin, and CRP values between the two groups. Serum cholesterol concentrations were higher in elderly men with ESR>/=15.0 mm/h (248.9+/-43.5 mg/dl), compared to those with ESR<2.0 mm/h (199.5+/-31.7 mg/dl, p<0.01). Serum cholesterol concentrations showed no associations with red cell indices but correlated significantly with ESR in elderly men (r=0.24, p<0.01) and postmenopausal women (r=0.21, p<0.01). CONCLUSION: Hypercholesterolemia does not appear to influence MCV but significantly accelerates ESR, especially in elderly men.

Aged↗
PubMed2006

Comparison of the lipid-modifying efficacy and safety profiles of ezetimibe coadministered with simvastatin in older versus younger patients with primary hypercholesterolemia: a post Hoc analysis of subpopulations from three pooled clinical trials.

BACKGROUND: Despite the need for effective and well-tolerated lipid-lowering therapies for primary hypercholesterolemia in older patients, there is a relative paucity of published data on such treatments in this population. OBJECTIVE: We conducted a post hoc analysis to examine the lipid-modifying efficacy and safety profile of simvastatin (SIMVA) monotherapy, and the coadministration of ezetimibe (EZE) and SIMVA (EZE/SIMVA) in older (ie, aged>or=65 years) versus younger (ie, aged<65 years) patients with primary hypercholesterolemia. METHODS: We analyzed pooled data from 3 previously published, similarly designed, randomized, double-blind, placebo-controlled studies in patients with primary hypercholesterolemia. After a 6- to 8-week washout, a 4-week dietary stabilization period, and a 4-week placebo run-in period, patients with low-density lipoprotein cholesterol (LDL-C) of 145 to 250 mg/dL were randomized to EZE/SIMVA 10/10, 10/20, 10/40, or 10/80 mg; SIMVA 10, 20, 40, or 80 mg; EZE 10 mg; or placebo for 12 weeks. In this post hoc analysis, the percent change from baseline to week 12 in LDL-C, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoprotein B (apo B), triglycerides (TG), and high-sensitivity C-reactive protein (hs-CRP) for EZE/SIMVA (pooled across doses) versus SIMVA alone (pooled across doses) was compared between older and younger patients with primary hypercholesterolemia. Tolerability was assessed by adverse event reports and laboratory and vital signs assessments throughout the study. RESULTS: A total of 3083 patients aged 20 to 87 years were included in the 3 studies (2320 were aged<65 years and 763 were aged>or=65 years). Baseline lipid values and patient characteristics were similar among all treatment groups for patients aged<65 years versus those aged>or=65 years except that there was a higher percentage of females (62% vs 50%) and patients with hypertension (46% vs 29%) in the older versus younger subgroup (both, P<0.001). EZE/SIMVA was associated with greater improvements than SIMVA alone in LDL-C, non-HDL-C, apo B, TG, and hs-CRP (all, P<0.001); these effects did not appear to differ between the older and younger sub-groups (all, P=NS). Changes in HDL-C did not differ significantly between the EZE/SIMVA and SIMVA groups. More patients receiving EZE/SIMVA than SIMVA monotherapy achieved the target LDL-C level<100 mg/dL (P<0.001), regardless of age subgroup (77% vs 41% for patients aged<65 years and 85% vs 48% for patients aged>or=65 years). In the younger sub-group, the incidence of creatinine phosphokinase (CK) elevations>or=10x the upper limit of normal (ULN) was or=10x ULN were reported. In younger patients, the incidence of consecutive alanine amino-transferase or aspartate aminotransferase levels>or=3x ULN was 0% for placebo and EZE, <1% for SIMVA, and 2% for EZE/SIMVA; in older patients, it was 1% for placebo and EZE, <1% for SIMVA, and 0% for EZE/SIMVA. CONCLUSION: This post hoc analysis of pooled data from 3 previously published large clinical trials suggests that EZE/SIMVA was well tolerated and associated with improved lipid profiles in both older and younger patients with primary hypercholesterolemia.

Adult↗
PubMed2005

CD40 ligand enhances monocyte tissue factor expression and thrombin generation via oxidative stress in patients with hypercholesterolemia.

OBJECTIVES: We tested the hypothesis that CD40 ligand (CD40L) induces a prothrombotic state by enhancing oxidative stress. BACKGROUND: Patients with hypercholesterolemia show an ongoing prothrombotic state, but the underlying mechanism is still unclear. METHODS: Circulating levels of the soluble form of CD40L (sCD40L), prothrombin fragment (F1+2, a marker of thrombin generation), and 8-hydroxy-2'-deoxyguanosine (8-OHdG, a marker of oxidative stress) were measured in 40 patients with hypercholesterolemia and in 20 age- and gender-matched healthy subjects. RESULTS: Patients with hypercholesterolemia showed significantly higher levels of sCD40L (p <0.005), 8-OHdG (p <0.005), and prothrombin F1+2 (p <0.005), as compared with control subjects. Soluble CD40L significantly correlated with 8-OHdG (r=0.85, p <0.0001) and prothrombin F1+2 (r=0.83, p <0.0001); a significant correlation between 8-OHdG and prothrombin F1+2 was also observed (r=0.64, p <0.0001). An in vitro study demonstrated that CD40L-stimulated monocytes from patients with hypercholesterolemia expressed more tissue factor (TF) and prothrombin F1+2 than monocytes from controls; co-incubation of monocytes with either an inhibitor of NADPH oxidase or an inhibitor of phosphatidylinositol-3-kinase significantly reduced CD40L-mediated clotting activation. A marked inhibition of CD40L-mediated clotting activation was also observed in two male patients with hereditary deficiency of gp91 phox, the central core of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Finally, we demonstrated that CD40L-mediated clotting activation was significantly inhibited by vitamin C, a known antioxidant. CONCLUSIONS: This study indicates that in patients with hypercholesterolemia, CD40L over-expresses TF and increases the thrombin generation rate by an oxidative stress-mediated mechanism that requires the activation of NADPH oxidase.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

G-protein beta 3 subunit polymorphism C1429T and low-density lipoprotein receptor-related protein 5 polymorphism A1330V are risk factors for hypercholesterolemia in Japanese males--a prospective study over 5 years.

We examined the relationship between the C825T, C1429T, and A-350G variants in the G-protein beta 3 subunit (GNB3) gene, the A1330V and Q89R variants in the low-density lipoprotein receptor-related protein 5 (LRP5) gene, and the risk of hypercholesterolemia in a prospective study in Japanese workers. This study included observations over a 5-year period from 1997 to 2002 on 936 males and 662 females who were not hypercholesterolemic on entry. Hypercholesterolemia was defined as a serum total cholesterol level of 240 mg/dL or higher. Pooled logistic regression analyses were performed using either of the gene variants with age, body mass index, smoking, alcohol consumption, and habitual exercise as the covariates. The risk of the development of hypercholesterolemia was 2.27 times higher in males with the TT genotype of GNB3/C1429T than in males with the CC genotype (95% confidence interval, 1.04-4.94), after adjustment for the effects of other potential covariates. Simultaneously, the risk was 1.49 times higher in males with the AV genotype of LRP5/A1330V than in males with the AA genotype (95% confidence interval, 1.04-2.12) after adjustment for the effects of other potential covariates. This study indicates the GNB3/C1429T and LRP5/A1330V are independent risk factors for hypercholesterolemia in Japanese males and suggests that targeting these polymorphisms may be beneficial when attempting to prevent hypercholesterolemia in the general Japanese male population.

Adult↗
PubMed2006

Long-term effect of experimental hypercholesterolemia on cavernosal tissues.

OBJECTIVES: To determine the effect of long-term experimental hypercholesterolemia on cavernosal tissues and to evaluate whether these alterations are reversible after improvement of hypercholesterolemia. METHODS: Thirty-seven New Zealand male rabbits with a mean age of 5 to 6 months and a weight of 2 to 2.5 kg were included in this study. The control group (group 1, n = 7) was fed with normal standard rabbit chow for 24 weeks, the hypercholesterolemia group (group 2, n = 17) was fed with a 1% pure cholesterol diet for 24 weeks, and the reversibility group (group 3, n = 13) was fed first with the 1% pure cholesterol diet for 24 weeks and then with normal standard rabbit chow for 12 weeks. The basal and 24-week serum lipid profiles of all groups and the 36-week serum lipid profiles of group 3 were measured. Core tissue samples 4 mm in diameter taken from formalin-fixed, paraffin-embedded tissue blocks of rabbit corpus cavernosum were examined for Masson trichrome histochemically and desmin and smooth muscle actin by the tissue array method using immunohistochemistry. RESULTS: Hypercholesterolemia was observed in groups 2 and 3 at 24 weeks compared with group 1. In group 3, at 36 weeks, the cholesterol levels were decreased. A statistically significant (P < 0.05) irreversible decrease was observed in smooth muscle actin level in group 3 (reversibility group) by immunohistochemical analysis. The decrease in desmin was reversible, and no significant difference was observed in collagen among the three groups. CONCLUSIONS: Long-term chronic effects of experimental hypercholesterolemia on cavernosal smooth muscles might be irreversible and this might alter erectile function.

Actins↗
PubMed2003

Effects of mental stress on flow-mediated brachial arterial dilation and influence of behavioral factors and hypercholesterolemia in subjects without cardiovascular disease.

Mental and emotional arousal are known to trigger coronary events. The relation between hypercholesterolemia, behavioral factors, and mental stress-induced alterations in endothelial function are not well defined. Flow-mediated brachial arterial vasodilation has been established as a measure of arterial endothelial function. High-resolution ultrasound was used to measure mental stress-mediated, flow-mediated, and the combination of mental stress- and flow-mediated brachial artery dilation in 38 subjects, 20 of whom had total cholesterol levels > or =200 mg/dl. Mental stress was provoked by anger recall and mental arithmetic and trait hostility were assessed using the Cook-Medley scale. Under mental stress, participants with hypercholesterolemia showed less vasodilation than participants without hypercholesterolemia, even after adjustment for age and the magnitude of blood pressure response to mental stress. Mental stress attenuated flow-mediated brachial arterial vasodilation. There was an inverse relation between hostile affect and percent change in brachial artery diameter after mental stress combined with hyperemia (r = -0.57, p <0.001). Thus, hypercholesterolemia is associated with impaired vasodilation in response to mental stress. Mental stress inhibits flow-mediated vasodilation in normal subjects and those with hypercholesterolemia. The magnitude of this inhibition is associated with hostility.

Adult↗
PubMed1991

Hypercholesterolemia impairs endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle.

The majority of cases of impotence are associated with vascular risk factors such as diabetes, hypercholesterolemia, hypertension and smoking. These factors induce impairment of endothelium-dependent relaxation of blood vessels in man and in experimental animals. In this study the effects of hypercholesterolemia on the reactivity of rabbit corpus cavernosum smooth muscle strips to endothelium-dependent and endothelium-independent agents were investigated. New Zealand White rabbits (n = 14) were randomly divided into control and treatment groups. The control group (n = 7) received a regular diet while the treatment group (n = 7) was fed a diet of 0.5% cholesterol and 4% peanut oil for 10 weeks. Animals were then sacrificed and the corporal tissue studied in organ chambers for isometric tension measurement. Tissue was contracted with phenylephrine and concentration-dependent relaxation to acetylcholine, in the presence and absence of indomethacin, and to nitroprusside were examined. Blood level of cholesterol in the cholesterol-fed group was significantly higher compared to the control group. Contractions to phenylephrine were similar in both groups. Hypercholesterolemia, however, inhibited relaxation to acetylcholine but did not alter relaxation to nitroprusside, a cyclic guanosine monophosphate (cGMP)-dependent, direct smooth muscle dilator. Indomethacin enhanced the relaxations to acetylcholine in both control and cholesterol-fed groups but did not correct the difference in the relaxation to acetylcholine between both groups. It is concluded that hypercholesterolemia impairs endothelium-mediated relaxation of rabbit corpus cavernosum smooth muscle. The mechanism for the endothelial dysfunction does not appear to involve alteration in cyclooxygenase products of arachidonate or the cGMP-dependent relaxation of corporal smooth muscle. Impairment of endothelium-dependent relaxation of corporal smooth muscle may contribute to the pathophysiology of impotence associated with hypercholesterolemia in man.

Acetylcholine↗
PubMed2000

[Apolipoprotein E gene polymorphism and risk of hypercholesterolemia: a case control study in a working population of Valencia].

BACKGROUND: The apolipoprotein E (apoE) gene is polymorphic with three common alleles (epsilon 2, epsilon 3, epsilon 4) whose allelic frequency and association with lipid levels varies from population to population. The aim of this study was to estimate the association between these genetic variants and the risk of hypercholesterolemia in a Mediterranean Spanish population. PATIENTS AND METHODS: A case-control study in a working population from Valencia was carried out. A total of 330 cases (148 men and 182 women) with moderate hypercholesterolemia (total cholesterol > 200 mg/dl or with lipid lowering treatment) and age range 20 to 60 years, were identified. 330 normocholesterolemic controls matched by age and sex were selected. From all of them data of apoE genotype, body mass index, lipid and lipoprotein levels, socioeconomic and life-style variables were obtained. RESULTS: The epsilon 2 allele frequency was statistically lower in cases (0.033) than in controls (0.086). The epsilon 4 allele frequency was higher in cases (0.115) than in controls (0.039). In the crude logistic regression analysis, the apoE polymorphism was related (p < 0.001) to the risk of hypercholesterolemia. After adjustment by age, body mass index, educational level, tobacco smoking, alcohol consumption and physical activity the epsilon 2 allele was associated with a lower risk of hypercholesterolemia (odds ratio [OR] = 0.36; 95% confidence interval (CI): 0.20-0.64), and the epsilon 4 allele was associated with a higher risk (OR = 3.04; 95% CI: 1.82-5.06). CONCLUSIONS: The apoE genotype was significantly related to the risk of moderate hypercholesterolemia in the Mediterranean Spanish population.

Adult↗
PubMedDate not supplied

Effects of cerivastatin sodium, a new HMG-CoA reductase inhibitor, on biliary lipid metabolism in patients with hypercholesterolemia.

The use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has become common in the treatment of hypercholesterolemia. The present uncontrolled study was undertaken to determine the effect of cerivastatin sodium (BAY w 6228), a new HMG-CoA reductase inhibitor, on biliary lipid levels in patients with hypercholesterolemia. Twenty-one hypercholesterolemic patients (World Health Organization type IIa = 16 patients; type IIb = 5 patients) received placebo during a 4- to 6-week observation period, after which they received cerivastatin sodium 0.2 mg/d for 12 weeks. Fasting blood samples were drawn for the measurement of serum lipid levels early in the morning before the start of treatment and once a month for each of the 12 weeks of cerivastatin sodium treatment. Gallbladder bile samples were aspirated with a duodenal tube by cerulein stimulation to assess bile lithogenicity. Serum total cholesterol levels decreased markedly after 12 weeks. However, no significant difference was found in the molar percentage composition of biliary lipids (e.g., cholesterol, phospholipids, and total bile acids) or in individual biliary bile acids. Consequently, no significant change in bile cholesterol saturation index was found. The index values before and after 12 weeks of treatment were 0.81 +/- 0.38 and 0.80 +/- 0.47, respectively, whereas when patients were grouped by type of hypercholesterolemia, there was a tendency toward decreased lithogenicity in patients with type IIb but not type IIa hypercholesterolemia. We concluded that cerivastatin sodium was an effective cholesterol-lowering drug that did not appear to worsen biliary lipid metabolism and that may decrease lithogenicity in patients with type IIb hypercholesterolemia.

Adult↗
PubMed1999

Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction.

OBJECTIVES: We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5'-nucleotidase which plays a key role in the IP-induced cardioprotection. BACKGROUND: The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects. METHODS: Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5'-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure. RESULTS: This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5'-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold). CONCLUSIONS: Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5'-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5'-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP.

5'-Nucleotidase↗
PubMed1995

Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of hypercholesterolemia alone and combined hyperlipidemia.

High levels of low-density lipoprotein cholesterol (LDL) (hypercholesterolemia) are commonly present in the nephrotic syndrome. Another pattern of dyslipidemia in nephrotic patients is an elevation of both cholesterol and triglyceride levels (combined hyperlipidemia). It has been postulated that the underlying cause of nephrotic dyslipidemia is an hepatic overproduction of apolipoprotein B (apo B)-containing lipoproteins. To examine this hypothesis, the metabolism of LDL-apo B was compared between nephrotic patients with hypercholesterolemia and with combined hyperlipidemia. Thirteen patients (7 with hypercholesterolemia, and 6 with combined hyperlipidemia) underwent measurements of turnover rates of autologous LDL apo B. The results were compared to normolipidemic controls and to patients with primary combined hyperlipidemia previously studied in our laboratory. Nephrotic patients with hypercholesterolemia generally had: (a) lower fractional catabolic rates of LDL apo B than normolipidemic healthy individuals; (b) LDL particles enriched in cholesterol; but (c) no overproduction of LDL apo B. In contrast, patients with combined hyperlipidemia were found to have: (a) high fractional catabolic rates for LDL apo B compared to normolipidemic controls; (b) cholesterol-poor LDL particles; and (c) markedly elevated production rates for LDL. Also, for the group as a whole, there was a positive correlation between plasma triglyceride levels and fractional catabolic rates. These data indicate that the metabolism of LDL is strikingly different between the two forms of nephrotic dyslipidemia. Although there may be common mechanisms contributing to LDL levels in nephrotic patients, there also appears to be a divergence of mechanisms depending on whether hypertriglyceridemia is associated with hypercholesterolemia.

Adolescent↗
PubMed2002

Obesity, weight change and risks for hypertension, diabetes and hypercholesterolemia in Japanese men.

OBJECTIVE: To examine the effects of the degree of body mass index and weight gain as the risks for hypertension, hypercholesterolemia and diabetes in Japanese men, and to compare that to the corresponding effects in a Caucasian population. DESIGN: Prospective cohort study. SETTING: Cohort of all male employees at a company. SUBJECTS: A total of 4737 male employees followed until retirement or for 4 y (longest term 4 y). RESULTS: Increase of body mass index beyond 22 kg/m(2) related to an increased risk for hypertension even after being adjusted for possible confounding factors such as age, smoking status, alcohol intake, family history and baseline value of systolic blood pressure. The risks greatly increased in subjects with a body mass index above 27 kg/m(2) for hypertension, and 29 kg/m(2) for diabetes and hypercholesterolemia. Weight gain (more than 2 kg) was strongly related to an increased risk for hypertension and hypercholesterolemia after being adjusted for possible confounding factors. However, weight gain was not related to diabetes, and weight loss did not decrease the risks for any of the three diseases. CONCLUSIONS: Among Japanese, the degrees of body mass index associated with risks for hypertension, diabetes and hypercholesterolemia were lower than those in Caucasians. The risks for hypertension and hypercholesterolemia were strongly associated with weight gain in a Japanese male population who showed a low prevalence of severe obesity, and the risks were similar to or somewhat higher than those in a Caucasian population with a high prevalence of severe obesity. SPONSORSHIP: Health Science Research Grant by the Ministry of Health and Welfare of Japan.

Adolescent↗
PubMed2000

Trends in lipid levels and hypercholesterolemia in hypertensive and normotensive finnish adults from 1982 to 1997.

OBJECTIVES: To assess the trends in lipid levels and awareness of hypercholesterolemia in hypertensive and normotensive population in Finland from 1982 to 97. DESIGN: Four independent cross-sectional population surveys conducted in 1982, 1987, 1992 and 1997. SETTING: The provinces of North Karelia and Kuopio in eastern Finland and the region of Turku-Loimaa in south-western Finland. SUBJECTS: Men and women aged 25-64 years, selected randomly from the national population register. The subjects were classified to four groups according to their blood pressure level and treatment status: normotensive, unaware hypertensive, aware but not treated hypertensive and treated hypertensive. The total number of participants was 24 083. MAIN OUTCOME MEASURES: We assessed the mean serum total cholesterol and HDL cholesterol concentrations, the prevalence of hypercholesterolemia (total cholesterol >/=6.5 mmol L-1 or the use of lipid-lowering drugs), the prevalence of a high ratio of total cholesterol to HDL cholesterol (ratio >/=5) and the awareness of hypercholesterolemia amongst the four study groups. RESULTS: Mean total cholesterol, the prevalence of hypercholesterolemia and the prevalence of a high ratio of total to HDL cholesterol decreased, whereas the awareness of hypercholesterolemia increased significantly in all study groups. The decline in mean total cholesterol was largest in treated hypertensive subjects of both sexes (13% in men, 14% in women). Mean HDL cholesterol increased significantly in all study groups except in the unaware hypertensive men, but it remained significantly lower in treated hypertensive patients in both sexes compared with the other groups (P < 0.001). CONCLUSIONS: The lipid profile of both the hypertensive and normotensive population has significantly improved in both the hypertensive and normotensive population in Finland from 1982-97. The introduction of newer antihypertensive drugs has not had any effect on the HDL cholesterol level amongst treated hypertensive patients at the population level.

Adult↗
PubMed2005

Severe preeclampsia is associated with a positive family history of hypertension and hypercholesterolemia.

OBJECTIVE: To investigate an association between a family history of cardiovascular disease and severe preeclampsia and/or HELLP syndrome (Haemolysis, Elevated Liver enzymes, Low Platelets). METHODS: One hundred twenty-eight women with a history of severe preeclampsia and/or HELLP syndrome and 123 women with previous uncomplicated pregnancies only were included in the study. All participants completed questionnaires about diagnoses of cardiovascular diseases, hypertension, and hypercholesterolemia among their first-degree relatives, which were subsequently confirmed by the relatives' general practitioners. The main outcome measures were the prevalence of cardiovascular diseases, hypertension, and hypercholesterolemia among first-degree relatives of both groups. Statistical analysis was done using chi(2)-analysis. RESULTS: The prevalence of familial cardiovascular disease among women with a history of severe preeclampsia and/or HELLP syndrome (23%) compared to controls (19%) was not significantly different (OR 1.3, 95%CI 0.7-2.5). However, women with a history of severe preeclampsia and/or HELLP syndrome more often had one or more first-degree relatives with hypertension and/or hypercholesterolemia before the age of 60 years compared to controls (54% vs. 32%, respectively; OR 2.6, 95%CI 1.5-4.3). The prevalence of hypertension and hypercholesterolemia among first-degree relatives, irrespective of age, also was significantly higher among women with a history of severe preeclampsia and/or HELLP syndrome as compared to controls (60% vs. 42%, respectively; OR 2.0, 95%CI 1.2-3.4). CONCLUSION: Severe preeclampsia is associated with a positive family history of hypertension and/or hypercholesterolemia.

Adult↗
PubMed2002

The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol-lowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis.

It has long been postulated that pathogenic events during fetal development influence atherosclerosis-related diseases later in life, but the mechanisms involved are unknown. This review focuses on the evidence indicating that maternal hypercholesterolemia during pregnancy is responsible for one cascade of pathogenic events. Maternal hypercholesterolemia is associated with greatly increased fatty streak formation in human fetal arteries and accelerated progression of atherosclerosis during childhood. Recent experiments in genetically more homogeneous rabbits established that temporary diet-induced maternal hypercholesterolemia is sufficient to enhance fetal lesion formation. More important, maternal hypercholesterolemia or ensuing pathogenic events in the fetus increase postnatal atherogenesis in response to hypercholesterolemia. Maternal treatment with cholesterol-lowering agents or antioxidants greatly reduces fetal and postnatal atherogenesis, indicating a pathogenic role of lipid peroxidation and a potential involvement of oxidation-sensitive signaling pathways. Experiments in a murine model showed that differences in arterial gene expression between offspring of normo- and hypercholesterolemic mothers persist long after birth, supporting the assumption that fetal lesion formation is associated with genetic programming, which may in turn affect postnatal atherogenesis. A better understanding of pathogenic programming events in utero may lead to the identification of genes determining the susceptibility to atherosclerosis and define novel preventive approaches.

Animals↗