Body weight change and carotid artery wall thickness. The Atherosclerosis Risk in Communities (ARIC) Study

The impact of weight change in adulthood on cardiovascular disease is controversial. This study examined the association of change in body weight, from young adulthood to middle age, with average carotid artery intimal-medial wall thickness by B-mode ultrasound measured in middle age. Participants were 13,282 men and women aged 45-64 years from the baseline examination of the Atherosclerosis Risk in Communities (ARIC) Study (1987-1989). Weight change was calculated as the difference between weight at the baseline examination and self-reported weight at age 25. White men gained a mean of 9.7 kg; black men, 10.1 kg; white women, 12.0 kg; and black women, 20.8 kg. Weight change was positively, albeit modestly, associated with intimal-medial thickness in black men and white men and in white women, but not in black women. Adjusted for age, examination center, smoking, education, sports activity level, height, and body mass index at age 25, the differences in intimal-medial thickness associated with a 10-kg increment in weight change were 0.016 (95% confidence interval 0.010 to 0.022) mm in white men, 0.008 (95% confidence interval 0.001 to 0.015) mm in black men, 0.013 (95% confidence interval 0.009 to 0.017) mm in white women, and 0.002 (95% confidence interval -0.002 to 0.006) mm in black women. These findings support the hypothesis that weight gain in adulthood promotes atherosclerotic changes in white men and women and in black men.     

Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study

The objective of this study was to examine the relationships of serum and dietary magnesium (Mg) with prevalent cardiovascular disease (CVD), hypertension, diabetes mellitus, fasting insulin, and average carotid intimal-medial wall thickness measured by B-mode ultrasound. A cross-sectional design was used. The setting was the Atherosclerosis Risk in Communities (ARIC) Study in four US communities. A total of 15,248 participants took part, male and female, black and white, aged 45-64 years. Fasting serum Mg, lipids, fasting glucose and insulin were measured; as was usual dietary intake by food frequency questionnaire and carotid intima-media thickness by standardized B-mode ultrasound methods. The results showed that serum Mg levels and dietary Mg intake were both lower in blacks than whites. Mean serum Mg levels were significantly lower in participants with prevalent CVD, hypertension, and diabetes than in those free of these diseases. In participants without CVD, serum Mg levels were also inversely associated with fasting serum insulin, glucose, systolic blood pressure and smoking. Dietary Mg intake was inversely associated with fasting serum insulin, plasma high density lipoprotein-cholesterol, systolic and diastolic blood pressure. Adjusted for age, race, body mass index, smoking, hypertension, Low density lipoprotein-cholesterol, and field center, mean carotid wall thickness increased in women by 0.0118 mm (p = 0.006) in diuretic users and 0.0048 mm (p = 0.017) in nonusers for each 0.1 mmol/l decrease in serum Mg level; the multivariate association in men was not significant. In conclusion, low serum and dietary Mg may be related to the etiologies of CVD, hypertension, diabetes, and atherosclerosis.     

Body mass index, waist/hip ratio, and coronary heart disease incidence in African Americans and whites. Atherosclerosis Risk in Communities Study Investigators

To study the relation of the amount and distribution of body fat with incident coronary heart disease in two ethnic groups, the authors analyzed prospective data from the Atherosclerosis Risk in Communities Study. Among 14,040 participants aged 45-64 years and free of coronary disease at baseline in 1987-1989, we identified 398 events through 1994, an average of 6.2 years of follow-up. Among African-American women, the multivariable-adjusted relative risks of coronary heart disease across quartiles of body mass index were 1.0, 1.91. 1.54, and 2.15 (p for trend=0.27), and those for waist/hip ratio were 1.0, 2.07, 2.33, and 4.22 (p for trend=0.02). Among African-American men, these respective relative risks were 1.0, 1.03, 0.83, and 1.20 (p for trend=0.76) for body mass index and 1.0, 1.08, 1.87, and 1.68 (p for trend=0.06) for waist/hip ratio. Relative risks for whites were generally similar to those for African Americans. Relative risks were stronger for never smokers than for the overall cohort. Unlike some previous studies, our results suggest that Africa Americans, like whites, are not spared from the coronary heart disease risks accompanying obesity.     

Does the association of risk factors and atherosclerosis change with age? An analysis of the combined ARIC and CHS cohorts. The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) investigators

INTRODUCTION: A decrease in the estimated relative risk of cerebrovascular and cardiovascular diseases associated with known disease risk factors has been observed among elderly cohorts, perhaps suggesting that continued risk factor management in the elderly may not be as efficacious as with younger age groups. In this paper, the differential magnitude of the association of risk factors with atherosclerosis across the age spectrum from 45 years to older than 75 years is presented. METHODS: Subclinical atherosclerosis as measured by carotid ultrasonography and risk factor prevalence were assessed using similar methods among participants aged 45 to 64 years in the Atherosclerosis Risk in Communities (ARIC) study and among participants 65 years and older in the Cardiovascular Health Study (CHS). Pooling these two cohorts provided data on the relationship of risk factors and atherosclerosis on nearly 19,000 participants over a broad age range. Regression analyses were used to assess the consistency of the magnitude of the association of risk factors with atherosclerosis across the age spectrum separately for black and white participants in cross-sectional analyses. RESULTS: As expected, each of the risk factors was globally (across all ages) associated with increased atherosclerosis. However, the magnitude of the association did not differ across the age spectrum for hypertension, low density lipoprotein cholesterol (LDL-c), fibrinogen, or body mass index (BMI). For whites, there was a significantly greater impact of smoking and HDL-C among older age strata but a smaller impact of diabetes. For black women, the impact of HDL-C decreased among the older age strata. CONCLUSIONS: These data suggest that most risk factors continue to be associated with increased atherosclerosis at older ages, possibly suggesting a continued value in investigation of strategies to reduce atherosclerosis by controlling risk factors at older ages.     

Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: the Insulin Resistance Atherosclerosis Study

OBJECTIVE: To assess whether people with impaired glucose tolerance (IGT) exhibit an increased risk of atherosclerosis as measured by the thickness of the carotid artery. RESEARCH DESIGN AND METHODS: We examined the relationship between glucose tolerance status and subclinical atherosclerosis in the Insulin Resistance Atherosclerosis Study (IRAS). The IRAS is an epidemiological study of 1,625 Hispanic, African-American, and white men and women, with approximately equal numbers of subjects with normal glucose tolerance (NGT), IGT, and type 2 diabetes as assessed by an oral glucose tolerance test. Half of those with diabetes were previously unaware of their condition and were defined as having new diabetes. Persons using insulin were excluded. The intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA) was measured as an index of subclinical atherosclerosis using B-mode ultrasonography. RESULTS: Adjusted for demographics and smoking, CCA-IMT increased most notably at the level of established diabetes (802, 822, 831, and 896 microm for NGT, IGT, new diabetes, and established diabetes, respectively). Adjustment for coronary heart disease (CHD) risk factors, which tended to worsen across glucose tolerance category, further minimized the slightly graded relationship. The relationship with the ICA-IMT was steeper and again suggested that the increased wall thickness is associated with diabetes, not with IGT. The relationship between glucose tolerance category and IMT was similar in men and women. CONCLUSIONS: We observed considerably greater IMT among persons with established diabetes but no significant increase in persons with IGT. These data suggest that the increased risk of CHD observed in persons with diabetes may largely develop after the onset of overt diabetes.     

The effect of age on risk factors for ischemic heart disease: the Manitoba Follow-Up Study, 1948-1993

PURPOSE: The purpose of this paper is to determine the age-specific relationships between risk factors at age 40 through 75 years and ischemic heart disease (IHD), and to determine the effects of aging on these relationships in a cohort of 3983 Canadian males. METHODS: The Manitoba Follow-Up Study is the prospective investigation of cardiovascular disease as it develops in a cohort of 3983 young men. Over a period of 45 years, from 1948 to 1993, 1094 study members (27%) developed clinical evidence of IHD. Blood pressure, body weight, smoking, and presence of diabetes mellitus have been recorded at regular intervals throughout the follow-up period. Using measurements from examinations every 5 years between ages 40 and 75 years, age-specific Cox proportional hazard models were fit to relate these risk factors to IHD. RESULTS: The adjusted relative risk of IHD for systolic blood pressure, diastolic blood pressure and smoking were found to significantly (p < 0.001) decline with advancing age. The adjusted relative risk for body mass index and presence of diabetes mellitus for ischemic heart disease did not vary with age (p > 0.05). After age 65 years, these risk factors were of little value for the prediction of IHD. CONCLUSIONS: The relative risk and statistical significance of blood pressure and smoking, as risk factors for IHD, decline with age.     

Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis

BACKGROUND: The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls. DESIGN: The European Lacidipine Study on Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multinational trial comparing effects of 4-year treatment based on the long-acting, highly lipophilic calcium antagonist lacidipine with those of treatment based on the beta-blocker atenolol on the development of carotid artery wall alterations in patients (aged 45-75 years) with mild-to-moderate hypertension (systolic blood pressure 150-210 mmHg and diastolic blood pressure 95-115 mmHg). While the intervention study is progressing, this article summarizes baseline data obtained from the whole cohort of 2259 patients randomly allocated to treatment. METHODS: Baseline ultrasound data were obtained from two replicate examinations performed shortly before random allocation to treatment by certified sonographers at 23 referral centres and read at the ultrasound coordinating centre at the Wake Forest University School of Medicine. Intima-media thickness was measured at up to 12 different sites in the carotid artery tree and expressed as the mean of the maxima at these sites (Mmax), the mean of the maxima at four sites in the distal common carotid artery and bifurcation (CBMmax) and the maximum intima-media thickness (Tmax). Baseline demographic and clinical measurements were performed by investigators in 410 peripheral clinical units and 24 h ambulatory blood pressure monitorings read and validated by members of a centralized unit at the University of Milan. The statistical analysis centre at the Technische Universit?t München received and analysed all baseline data, by calculating means +/- SD, medians and ranges and performing correlation (Spearman correlation coefficients) and multiple regression analyses. RESULTS: Prevalence of carotid artery wall alterations among the hypertensive patients randomly allocated to treatment in the ELSA was very high: 82% had Tmax > or = 1.3 mm ('plaques' according to protocol) and 17% had Tmax > or = 1.0 and < 1.3 mm ('thickening'), with a median of two plaques per patient. We found significant correlations between ultrasound measurements and the following demographic and clinical variables: age, sex, systolic blood pressure and pulse pressure (both clinic and ambulatory), concentrations of total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides, smoking habit and duration of hypertension. We found no significant correlation to diastolic blood pressure and glucose concentration. A multiple regression analysis indicated significant variables in the following rank order: age, 24 h ambulatory pulse pressure, sex, low-density lipoprotein cholesterol concentration, triglyceride concentration, smoking and clinic systolic blood pressure. CONCLUSIONS: Analysis of baseline data from the ELSA has shown that there is an extremely marked prevalence of carotid artery wall alterations among mild-to-moderate, middle-aged hypertensive patients. In addition to age, systolic blood pressure and pulse pressure, particularly if they are accurately measured by ambulatory monitoring, play a major role, somewhat greater than those of sex, low-density lipoprotein cholesterol concentration and smoking, in influencing intima-media thickness.     

Fasting hyperinsulinemia and cardiovascular disease risk factors in nondiabetic adults: stronger associations in lean versus obese subjects. Atherosclerosis Risk in Communities Study Investigators

The association between hyperinsulinemia and atherogenic risk factors has not been well studied in blacks and may be different for obese versus lean individuals. To investigate this possibility and to confirm the associations of hyperinsulinemia with cardiovascular disease risk factors in blacks and whites, we analyzed the joint associations of fasting serum insulin and obesity with risk factors in the Atherosclerosis Risk in Communities (ARIC) Study (1,293 black men, 4,797 white men, 2,033 black women, and 5,445 white women). Insulin values > or = 90th percentile (> or = 21 microU/mL) constituted hyperinsulinemia; body mass index (BMI) values > or = 27.3 kg/m2 for women and > or = 27.8 for men constituted obesity. Participants with hyperinsulinemia in all four race-sex groups had more atherogenic levels of most risk factors studied than those with normoinsulinemia. Among black men and women, mean levels of triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo) B, glucose, and fibrinogen (men only) were higher in hyperinsulinemic lean participants as compared with the normoinsulinemic obese group. Furthermore, most associations between insulin level and risk factors were stronger among lean versus obese subjects. For example, among lean black men, the difference in mean triglyceride concentration between those with hyperinsulinemia and those with normoinsulinemia was 147 - 99 = 48 mg/dL; among obese black men, the difference was 155 - 121 = 34 mg/dL (P < .05 for the interaction). Generally, similar negative interactions between BMI and insulin concentration were also observed among whites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clustering and interrelationships of coronary heart disease risk factors in schoolchildren, ages 6-19

Clustering and interrelationships of common and easily identifiable risk factors in 951 children (ages 6-19) from the Cincinnati Lipid Research Clinic's Princeton School of District Study were assessed. Several patterns of partial correlation coeffieients appeared after multiple regression analysis with adjustment for age, sex, Quetelet index, and race. Systolic blood pressure (SBP) was positively correlated with plasma cholesterol and triglyceride, and with saturated fat intake. Plasma high density lipoprotein cholesterol (C-HDL) was positively associated with occupation of the head of the household and inversely associated with cigarette smoking and sucrose intake. Using multiple regression equations, from 29-41% of the variance for SBP and diastolic blood pressure (DBP) could be explained by the measured variables, with age, skinfold thickness, Quetelet, occupation, and education of the head of the household recurrently appearing in the regression equatons. Low density lipoprotein cholesterol (C-HDL) was the variable for which the lowest amount of variance could be explained in the four race-sex groups. Discriminant function analysis allowed an assessment of interrelationships of C-LDL-C-HDL aggregate groups to other risk factor mean residuals. The variables which contributed significantly to the discrimination between lipoprotein groups were Quetelet index, skinfold thickness, and DBP. Children in the highest C-LHL-lowest C-HDL quintile group had by far the highest residual Quetelet index and skinfold thickness, along with above average SBP, while those in The lowest C-LDL-highest C-HDL quintile group had the lowest residual Quetelet index, skinfold thickness, and SBP. Common risk and anti-risk factors for coronary heart disease (CHD) in children cluster, allowing identification of groups of children putatively at relatively high and low CHD risk as adults.     

Risk factors associated with retinopathy of prematurity (ROP) in northern Jutland, Denmark 1990-1993

This population-based, historical, follow-up study analysed possible risk factors for retinopathy of prematurity (ROP) and resulting visual impairment in newborns over a period of 3 1/2 years in the County of Northern Jutland, Denmark. The study subjects were 141 infants with birth weight < or = 1500 grams and gestational age < 35 completed weeks who survived to a first eye examination at 5 weeks. The incidence of ROP (all stages) was 18%, and the frequency of severe visual impairment from ROP was 14/100,000 live births. A logistic regression analysis identified low gestational age, multiple births, continuous oxygen treatment, and male sex as risk factors for ROP. The main factor in the prevention of ROP is to prevent preterm births.     

Cholesterol and lipoprotein(a) as risk factors for coronary heart disease in elderly subjects

The changes in lipoprotein(a) concentration that occur with age as a result of its association with an increased risk of coronary artery disease were investigated. Lipoprotein(a) concentrations were measured in serum samples from healthy volunteers, individuals with premature coronary artery disease, individuals with hyperlipidaemia but without evidence of premature coronary artery disease, and also in elderly men and women who had hyperlipidaemia. Concentrations in individuals with premature coronary artery disease were the same as those of the healthy volunteers, while in both these groups they were lower than those found in hyperlipidaemic elderly men and women, and those found in hyperlipidaemic women aged 36-68 years. No association between raised lipoprotein(a) concentration and mortality as a result of premature coronary artery disease was demonstrated. Raised lipoprotein(a) levels found in the hyperlipidaemic individuals also suggested that it may not be an independent risk factor.     

Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S)

BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) randomized 4444 patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0 mmol/L (213 to 310 mg/dL) with triglycerides < or =2.5 mmol/L (220 mg/dL) to simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of the 2223 patients in the placebo group and 431 (19%) of the 2221 patients in the simvastatin group (34% risk reduction, P<.00001). Simvastatin produced substantial changes in several lipoprotein components, which we have attempted to relate to the beneficial effects observed. METHODS AND RESULTS: The Cox proportional hazards model was used to assess the relationship between lipid values (baseline, year 1, and percent change from baseline at year 1) and MCEs. The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol, apolipoprotein B, and less so with HDL cholesterol, but there was no clear relationship with triglycerides. We estimate that each additional 1% reduction in LDL cholesterol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; P<.00001). CONCLUSIONS: These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol, and they are consistent with current guidelines that emphasize aggressive reduction of this lipid in CHD patients.     

Ultrasonographically assessed maximum carotid artery wall thickness in Mexico City residents and Mexican Americans living in San Antonio, Texas. Association with diabetes and cardiovascular risk factors

Measurements of carotid artery wall thickness are often used as a surrogate for atherosclerosis. However, few studies have performed these measurements in populations of Mexican origin. Since Mexicans in Mexico City consume high-carbohydrate diets and have carbohydrate-induced dyslipidemia (high triglyceride and low HDL cholesterol levels) compared with Mexican Americans living in San Antonio, Tex, we questioned whether they also had more atherosclerosis than San Antonio Mexican Americans. Mean maximum intimal-medial thickness (IMT) of the common (CCA) and internal (ICA) carotid arteries were measured in 867 subjects aged 35 to 64 years (40% men) in two Mexican-origin populations, one from San Antonio (n = 202) and the other from Mexico City (n = 665). IMT's in the two cities were compared, and their associations with cardiovascular risk factors were analyzed. Older age, male sex, high levels of total cholesterol, low levels of HDL cholesterol, and high systolic blood pressure were positively associated with both CCA IMT and ICA IMT. Cigarette smoking was significantly associated with ICA IMT. CCA and ICA IMTs in diabetic subjects were thicker than in nondiabetic subjects in both men and women (all P < = .05). CCA IMT was thicker in the San Antonio than the Mexico City subjects after adjustment for cardiovascular risk factors (0.81 versus 0.76 mm in men and 0.77 versus 0.71 mm in women; P < .001 for city difference). San Antonio men also had thicker ICA IMT than their counterparts in Mexico City (0.88 versus 0.83 mm), but the reverse was true for women (0.73 versus 0.77 mm; interaction between sex and city, P < .05). Our results indicate that men had higher carotid IMTs than women. CCA IMT was thicker in San Antonio Mexican Americans than in Mexico City residents. The differences in ICA IMTs between San Antonio and Mexico City were inconsistent. Thus, since Mexico City residents consume high-carbohydrate diets, the data do not support an atherogenic effect of such diets. The interaction between sex and city on ICA IMT deserves further study.     

Lipoprotein(a) and general risk factors in patients with angiographically assessed peripheral arterial disease

High lipoprotein(a) [Lp(a)] has been observed in patients with ischemic heart disease and cerebrovascular disease. Lp(a) is actually thought to be an independent risk factor for coronary disease. We therefore carried out a case-control study, evaluating plasma Lp(a) in 61 patients with angiographically documented peripheral arterial disease (PAD) and in 61 age- and sex-matched patients with no cardiovascular disease. General risk factors for vascular disease were also taken into account. Lp(a) was significantly higher in patients than controls (257.0 +/- 34.8 vs 146.5 +/- 23.5 mg/l p < 0.05), as were cigarette smoking, diabetes, cholesterolemia, fibrinogenemia and the waist-to-hip circumference ratio. Stepwise logistic regression analysis showed that, in addition to cigarette smoking, diabetes, cholesterol and fibrinogen, Lp(a) is a significant independent risk indicator for PAD. This result suggests that high plasma Lp(a) is associated with enhanced risk of PAD and must therefore be evaluated alongside traditional risk factors.     

Lifelong teetotallers, ex-drinkers and drinkers: mortality and the incidence of major coronary heart disease events in middle-aged British men

A simplified method for the preparation and long-term cultivation of granulosa-luteal cells in serum-free medium is described. The cells were harvested from women undergoing in-vitro fertilization, enriched by sedimentation and dissociated by enzymatic treatment. We demonstrated, by introducing a synthetic serum replacement (SSR2), that these primary cell cultures cultivated in monolayers on an extracellular matrix may be used in experiments exceeding 7 days with low cell loss and cell death. No adverse effect on progesterone production was found. There was a high diversity in progesterone production between cells from individual patients. After several days in culture, the cells were challenged with human chorionic gonadotrophin which revived the rapidly decreasing progesterone production. We were unable to demonstrate an increase in cell number after 7 days of cultivation when the cells were grown in medium supplemented with either serum or SSR2. The mitogens epidermal growth factor and basic fibroblast growth factor had no influence on proliferation. We also found that the present method prevents leukocyte contamination in the granulosa-luteal cell cultures. Compared with the common method based on the enrichment of granulosa-luteal cells on a density gradient (Ficoll/Percoll), this method saves time, labour and expense, in addition to augmenting purity.     

Smoking, lipoproteins and coronary heart disease risk. Data from the Münster Heart Study (PROCAM)

AIMS: The mechanism of the increase in coronary heart disease risk associated with smoking is unclear, but may partly be due to smoking-related changes in intermediate risk factors such as lipid levels, fibrinogen and blood pressure. We therefore examined the distribution of these variables among smokers and non-smokers in the Münster Heart Study. METHODS: 20696 men, aged 41.7+/-2.7 years (mean +/- SD) and 10212 women, aged 37.0+/-2.6 years, were enrolled between 1978 and 1995. Thirty-two percent of women and 36% of men smoked. Compared to non-smokers, mean levels of low density lipoprotein cholesterol, total cholesterol, triglycerides and fibrinogen were increased, respectively, by 1.4%, 0.9%, 15% and 12.1% in male and by 2.0%, 5.5%, 12% and 3.4% in female smokers. Mean high density lipoprotein cholesterol levels, body mass index and blood pressure were reduced, respectively, by 6.4%, 3.8%, and 2% in male, and by 6.7% 1.2% and 2% in female smokers. In the subgroup of 4639 men aged 40 to 65 with 8 years of follow-up, the coronary event rate (definite myocardial infarction, sudden cardiac death) in cigarette smokers was more than twice that of non-smokers with otherwise identical risk factors. CONCLUSION: In the Münster Heart Study, smoking was associated with adverse changes in lipids (of greater magnitude in women), and fibrinogen (of greater magnitude in men). However, these changes explained only a small part of the smoking-related increase in coronary heart disease risk.