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Theodore A Kotchen

Publications and source records attributed to Theodore A Kotchen.

At least 19 recordsLinked to original sources
PubMed2006

Association of adrenal steroids with hypertension and the metabolic syndrome in blacks.

Blacks have a high prevalence of hypertension and adrenal cortical adenomas/hyperplasia. We evaluated the hypothesis that adrenal steroids are associated with hypertension and the metabolic syndrome in blacks. Ambulatory blood pressures, anthropometric measurements, and measurements of plasma renin activity (PRA), aldosterone, fasting lipids, glucose, and insulin were obtained in 397 subjects (46% hypertensive and 50% female) after discontinuing antihypertensive and lipid-lowering medications. Hypertension was defined as average ambulatory blood pressure >130/85 mm Hg. Late-night and early morning salivary cortisol, 24-hour urine-free cortisol, and cortisone excretion were measured in a consecutive subsample of 97 subjects (40% hypertensive and 52% female). Compared with normotensive subjects, hypertensive subjects had greater waist circumference and unfavorable lipid profiles, were more insulin resistant, and had lower PRA and higher plasma aldosterone and both late-night and early morning salivary cortisol concentrations. Twenty-four-hour urine-free cortisol and cortisone did not differ. Overall, ambulatory blood pressure was positively correlated with plasma aldosterone (r=0.22; P<0.0001) and late-night salivary cortisol (r=0.23; P=0.03) and inversely correlated with PRA (r=-0.21; P<0.001). Plasma aldosterone correlated significantly with waist circumference, total cholesterol, triglycerides, insulin, and the insulin-resistance index. Based on Adult Treatment Panel III criteria, 17% of all of the subjects were classified as having the metabolic syndrome. Plasma aldosterone levels, but not PRA, were elevated in subjects with the metabolic syndrome (P=0.0002). The association of aldosterone with blood pressure, waist circumference, and insulin resistance suggests that aldosterone may contribute to obesity-related hypertension in blacks. In addition, we speculate that relatively high aldosterone and low PRA in these hypertensive individuals may reflect a mild variant of primary aldosteronism.

Adolescent↗
PubMed2006

Hypertension: trends in prevalence, incidence, and control.

Hypertension is the leading cause of cardiovascular disease worldwide. Prior to 1990, population data suggest that hypertension prevalence was decreasing; however, recent data suggest that it is again on the rise. In 1999-2002, 28.6% of the U.S. population had hypertension. Hypertension prevalence has also been increasing in other countries, and an estimated 972 million people in the world are suffering from this problem. Incidence rates of hypertension range between 3% and 18%, depending on the age, gender, ethnicity, and body size of the population studied. Despite advances in hypertension treatment, control rates continue to be suboptimal. Only about one third of all hypertensives are controlled in the United States. Programs that improve hypertension control rates and prevent hypertension are urgently needed.

Health Services Needs and Demand↗
PubMed2006

Outcomes of National Institutes of Health peer review of clinical grant applications.

PURPOSE: We previously reported that National Institutes of Health (NIH) peer review outcomes in 2002 were slightly but significantly less favorable for grant applications for clinical research than for laboratory research. The present analysis was undertaken to determine if factors related to the review process might contribute to this difference. METHODS: The impact of each of the following factors on median priority scores and funding rates for clinical and nonclinical R01 grant applications was evaluated: (1) the percentage of clinical applications assigned for review to a study section, (2) the requested direct costs, and (3) the clinical research experience of the reviewers. RESULTS: Confirming our previous observation, in both 1994 and 2004, median priority scores and funding rates for R01 applications were less favorable for clinical research. In 1994, clinical applications did not fare as well in study sections reviewing relatively low percentages of clinical applications. This was not the case in 2004. Although requested direct costs were greater for clinical than for nonclinical R01 applications, median priority scores within each category were actually more favorable for applications requesting greater funding. Assignment of priority scores was not different for reviewers with or without experience conducting clinical research. CONCLUSION: These data do not support the hypothesis that the less favorable review outcomes for clinical applications are related to these review factors. We suggest that peer review outcomes for clinical research will benefit from the recent refinement of NIH review criteria, emphasizing the unique contributions of clinical investigation, and from increased training opportunities for clinical investigators.

Biomedical Research↗
PubMed2005

Genome-wide scan for linkage to obesity-associated hypertension in French Canadians.

Essential hypertension is a heterogeneous disorder that is thought to develop because of several overlapping subsets of underlying mechanisms. One such causal pathway may involve pathophysiological alterations induced by obesity. In the present study, we examined whether investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, facilitates the search for its genes. Fifty-five extended families were selected on the basis of having > or =2 siblings affected by hypertension from a geographically remote French-Canadian population. Fifteen of these families showed a high prevalence (> or =70%) of obesity. Genome-wide scan using qualitative multipoint linkage analysis (GeneHunter 2.1; marker density <10 cM) was performed in the entire set of hypertensive families and the subset with high prevalence of obesity. In the scan involving all 55 families, the most significant loci (logarithm of odds [LOD] score=2.5) were identified on chromosomes 1 (D1S1597) and 11 (D11S1999). In the scan including only the subset of families with obesity-hypertension, the most significant locus (LOD score=3.1) was found on chromosome 1 in the same region as the scan involving all families (D1S1597). Genotyping additional markers increased the significance of this locus (LOD score=3.5) and refined its position (D1S2672). Several candidate genes of obesity-hypertension are located in close proximity; these include the tumor necrosis factor receptor 2 and atrial natriuretic peptide genes. These results suggest that investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, may facilitate the search for genes of this complex disorder.

Atrial Natriuretic Factor↗
PubMed2005

Hyperaldosteronism and hypertension: ethnic differences.

The purpose of this study is to evaluate the relationship between aldosterone and blood pressure in a total of 220 normotensive and 293 essential hypertensive subjects in 2 genetically distinct populations-blacks and white French Canadians. The 24-hour blood pressure monitoring was performed under standardized conditions after discontinuing antihypertensive medications. Plasma renin activity and plasma aldosterone were measured in the supine position and after standing for 10 minutes. Plasma atrial natriuretic factor was also measured. Supine and standing plasma renin activities were lower (P< or =0.01), plasma aldosterone was higher (P<0.0001), and the aldosterone/renin ratios were higher (P<0.0001) in the hypertensive subjects. Atrial natriuretic factor was also higher in the hypertensive subjects (P<0.0001). Among blacks, blood pressures did not correlate with plasma renin activity. However, both average daytime and nighttime systolic and diastolic blood pressures were correlated with supine and standing plasma aldosterone and with the aldosterone/renin ratio (P<0.005 or less). In French Canadians, blood pressures tended to be positively correlated with standing plasma renin activity and aldosterone, but not with the aldosterone/renin ratio. Correlations of blood pressure with aldosterone were more consistent and more striking in blacks than in French Canadians. In both ethnic groups, there were inconsistent correlations of blood pressure with atrial natriuretic factor. These observations are consistent with the hypothesis that aldosterone-induced volume expansion is an important contributor to hypertension, especially in blacks.

Adult↗
PubMed2004

NIH peer review of grant applications for clinical research.

CONTEXT: Support of research to facilitate translation of scientific discoveries to the prevention and treatment of human disease is a high priority for the US National Institutes of Health (NIH). Nevertheless, a perception exists among clinical investigators that the NIH peer review process may discriminate against clinical research. OBJECTIVE: To describe recent trends and outcomes of peer review of grant applications to NIH requesting support for clinical research. DESIGN AND SETTING: Peer review outcomes of grant applications submitted to NIH by MDs were compared with those of non-MDs, and outcomes of applications involving inclusion of human subjects were compared with those not involving human subjects. Analyses were carried out using an inclusive definition of clinical research and after stratifying clinical research into specific categories. MAIN OUTCOME MEASURES: Median priority scores and funding rates. RESULTS: Between 1997 and 2002, on average, 25.2% of total grant applications (ranging from 27 607 to 34 422 per year) were submitted by MDs, and 27.5% of awards (ranging from 8495 to 10 769 awards per year) were made to MDs. Median priority scores (239.0 vs 250.0) and funding rates (31.4% vs 29.1%) reviewed in 2 grant cycles in 2002 were more favorable for MDs than for non-MDs (P<.001). However, median priority scores (254.0 vs 244.0) and funding rates (23.9% vs 28.1%) were less favorable (P<.001) for R01 applications for clinical research (n = 7227 applications) than for nonclinical research (n = 10 209). This trend was most convincingly observed for clinical research categorized as mechanisms of disease (P =.006) or clinical trials and interventions (P =.001). Similar trends were observed for grant mechanisms other than R01. Concerns about safety and privacy of human subjects may have contributed to the less favorable outcomes of clinical research applications. CONCLUSION: Although physicians compete favorably in the peer review process, review outcomes are modestly less favorable for grant applications for clinical research than for laboratory research.

Biomedical Research↗
PubMed2003

Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988-2000.

CONTEXT: Prior analyses of National Health and Nutrition Examination Survey (NHANES) data through 1991 have suggested that hypertension prevalence is declining, but more recent self-reported rates of hypertension suggest that the rate is increasing. OBJECTIVE: To describe trends in the prevalence, awareness, treatment, and control of hypertension in the United States using NHANES data. DESIGN, SETTING, AND PARTICIPANTS: Survey using a stratified multistage probability sample of the civilian noninstitutionalized population. The most recent NHANES survey, conducted in 1999-2000 (n = 5448), was compared with the 2 phases of NHANES III conducted in 1988-1991 (n = 9901) and 1991-1994 (n = 9717). Individuals aged 18 years or older were included in this analysis. MAIN OUTCOME MEASURES: Hypertension, defined as a measured blood pressure of 140/90 mm Hg or greater or reported use of antihypertensive medications. Hypertension awareness and treatment were assessed with standardized questions. Hypertension control was defined as treatment with antihypertensive medication and a measured blood pressure of less than 140/90 mm Hg. RESULTS: In 1999-2000, 28.7% of NHANES participants had hypertension, an increase of 3.7% (95% confidence interval [CI], 0%-8.3%) from 1988-1991. Hypertension prevalence was highest in non-Hispanic blacks (33.5%), increased with age (65.4% among those aged > or =60 years), and tended to be higher in women (30.1%). In a multiple regression analysis, increasing age, increasing body mass index, and non-Hispanic black race/ethnicity were independently associated with increased rates of hypertension. Overall, in 1999-2000, 68.9% were aware of their hypertension (nonsignificant decline of -0.3%; 95% CI, -4.2% to 3.6%), 58.4% were treated (increase of 6.0%; 95% CI, 1.2%-10.8%), and hypertension was controlled in 31.0% (increase of 6.4%; 95% CI, 1.6%-11.2%). Women, Mexican Americans, and those aged 60 years or older had significantly lower rates of control compared with men, younger individuals, and non-Hispanic whites. CONCLUSIONS: Contrary to earlier reports, hypertension prevalence is increasing in the United States. Hypertension control rates, although improving, continue to be low. Programs targeting hypertension prevention and treatment are of utmost importance.

Adult↗
PubMed2003

Impact of female hormones on blood pressure: review of potential mechanisms and clinical studies.

In recent studies, it has been found that postmenopausal hormonal therapy is associated with an increased incidence of cardiovascular disease. Experimental studies suggest several potential mechanisms by which estrogens might decrease blood pressures, and estrogen administration attenuates hypertension in several animal models. In humans, although oral contraceptive agents are frequently associated with increases in blood pressure, blood pressure was not increased or was minimally increased in prospective clinical trials of hormone therapy in postmenopausal women. These observations suggest that the excess rates of cardiovascular disease are not caused by increased blood pressure.

Animals↗
PubMed2002

Primary prevention of hypertension: clinical and public health advisory from The National High Blood Pressure Education Program.

The National High Blood Pressure Education Program Coordinating Committee published its first statement on the primary prevention of hypertension in 1993. This article updates the 1993 report, using new and further evidence from the scientific literature. Current recommendations for primary prevention of hypertension involve a population-based approach and an intensive targeted strategy focused on individuals at high risk for hypertension. These 2 strategies are complementary and emphasize 6 approaches with proven efficacy for prevention of hypertension: engage in moderate physical activity; maintain normal body weight; limit alcohol consumption; reduce sodium intake; maintain adequate intake of potassium; and consume a diet rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat. Applying these approaches to the general population as a component of public health and clinical practice can help prevent blood pressure from increasing and can help decrease elevated blood pressure levels for those with high normal blood pressure or hypertension.

Adult↗
PubMed2002

Gender-specific correlates of leptin with hypertension-related phenotypes in African Americans.

Leptin may be a link in the relationship of obesity with hypertension. We evaluated associations of leptin with blood pressure (BP) in 54 normotensive and 114 hypertensive African American individuals. Plasma leptin was higher (P <.03) in hypertensive women than in normotensive women, although body mass index did not differ (30.5 +/- 0.5 v 30.2 +/- 0.8 kg/m(2)). After adjusting for obesity and insulin resistance, there were no significant relationships between leptin and BP; however, leptin independently predicted 28% of the variability of heart rate in hypertensive men (P <.01) and 18% of the variability of lithium clearance in hypertensive women (P <.01). Thus, in these obese hypertensive African American women, there is no direct or independent association of leptin with BP. However, leptin may contribute to hypertension in these women by increasing renal tubular sodium reabsorption.

Adult↗
PubMed2002

A genealogical study of essential hypertension with and without obesity in French Canadians.

OBJECTIVES: To investigate genetic homogeneity in a set of hypertensive families and in subsets chosen for high and low prevalence of obesity; and to compare fasting insulin and lipids, ion transport, and water homeostasis in the obese and lean families. RESEARCH METHODS AND PROCEDURES: The study was carried out in a relative population isolate of the Saguenay/Lac St. Jean region in Canada. Genetic homogeneity was evaluated with the mean coeffigcients of kinship (phi) and inbreeding (F) computed with ascending genealogies. Serum insulin and lipids were measured after overnight fasting. Total body water was estimated with bioelectrical impedance. Sodium-lithium countertransport and sodium-potassium co-transport were determined in freshly isolated erythrocytes. RESULTS: F and phi were increased in hypertensive families compared with families selected at random. F and phi were further increased within the subsets of obese and lean families. In addition, fasting insulin, total body water, sodium-lithium countertransport, and sodium-potassium co-transport were higher in the obese than in the lean families. The two subsets of families did not differ by fasting lipids. DISCUSSION: In the Saguenay/Lac St. Jean population, the degree of genetic homogeneity was increased in families selected for hypertension, and it was further increased in subsets of hypertensive families with high and low prevalence of obesity. This suggests that hypertension in lean and obese individuals may represent, at least in part, separate genetic entities. Some of the extra genes shared in common within the subsets may contribute to their differences in body weight, insulin sensitivity, ion transport, and water homeostasis.

Antiporters↗
PubMed2002

Identification of hypertension-related QTLs in African American sib pairs.

To link hypertension-related phenotypes with chromosomal loci, genome scans were performed in 150 African American sib pairs concordant for essential hypertension. Phenotypes included blood pressure, anthropomorphic measurements, and estimates of body fluid compartments as determined by impedance plethysmography. These phenotypes were also measured in 335 normotensive African Americans. Phenotypes with LOD scores >3.3 were further evaluated for significance by use of permutation procedures. Significant linkage was detected for body mass index (BMI) on chromosomes 1 and 8 and for the ratio of extracellular water to total body water (ECF/TBW) on chromosomes 3, 5, 6, and 7. Both BMI and ECF/TBW were greater in hypertensive sibs than in normotensive subjects (P<0.001). In a subset of hypertensive sibs and normotensive subjects, average 24-hour blood pressures were correlated with ECF/TBW (P<0.01). A region linked to BMI in the hypertensive sibs corresponds to a region of conserved synteny containing blood pressure-related QTLs in an F2 cross of Brown NorwayxDahl salt-sensitive rats. Focusing on hypertension-related phenotypes is a promising approach for identifying the genetic determinants of hypertension.

Adolescent↗