Blood pressure, cholesterol, and stroke in eastern Asia. Eastern Stroke and Coronary Heart Disease Collaborative Research Group.

[No authors listed]

BACKGROUND: Stroke is a major cause of death and disability in most populations of eastern Asia, and the incidence, particularly of haemorrhagic stroke, is generally higher than in western populations. This study aimed to assess the contributions of blood pressure and blood cholesterol concentrations to stroke risk in populations from eastern Asia. METHODS: The project included 13 cohorts from the People's Republic of China and five from Japan (124,774 participants, 837,214 person-years of observation). All 18 cohorts provided data on blood pressure and 12 (69,767 participants) provided data on cholesterol concentrations. Parametric and non-parametric analyses were done, with adjustments for several potential confounding factors. Analyses were based on estimated usual diastolic blood pressure and cholesterol concentration during follow-up, rather than baseline measurements, to avoid regression dilution bias. FINDINGS: Overall mean blood pressure was 124/78 mm Hg and mean cholesterol concentration was 4.5 mmol/L. 1798 strokes occurred; 751 (42%) were classified as haemorrhagic and 707 (39%) were confirmed by computed tomography or necropsy. Each 5 mm Hg lower usual diastolic blood pressure was associated with lower risk of non-haemorrhagic stroke (odds ratio 0.61 [95% CI 0.57-0.66]) and lower risk of haemorrhagic stroke (0.54 [0.50-0.58]). With decreasing cholesterol concentrations there were trends towards a decrease in risk of non-haemorrhagic stroke (odds ratio for 0.6 mmol/L decrease, 0.77 [0.57-1.06]) and an increase in risk of haemorrhagic stroke (1.27 [0.84-1.91]). Overall, there was no clear evidence of any interaction between cholesterol and diastolic blood pressure. INTERPRETATION: Blood pressure is an important determinant of stroke risk in eastern Asian populations, whereas cholesterol concentration is less important, affecting the proportions of stroke subtypes more than overall stroke numbers. The association between blood pressure and stroke seems stronger than in western populations; a population-wide reduction of 3 mm Hg in diastolic blood pressure should eventually decrease the number of strokes by about a third.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9851379&dopt=Abstract cholesterol




Testosterone, sex hormone-binding globulin, lipoproteins, and vascular disease risk.

Dickerman RD, McConathy WJ, Zachariah NY.

Department of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth 76107-2699, USA.

BACKGROUND: That men have a higher risk of coronary heart disease has implicated testosterone as a risk factor. Lipoprotein levels have been reported to be altered by androgens, thus increasing the risk of coronary heart disease, myocardial infarction, and sudden death. The increasing abuse of anabolic steroids and reports of cases of sudden death and myocardial infarction among bodybuilders have raised concerns about an increase in cardiovascular risk for this population. METHODS: Twelve competitive bodybuilders were recruited for a comprehensive study on the cardiovascular risks associated with use of anabolic steroids. Six competitive heavyweight bodybuilders ingesting self-directed regimens of anabolic steroids (steroid group) and six competitive heavyweight drug-free bodybuilders were used for cardiovascular risk assessment. Apolipoproteins A-I and B, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, testosterone, and sex hormone-binding globulin levels were determined in each athlete. RESULTS: Total, HDL and LDL cholesterol, apolipoproteins A-I and B, and triglyceride levels were significantly lower in members of the steroid group. As expected, testosterone level was significantly higher in members of the steroid group; sex hormone-binding globulin level was significantly lower. Apolipoprotein and lipoprotein levels were lower in members of the steroid group, whereas the total: HDL cholesterol ratio was significantly higher for members of the steroid group. CONCLUSIONS: Consistently with previous reports, androgens were associated with decreases in HDL cholesterol and apolipoprotein A-I levels. However, androgens were also associated with reduced LDL cholesterol and apolipoprotein B levels. Despite the significantly higher total: HDL cholesterol ratio, the low serum total cholesterol levels (within the fifth percentile) and low plasma triglyceride levels in members of the steroid group raise questions concerning the exact role of androgens in increasing risk of cardiovascular disease.

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Treatment goals for low-density lipoprotein cholesterol in the secondary prevention of coronary heart disease: absolute levels or extent of lowering?

Cullen P, Assmann G.

Institute of Arteriosclerosis Research at the University of Munster, Germany.

The results of the Scandinavian Simvastatin Survival Study (4S) and the Cholesterol and Recurrent Events (CARE) study make abundantly clear the benefits of lowering low-density lipoprotein (LDL) cholesterol in patients with a history of coronary artery disease. Current guidelines in the United States and Germany recommend a treatment goal for LDL cholesterol of 100 mg/dl. However, the evidence for setting such a goal is not consistent among trials. It has even been argued that setting an absolute LDL goal may be unhelpful, per se, because the higher the patient's pretreatment LDL cholesterol, the more difficult achieving this goal becomes. It has also been recognized that measures to lower LDL cholesterol, and medications in particular, produce a relative rather than an absolute degree of reduction in circulating levels. For example, most statins produce a similar proportional decrease in LDL cholesterol irrespective of baseline LDL. Thus, if the baseline LDL is 180 mg/dl, the decrease in LDL with a particular statin dose may be 60 to 120 mg/dl, whereas if the baseline LDL is 120 mg/dl, the expected decrease in LDL with the same statin dose would be only 40 to 80 mg/dl (i.e., a 30% reduction in each case). These points have led some investigators to suggest that it may be more practicable to recommend the amount by which LDL should be lowered rather than by specifying an absolute level of LDL cholesterol which should be achieved. This report summarizes the proceedings of an international symposium held on this topic on October 4, 1996, in Berlin by the International Task Force for Prevention of Coronary Heart Disease and the Institute of Arteriosclerosis Research at the University of Munster.

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Effects of vitamin K2 (menatetrenone) on atherosclerosis and blood coagulation in hypercholesterolemic rabbits.

Kawashima H, Nakajima Y, Matubara Y, Nakanowatari J, Fukuta T, Mizuno S, Takahashi S, Tajima T, Nakamura T.

Pharmacological Evaluation Section, Tokyo Research Laboratoires, Eisai Co., Ltd., Koishikawa, Japan.

Gamma-Carboxyglutamic acid (Gla)-containing protein, synthesized in the presence of vitamin K, has been found in atherogenic plaques, but the pharmacological effect of vitamin K on atherosclerosis is unclear. We examined whether vitamin K2 (menatetrenone) could affect the progression of both atherosclerosis and hypercoagulability in hypercholesterolemic rabbits. Vitamin K2 in daily doses of 1, 10 and 100 mg/kg was given with a 0.5% cholesterol diet for 10 weeks to 8 rabbits each. The plasma levels of total-cholesterol in the vitamin K2-treated groups were clearly lower than that of the hypercholesterolemic control group. The excessive dose of vitamin K2, even at the high dose of 100 mg/kg/day for 10 weeks, did not accelerate the progression of atherosclerosis and did not promote the coagulative tendency in the rabbits. In contrast, the vitamin K2 treatment (1 to 10 mg/kg/day) suppressed the progression of atherosclerotic plaques, intima-thickening and pulmonary atherosclerosis, the increase of ester-cholesterol deposition in the aorta, and both the elevation in plasma factor X level and increase in Hepaplastin test value in the rabbits. These results indicate that the pharmacological dose of vitamin K2 prevents both the progression of atherosclerosis and the coagulative tendency by reducing the total-cholesterol, lipid peroxidation and factor X activity in plasma, and the ester-cholesterol deposition in the aorta in hypercholesterolemic rabbits.

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Vitamin A and vitamin E statuses of preschool children of socioeconomically disadvantaged families living in the midwestern United States.

Spannaus-Martin DJ, Cook LR, Tanumihardjo SA, Duitsman PK, Olson JA.

Department of Biochemistry and Biophysics, Iowa State University, Ames 50011, USA.

OBJECTIVE: To determine the vitamin A and vitamin E statuses of socioeconomically disadvantaged preschool American children. DESIGN: Cross-sectional study of preschool children from socioeconomically disadvantaged families. SETTING: Central Iowa, USA. SUBJECTS: A group of 77 apparently healthy children was studied with the following characteristics: 5 mo-6 y; 37 males, 40 females, 56 non-Hispanic Caucasians, 3 Hispanics, 18 Afro-Americans. METHODS: Modified relative dose response (MRDR) test for vitamin A status assessment; serum retinol, alpha-tocopherol, cholesterol, and carotenoids; weight for age. RESULTS: Although the mean weight for age was the 53rd percentile of the NCHS standard, a significant number of children (P = 0.006, chi(2)) were either markedly underweight or overweight. Ratios of 3,4-didehydroretinol to retinol (DR/R) were > 0.030, in 32% of the children. Mean serum retinol, alpha-tocopherol and cholesterol (+/- s.d.) were 1.09 +/- 0.23 microM/L, 16.8 +/- 6.3 microM/L and 4.01 +/- 0.8 microM/L. Three children (3.9%) showed a serum retinol value < 0.7 microM/L. One child with a serum retinol value < 0.7 microM/L and one additional child showed a ratio of alpha-tocopherol to cholesterol < 1.44 mumol/mmol. The mean alpha-tocopherol to cholesterol ratio for the group (4.31 +/- 1.71 mumol/mmol), however, was satisfactory. The only significant (P < or = 0.05) age-related changes were an increase in the serum cholesterol (P = 0.005) and decrease in the alpha-tocopherol to cholesterol ratio (P < 0.005) between the 0-2 y and the 2-4 y groups. Serum cholesterol (P = 0.0165, two-tailed) and lycopene (P = 0.004) concentrations of Afro-Americans were significantly higher than those of Caucasians. Median serum concentrations of alpha-carotene and beta-carotene were lower and, of lycopene higher than those found in children studied in a national survey. Serum carotenoid concentrations generally increased with age. CONCLUSIONS: Larger percentages of underweight and overweight children and a significant degree (32%) of inadequate vitamin A status were found in this group of socioeconomically disadvantaged children. Afro-Americans showed higher serum cholesterol and lycopene concentrations than did Caucasians, but otherwise were nutritionally similar. Age-related changes were small. Of nutritional parameters considered, the vitamin A status of socioeconomically disadvantaged segments of our population clearly needs attention.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9426362&dopt=Abstract cholesterol




Early diet influences hepatic hydroxymethyl glutaryl coenzyme A reductase and 7alpha-hydroxylase mRNA but not low-density lipoprotein receptor mRNA during development.

Devlin AM, Innis SM, Shukin R, Rioux MF.

Department of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.

Plasma cholesterol levels increase after birth, and to a greater extent in breast-fed versus formula-fed infants. This increase is believed to be due to the high fat and cholesterol content of the infant diet, but little is known about the effects of early diet on the expression of proteins involved in regulating cholesterol metabolism. This study examined changes in the expression of hepatic proteins regulating cholesterol metabolism during development. Newborn piglets were fed sow milk or one of four formulas for 18 days. The formulas had similar levels of palmitic acid (16:0) as in milk, supplied as palm olein oil with 16:0 esterified predominantly to the sn-1,3 position or as synthesized triglyceride (TG) with 16:0 esterified mainly to the sn-2 position of glycerol, each with no cholesterol (<0.10 mmol/L) or 0.65 mmol/L cholesterol added. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of mRNA levels was used to assess the effects of diet on hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, low-density lipoprotein (LDL) receptor, and 7alpha-hydroxylase (C7H). LDL receptor mRNA levels showed no appreciable difference between milk- and formula-fed piglets. However, the levels of HMG-CoA reductase and C7H mRNA were higher (P < .05) in all formula-fed versus milk-fed piglets, irrespective of the formula TG source or cholesterol content. The lower levels of HMG-CoA reductase and C7H mRNA in milk-fed piglets were accompanied by higher (P < .05) plasma total, high-density lipoprotein (HDL), and apolipoprotein (apo) B-containing cholesterol. These studies show that the levels of hepatic HMG-CoA reductase and C7H mRNA, but probably not LDL receptor mRNA, are altered by early diet.

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Overexpression of human lecithin:cholesterol acyltransferase in cholesterol-fed rabbits: LDL metabolism and HDL metabolism are affected in a gene dose-dependent manner.

Brousseau ME, Santamarina-Fojo S, Vaisman BL, Applebaum-Bowden D, Berard AM, Talley GD, Brewer HB Jr, Hoeg JM.

Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Lecithin:cholesterol acyltransferase (LCAT) is an enzyme well known for its involvement in the intravascular metabolism of high density lipoproteins; however, its role in the regulation of apolipoprotein (apo) B-containing lipoproteins remains elusive. The present study was designed to investigate the metabolic mechanisms responsible for the differential lipoprotein response observed between cholesterol-fed hLCAT transgenic and control rabbits. 131I-labeled HDL apoA-I and 125I-labeled LDL kinetics were assessed in age- and sex-matched groups of rabbits with high (HE), low (LE), or no hLCAT expression after 6 weeks on a 0.3% cholesterol diet. In HE, the mean total cholesterol concentration on this diet, mg/dl (230 +/- 50), was not significantly different from that of either LE (313 +/- 46) or controls (332 +/- 52) due to the elevated level of HDL-C observed in HE (127 +/- 19), as compared with both LE (100 +/- 33) and controls (31 +/- 4). In contrast, the mean nonHDL-C concentration for HE (103 +/- 33) was much lower than that for either LE (213 +/- 39) or controls (301 +/- 55). FPLC analysis of plasma confirmed that HDL was the predominant lipoprotein class in HE on the cholesterol diet, whereas cholesteryl ester-rich, apoB-containing lipoproteins characterized the plasma of LE and, most notably, of controls. In vivo kinetic experiments demonstrated that the differences in HDL levels noted between the three groups were attributable to distinctive rates of apoA-I catabolism, with the mean fractional catabolic rate (FCR, d-1) of apoA-I slowest in HE (0.282 +/- 0.03), followed by LE (0.340 +/- 0.01) and controls (0.496 +/- 0.04). A similar, but opposite, pattern was observed for nonHDL-C levels and LDL metabolism (h-1), such that HE had the lowest nonHDL-C levels with the fastest rate of clearance (0.131 +/- 0.027), followed by LE (0.057 +/- 0.009) and controls (0.031 +/- 0.001). Strong correlations were noted between LCAT activity and both apoA-I (r= -0.868, P < 0.01) and LDL (r = 0.670, P = 0.06) FCR, indicating that LCAT activity played a major role in the mediation of lipoprotein metabolism. In summary, these data are the first to show that LCAT overexpression can regulate both LDL and HDL metabolism in cholesterol-fed rabbits and provide a potential explanation for the prevention of diet-induced atherosclerosis observed in our previous study.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9458277&dopt=Abstract cholesterol




High-density lipoprotein cholesterol strongly discriminates between healthy free-living and disabled octo-nonagenarians: a cross sectional study. Associazione Medica Sabin.

Zuliani G, Palmieri E, Volpato S, Bader G, Mezzetti A, Costantini F, Sforza GR, Imbastaro T, Romagnoni F, Fellin R.

Department of Internal Medicine II, University of Ferrara, Italy.

Aging is frequently associated with a deterioration in health and functional status, which often induces important modifications in several biological parameters, including plasma lipids; as a consequence, the real "meaning" of lipoprotein parameters in old individuals is complex. A cross sectional study was carried out in order to investigate the lipoprotein profile in very old individuals with or without disability, and evaluate the possible influence of other biological variables on plasma lipids. One hundred selected healthy free-living (FL) and 62 disabled (DIS) subjects aged over 80 were enrolled; 91 healthy adults matched for origin were included as controls. Lipoprotein profile [total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apoprotein A-I and B], anthropometric parameters, and ADL were measured. The FL octo-nonagenarians featured higher HDL-cholesterol levels than adult controls. DIS octo-nonagenarians showed lower total and HDL-C levels than FL. Discriminant analysis indicated that HDL-cholesterol and apoprotein A-I, but not total cholesterol, strongly discriminated between FL and DIS octo-nonagenarians. Multivariate analysis demonstrated that the waist/hip ratio, an index of visceral adiposity, was negatively associated with HDL-C levels in FL, but not in DIS elderly. We conclude that: 1) in very old individuals, the absence or presence of disability is strongly associated with high or low HDL-cholesterol values, respectively; 2) HDL-C and apo A-I are the parameters which better discriminate between FL and DIS octo-nonagenarians; and 3) the differences in HDL-C levels between FL and DIS are not due to modifications in anthropometric parameters. Prospective studies are needed to better understand the relationship between high-density lipoprotein levels, disability and aging.

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High prevalence of metabolic risk factors for cardiovascular diseases among Saudi population, aged 30-64 years.

Rahman Al-Nuaim A.

King Khalid Univ. Hospital, King Saud University, Riyadh, Saudi Arabia.

OBJECTIVE: Study the prevalence of metabolic risk factors for cardiovascular diseases, obesity, diabetes mellitus, hypercholesterolemia and other cholesterol related risk factors among Saudi population, aged 30-64 years. DESIGN: Cross sectional national epidemiological randomized household survey. SUBJECT: 2059 Saudi subjects, aged 30-64 years. Sample was representative and in accordance with the national population distribution with respect to age, gender, regional and residency, urban vs. rural, population distribution. MEASUREMENT: Height and weight with calculation of body mass index, blood samples were drawn and assayed for glucose, total cholesterol, triglyceride and high density lipoprotein. Low density lipoprotein and cholesterol/high density lipoprotein ratio were calculated. Oral glucose tolerance test was done for subjects with borderline random glucose concentration. The overall prevalence of diabetes mellitus was calculated. RESULTS: Mean body mass index (BMI) was significantly higher among female subjects 28.3(6) vs. 26.6(4.6), P=0.0001. The 90th percentile of BMI was higher among female subjects across all age groups. The 90th percentile of BMI for Saudi subjects were higher across all age group than sex and age matched European subjects. Mean serum total cholesterol (TC) concentration was higher, however, not significant among female, compared with male subjects. The 90th percentile of serum TC concentration was higher among female, compared with male subjects for all age groups after the age of 40 years. The 90th percentile of serum TC concentration for Saudi subjects was lower across all age groups than sex and age matched European subjects. The prevalence of overweight was significantly higher among male subjects whereas the prevalence of obesity was significantly higher among female subjects. The prevalence of diabetes mellitus was significantly higher among female subjects whereas the prevalence of impaired glucose tolerance was significantly higher among male subjects. The prevalence of hypercholesterolemia, whether using cut-off levels of >5.2 mmol/l or >6.2 mmol/l. were similar between male and female subjects. They were lower than the prevalence of hypercholesterolemia among sex and age matched subjects whether from developed or from some developing countries. The prevalence of hypo HDL cholesterolemia, <0.9 mmol/l, was significantly higher among male subjects. The prevalence of total cholesterol/high density lipoprotein ratio, >6.5, for Saudi subjects was higher than some other developing countries. CONCLUSION: This study has shown high prevalence of metabolic risk factors for CVD. As atherosclerosis is ongoing process and considering the young nature of this country with 60% of population are <30 years old, one would expect the magnitude of CVD to multiply in the future especially with the continuous exposure to metabolic and non-metabolic risk factors. Several of the metabolic risk factors are modifiable either through change of lifestyle or medical treatment. There is a need to address such risk factors at national and regional level with aim of early identification and prevention. There is a need to monitor the trend of CVD and the risk factors which can be used to assess the efficacy of control programs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9476683&dopt=Abstract cholesterol