Hypertension Is Associated with White Matter Disruption in Apparently Healthy Middle-Aged Individuals.

BACKGROUND AND PURPOSE: Traditional cardiovascular risk factors have been associated with white matter disease. Because hypertension results in vascular stiffness and impaired cerebral perfusion, we hypothesized that it would be the most relevant risk factor for microstructural white matter disruption in apparently healthy middle-aged individuals with a family history of early-onset coronary artery disease. MATERIALS AND METHODS: This was a cross-sectional analysis of participants in the Genetic Study of Atherosclerosis Risk with DTI. Regional fractional anisotropy of 181 segmented brain regions was measured using Eve WM Atlas. Risk factors were examined using univariate analysis for 48 regions representing deep WM structures. Minimal multivariable linear regression models adjusting for age, sex, and race and maximal linear regression models adjusting for cardiovascular risk factors were performed for regions meeting the Bonferroni threshold in the initial analysis. RESULTS: Included were 116 subjects (mean age, 49 ± 11 years; 57% men) with a moderate load of cardiovascular risk factors. Subjects with hypertension had significantly lower regional fractional anisotropy in the right cingulum and left stria terminalis in the minimal and maximal regression models. Additionally, there was lower regional fractional anisotropy in the left fornix in the maximal model and right sagittal stratum in the minimal model. Systolic blood pressure values were significantly associated with regional fractional anisotropy in the left superior longitudinal fasciculus in the maximal model. There were no significant differences among regional fractional anisotropy values for other cardiovascular risk factors. CONCLUSIONS: In middle-aged apparently healthy individuals with susceptibility to vascular disease, among all known cardiovascular risk factors, hypertension was associated with microstructural WM disruption.

Genome-wide meta-analyses of smoking behaviors in African Americans.

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (ß = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

Heritability of platelet function in families with premature coronary artery disease.

BACKGROUND: Variations in platelet function among individuals may be related to differences in platelet-related genes. The major goal of our study was to estimate the contribution of inheritance to the variability in platelet function in unaffected individuals from white and African American families with premature coronary artery disease. METHODS: Platelet reactivity, in the absence of antiplatelet agents, was assessed by in vitro aggregation and the platelet function analyzer closure time. Heritability was estimated using a variance components model. RESULTS: Both white (n = 687) and African American (n = 321) subjects exhibited moderate to strong heritability (h(2)) for epinephrine- and adenosine diphosphate-induced aggregation (0.36-0.42 for white and >0.71 for African American subjects), but heritability for collagen-induced platelet aggregation in platelet-rich plasma was prominent only in African American subjects. Platelet lag phase after collagen stimulation was heritable in both groups (0.47-0.50). A limited genotype analysis demonstrated that the C825T polymorphism of GNB3 was associated with the platelet aggregation response to 2 muM epinephrine, but the effect differed by race. CONCLUSIONS: Considering the few and modest genetic effects reported to affect platelet function, our findings suggest the likely existence of undiscovered important genes that modify platelet reactivity, some of which affect multiple aspects of platelet biology.

Building a gateway to promote cardiovascular health research in African-American communities: lessons and findings from the field.

African American communities traditionally mistrust academic research. This forms a significant barrier to understanding cardiovascular risk factors in this population, which bears an excess risk of cardiovascular disease and stroke. A clergy/academic partnership was established to build a gateway for salient research and for improving resources for reducing cardiovascular disease risk in the community. From this partnership emanated the African American Family Heart Study. People with a family history of premature coronary heart disease (CHD) have an increased risk for the disease--as high as 12 times that of the general population, if among siblings. Considerably less is known about the actual remediable risk factors in African American families with premature CHD. We initiated the Family Heart Study with a full characterization of 161 apparently healthy, unaffected 30- to 59-year-old African Americans whose siblings were 85 African American index cases with documented premature CHD prior to 60 years of age. We compared their risk factor values to population reference norms obtained in the Third National Health and Nutrition Examination Survey (NHANES III) and the National Health Interview Survey (NHIS) for cigarette smoking. Only 13% of African American male siblings and 14% of female siblings from these families were without any major remediable risk factors. The fact that so many siblings were at extremely high risk calls into question the current applications by provider systems of national guidelines in high-risk African American families. This is an easily identifiable population that would be likely to benefit greatly from targeted screening and culturally sensitive and appropriate treatment.

Racial differences in low-density lipoprotein particle size in families at high risk for premature coronary heart disease.

OBJECTIVE: Although small, dense low-density lipoprotein (LDL) has been implicated in atherogenesis and coronary heart disease (CHD) events, little is known about possible racial differences in LDL particle size. This study was designed to examine racial differences in the prevalence of small, dense LDL among 159 African-American and 477 White siblings of persons with premature (<60 years of age) CHD. METHODS AND RESULTS: This study examined fasting levels of total cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, apolipoprotein B (ApoB), apolipoprotein A-1, and triglycerides, as well as factors known to be associated with small, dense LDL, including age, sex, obesity, hypertension, and diabetes. Relative LDL particle size was defined by the LDL cholesterol to ApoB ratio. Direct measurement of LDL particle size was obtained by proton NMR spectroscopy in a subset of 64 siblings. Despite similar levels of total and LDL cholesterol, White siblings were more likely to have low LDL cholesterol to ApoB ratios, indicative of atherogenic small, dense LDL, compared with African-American siblings. Multiple logistic regression analysis predicting the presence of LDL cholesterol/ApoB < or = 1.0 demonstrated that race (P = .009), triglyceride level (P = .0001), and diabetes (P = .02) were independent predictors, controlling for age and all other variables. Direct measurement of LDL particle size by NMR spectroscopy supported these findings. CONCLUSION: These findings provide the first known evidence that White individuals from a population at high risk for premature CHD have a greater probability of having a preponderance of small, dense LDL particles than do African Americans, independent of triglyceride levels, and despite comparable levels of total and LDL cholesterol.

Improving compliance in your dyslipidemic patient: an evidence-based approach.

PURPOSE: To synthesize the evidence from landmark clinical studies of lipid-lowering pharmacotherapy and nurse management of hyperlipidemia, discuss issues related to nonadherence, and proposes strategies for achieving long-term cholesterol control. DATA SOURCES: All publications of lipid-lowering clinical trials related to pharmacotherapy for dyslipidemias were accessed from a thorough Medline Search and reviewed by two nurse experts. CONCLUSIONS: Randomized controlled studies provide compelling evidence that reduction of blood cholesterol with pharmacotherapy reduces both first and subsequent coronary events. Nonetheless, inadequate provider and patient adherence to guidelines for lipid lowering remains prevalent. Studies show that nurses provide safe and effective care for patients with abnormal lipids. IMPLICATIONS: This article assists nurse practitioners in playing an active role in the implementation of the National Cholesterol Education Program Adult Treatment Panel III Report to be released in Spring 2001, where a strong emphasis will be placed on multidisciplinary approaches and adherence.

Dietary Counseling for High Blood Cholesterol in Families at Risk of Coronary Disease.

A positive family history of coronary heart disease alone confers an increased risk, which may be affected by untreated hypercholesterolemia. Dietary counseling is a first-line treatment approach. To determine whether nurse counseling can provide additional benefits over usual physician efforts to lower dietary fat in high-risk persons, 117 apparently healthy adult siblings of persons with premature coronary heart disease were counseled by a registered nurse using adapted national guidelines. Reductions in total fat, saturated fat, and cholesterol were significantly greater in the nurse group compared to those in the usual care group. Total fat intake decreased by 14 g in the nurse group, compared with an increase of 5 g in the usual care group (p=0.0001). Assignment to the nurse group was also a significant predictor of a greater reduction in the percentage of total fat calories (p=0.008). The authors conclude that a registered nurse may serve as a complement to usual care in efforts to lower dietary fat and cholesterol in high-risk families. (c)2001 CHF, Inc.

Project Joy: faith based cardiovascular health promotion for African American women.

OBJECTIVE: The authors tested the impact on cardiovascular risk profiles of African American women ages 40 years and older after one year of participation in one of three church-based nutrition and physical activity strategies: a standard behavioral group intervention, the standard intervention supplemented with spiritual strategies, or self-help strategies. METHODS: Women were screened at baseline and after one year of participation. The authors analyzed intention-to-treat within group and between groups using a generalized estimating equations adjustment for intra-church clustering. Because spiritual strategies were added to the standard intervention by participants themselves, the results from both active groups were similar and, thus, combined for comparisons with the self-help group. RESULTS: A total of 529 women from 16 churches enrolled. Intervention participants exhibited significant improvements in body weight (-1.1 lbs), waist circumference (-0.66 inches), systolic blood pressure (-1.6 mmHg), dietary energy (-117 kcal), dietary total fat (-8 g), and sodium intake (-145 mg). The self-help group did not. In the active intervention group, women in the top decile for weight loss at one year had even larger, clinically meaningful changes in risk outcomes (-19.8 lbs). CONCLUSIONS: Intervention participants achieved clinically important improvements in cardiovascular disease risk profiles one year after program initiation, which did not occur in the self-help group. Church-based interventions can significantly benefit the cardiovascular health of African American women.

Building a gateway to promote cardiovascular health research in African American communities: lessons and findings from the field.

African American communities traditionally mistrust academic research. This forms a significant barrier to understanding cardiovascular risk factors in this population, which bears an excess risk of cardiovascular disease and stroke. A clergy/academic partnership was established to build a gateway for salient research and for improving resources for reducing cardiovascular disease risk in the community. From this partnership emanated the African American Family Heart Study. People with a family history of premature coronary heart disease (CHD) have an increased risk for the disease--as high as 12 times that of the general population, if among siblings. Considerably less is known about the actual remediable risk factors in African American families with premature CHD. We initiated the Family Heart Study with a full characterization of 161 apparently healthy, unaffected 30- to 59-year-old African Americans whose siblings were 85 African American index cases with documented premature CHD prior to 60 years of age. We compared their risk factor values to population reference norms obtained in the Third National Health and Nutrition Examination Survey (NHANES III) and the National Health Interview Survey (NHIS) for cigarette smoking. Only 13% of African American male siblings and 14% of female siblings from these families were without any major remediable risk factors. The fact that so many siblings were at extremely high risk calls into question the current applications by provider systems of national guidelines in high-risk African American families. This is an easily identifiable population that would be likely to benefit greatly from targeted screening and culturally sensitive and appropriate treatment.

Introduction of DNA into yeast cells.

The most commonly used yeast transformation protocol is the lithium acetate procedure (described here). It is reasonably fast and provides a transformation efficiency of 10(5) to 10(6) transformants/microg. This efficiency rivals that achieved for most, but not all, strains with the more difficult and time-consuming spheroplast procedure presented here. However, the fastest and easiest of the transformation methods is electroporation, as described in this unit. For a number of strains, electroporation offers the highest transformation efficiency, and may prove especially useful with limiting quantities of transforming DNA. Unlike the lithium acetate procedure, however, electroporation saturates at low DNA levels, restricting its general utility.

Comparison of the effectiveness of a telephone 24-hour dietary recall method vs an in-person method among urban African-American women.

OBJECTIVE: To examine the comparative accuracy of telephone and in-person 24-hour dietary recall methods. SUBJECTS: One hundred eighty-five African-American females, aged 40 years and older, recruited from Sunday church services in Baltimore City, Md. METHODS: Participants were trained to estimate portion size with plastic food models and a 2-dimensional food recall booklet. Dietary intake was then assessed with 2 in-person 24-hour dietary recalls and 1 telephone 24-hour dietary recall, all using a computer-assisted, multiple pass approach. Results from the 2 in-person recalls were averaged and compared with the results from the telephone recall. STATISTICAL ANALYSES: Cross-tabulation, paired t test, Pearson's correlation, chance-corrected agreement, and stepwise linear regression analyses were performed. RESULTS: There were no significant differences between the telephone and in-person methods for any nutrient. Agreement between methods was moderate for all major dietary components, with corrected correlations between methods ranging from 0.26 to 0.97 (P<.001), and kappas ranging from 0.155 to 0.372 (P<.01). Levels of low-energy reporting were high (88% telephone, 91% in-person), though there were no significant differences between methods. CONCLUSIONS: The telephone 24-hour dietary recall method appears to be comparable to the standard in-person method among older African-American women. Portion-size training in person may make subsequent telephone dietary recalls acceptable in this population.

The role of spiral volumetric computed tomography in the diagnosis of pulmonary embolism.

To evaluate the evidence for the use of spiral volumetric computed tomography (SVCT) in the diagnosis of acute pulmonary embolism (PE), the 11 English-language studies published through July 1998 that compared SVCT with a reference standard for PE were systematically reviewed. Among the reviewed studies, methodological problems were common. Only 5 of these studies fulfilled 5 of 11 basic standards addressing important issues in diagnostic test research. The reported sensitivities of SVCT compared with pulmonary angiography varied widely (64%-93%), which was likely the result of differences in study populations. Spiral volumetric computed tomography may be relatively sensitive and specific for diagnosing central pulmonary artery PEs, but it is insensitive for diagnosing subsegmental clots. Spiral volumetric computed tomography may have a role as a "rule-in" test for large central emboli, but additional research is required to establish its place in clinical practice.

Body image preferences among urban African Americans and whites from low income communities.

OBJECTIVE: The purpose of this study was to determine (1) how African-American and white men and women from similar low income communities perceive their body mass relative to others in the population; and (2) whether ethnic and gender differences exist in the selection of ideal body image sizes for the same and opposite sex. DESIGN: A street survey of African-American and white men and women was conducted using a census tract sampling schema. Participants (N = 927) were interviewed and asked to provide their height and weight and to select body size images from a standardized ethnic-specific Figure Rating Scale to represent their current self, ideal self, and their estimation of ideals for the opposite sex. Sociodemographics and co-morbidity were assessed by self-report. RESULTS: All ethnic and gender groups showed a significant correlation between their body mass index and selected body image size, r = .63 to .74, all P<.001. Average ideal body image size for self was the same for African-American and white men, while African-American women had a significantly greater ideal image size compared with white women (P = .004). Ideal body image size preferences for members of the opposite sex were greater for African-Americans. White women had a notable preference for the smallest body image sizes. Multiple linear regression analyses showed that, independent of sociodemographic variables and co-morbidity, body image sizes for current self, ideal self, and ideal for the opposite sex were all significantly greater in African-Americans. CONCLUSION: Strategies to ameliorate overweight and its attendant diseases may require a shift in social norms, particularly among African-American women in low socioeconomic communities. This has implications for the design of community-based interventions and suggests a need for ethnic-specific interventions.

Higher prevalence of GPIIIa PlA2 polymorphism in siblings of patients with premature coronary heart disease.

BACKGROUND: The Pl(A2) polymorphism of GPIIIa has been associated with unstable coronary syndromes in some studies, but the association has remained debated. None of the previous studies have focused on families at high risk. Risk factors tend to cluster within kindreds with high prevalence of premature coronary heart disease (CHD). Therefore, a heightened prevalence of the Pl(A2) polymorphism among siblings of patients with CHD would support the hypothesis that Pl(A2) is linked, directly or indirectly, to CHD. OBJECTIVES: To measure the prevalence of the Pl(A2) polymorphism among siblings of patients with CHD before the age of 60 years and to seek an association between the Pl(A2) polymorphism and established atherosclerotic and thrombogenic risk factors. METHODS: From January 1994 to April 1996, we genotyped 116 asymptomatic siblings (60 Caucasians, 56 Afro-Caribbeans) of patients with CHD manifestations before the age of 60 years for the Pl(A) polymorphism (also called HPA-1). A control cohort was used for comparison, consisting of individuals that were matched for race and geographic area but were free of CHD (n = 268, 168 Caucasians and 100 Afro-Caribbeans). In addition, we have characterized the sibling cohort for other atherogenic and thrombogenic risk factors. RESULTS: The prevalence of Pl(A2)-positive individuals (Pl(A2)[+], Pl(A1/A2) heterozygotes plus Pl(A2/A2) homozygotes) in the sibling cohort was high: 41.4%. When analyzed separately, the prevalence of Pl(A2)(+) siblings was 53.3% among Caucasians and 28.6% among Afro-Caribbeans. There was no association between Pl(A2) and other established atherogenic or thrombogenic risk factors. Interestingly, the clustering of other risk factors was lesser among Pl(A2)(+) siblings than their Pl(A1) counterparts. CONCLUSIONS: This study supports the hypothesis that the prevalence of Pl(A2)(+) individuals is high in kindreds with premature CHD. Hence, like the established risk factors that tend to cluster in families with premature CHD and contribute strongly to the accelerated atherosclerotic process affecting these individuals, the Pl(A2) polymorphism of GPIIIa may represent an inherited risk that promotes the thromboembolic complications of CHD. That these asymptomatic Pl(A2)(+) siblings had overall less established risk factors than their Pl(A1) counterparts might represent an explanation for why they remained asymptomatic despite their Pl(A2) positivity.

Dietary fat patterns in urban African American women.

The purpose of this study was to describe the scope of fatty food preferences of urban African American women and to examine factors associated with the selection of high fat foods. A volunteer sample of urban African American women church-goers were invited for dietary and risk factor screening at health fairs held following Sunday services. A standardized instrument, the Fat Intake Scale (FIS), was administered primarily by dietitians to estimate dietary fat intake and usual food choices. A sum score of 25 or more is thought to be associated with higher fat and cholesterol intake. As a validation of the FIS, a 24-hour recall was administered to a subsample. Sociodemographics, smoking status and comorbidity were assessed by self-report. Body weight, height, and total blood serum cholesterol were assessed using standardized measurement techniques. In the 521 participating women, 61% were classified as obese based on national reference norms for body mass index (BMI). More than 81% had an FIS of 25 or greater. On multiple logistic regression analysis, significant predictors of a higher fat diet (FIS > or = 25) included age greater than 45 years, obesity, and the absence of comorbidity. These findings suggest that there are independent predictors of selection of a diet high in fat. This has implications for planning and targeting community-based nutrition interventions for African American women who exhibit among the highest rates of obesity in the U.S. and who suffer an excess burden of obesity-related diseases.

Markedly high prevalence of coronary risk factors in apparently healthy African-American and white siblings of persons with premature coronary heart disease.

Among persons with a family history of premature coronary heart disease (CHD), siblings bear an excess risk of CHD that is as high as 12 times that of the general population. Aggressive, new, national guidelines for CHD risk reduction have focused on high-risk families, yet little is known about actual remediable risk factors in siblings of persons with premature CHD. To determine the magnitude of the problem relative to the general population, we screened 846 unaffected siblings (ages 30 to 59 years) of persons with documented CHD before age 60 years and compared their risk factor values with population reference norms obtained in the Third National Health and Nutrition Examination Survey (NHANES III) and the National Health Interview Survey (NHIS). Mean levels of low-density lipoprotein cholesterol were 0.52 mmol/L (20 mg/dl) higher in siblings; the prevalence of low-density lipoprotein cholesterol > or =4.14 mmol/L (160 mg/dl) was nearly twice that of race, sex, and age-specific values from NHANES III. Levels of high-density lipoprotein cholesterol <0.91 mmol/L (35 mg/dl) were similar between siblings and NHANES III (11% and 12%, respectively). Only 4% of all siblings had triglyceride levels > or =4.52 mmol/L (400 mg/dl). Hypertension prevalence was twice as high among siblings as among the NHANES III. Current smoking was 33.9% in white siblings and 25.5% in the NHIS, whereas smoking in African-Americans was similar to that in the NHIS (31.1% vs 29.2%). A mere 13% to 29% of siblings were without any major remediable risk factors. The overwhelming need for risk factor modification in this easily identifiable high-risk population supports aggressive national guidelines and demonstrates the lack of adequate treatment of apparently healthy siblings of persons with premature CHD.

Nurse-mediated cholesterol management compared with enhanced primary care in siblings of individuals with premature coronary disease.

BACKGROUND: Siblings of individuals with premature coronary heart disease have a high prevalence of low-density lipoprotein cholesterol (LDL-C) levels requiring treatment. OBJECTIVE: To evaluate management strategies for high LDL-C levels in apparently healthy 30- to 59-year-old siblings of individuals with documented coronary heart disease prior to age 60 years. METHODS: In a 2-year trial of care provided by either a nurse trained in lipid management (NURS) or enhanced primary care (EPC), in which physicians received recommendations based on national guidelines, 156 siblings with LDL-C levels of 4.14 mmol/L (160 mg/dL) were randomized by family. The LDL-C goal levels below 3.36 mmol/L (130 mg/dL) were compared between and within intervention groups. Multiple logistic regression analyses were applied to predict 2-year achievement of the goal. RESULTS: The NURS group achieved a significantly greater percentage of goal LDL-C levels than the EPC group (26% vs 10%; P=.008). The NURS LDL-C levels decreased an average of 0.91 mmol/L (35 mg/dL) while EPC levels decreased by 0.52 mmol/L (24 mg/dL) (P=.09). In the final multivariate model, siblings taking lipid-lowering drug treatment were 6.02 times more likely (95% confidence interval, 2.24-16.18) than those not receiving pharmacotherapy to achieve LDL-C goals; nurse management (P=.09) was marginally significant. Pharmacotherapy was instituted in 45.2% of NURS and 16.7% of EPC siblings (P=.001). CONCLUSIONS: High LDL-C levels in siblings were more effectively treated by a trained nurse, probably related to greater adherence to the application of national guidelines. Nonetheless, the majority of siblings with high LDL-C levels did not meet goal levels 2 years after an index case coronary heart disease event.

Hypertension among siblings of persons with premature coronary heart disease.

To determine the extent to which the Fifth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V) guidelines were implemented in high-risk families with premature coronary heart disease, we examined the prevalence of hypertension and associated coronary risk factors in asymptomatic siblings of persons with documented premature coronary disease (<60 years of age). A total of 859 apparently healthy siblings (51% male, 19% African American) were screened for coronary risk factors. Siblings were classified as normotensive or hypertensive (BP > or = 140/90 and/or current antihypertensive pharmacotherapy). The prevalence of hypertension, awareness, treatment, and control among siblings was compared with published national estimates from the third National Health and Nutrition Examination Survey. The prevalence of hypertension in siblings was 44%. Among all hypertensives, only 60% were aware of being hypertensive, 45% were being treated, and 16% were under control. A high prevalence of other coronary risk factors was found among hypertensive siblings: 72% were hypercholesterolemic; 61% were obese; 29% were current smokers; 82% were consuming >30% of calories from fat; and only 14% were participating in vigorous physical activity three or more times per week. Comparisons with the national reference population revealed siblings to have a significantly higher prevalence of hypertension, along with significantly lower levels of awareness, treatment, and control. These findings demonstrate the intersection of multiple risk factors among hypertensive siblings and emphasize the need for more aggressive screening and treatment in this easily identifiable high-risk population.