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Biomedical subjects

Stephen T Turner

Publications and source records attributed to Stephen T Turner.

At least 55 records · Page 3Linked to original sources
PubMed2005

A novel quantitative trait locus on chromosome 1 with pleiotropic effects on HDL-cholesterol and LDL particle size in hypertensive sibships.

BACKGROUND: High-density lipoprotein (HDL)-cholesterol, triglycerides, and LDL particle size are correlated lipid traits. Abnormal levels of these traits are frequent in hypertensive individuals and contribute to increased risk of coronary heart disease (CHD). We performed univariate and bivariate linkage analyses to identify genomic regions that influence levels of these traits and exert pleiotropic effects on the traits in hypertensive sibships. METHODS: Subjects included 691 non-Hispanic white individuals (mean age 63.1+/-8.5 years, 57% women, 78% hypertensive) ascertained through sibships with two or more individuals diagnosed with hypertension before age 60 years. The LDL particle size was measured by polyacrylamide gel electrophoresis and triglycerides were log-transformed to reduce skewness. Genotypes were measured at 366 microsatellite marker loci distributed across the 22 autosomes. Univariate and bivariate linkage analyses were performed using a variance components approach. RESULTS: Significant (P < .001) genetic correlations were confirmed for all pairwise combinations of the traits. Univariate linkage analyses demonstrated evidence of linkage (defined as multipoint LOD scores > or =1.3) for HDL-cholesterol on chromosomes 1p, 3p, 9q, and 18q; for log triglycerides on chromosome 10q; and for LDL particle size on chromosomes 2p and 8p. Pairwise bivariate linkage analyses of the three traits revealed a region with pleiotropic effects on HDL-cholesterol and LDL particle size on chromosome 1p (LOD score 4.48). CONCLUSIONS: These findings indicate the presence of a quantitative trait locus on chromosome 1 that has pleiotropic effects on HDL-cholesterol and LDL particle size and may therefore influence CHD susceptibility in hypertensive sibships.

Aged↗
PubMed2005

Demographic, environmental, and genetic predictors of metabolic side effects of hydrochlorothiazide treatment in hypertensive subjects.

BACKGROUND: Thiazide diuretics are recommended for first-line treatment of hypertension. Although considered safe and effective, their use is associated with dyslipidemia, hyperglycemia, and an increased risk of developing type 2 diabetes. The aim of this study was to characterize interindividual variation in glucose and lipid responses to hydrochlorothiazide and to identify demographic, environmental, and genetic predictors associated with this variation. METHODS: A community-based sample of 585 adults with essential hypertension (291 African Americans [150 women and 141 men] and 294 non-Hispanic whites [126 women and 168 men]) underwent monotherapy with hydrochlorothiazide for 4 weeks. Linear regression was used to construct prediction models for the changes in plasma total cholesterol, triglyceride, and glucose concentrations. RESULTS: The mean changes (+/- standard deviation) in response to hydrochlorothiazide were 6.13 +/- 22.8 mg/dL for total cholesterol, 17.21 +/- 70 mg/dL for triglycerides, and 3.5 +/- 9.5 mg/dL for plasma glucose. Ethnicity and baseline levels of the analytes were the only predictors that were significant for more than one response. Therefore, the mechanism for these metabolic effects are not entirely shared. CONCLUSIONS: Taken together, demographic, environmental, and genetic factors accounted for only 13% of the total variation in total cholesterol response, 17% of the variation in triglyceride response, and 11% of the variation in glucose response to hydrochlorothiazide, and less than half of this predicted variation in response was explained by measured genotypes.

Adult↗
PubMed2005

C-reactive protein is related to arterial wave reflection and stiffness in asymptomatic subjects from the community.

BACKGROUND: Emerging data suggest that C-reactive protein (CRP), a marker of inflammation, is associated with functional properties of arteries. We investigated the relationship of CRP to measures of arterial wave reflection and stiffness (aortic augmentation index [AIX], carotid-femoral pulse wave velocity [PWV], and pulse pressure) in asymptomatic individuals from the community. METHODS: Subjects (n = 214) had a mean age of 59 years and 53% were men. CRP was measured by a high-sensitivity assay and values were log-transformed to reduce skewness. Radial artery waveforms were obtained by applanation tonometry, a validated transfer function was used to derive an ascending aortic pressure waveform, and AIX calculated. PWV was calculated from electrocardiogram-gated waveforms of the right carotid and right femoral artery obtained by applanation tonometry. RESULTS: Log CRP was correlated with AIX (r = 0.24, P = .0005), PWV (r = 0.25, P = .0002), and pulse pressure (r = 0.29, P < or = .0001). In separate backward elimination multiple regression analyses, log CRP was significantly associated with AIX (P = .038) and pulse pressure (P = .036), and marginally significantly associated with PWV (P = .054), after adjustment for heart rate, height, and coronary heart disease (CHD) risk factors (age, sex, body mass index, mean arterial pressure, total cholesterol, HDL cholesterol, diabetes, hypertension, and history of smoking). CONCLUSIONS: These results suggest that CRP, a marker of systemic inflammation, is related to measures of arterial wave reflection and stiffness in asymptomatic subjects from the community. Further studies are needed to understand the mechanisms underlying this association and the implications for assessment and management of CHD risk.

Aged↗
PubMed2005

Blood pressure variation in healthy humans: a possible interaction with beta-2 adrenergic receptor genotype and renal epithelial sodium channels.

Renal control of Na(+) regulation is a critical component to blood pressure regulation. It has recently been suggested that the beta-2 adrenergic receptor plays a role in blood pressure regulation possibly via renal epithelial sodium channels (ENaC). In the kidneys, gain of function mutations of the ENaC leads to increased salt-sensitivity and hypertension (Liddle's syndrome). In contrast, loss of function mutations of the ENaC leads to pseudohypoaldosteronism and is characterized by hypotension. Polymorphic variation of the beta-2 adrenergic receptor (beta2AR, the Arg16Gly polymorphism) leads to differences in physiologic function, in vivo. Specifically, subjects homozygous for Glycine at amino acid 16 have been shown to have enhanced forearm blood flow in response to isoproterenol and better airway function at baseline and during exercise when compared to subjects homozygous for Arginine at amino acid 16. We hypothesize, therefore, that subjects that are homozygous for Gly at amino acid 16 of the beta2AR have higher baseline blood pressure than Arg16 homozygotes due to beta2AR-mediated increases in ENaC activity in the kidney, caused, at least in part, by greater beta2AR density or enhanced beta2AR function of the Gly16 group.

Adult↗
PubMed2005

A multilocus approach to the antihypertensive pharmacogenetics of hydrochlorothiazide.

OBJECTIVES: To assess the influence of variations in multiple candidate genes on inter-individual variation in diastolic blood pressure (DBP) response to hydrochlorothiazide. METHODS: A community-based sample of 585 adults with essential hypertension underwent monotherapy with hydrochlorothiazide for 4 weeks. In a nested case-control design, 195 individuals in the highest tertile of DBP response (responders) and 195 individuals in the lowest tertile of DBP response (non-responders) were genotyped for 45 polymorphisms in 19 candidate genes. For those polymorphisms where the set association approach found to be significantly associated with DBP response, logistic regression was performed to estimate the odds ratio (OR) for response associated variation in the identified genotype/haplotype. RESULTS: Two polymorphisms in the sodium channel gamma-subunit promotor gene, and a polymorphism in the endothelial nitric oxide synthase gene, were significantly associated with blood pressure response to hydrochlorothiazide. In the final experiment for the set association model P=0.038. In the logistic regression analyses, compared to subjects with the CT/CT haplotype of the SCNN1G gene, those with the GA/GA haplotype had OR 5.21 of being a DBP responder [95% CI 1.65-16.47]. Compared to subjects with the GT genotype of the ENOSA_rs1799983 polymorphism, those with the GG genotype had an OR 2.19 of being a DBP responder [95% CI 1.27-3.77]. CONCLUSIONS: Two polymorphisms in the sodium channel gamma-subunit promotor gene, and a polymorphism in the endothelial nitric oxide synthase gene, were associated with significant differences in odds of DBP response to hydrochlorothiazide. Follow-up studies are needed to define the functional genetic variations and their mechanisms of pharmacogenetic effects.

Antihypertensive Agents↗
PubMed2005

Screening for primary aldosteronism in essential hypertension: diagnostic accuracy of the ratio of plasma aldosterone concentration to plasma renin activity.

BACKGROUND: The ratio of plasma aldosterone concentration to plasma renin activity (PRA) is considered the screening test of choice for primary aldosteronism. Uncertainty exists, however, regarding its diagnostic accuracy and the effects of antihypertensive drugs and dietary sodium balance on test characteristics. METHODS: We measured PRA and aldosterone in 118 white adults [71 men and 47 women; mean (SD) age, 51 (7) years] with previously diagnosed essential hypertension. Measurements were made while individuals were on antihypertensive drug therapy, after a 2-week drug-free period, after 4 days of dietary sodium loading, and after acute furosemide diuresis. We measured 24-h urine aldosterone excretion and PRA on the 4th day of dietary sodium loading to establish the diagnosis of primary aldosteronism. ROC curves were constructed for ratios measured under each clinical condition, and likelihood ratios were determined for individuals on or off antihypertensive drug therapy. RESULTS: Fifteen patients [13%; 95% confidence interval (CI), 7-20%] met the reference standard for primary aldosteronism. The mean (SD) areas under the ROC curves did not differ significantly across conditions of measurement [range, 0.80 (0.10) to 0.85 (0.04); P = 0.72]. When measured on and off antihypertensive drug therapy, the 95% CIs for the optimum cutpoint for the ratio overlapped. Point estimates of sensitivity on and off therapy were 73% (95% CI, 50-96%) and 87% (70-100%), respectively, and specificities were 74% (65-83%) and 75% (66-84%). Under either condition, increased ratios were associated with 2.4- to 13-fold increases of posttest odds above pretest odds. CONCLUSIONS: The aldosterone:PRA ratio provides only fair diagnostic accuracy in screening for primary aldosteronism, but concomitant antihypertensive drug therapy or acute variation in dietary sodium balance does not adversely affect test accuracy. Reporting of likelihood ratios associated with ranges of values of the aldosterone:PRA ratio, rather than use of a single "optimum" cutpoint, may enhance the usefulness of the test.

Adult↗
PubMed2005

Hypertension pharmacogenomics: current status and future directions.

Hypertension is the most common chronic disease in the Western world, and while there are many drug classes from which to choose therapy, only 34% of North Americans currently have their blood pressure controlled. The potential clinical utility of pharmacogenomics in helping to guide antihypertensive drug therapy selection is described. The hypertension pharmacogenetics literature is reviewed, which highlights that only a small fraction of the genes that likely contribute to antihypertensive response have been studied to date. The genes for alpha-adducin (diuretic response), the beta1-adrenergic receptor (beta-blocker response) and angiotensinogen (response to multiple drug classes) are among the genes with the most compelling data (based on replication) as pharmacogenetic candidates. Potential limitations of current studies are also discussed. These include reliance on clinic blood pressure, which is probably a suboptimal response phenotype, and the relatively small sample sizes of most studies to date. Also discussed is the relatively simplistic genetic approach that has been taken, which has focused largely on a single gene or single nucleotide polymorphism within a gene. Multiple ways to overcome these potential limitations are described. Hypertension pharmacogenomics holds tremendous potential for providing a mechanism by which management of hypertensive patients might be improved, and future studies should help move this field towards its clinical potential.

Humans↗
PubMed2004

Sex-specific associations of lipoprotein(a) with presence and quantity of coronary artery calcification in an asymptomatic population.

BACKGROUND: Lipoprotein(a) (Lp(a)) is a potential risk factor for coronary artery disease (CAD). The relationship between serum Lp(a) and coronary artery calcification (CAC), a measure of subclinical coronary artery atherosclerosis, has not been extensively explored. MATERIAL/METHODS: Electron beam computed tomography was performed on 616 asymptomatic, white individuals (285 men) from a community-based study. Mean age was 57.2 years. Serum Lp(a) levels were measured by an immunoturbidimetric assay. Tobit regression was used to determine the sex-specific association of Lp(a) levels with presence and quantity of CAC. RESULTS: In women, Lp(a) was a significant predictor (P=0.0426) of presence and quantity of CAC after adjustment for age, hypertension status, waist circumference, presence of high low-density lipoprotein cholesterol (LDL-C), and history of smoking. In men, after adjusting for age, hypertension status, body mass index, presence of high LDL-C, and history of smoking, a positive interaction between Lp(a) and history of smoking (P=0.0387) was significantly associated with presence and quantity of CAC. CONCLUSIONS: Sex-specific relationships between Lp(a) and CAC provide evidence supporting sex-specific risk factor profiling for CAD. In women, Lp(a) alone may be an independent risk factor for coronary atherosclerosis, while in men, Lp(a) may confer higher risk conditional on the presence and level of other risk factors. The role of Lp(a) in the prediction and pathogenesis of subclinical coronary atherosclerosis needs to be further elucidated.

Adolescent↗
PubMed2004

Evaluation and clinical implications of aortic valve calcification measured by electron-beam computed tomography.

BACKGROUND: Electron-beam computed tomography (EBCT) is used to measure coronary calcification but not for aortic valve calcification (AVC). Its accuracy, association with aortic stenosis (AS) severity, and diagnostic and prognostic value with respect to AVC are unknown. METHODS AND RESULTS: In 30 explanted aortic valves, the AVC score by EBCT (1125+/-1294 Agatston units [AU]) showed a strong linear correlation (r=0.96, P<0.0001) with valvular calcium weight (653+/-748 mg) by pathology that allowed estimation of calcium weight as AVC score/1.7, with a small standard error of the estimate (53 mg). In 100 consecutive clinical patients, we measured AVC by EBCT and AS severity by echocardiographic aortic valve area (AVA). The AVC score was 1316+/-1749 AU (range 0 to 7226 AU). Intraobserver and interobserver variabilities were excellent (4+/-4% and 4+/-10%, respectively). AVC and AVA were strongly associated (r=0.79, P<0.0001) but had a curvilinear relationship that suggested that AVC and AVA provide complementary information. AVC score > or =1100 AU provided 93% sensitivity and 82% specificity for diagnosis of severe AS (AVA <1 cm2), with a receiver operator characteristic curve area of 0.89. AVC assessment by echocardiography was often more severe than by EBCT (P<0.0001). During follow-up, 22 patients either died, developed heart failure, or required surgery. With adjustment for age, sex, symptoms, ejection fraction, and AVA, the AVC score was independently predictive of event-free survival (risk ratio 1.06 per 100-AU increment [1.02 to 1.10], P<0.001), even after adjustment for echocardiographic calcifications. CONCLUSIONS: AVC is accurately and reproducibly measured by EBCT and shows a strong association and diagnostic value for severe AS. The curvilinear relationship between AVC and AVA suggests these measures are complementary, and indeed, AVC provides independent outcome information. Thus, AVC is an important measurement in the evaluation of patients with AS.

Aortic Valve↗
PubMed2004

Ethnic and sex differences in the prevalence, treatment, and control of dyslipidemia among hypertensive adults in the GENOA study.

BACKGROUND: Two ethnically different, community-based samples of hypertensive adults were evaluated to determine the prevalence of dyslipidemia and how often dyslipidemia is drug-treated and controlled by such treatment. METHODS: We studied 1286 non-Hispanic black hypertensive subjects from Jackson and 1070 non-Hispanic white hypertensive subjects from Rochester who participated in the Genetic Epidemiology Network of Arteriopathy study. Subjects were categorized according to presence of coronary heart disease and risk factors for coronary heart disease. RESULTS: Prevalence of dyslipidemia was significantly greater among whites than blacks (women, 64.7% vs 49.5%; and men, 78.4% vs 56.7%; P<.001 for both) and among men than women (P</=.02 in each ethnic group). Among dyslipidemic subjects, treatment with lipid-regulating drugs was significantly more common among whites than blacks (women, 25.4% vs 16.4%, P =.001; and men, 32.6% vs 12.8%; P<.001), and among whites, treatment was significantly more common among men than women (P =.03). With drug treatment, control of dyslipidemia varied from 33.9% (white men) to 51.9% (black men), but the differences among ethnic-sex groups were not statistically significant. CONCLUSIONS: Dyslipidemia is highly prevalent in hypertensive adults. Fewer than one third of these adults are drug-treated, and fewer than half of those treated achieve recommended goals. Our findings suggest that an alarming 9 of 10 dyslipidemic hypertensive adults have untreated or undertreated dyslipidemia.

Adult↗
PubMed2004

Familial aggregation of hypertension treatment and control in the Genetic Epidemiology Network of Arteriopathy (GENOA) study.

PURPOSE: To assess if the treatment and control of hypertension aggregates in families. METHODS: The Genetic Epidemiology Network of Arteriopathy (GENOA) study enrolled sibships between 1997 and 1999, including 1329 hypertensive non-Hispanic blacks (1057 sibling pairs) from Jackson, Mississippi, 1133 hypertensive non-Hispanic whites (859 sibling pairs) from Rochester, Minnesota, and 752 hypertensive Hispanic whites (627 sibling pairs) from Starr County, Texas. Hypertension awareness and drug treatment were ascertained at examination; control was defined by blood pressure levels <140/90 mm Hg. As a measure of familial aggregation, odds ratios were calculated to assess concordance between sibling pairs in the treatment and control of hypertension. RESULTS: Overall, 90.5% of subjects were aware of their hypertension; 90.6% of those who were aware were treated with antihypertensive drugs and 56.0% of those treated had their hypertension controlled. There was statistically significant sib-sib concordance in the treatment of hypertension (odds ratio [OR] = 1.61; 95% confidence interval [CI]: 1.25 to 2.47; P = 0.003) and in the control of drug-treated hypertension (OR = 1.51; 95% CI: 1.25 to 1.81; P <0.0001). CONCLUSION: These findings suggest that the treatment and control of hypertension aggregates in families.

Black or African American↗
PubMed2004

The Arg16/Gly beta2-adrenergic receptor polymorphism is associated with altered cardiovascular responses to isometric exercise.

A polymorphism in the gene encoding the beta(2)-adrenergic receptor (arginine or glycine at amino acid position 16) is associated with altered vasodilator responses to beta(2)-agonists, which may modulate the pressor response to endogenous catecholamines during stress. To test the hypothesis that the Arg16/Gly polymorphism is associated with differences in acute pressor responses to sympathoexcitation, we measured mean arterial pressure (MAP, Finapres) and heart rate (HR, ECG) during mental stress (MS), cold pressor test (CPT), and handgrip (HG) to fatigue in 31 healthy, nonobese, normotensive adults (mean age +/- SE: 31 +/- 1; 16 females). Subjects were homozygous for Gly16 (n = 16) or Arg16 (n = 15). Both groups had similar baseline MAP (Arg16, 86 +/- 3 mmHg; Gly16, 89 +/- 2 mmHg; P = 0.4) and HR (Arg16, 68 +/- 2 beats/min; Gly16, 65 +/- 3 beats/min; P = 0.3). For MS and CPT, MAP and HR did not differ between genotype groups. Handgrip also produced similar increases in MAP; however, the change in HR was greater in the Gly16 homozygotes (P(ANOVA) = 0.001, genotype-by-time interaction). During HG, peak HR at fatigue was 100 +/- 4 beats/min for Gly16 (54% increase from rest) vs. 93 +/- 3 beats/min for Arg16 (37% increase). We conclude that the cardiovascular responses to MS and CPT do not differ between Gly16 and Arg16 homozygotes. However, the greater HR response to exercise in the Gly16 homozygotes may serve to maintain the pressor response (increased cardiac output) in the face of augmented peripheral vasodilation (decreased total peripheral resistance) in this group.

Adult↗
PubMed2004

Positional identification of hypertension susceptibility genes on chromosome 2.

Chromosome 2 has been consistently identified as a genomic region with genetic linkage evidence suggesting that one or more loci contributes to blood pressure and hypertension status. As with all complex disease traits, following-up linkage evidence to identify the underlying susceptibility gene(s) is an arduous yet biologically and clinically important task. Using combined positional candidate gene methods, the Family Blood Pressure Program (FBPP) has concentrated efforts in narrowing a large region of chromosome 2, demonstrating evidence for linkage in several populations, and identifying underlying candidate hypertension susceptibility gene(s). Initial informatics efforts identified the boundaries of the region and the known genes within it. A total of 82 polymorphic sites in 8 genes were genotyped in a large hypothesis-generating sample consisting of 1640 African Americans, 1339 whites, and 1616 Mexican Americans. After resampling-based false discovery adjustment, SLC4A5, a sodium bicarbonate transporter, was identified as a primary candidate gene for hypertension. Polymorphisms in SLC4A5 were subsequently genotyped and analyzed for validation in two other subcomponents of the FBPP, each contributing African Americans (N=461; N=778) and whites (N=550; N=967). Again, single nucleotide polymorphisms within this gene were significantly associated with blood pressure levels and hypertension status. Although not identifying a single causal gene variant that is significantly associated with blood pressure levels and hypertension status across all samples, the results further implicate SLC4A5 as a candidate hypertension susceptibility gene. Moreover, the present study validates previous evidence for one or more genes on chromosome 2 that influence hypertension-related phenotypes in the population-at-large.

Chromosomes, Human, Pair 2↗
PubMed2004

Heritability of leukoaraiosis in hypertensive sibships.

Ischemic damage to the subcortical white matter of the brain, referred to as leukoaraiosis, is a frequent complication of hypertension-related microvascular disease and contributes to the risk of stroke and vascular dementia. A large genetic contribution to this late-life form of target organ damage was suggested by a study of elderly male twins. As part of the Genetic Epidemiology Network of Arteriopathy (GENOA), 483 non-Hispanic white subjects were recruited to undergo MRI for determination of the brain volume of leukoaraiosis (291 women and 192 men from 210 sibships providing 434 sibling pairs; mean age+/-SD=65.2+/-7.3 years). The GENOA-Rochester sibships contain 2 or more siblings with essential hypertension diagnosed before age 60. The frequency distribution of the volume of leukoaraiosis was positively skewed, with a median value of 6.61 cm3 (interquartile range: 4.77 to 9 0.83 cm3). Variance component models were used to estimate the heritability (ie, the proportion of phenotypic variation caused by additive genetic factors). After logarithm transformation of the volume of leukoaraiosis, the estimated heritability (+/-SE) was 0.802+/-0.102 (P<0.0001). Adjustments for sex, age, systolic blood pressure, and brain volume reduced the heritability estimate to 0.671+/-0.110 (P<0.0001). This evidence of strong genetic influence on the susceptibility to leukoaraiosis justifies efforts to localize the responsible genes and characterize the predisposing genetic polymorphisms.

Aged↗
PubMed2004

Multivariate linkage analysis of blood pressure and body mass index.

Multivariate linkage analyses of correlated traits provide greater statistical power to identify genetic loci with effects too small to be detected in single trait analyses. We conducted genomewide multivariate analyses of systolic BP, diastolic BP, and body mass index (BMI) in 1,848 non-Hispanic white subjects (968 females, 880 males) from 279 multigenerational pedigrees from Rochester, Minnesota. Blood pressure was measured by random zero sphygmomanometer; body mass index was calculated from measurements of height and weight; and genotypes were measured at 520 microsatellite marker loci distributed across the 22 autosomes. Univariate linkage analyses demonstrated tentative evidence of linkage (defined by univariate LOD scores of 1.30-1.99) for diastolic BP on chromosome 18 and for BMI on chromosomes 3, 10, and 18. Bivariate linkage analyses showed tentative evidence of linkage (defined by bivariate LOD scores of 2.06-2.86) for systolic and diastolic BP on chromosome 14 and for either measure of BP and BMI on chromosomes 2, 3, 10, and 18; and suggestive evidence of linkage (defined by bivariate LOD scores of 2.87-3.99) for either measure of BP and BMI on chromosomes 10 and chromosome 15. Trivariate linkage analyses of systolic and diastolic BP and BMI provided evidence of a region influencing all three traits on chromosome 10, where the trivariate LOD score rose to a maximum value of 4.09 (at 144 cM, P=0.0007), and possibly on chromosome 2, where it rose to a maximum value of 2.80 (at 77 cM, P=0.0075). For genomewide linkage analyses to succeed in localizing genes influencing BP, it may be advantageous to exploit the greater statistical power of multivariate linkage analyses to identify loci with pleiotropic effects on correlated traits.

Adult↗
PubMed2004

Low-density lipoprotein particle size and coronary atherosclerosis in subjects belonging to hypertensive sibships.

BACKGROUND: Dyslipidemia in hypertensive sibships may be characterized by atherogenic small low-density lipoprotein (LDL) particles. Whether LDL particle size is associated with the extent of coronary atherosclerosis in hypertensive sibships is unknown. METHODS: Subjects (n = 792, mean age 62 years, 60% women) were ascertained through sibships containing at least two individuals with essential hypertension diagnosed before age 60 years. The LDL particle size was measured by polyacrylamide gel electrophoresis. Coronary artery calcium (CAC) was measured noninvasively by electron beam computed tomography, and CAC score was calculated using the method of Agatston et al. Sex-specific multiple regression models were used to assess independent predictors of LDL particle size and the association of LDL particle size with CAC. RESULTS: In all, 76% of women and 77% of men were hypertensive. In each sex, independent predictors of smaller LDL particle size were total cholesterol, triglycerides, and lower HDL cholesterol. In women, greater age was an additional predictor of smaller LDL particle size. After adjustment for age and statin use, LDL particle size was significantly associated with the amount of CAC in women but not in men. After further adjustment for HDL cholesterol, triglycerides, diabetes, smoking, and hypertension, LDL particle size was not independently associated with CAC in either sex. CONCLUSIONS: After adjustment for age and statin use, LDL particle size was found to be significantly related to CAC quantity in women but not in men belonging to hypertensive sibships. In women, LDL particle size may mediate some of the atherogenic effects of low-HDL cholesterol-high-triglyceride dyslipidemia, but does not appear to be independently associated with the extent of coronary atherosclerosis in either sex.

Aged↗
PubMed2004

Relationships between insulin sensitivity and measures of body fat in asymptomatic men and women.

OBJECTIVE: To assess whether measures of body fat by DXA scanning can improve prediction of insulin sensitivity (S(I)) beyond what is possible with traditional measures, such as BMI, waist circumference, and waist-to-hip ratio (WHR). RESEARCH METHODS AND PROCEDURES: Frequently sampled intravenous glucose tolerance tests were performed in 256 asymptomatic non-Hispanic white subjects from Rochester, MN (age 19-60 years; 123 men and 133 women) to determine the S(I) index by Bergman's minimal model technique. Height, weight, and waist and hip circumferences were measured for calculation of BMI and WHR; DXA was used to determine fat in the head, upper body, abdomen, and lower body. Linear regression was used to assess their relationships with S(I) after sex stratification and adjustment for age. RESULTS: After controlling for age, increases in traditional and DXA measures of fat were consistently associated with smaller declines in S(I) among women than among men. In men, after controlling for age, all of the predictive information of S(I) was provided by waist circumference (additional R2 = 0.39, p < 0.001); none of the DXA measures improved the ability to predict S(I). In women, after adjustment for age, BMI, and WHR, the only DXA measure that improved the prediction of S(I) was percentage head fat (additional R2 = 0.03, p < 0.001). DISCUSSION: Equivalent increases in most measures of body fat had lesser impact on S(I) in women than in men. In both sexes, the predictive information provided by DXA measures is approximately equal to, but not additive to, that provided by simpler, traditional measures.

Absorptiometry, Photon↗