Obesity: Falkner B

Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM, Anonymous00014. · No affiliation provided · Circulation. · Pubmed #18574054 links to  free full text

Abstract: Resistant hypertension is a common clinical problem faced by both primary care clinicians and specialists. While the exact prevalence of resistant hypertension is unknown, clinical trials suggest that it is not rare, involving perhaps 20% to 30% of study participants. As older age and obesity are 2 of the strongest risk factors for uncontrolled hypertension, the incidence of resistant hypertension will likely increase as the population becomes more elderly and heavier. The prognosis of resistant hypertension is unknown, but cardiovascular risk is undoubtedly increased as patients often have a history of long-standing, severe hypertension complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. The diagnosis of resistant hypertension requires use of good blood pressure technique to confirm persistently elevated blood pressure levels. Pseudoresistance, including lack of blood pressure control secondary to poor medication adherence or white coat hypertension, must be excluded. Resistant hypertension is almost always multifactorial in etiology. Successful treatment requires identification and reversal of lifestyle factors contributing to treatment resistance; diagnosis and appropriate treatment of secondary causes of hypertension; and use of effective multidrug regimens. As a subgroup, patients with resistant hypertension have not been widely studied. Observational assessments have allowed for identification of demographic and lifestyle characteristics associated with resistant hypertension, and the role of secondary causes of hypertension in promoting treatment resistance is well documented; however, identification of broader mechanisms of treatment resistance is lacking. In particular, attempts to elucidate potential genetic causes of resistant hypertension have been limited. Recommendations for the pharmacological treatment of resistant hypertension remain largely empiric due to the lack of systematic assessments of 3 or 4 drug combinations. Studies of resistant hypertension are limited by the high cardiovascular risk of patients within this subgroup, which generally precludes safe withdrawal of medications; the presence of multiple disease processes (eg, sleep apnea, diabetes, chronic kidney disease, atherosclerotic disease) and their associated medical therapies, which confound interpretation of study results; and the difficulty in enrolling large numbers of study participants. Expanding our understanding of the causes of resistant hypertension and thereby potentially allowing for more effective prevention and/or treatment will be essential to improve the long-term clinical management of this disorder.

Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM. · No affiliation provided · Hypertension. · Pubmed #18391085 links to  free full text

Abstract: Resistant hypertension is a common clinical problem faced by both primary care clinicians and specialists. While the exact prevalence of resistant hypertension is unknown, clinical trials suggest that it is not rare, involving perhaps 20% to 30% of study participants. As older age and obesity are 2 of the strongest risk factors for uncontrolled hypertension, the incidence of resistant hypertension will likely increase as the population becomes more elderly and heavier. The prognosis of resistant hypertension is unknown, but cardiovascular risk is undoubtedly increased as patients often have a history of long-standing, severe hypertension complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. The diagnosis of resistant hypertension requires use of good blood pressure technique to confirm persistently elevated blood pressure levels. Pseudoresistance, including lack of blood pressure control secondary to poor medication adherence or white coat hypertension, must be excluded. Resistant hypertension is almost always multifactorial in etiology. Successful treatment requires identification and reversal of lifestyle factors contributing to treatment resistance; diagnosis and appropriate treatment of secondary causes of hypertension; and use of effective multidrug regimens. As a subgroup, patients with resistant hypertension have not been widely studied. Observational assessments have allowed for identification of demographic and lifestyle characteristics associated with resistant hypertension, and the role of secondary causes of hypertension in promoting treatment resistance is well documented; however, identification of broader mechanisms of treatment resistance is lacking. In particular, attempts to elucidate potential genetic causes of resistant hypertension have been limited. Recommendations for the pharmacological treatment of resistant hypertension remain largely empiric due to the lack of systematic assessments of 3 or 4 drug combinations. Studies of resistant hypertension are limited by the high cardiovascular risk of patients within this subgroup, which generally precludes safe withdrawal of medications; the presence of multiple disease processes (eg, sleep apnea, diabetes, chronic kidney disease, atherosclerotic disease) and their associated medical therapies, which confound interpretation of study results; and the difficulty in enrolling large numbers of study participants. Expanding our understanding of the causes of resistant hypertension and thereby potentially allowing for more effective prevention and/or treatment will be essential to improve the long-term clinical management of this disorder.

Falkner B, DeLoach S. · No affiliation provided · Hypertension. · Pubmed #19414644 No free full text.

This publication has no abstract.

Falkner B. · No affiliation provided · Circulation. · Pubmed #17893285 links to  free full text

This publication has no abstract.

Cossrow N, Falkner B. · IMS Health, Blue Bell, Pennsylvania 19422, USA. · J Clin Endocrinol Metab. · Pubmed #15181028 links to  free full text

Abstract: The prevalence of obesity is increasing among all age and racial groups in the United States. There is, however, a disproportionate rise in the prevalence of obesity among African-Americans and Hispanic/Mexican Americans. Obesity is a major contributor to the insulin resistant syndrome (IRS), a condition of multiple metabolic abnormalities that is a precursor to type 2 diabetes, and confers a high risk for cardiovascular events. The estimated prevalence of IRS is also greater in Mexican Americans and African-Americans than in Caucasians. The IRS is identifiable in children, and as with adults, there are racial differences in its expression even at a young age. The obesity-associated diseases, including diabetes and hypertension, are found at higher rates within the minority races compared with Caucasians. However, there are differences, in that obesity-related hypertension occurs at higher rates among African-Americans, and obesity-related diabetes occurs at higher rates among Mexican Americans. Race/ethnic differences in lifestyle behaviors and economic disadvantage may account for some of the race disparity in obesity-related diseases and disease outcomes. Environmental factors, however, do not explain all of the race disparity in disease expression, indicating that there are genetic/molecular factors that are operational as well.

Falkner B, Michel S. · MCP Hahnemann University, Philadelphia, Pennsylvania 19129-1191, USA. · Ethn Dis. · Pubmed #10421092 No free full text.

Abstract: The prevalence of obesity has increased over the past three decades, in children as well as in adults. When obesity develops in the childhood years, excess adiposity generally continues into adult years, and adult obesity with childhood onset is frequently more severe. The health consequences of obesity in adults are well established, including greater rates of hypertension, non-insulin dependent diabetes mellitus, and heart disease. This paper will discuss the risk factors for these adult disorders that are detectable in obese children. Compared to normal weight children, obese children have higher blood pressure, higher plasma insulin levels, and a more atherogenic lipid pattern. Thus, the characteristic features of Syndrome X, or the insulin resistant syndrome, can be detected in obese children and adolescents. The vascular consequences of exposure to these metabolic risk factors beginning in childhood have yet to be completely determined. However, it is very likely that childhood obesity does contribute significantly to cardiovascular disease. For these reasons, greater efforts should be mounted to reduce the currently rising rates.

Sumner AE, Falkner B, Diffenderfer MR, Barrett PH, Marsh JB. · Department of Biochemistry, MCP-Hahnemann University School of Medicine, Philadelphia, Pennsylvania 19129, USA. · Proc Soc Exp Biol Med. · Pubmed #10460697 No free full text.

Abstract: The purpose of this study was to determine the relationship between insulin resistance and apoB100 metabolism in African American males. Fifteen subjects, 33 +/- 7.6 years old, were divided into two groups, insulin-resistant (IR) or insulin-sensitive (IS), based on the sum of the plasma insulin concentrations during an oral glucose tolerance test. The IR group (n = 8) differed significantly from the IS group (n = 7) with respect to body mass index (BMI) (30.1 vs 23.1 kg/m2; P = 0.0003), fasting triglycerides, (118 vs 54 mg/dl, P = 0. 013), and total plasma apolipoprotein B100 (80 vs 59 mg/dl, P = 0.014). Significantly elevated apoB100 levels in the IR group were seen in very low density lipoprotein (VLDL) (5.1 vs 3.4 mg/dl, P = 0.045) and intermediate density lipoprotein (IDL) (18 vs 12 mg/dl, P = 0.017) but not in low density lipoprotein (LDL) (57 vs 46 mg/dl, P = 0.19). Total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A-I, and blood pressure were not significantly different between the two groups. There was a high correlation between the sum of insulins during the oral glucose tolerance test and the BMI (rho = 0.88, P = 0.0001). In five IR and five IS subjects, apoB100 kinetics were determined in the fasting state using a bolus dose of deuteroleucine and multicompartmental modeling. IR subjects had significantly lower fractional catabolic rates (FCR) in the larger VLDL1 (-70%), the smaller VLDL2 (-71%), and the IDL (-53%) fractions. No significant differences in production rates were observed for any lipoprotein class. There was a significant correlation between the sum of insulins and the FCR of the apoB100 of VLDL1 (rho = -0.65, P = 0.05) and of IDL (rho = -0.85, P = 0.004). The correlation coefficient of the sum of insulins and the FCR of VLDL2 was -0.61 with P = 0.067. We conclude that in this population of African American males, IR is correlated with a decreased FCR of apoB100 in VLDL and IDL and elevated plasma levels of apoB and triglycerides (TG). These changes might be explained by decreased clearance of the TG-rich lipoproteins. We postulate that this may reflect decreased lipoprotein and/or hepatic lipase activity related to insulin resistance and its association with obesity.

Lande MB, Adams H, Falkner B, Waldstein SR, Schwartz GJ, Szilagyi PG, Wang H, Palumbo D. · Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA. · J Pediatr. · Pubmed #18823913 No free full text.

Abstract: OBJECTIVE: To determine the relations between hypertension and parental ratings of behavior and executive functions in children with primary hypertension and to examine the potential moderating influence of obesity. STUDY DESIGN: Hypertensive and normotensive control groups were matched for age, sex, race, intelligence quotient, maternal education, household income, and obesity. Parents completed the Child Behavior Checklist to assess Internalizing and Externalizing problems and the Behavior Rating Inventory of Executive Function to assess behavioral correlates of executive function. RESULTS: Thirty-two hypertensive subjects and 32 normotensive control subjects (aged 10 to 18 years) were enrolled. On the Child Behavior Checklist, hypertensives had higher Internalizing T-scores (53 vs 44.5, P = .02) with 37% falling within the clinically significant range vs 6% of control subjects (P = .005). Internalizing score increased with increasing body mass index percentile in hypertensive but not normotensive subjects. Hypertensives had worse Behavior Rating Inventory of Executive Function Global Executive Composite T-scores compared with control subjects (50 vs 43, P = .009). CONCLUSIONS: Children with both hypertension and obesity demonstrate higher rates of clinically significant internalizing problems, and hypertensives (irrespective of obesity) demonstrate lower parental ratings of executive function compared with normotensive control subjects.

Falkner B, Gidding SS, Portman R, Rosner B. · Department of Medicine, Thomas Jefferson University, 833 Chestnut St, Suite 700, Philadelphia, PA 19107, USA. · Pediatrics. · Pubmed #18676538 No free full text.

Abstract: OBJECTIVE: There is little information in pediatrics on the persistence of the prehypertension and hypertension classifications or on the progression of prehypertension to hypertension. This study aimed to examine those issues. METHODS: An analysis of data from the National Childhood Blood Pressure database was conducted to examine the longitudinal blood pressure outcomes for adolescents classified after a single measurement of blood pressure. Adolescent subjects (N = 8535) for whom serial single blood pressure measurements were obtained at intervals of 2 years were identified. Subjects were stratified according to blood pressure status at the initial measurement, as having normotension, prehypertension, or hypertension. RESULTS: Among subjects designated as having prehypertension (n = 1470), 14% of boys and 12% of girls had hypertension 2 years later. Among subjects designated as having hypertension, 31% of boys and 26% of girls continued to exhibit hypertension, and 47% of boys and 26% of girls had blood pressure values in the prehypertensive range. Regression models showed no significant effect of race on blood pressure changes but significant effects of initial BMI and changes in BMI. CONCLUSIONS: These data indicated that the rate of progression of prehypertension to hypertension was approximately 7% per year. Prehypertension can be predictive of future hypertension and may benefit from preventive interventions, especially lifestyle changes.

Sharma K, Ramachandrarao S, Qiu G, Usui HK, Zhu Y, Dunn SR, Ouedraogo R, Hough K, McCue P, Chan L, Falkner B, Goldstein BJ. · Translational Research in Kidney Disease, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, MC 0711, La Jolla, California 92093-0711, USA. · J Clin Invest. · Pubmed #18431508 links to  free full text

Abstract: Increased albuminuria is associated with obesity and diabetes and is a risk factor for cardiovascular and renal disease. However, the link between early albuminuria and adiposity remains unclear. To determine whether adiponectin, an adipocyte-derived hormone, is a communication signal between adipocytes and the kidney, we performed studies in a cohort of patients at high risk for diabetes and kidney disease as well as in adiponectin-knockout (Ad(-/-)) mice. Albuminuria had a negative correlation with plasma adiponectin in obese patients, and Ad(-/-) mice exhibited increased albuminuria and fusion of podocyte foot processes. In cultured podocytes, adiponectin administration was associated with increased activity of AMPK, and both adiponectin and AMPK activation reduced podocyte permeability to albumin and podocyte dysfunction, as evidenced by zona occludens-1 translocation to the membrane. These effects seemed to be caused by reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes. Ad(-/-) mice treated with adiponectin exhibited normalization of albuminuria, improvement of podocyte foot process effacement, increased glomerular AMPK activation, and reduced urinary and glomerular markers of oxidant stress. These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes.

Rosner B, Cook N, Portman R, Daniels S, Falkner B. · Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. · Am J Epidemiol. · Pubmed #18230679 links to  free full text

Abstract: Blood pressure in children has consistently been related to adult blood pressure, with implications for long-term prevention of cardiovascular disease. The epidemic of obesity in children has resulted in corresponding increases in childhood blood pressure. In this paper, the authors develop norms for childhood blood pressure among normal-weight children (body mass index <85th percentile based on Centers for Disease Control and Prevention guidelines) as a function of age, sex, and height, using data from 49,967 children included in the database of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (the Pediatric Task Force). The authors considered three types of models for pediatric blood pressure data, including polynomial regression, restricted cubic splines, and quantile regression, with the latter providing the best fit. The sex-specific norms presented here are a nonlinear function of both age and height and are generally slightly lower than previously developed norms based on Pediatric Task Force data including both normal-weight and overweight children.

Koenigsberg J, Boyd GS, Gidding SS, Hassink SG, Falkner B. · Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA. · J Cardiometab Syndr. · Pubmed #17679813 No free full text.

Abstract: To determine the effect of age and sex on cardiovascular risk factor expression in overweight children, data from clinical records of 497 overweight children (2-18 years of age) were examined. Data included average blood pressure (BP), fasting lipids, glucose, and insulin. The sample was stratified by age (younger than 11 and 11 years and older) and analyzed by sex. Subjects with an average BP > or = 90th percentile were classified as having high BP. Insulin and glucose were used in equations to estimate insulin sensitivity. Among subjects 11 years and older (n = 268), 52.6% of males had high BP compared with 32.6% of females (P < .001). Mean high-density lipoprotein cholesterol was lowest in the males 11 years and older compared with the females and younger males (P < .01). Triglyceride levels trended higher in males independent of age. In multivariate analyses, high BP was most strongly associated with age and severity of overweight while triglyceride level was most associated with sex and insulin resistance. The prevalence of high BP and dyslipidemia in overweight children is high. Overweight males 11 years and older have a higher prevalence of high BP and low high-density lipoprotein cholesterol than females and younger males. Greater cardiovascular risk factor expression in overweight males 11 years and older may explain the earlier appearance of cardiovascular disease end points in overweight men.

Falkner B. · Thomas Jefferson University, Philadelphia, PA 19107, USA. · Pediatr Ann. · Pubmed #17153125 No free full text.

Abstract: Essential, or primary, hypertension is detectable in childhood. Due to the rising rates of childhood obesity, the expression of essential hypertension in childhood is increasing. Despite this trend, the possibility of secondary hypertension should be considered in a child with documented hypertension. Children and adolescents with suspected secondary hypertension may require a more extensive evaluation compared with those expressing characteristics of essential hypertension. Whether the hypertension is determined to be secondary or essential, these children require careful monitoring, interventions to control the blood pressure, and long-term follow-up. Considering the long-term morbidity and mortality associated with essential hypertension, interventions, including preventive interventions, that focus on blood pressure control beginning in the young are an important component of healthcare for children and adolescents.

Falkner B, Gidding SS, Ramirez-Garnica G, Wiltrout SA, West D, Rappaport EB. · Departments of Medicine and Pediatrics, Thomas Jefferson University, 833 Chestnut Street, Philadelphia, PA 19107, USA. · J Pediatr. · Pubmed #16492428 No free full text.

Abstract: OBJECTIVE: To determine whether an association of overweight, or risk of overweight, and blood pressure can be detected in children in the pediatric primary care practice setting. STUDY DESIGN: We examined electronic medical record (EMR) data from primary care practices on 18,618 children age 2 to 19 years. Each child was classified on the basis of age- and sex-specific body mass index (BMI) percentile as normal weight (BMI < 85th percentile), at risk for overweight (BMI > or = 85th and < 95th percentile), or overweight (BMI > or = 95th percentile). BMI Z-score and height Z-score were computed. Systolic and diastolic blood pressures were compared among age-sex-BMI groups. RESULTS: Among children in primary care pediatric practices, 16.7% were at risk of overweight and 20.2% were overweight. With increasing BMI status there was a significant increase in both systolic blood pressure (P < .001) and diastolic blood pressure (P < .001). The association of higher blood pressure with increasing BMI status was present in all age groups. CONCLUSIONS: Clinical data from pediatric primary care practices verify the high prevalence of childhood overweight. The effect of overweight on blood pressure is present in childhood and can be detected even in children as young as 2 to 5 years.

Moser M, Falkner B, Weber MA, Keilson LM. · Yale University School of Medicine, New Haven, CT, USA. · J Clin Hypertens (Greenwich). · Pubmed #16407688 No free full text.

Abstract: Following a hypertension symposium in Portland, ME, in October 2005, a roundtable was convened to discuss the metabolic syndrome and its significance. Dr. Marvin Moser of the Yale University School of Medicine, New Haven, CT, moderated the discussion. Participating in the discussion were Dr. Bonita Falkner of the Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA; Dr. Michael A.Weber of SUNY Downstate College of Medicine, New York, NY; and Dr. Leonard Mark Keilson of the University of Vermont College of Medicine.

Boyd GS, Koenigsberg J, Falkner B, Gidding S, Hassink S. · Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. · Pediatrics. · Pubmed #16061601 links to  free full text

Abstract: OBJECTIVE: To examine the extent of blood lipid abnormalities in overweight children and to determine whether the prevalence of dyslipidemia is different in overweight children with elevated blood pressure (BP) compared with overweight children with normal BP (NBP). METHODS: A retrospective, case-control study on 497 patients 2 to 18 years of age at the Nemours Weight Management Clinic of duPont Hospital for Children was conducted to compare the prevalence of abnormal plasma lipid levels in overweight children with high BP with overweight children with NBP. RESULTS: Elevated BP was detected in 34.7% of the sample; 27.9% had prehypertension (pre-HTN), and 6.8% had HTN. The rates of abnormal plasma lipid levels were high among overweight children with both NBP and HTN. Significantly more boys with high BP had low high-density lipoprotein cholesterol compared with boys with NBP (49.4% vs 27.6%). Significantly more severely obese boys had low high-density lipoprotein cholesterol compared with moderately obese boys (40.3% vs 29.3%). The prevalence of elevated BP was much greater in severely obese boys and girls (46.5% and 39%) than moderately obese boys and girls (28.1% and 23.1%). CONCLUSIONS: The high prevalence of dyslipidemia found in this overweight sample supports recent recommendations to collect plasma lipid levels in not only overweight children with BP > or =90th percentile but also in all overweight children.

Campbell KL, Kushner H, Falkner B. · Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. · J Clin Hypertens (Greenwich). · Pubmed #15249791 No free full text.

Abstract: The high prevalence of insulin resistance syndrome in African Americans predisposes this population to higher morbidity and mortality from cardiovascular disease. To test the hypothesis that the combination of obesity and high blood pressure (BP) represents the physical phenotype of insulin resistance syndrome, 337 African-American men and women aged 32+/-4 years were examined and classified into four groups (nonobese-normal BP, nonobese-high BP, obese-normal BP, obese-high BP), according to presence or absence of obesity and high BP. Mean values of glucose, insulin, lipids, urinary albumin excretion, and clamp-derived insulin sensitivity were determined for each group. Prevalence of prediabetes (24.4%), diabetes (19.2%), and insulin resistance syndrome (87.2%) were highest in the obese-high BP group (p<0.001). Mean triglycerides, urinary albumin excretion, fasting glucose, fasting insulin, and insulin resistance were highest in the obese-high BP group (p<0.001). Subjects with both obesity and high BP showed greater expression of lipid and glucose abnormalities, higher urinary albumin excretion, and greater prevalence of prediabetes, undetected type 2 diabetes, and insulin resistance syndrome.

Falkner B. · Thomas Jefferson University School of Medicine, USA. · Ethn Dis. · Pubmed #14552445 No free full text.

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Murtaugh KH, Borde-Perry WC, Campbell KL, Gidding SS, Falkner B. · Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylvania, USA. · Ethn Dis. · Pubmed #12148703 No free full text.

Abstract: OBJECTIVES: To examine the associations between the combination of obesity and tobacco use and total cardiovascular risk score in young adult African Americans. DESIGN: A cross-sectional study of 323 African-American men (N = 117) and women (N = 206) aged 20-46 years. METHODS: Age, height, weight, and data on smoking behavior were obtained, as well as measurements of blood pressure, serum lipids, and measurements from an oral glucose tolerance test (OGTT). A cardiovascular risk score was calculated from the above data. RESULTS: Fasting insulin, fasting blood glucose, and blood glucose at 120 minutes of OGTT were significantly higher in obese (body mass index [BMI] > or = 30 kg/m2) men. Obese men also had significantly higher LDL cholesterol, lower HDL cholesterol and higher total risk scores. Obese women had significantly higher blood pressure, higher fasting insulin, lower LDL cholesterol, and higher total risk scores. Among the members of this cohort, 65% of men and 79% of women were obese and/or smoked. Of those who were obese and/or smoked, 68% of the men and 82% of the women had at least one other cardiovascular risk factor. CONCLUSIONS: The modifiable risk factors of obesity and smoking were present in a large majority of these young adult African Americans in association with other cardiovascular risk factors.

Falkner B, Hassink S, Ross J, Gidding S. · Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. · Pediatrics. · Pubmed #12093995 links to  free full text

Abstract: The clinical diagnosis of dysmetabolic syndrome in an adult defines a patient with abnormal glucose metabolism (or diabetes), hypertension, hyperlipidemia, and obesity. This disorder accelerates atherosclerosis and significantly raises the risk for cardiovascular events. With the marked rise in the prevalence of obesity in childhood, obesity-linked risk factors are being expressed at young ages. The case of a 12-year-old girl with dysmetabolic syndrome is described and discussed. Emerging clinical data now indicate that the presence of 1 risk factor for cardiovascular disease in an overweight child should prompt screening for additional clinical abnormalities, with the aim of finding treatable disorders.

Campbell KL, Borde-Perry WC, Murtaugh KH, Gidding SS, Falkner B. · Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylvania, USA. · Am J Med Sci. · Pubmed #12018664 No free full text.

Abstract: BACKGROUND: Patients with type 2 diabetes have higher rates of cardiovascular events. Among African Americans, there is a higher prevalence of both cardiovascular disease and type 2 diabetes. Few studies have examined longitudinally the change in glucose tolerance in younger adult African Americans. METHODS: To examine the longitudinal relationship of glucose tolerance with other cardiovascular risk factors, 30 African American men and women aged 20 to 43 years were examined twice at an interval of 4 to 5 years. Cardiovascular risk factors, glucose tolerance, and insulin sensitivity (determined from euglycemic hyperinsulinemic clamp procedure) were assessed at each examination. Known diabetics were excluded from initial enrollment. The relationship of glucose tolerance status (normal, impaired, or diabetic glucose tolerance) to body mass index, blood pressure, cholesterol, and insulin sensitivity were further investigated. RESULTS: Initial oral glucose tolerance test identified 24 of 130 (18.5%) subjects with impaired glucose tolerance and 2 of 130 (1.5%) subjects with diabetes. Of the remaining 104 subjects with normal glucose tolerance, subsequent 5-year examination detected 31 (29.8%) with impaired glucose tolerance and 5 (4.8%) with diabetes. Those who later developed diabetes had higher mean systolic blood pressure (133 versus 121, P = 0.037) at exam 1. By exam 2, those with abnormal glucose tolerance had worse cardiovascular risk profiles and increased insulin resistance (P < 0.001). CONCLUSION: Conversion to abnormal glucose tolerance is relatively frequent in young adult African Americans. Deterioration in glucose tolerance may be preceded by higher systolic blood pressure and is accompanied by worsening of other cardiovascular risk factors and insulin resistance.

Borde-Perry WC, Campbell KL, Murtaugh KH, Gidding S, Falkner B. · Department of Medicine and Pediatrics, Thomas Jefferson University, Philadelphia, PA 19107, USA. · J Clin Hypertens (Greenwich). · Pubmed #11821633 No free full text.

Abstract: Hypertension is a major cause of cardiovascular disease in African Americans. The excess morbidity and mortality due to cardiovascular disease in African Americans compared to Caucasians is not well explained. The purpose of this study was to examine the association between hypertension and other cardiovascular risk factors in young adult African Americans. A risk factor scoring system was developed, based on national guidelines for obesity, smoking, cholesterol levels, glucose tolerance, and blood pressure. Data from a previously studied cohort of 206 women and 117 men were analyzed for the association of hypertension with other risk factors. Among women, risk factor intensification is due to impaired glucose tolerance and obesity. Among men, intensification appears to be related to all major risk factor categories. These findings indicate that among hypertensive African Americans there is an amplification of other risk factors. The data also support the clinical management of multiple risk factors as well as the achievement of blood pressure control.

Falkner B, Sherif K, Michel S, Kushner H. · Departments of Medicine and Pediatrics, Thomas Jefferson University, Walnut Towers, 211 S Ninth St, Suite 630, Philadelphia, PA 19107. · Arch Pediatr Adolesc Med. · Pubmed #10980796 links to  free full text

Abstract: OBJECTIVE: To determine if blood pressure (BP) level is associated with dietary micronutrients in adolescents at risk for hypertension. DESIGN: Adolescents aged 14 to 16 years, with BP higher than the 90th percentile on 2 separate measurements in a school setting, had diet assessments. A 24-hour intake recall was obtained on 180 students (108 boys and 72 girls). Folic acid intake was used as an index of fruit, vegetable, and whole grain intake; the high folate group had a folate intake greater than the recommended daily allowance and the low folate group had a folate intake less than the recommended daily allowance. Data were analyzed by 2-way analysis of variance. RESULTS: Mean diastolic BP was significantly higher in the low folate vs the high folate group (boys: 72 vs. 67 mm Hg; girls: 76 vs. 73 mm Hg; P =.008). The difference in systolic blood pressure was not significant. There was no difference in body mass index between the diet groups. Sodium intake per 4184 kJ was not different. The low folate group had significantly lower intakes per 4184 kJ of potassium (P =.002), calcium (P = .001), magnesium (P<.001), and total intake of beta carotene, cholecalciferol, vitamin E, and all B vitamins. CONCLUSIONS: Among adolescents at risk for hypertension, BP was lower in those with higher intakes of a combination of nutrients, including potassium, calcium, magnesium, and vitamins. Dietary benefits on BP observed on diets rich in a combination of nutrients derived from fruits, vegetables, and low-fat dairy products could contribute to primary prevention of hypertension when instituted at an early age.

Sherif K, Barrett M, Kushner H, Falkner B. · Department of Medicine, MCP-Hahnemann School of Medicine, Philadelphia, Pennsylvania 19129, USA. · Am J Med Sci. · Pubmed #10910368 No free full text.

Abstract: BACKGROUND: African American women have disproportionately high rates of myocardial infarction and stroke. Left ventricular hypertrophy is an independent risk factor for cardiovascular disease. Increases in left ventricular mass (LVM) may precede the expression of hypertension. The purpose of this study was to determine whether LVM is related to cardiovascular risk variables in healthy, premenopausal African American women. METHODS: Normotensive or borderline hypertensive nondiabetic African American women (N = 52; mean age, 31 years) underwent anthropometric and blood pressure measurements, oral glucose tolerance test, euglycemic clamp, fasting lipid profile, and two-dimensional echocardiography. LVM was calculated by the cube root formula and adjusted for height [LVM index (LVMI)]. RESULTS: LVMI correlated with body mass index (r = .36, P = 0.009), systolic blood pressure (r = .44, P = 0.001), diastolic blood pressure (r = .43, P = 0.002), and central body fat (r = .42, P = 0.002). LVMI also directly correlated with lipoprotein (a) (r = .34, P = 0.02). Significant independent relationships of other metabolic variables with LVMI were not detected. DISCUSSION: These data show that increased LVMI is associated with body mass index and central obesity, but not with lipids, insulin resistance, or insulin sensitivity. LVMI is also associated with blood pressure before the expression of severe hypertension in healthy, premenopausal African American women.

Sumner AE, Kushner H, Sherif KD, Tulenko TN, Falkner B, Marsh JB. · Institute for Women's Health, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania, USA. · Diabetes Care. · Pubmed #10333906 links to  free full text

Abstract: OBJECTIVE: The purpose of this study was to determine if there are sex differences in African-Americans regarding the effect of obesity on sensitivity to insulin as a glucoregulatory and antilipolytic hormone. RESEARCH DESIGN AND METHODS: Data from study participants, 127 nondiabetic African-Americans (mean age 32 +/- 4 years), included anthropometric measurements, an oral glucose tolerance test (OGTT), a 2-h euglycemic-hyperinsulinemic clamp, and a fasting triglyceride level. Sensitivity to insulin as a glucoregulatory hormone was determined by M/FFM, where M is the mean glucose infusion rate during the second hour of the clamp and FFM is fat-free mass. Sensitivity to insulin's antilipolytic action was assessed during the OGTT by the percent suppression of free fatty acid (FFA) concentrations between 0 and 120 min. The higher the suppression of FFAs, the greater the sensitivity to insulin's antilipolytic action. RESULTS: The participants were classified by BMI into three groups: nonobese (31 men, 24 women), obese (17 men, 14 women), and severely obese (12 men, 29 women). The women had higher percentages of body fat (P < 0.001), and the men had greater FFM (P < 0.001). The M/FFM values for men versus women in each BMI group were nonobese, 8.8 +/- 2.8 vs. 10.8 +/- 4.4; obese, 7.2 +/- 3.4 vs. 8.5 +/- 3.4; and severely obese, 4.7 +/- 2.1 vs. 6.1 +/- 2.2. The difference between the BMI groups was significant (P < 0.001), as was the difference between men and women (P < 0.01). In addition, there was a significant sex difference in percent suppression of FFAS (P < 0.001). The men and women had similar fasting insulin and FFA concentrations; however, in the men only, the percent suppression of FFA declined with increasing obesity (nonobese, 83 +/- 15%; obese, 73 +/- 18%; and severely obese, 69 +/- 19%; P = 0.02). The women in all three BMI groups had lower FFA levels of 86-88%. CONCLUSIONS: Obese African-American men and women are resistant to insulin as a glucoregulatory hormone, but only obese men are resistant to insulin's antilipolytic action; obese African-American women are sensitive to insulin's antilipolytic action. The combined presence of sensitivity to insulin's antilipolytic action with resistance to insulin's glucoregulatory action in obese African-American women may contribute to their high prevalence of obesity and type 2 diabetes.