Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel.

There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein-related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid-lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B <90 mg dL(-1) in high-risk patients should be reassessed in the light of the new clinical trial results and a new ultra-low target of <80 mg dL(-1) be considered. The evidence also indicates that the apo B/apo A-I ratio is superior to any of the conventional cholesterol ratios in patients without symptomatic vascular disease or diabetes to evaluate the lipoprotein-related risk of vascular disease.

Gestational weight gain and postpartum behaviors associated with weight change from early pregnancy to 1 y postpartum.

OBJECTIVES: (1) To describe the relative importance of gestational weight gain, postpartum exercise, food intake and breastfeeding to weight change from early pregnancy to 1 y postpartum; and (2) to identify subgroups of women at greatest risk for major weight gain surrounding childbearing. DESIGN: A prospective cohort study of women who registered for obstetrical care in a hospital and primary care clinic system serving a 10 county area of upstate New York. SUBJECTS: A total of 540 healthy adult women who gave birth to full-term singleton infants. MEASUREMENTS: Sociodemographic characteristics, exercise, food-related behaviors and breastfeeding were assessed using the medical record and a mailed questionnaire. Body weight was measured at prenatal visits and 1 y postpartum. Weight retained and major weight gain (4.55 kg) at 1 y postpartum were the main outcomes. ANALYSIS: Linear and logistic regression analyses were conducted. RESULTS: Women were on average 1.51+/-5.95 kg heavier at 1 y postpartum than they were in early pregnancy. Nearly 25% of women experienced a major weight gain of 4.55 kg or more at 1 y postpartum. Gestational weight gain, exercise frequency, change in food intake and breastfeeding were each significantly related to postpartum weight retention. With the exception of breastfeeding, all of these factors were also associated with major weight gain. Women under 20 y or over 40 y at delivery, and single women retained significantly more weight. Lower income women with gestational weight gains above the Institute of Medicine (IOM) range retained 3.73 kg more than lower income women who gained within the range. They were also 4.7 times more likely to experience major weight gain with childbearing. The impact of exceeding the IOM gestational weight gain guidelines was three times greater in lower income women than it was in higher income women. CONCLUSION: Gestational weight gain, postpartum exercise frequency, and food intake are significantly associated with weight change from early pregnancy to 1 y postpartum and major weight gain with childbearing. Lower income women who gain more weight in pregnancy than the IOM recommends are at high risk for major weight gain with childbearing.

Capacity for research in minority health: the need for infrastructure plus will.

Cardiovascular mortality has continued to decline, but racial disparities in cardiovascular diseases (CVD) continue to grow. To build the capacity to address these racial disparities, two things will be required. First, a research and policy infrastructure must be in place to provide guidance on what to do and how to do it. Second, the will to implement and activate this infrastructure must be present at the community and policy-making levels. The Jackson Heart Study is an example of a research infrastructure with the economic resources, scientific expertise, and technical manpower required to monitor, organize, assess, and follow a cohort of individuals over time to study the burden, natural history, predictive factors, and level of care for CVD in an African American community. The creation of will within the community for CVD research may require additional strategies than in the majority community, such as community organization and local policy development. These additional efforts at the community level should create a fertile environment to develop research and, ultimately, test strategies for reducing national disparities in cardiovascular health.

Left ventricular hypertrophy as an independent predictor of acute cerebrovascular events in essential hypertension.

BACKGROUND: It is uncertain whether left ventricular hypertrophy (LVH) confers an increased risk for cerebrovascular disease in apparently healthy patients with essential hypertension. METHODS AND RESULTS: A total of 2363 initially untreated hypertensive patients (mean age 51+/-12 years, 47% women) free of previous cardiovascular disease were followed up for up to 14 years (mean 5 years). At entry, all patients underwent diagnostic tests, including ECG, echocardiography, and 24-hour ambulatory blood pressure (BP) monitoring. At entry, the prevalence of LVH was 17.6% by ECG (Perugia score) and 23.7% by echocardiography (LVM >125 g/m(2)). Over the subsequent years, 105 patients experienced a first stroke or transient ischemic attack. The cerebrovascular event rate was higher among patients with LVH at entry, diagnosed by either ECG or echocardiography, than among those without hypertrophy (both P<0.01). After control for the significant influence of age, sex, diabetes, and 24-hour mean ambulatory BP, LVH by ECG conferred an increased risk for cerebrovascular events (relative risk [RR] 1.79; 95% CI 1.17 to 2.76). LVH by echocardiography also conferred a higher risk for cerebrovascular events (RR 1.64; 95% CI 1.07 to 2.68). For each increase in LV mass of 1 SD (29 g/m(2)), there was a significant independent increase in the risk for cerebrovascular events (RR 1.31; 95% CI 1.09 to 1.58). CONCLUSIONS: In apparently healthy patients with essential hypertension, LVH diagnosed by ECG or echocardiography confers an excess risk for stroke and transient ischemic attack independently of BP and other individual risk factors.

Design issues in the combination of international data from two rural community cardiovascular intervention programs.

OBJECTIVES: To compare and contrast two rural cardiovascular community intervention programs (CCIP) in northern Sweden and the US by discussing the methods used to select and combine similar data from two separately designed and implemented CCIP in order to describe and evaluate their effectiveness in reducing cardiovascular risk. METHODS: Two rural intervention populations and their reference populations were compared. A comparison was made of the intensity and duration of the intervention programs using an overall intervention intensity score. Population-based surveys were conducted at 5-year intervals in both countries. The methods used for data pooling and comparison are described. A description of statistical analyses using a mixed analysis of variance model is provided. RESULTS: The data were pooled. taking into consideration comparable ages. New variables were created in order to define the relationship between similar data that did not permit direct comparison. CONCLUSIONS: Combination and comparison of international data from two programs allowed evaluation of community intervention programs that were developed independently for similar communities. The effectiveness of interventions can be compared using such methods.

The Otsego-Schoharie healthy heart program: prevention of cardiovascular disease in the rural US.

OBJECTIVES: To describe a rural, hospital-based public health intervention program and to evaluate its effectiveness in cardiovascular disease (CVD) risk reduction using cross-sectional studies and a panel study. METHODS: A rural population of 158,000 located in New York state comprised the intervention population. A similar but separate population was used for reference. A multifaceted, multimedia 5-year program provided health promotion and education initiatives to increase physical activity, decrease smoking, improve nutrition, and identify hypercholesterolemia and hypertension. To evaluate the effectiveness of the intervention, surveys were conducted at baseline in 1989 (cross-sectional) and at follow-up in 1994-95 (cross-sectional and panel). For cross-sectional studies, a random sample of adults was obtained using a three-stage cluster design. Self-reported and objective risk factor measurements were obtained. Comparison of pre- to post- changes in intervention versus reference populations was done using 2 x 2 randomized block ANOVA, 2 x 2 mixed ANOVA. and extension of the McNemar test. RESULTS: Smoking prevalence declined (from 27.9% to 17.6%) in the intervention population. Significant adverse trends were observed for high-density lipoprotein cholesterol and triglycerides. Systolic blood pressure was reduced while diastolic blood pressure remained stable. Body mass index increased significantly in both populations. CONCLUSIONS: This rural. 5-year CVD community intervention program decreased smoking. The risk reduction may be attributable to tailoring of a multifaceted approach (multiple risk factors, multiple messages, and multiple population subgroups) to a target rural population. The study period was too short to identify changes in CVD morbidity and mortality.

The Norsjö-Cooperstown healthy heart project: a case study combining data from different studies without the use of meta-analysis.

OBJECTIVES: This paper aims to develop and describe a method for combining. comparing, and maximizing the statistical power of two longitudinal studies of risk factors for cardiovascular disease that did not have identical data collection methodologies. METHODS: Subjects from a 1986 cross-sectional study (n = 180) were pair-matched with subjects of corresponding gender and age (+5 years) from a 1990 cross-sectional study. The methodology is described and results are calculated for various measures of cardiovascular risk or risk factors (e.g. cholesterol. Finnish Risk Score). RESULTS: Box's test of equality and symmetry of covariance matrices gave chi-square values of 223.8 and 710.0 for two cardiovascular risk factors (cholesterol and cardiac risk score, respectively); these values were highly significant (p=0.0001) For the North Karelia Risk Score, repeated measures ANOVA revealed a borderline significant interaction for treatment by time (p=0.054) and a significant interaction for treatment by time by country (p=0.035). These probabilities compared favorably with a randomized blocks model. CONCLUSIONS: Creation of a synthetic longitudinal control group resulted in a statistically valid ANOVA model that increased the statistical power of the study.

Different outcomes for different interventions with different focus!--A cross-country comparison of community interventions in rural Swedish and US populations.

OBJECTIVES: There is a need among healthcare providers to acquire more knowledge about small-scale and low budget community intervention programmes. This paper compares risk factor outcomes in Swedish and US intervention programmes for the prevention of cardiovascular disease (CVD). The aim was to explore how different intervention programme profiles affect outcome. METHODS: Using a quasi-experimental design, trends in risk factors and estimated CVD risk in two intervention areas (Norsjö. Sweden and Otsego-Schoharie County, New York state) are compared with those in reference areas (Northern Sweden region and Herkimer County, New York state) using serial cross-sectional studies and panel studies. RESULTS: The programmes were able to achieve significant changes in CVD risk factors that the local communities recognized as major concerns: changing eating habits in the Swedish population and reducing smoking in the US population. For the Swedish cross-sectional follow-up study cholesterol reduction was 12%, compared to 5% in the reference population (p for trend differences <0.000). The significantly higher estimated CVD risk (as assessed by risk scores) at baseline in the intervention population was below that of the Swedish reference population after 5 years of intervention. The Swedish panel study provided the same results. In the US, both the serial cross-sectional and panel studies showed a > 10% decline in smoking prevalence in the intervention population, while it increased slightly in the reference population. When pooling the serial cross-sectional studies the estimated risk reduction (using the Framingham risk equation) was significantly greater in the intervention populations compared to the reference populations. CONCLUSIONS: The overall pattern of risk reduction is consistent and suggests that the two different models of rural county intervention can contribute to significant risk reduction. The Swedish programme had its greatest effect on reduction of serum cholesterol levels whereas the US programme had its greatest effect on smoking prevention and cessation. These outcomes are consistent with programmatic emphases. Socially less privileged groups in these rural areas benefited as much or more from the interventions as those with greater social resources.

Fluorescence-based, nonradioactive method for efficient detection of the pentanucleotide repeat (TTTTA)(n) polymorphism in the apolipoprotein(a) gene.

BACKGROUND: The apolipoprotein(a) [apo(a)] gene is a major predictor of plasma lipoprotein(a) concentrations, an independent risk factor for cardiovascular disease. The apo(a) gene contains a pentanucleotide repeat (PNR) polymorphism, 1.4 kb upstream from the apo(a) gene reading frame. This polymorphism has been suggested to be important in control of apo(a) gene expression. METHODS: We developed a fluorescence-based, nonradioactive procedure to detect the PNR polymorphism. After amplification of the polymorphism by PCR, the respective PCR products were separated by denaturing polyacrylamide gel electrophoresis and detected using a 3'-end fluorescently labeled oligonucleotide as a probe. We used the method to characterize the PNR polymorphism pattern in 313 individuals, 195 Caucasians and 118 African Americans. The new method efficiently separated DNAs corresponding to the different PNR repeats. RESULTS: Among both ethnic groups, alleles containing eight PNRs were most common. Smaller PNRs were more common among African Americans, and larger PNRs were more common among Caucasians. CONCLUSIONS: We developed a nonradioactive technique that separates the PNR polymorphism in the apo(a) gene and can be used in other studies involving closely sized polymorphisms.

Translation of nutritional sciences into medical education: the Nutrition Academic Award Program.

For the past 40 y the scientific community has decried the inadequacy of the training of physicians and other health professionals in the subject of human nutrition. In 1997 the National Heart, Lung, and Blood Institute developed the Nutrition Academic Award (NAA) Program, an initiative to improve nutrition training across a network of US medical schools. The purpose of this funding, which began in 1998, is to support the development and enhancement of nutrition curricula for medical students, residents, and practicing physicians to learn principles and practice skills in nutrition. The NAA recipients developed the Nutrition Curricular Guide for Training Physicians, a plan to incorporate clinical guidelines into physician practice skills, create educational and assessment practice tools, and evaluate curricula, materials, and teaching tools. Dissemination of NAA activities and materials will be facilitated by a national website, presentations and publications, and consultants and advisors from the NAA nutrition education programs. The NAA Program constitutes a major new effort to enhance nutrition knowledge and skills among health care providers and to effectively apply the science of human nutrition to clinical medicine. This article describes the purpose and aims of the NAA Program, the organizational structure of the network of recipients, a profile of the recipients and individual programs at 21 medical schools, the various strategies to overcome barriers in training physicians in human nutrition, and collaborative and dissemination efforts.

Low fat and high monounsaturated fat diets decrease human low density lipoprotein oxidative susceptibility in vitro.

Oxidative modification of low density lipoprotein (LDL) is thought to play an important role in the development of atherosclerosis. Some studies have found that LDL enriched in monounsaturated fatty acids (MUFA) are less susceptible to oxidation than LDL enriched in polyunsaturated fatty acids (PUFA). A high MUFA diet is an alternative to a lower-fat blood cholesterol-lowering diet. Less is known about the effects of high MUFA versus lower-fat blood cholesterol-lowering diets on LDL oxidative susceptibility. The present study was designed to evaluate the effects of men and women consuming diets high in MUFA (peanuts plus peanut butter, peanut oil and olive oil) on LDL oxidative susceptibility, and to compare these effects with those of a Step II blood cholesterol-lowering diet. A randomized, double-blind, five-period crossover design (n = 20) was used to study the effects of the following diets on LDL-oxidation: average American [35% fat, 15% saturated fatty acids (SFA)], Step II (25% fat, 7% SFA), olive oil (35% fat, 7% SFA), peanut oil (35% fat, 7% SFA) and peanuts plus peanut butter (35% fat, 8% SFA). The average American diet resulted in the shortest lag time (57 +/- 6 min) for LDL oxidized ex vivo, whereas the Step II, olive oil and peanuts plus peanut butter diets resulted in a lag time of 66 +/- 6 min (P < or = 0.1). The slower rate of oxidation [nmol dienes/(min x mg LDL protein)] observed when subjects consumed the olive oil diet (24 +/- 2) versus the average American (28 +/- 2), peanut oil (28 +/- 2) and peanuts plus peanut butter diets (29 +/- 2; P < or = 0.05) was associated with a lower LDL PUFA content. The results of this study suggest that lower-fat and higher-fat blood cholesterol-lowering diets high in MUFA have similar effects on LDL oxidative resistance. In addition, our results suggest that different high MUFA sources varying in the ratio of MUFA to PUFA can be incorporated into a high MUFA diet without increasing the susceptibility of LDL to oxidation.

Bacillus cereus bacteremia and meningitis in immunocompromised children.

Two cases of Bacillus cereus meningitis in immunocompromised children at our hospital within a 2-month period prompted us to review B. cereus--related invasive disease. We identified 12 patients with B. cereus isolated in blood cultures from September 1988 through August 2000 at our institution. Three of these patients also had B. cereus isolated from CSF specimens; 1 additional patient had possible CNS involvement (33%, group A), whereas 8 patients had no evidence of CNS involvement (67%, group B). Patients in group A were more likely to have neutropenia at the onset of sepsis and were more likely to have an unfavorable outcome. They were also more likely to have received intrathecal chemotherapy in the week before the onset of their illness. Two patients from group A died. One survived with severe sequelae. The fourth patient had mild sequelae at follow-up. No sequelae or deaths occurred among patients in group B. In patients with unfavorable outcomes, the interval from the time of recognition of illness to irreversible damage or death was short, which demonstrates a need for increased awareness, early diagnosis, and more-effective therapy, particularly that which addresses B. cereus toxins.

Sex, drugs, and hypertension: a methodological approach for studying a sensitive subject.

Sexual dysfunction is a recognized side effect of hypertension and antihypertensive medications in men, but is not established as a side effect in women, due to the lack of established methodology. An ambulatory medical record-based, case-control study was designed to study sexual function in treated and untreated hypertensive women and healthy controls. The research was performed in a teaching hospital with satellite clinics in upstate New York. There were 3312 medical records reviewed, 640 premenopausal Caucasian women in heterosexual relationships subjects were eligible for participatic diagnosis of mild hypertension (BP > or =140/90 mmHg and < 160/100 mmHg) for cases; no other significant medical history. A total of 241 women agreed to participate, 224 (35%) completed both a self-administered questionnaire and a telephone interview (112 healthy, 112 hypertensive). There was an initial 74% response rate among those eligible to participate, with 35% completing the entire study. Age and average blood pressure were not significant between 224 participants and 416 nonparticipants by 2-tailed t-test analysis. Seven composite variables were formed from a 47-item sexual response questionnaire. Initial unadjusted chi2 results reported women with hypertension had more difficulty than did healthy controls achieving lubrication and orgasm. Seven questions, each with the highest correlation to its respective composite variable (by Spearman's correlation), formed an abbreviated questionnaire. Quality of female sexual function was quantified in an ambulatory outpatient setting. A method was described to address hypertension, pharmacotherapy, and sexual functioning by employing self-administered questionnaires and telephone interviews. Initial analysis suggested that hypertensive women may have an impaired physiological sexual response. The abbreviated questionnaire generated from questions with the highest correlation to their respective composite variables may be useful in further evaluating this issue.

Screening family members at high risk for coronary disease. Why isn't it done?

BACKGROUND: The National Cholesterol Education Program strongly recommends screening family members of patients with early cardiovascular disease (CVD) for coronary risk factors, but the physician and patient compliance with this recommendation has not been extensively studied. The American College of Cardiology Evaluation of Preventive Therapeutics (ACCEPT) study, a national survey conducted in 1996-1997, determined if physicians were screening first-degree relatives of patients with early CVD. SETTING/PARTICIPANTS: The ACCEPT study included 5553 patients with either their first bypass surgery, first angioplasty, an acute myocardial infarction, or myocardia ischemia, admitted to 53 hospitals throughout the United States. MAIN OUTCOME MEASURE: Self-reported screening of first-degree relatives obtained by interview follow-up 6 months after event. RESULTS: Less than 1% of inpatient medical records contained a discharge plan by the physician recommending screening family members of patients younger than age 55. Only 17.8% of these patients had their family screened within 6 months of their cardiovascular event, while only 19.6% with a recognized family history of premature coronary artery disease had their family screened. The only factors that were significant (p<0. 05) predictors of successful family screening were education (19.4%), having high cholesterol (16.4%), being widowed (18.1%), not smoking (16.4%), and being black (20.5%). CONCLUSIONS: U.S. physicians do not appear to follow national recommendations for the screening of family members of their high-risk patients. These data also suggest that physicians are not ready to use and exploit known genetic factors in treating CVD even as the human genome data become available for clinical use.

Capacity for research in minority health: the need for infrastructure plus will.

Cardiovascular mortality has continued to decline, but racial disparities in cardiovascular diseases (CVD) continue to grow. To build the capacity to address these racial disparities, two things will be required. First, a research and policy infrastructure must be in place to provide guidance on what to do and how to do it. Second, the will to implement and activate this infrastructure must be present at the community and policy-making levels. The Jackson Heart Study is an example of a research infrastructure with the economic resources, scientific expertise, and technical manpower required to monitor, organize, assess, and follow a cohort of individuals over time to study the burden, natural history, predictive factors, and level of care for CVD in an African American community. The creation of will within the community for CVD research may require additional strategies than in the majority community, such as community organization and local policy development. These additional efforts at the community level should create a fertile environment to develop research and, ultimately, test strategies for reducing national disparities in cardiovascular health.