Biomedical subjects

Stephen T Turner

Publications and source records attributed to Stephen T Turner.

At least 37 records · Page 2Linked to original sources

PubMed2006

Association of plasma homocysteine with coronary artery calcification in different categories of coronary heart disease risk.

OBJECTIVE: To Investigate the association of plasma homocystelne with coronary artery calcification (CAC) in strata based on 10-year risk of coronary heart disease (CHD) in a cohort enriched in persons with hypertension. PARTICIPANTS AND METHODS: Fasting plasma homocystelne was measured by liquid chromatography electrospray tandem mass spectrometry. Coronary artery calcification was measured noninvasively by electron beam computed tomography and CAC score calculated using the method of Agatston et al. The 10-year CHD risk was calculated based on the Framingham risk score. The association of homocysteine with log-transformed CAC score was assessed in the pooled sample and within each risk stratum by linear regression after adjustment for conventional risk factors. RESULTS: In the 1071 participants studied, homocysteine was associated with CAC quantity (P = .01) after adjustment for CHD risk factors (age, male sex, total and high-density lipoproteln cholesterol, diabetes, history of smoking, body mass Index, and systolic blood pressure), serum creatinine, and statin and hypertension medication use. When the association was assessed in strata based on 10-year CHD risk, homocysteine was significantly (P = .003) associated with CAC quantity in participants at Intermediate 10-year risk of CHD (6%-20%) independent of other risk factors but not in those at lower risk or higher risk. CONCLUSION: Plasma homocysteine is associated with quantity of CAC Independent of CHD risk factors. When studied in categories of 10-year CHD risk, the association was significant in participants at intermediate risk but not in those at low or high risk. Plasma homocysteine levels may have clinical utility as a marker of CHD risk in such individuals.

Aged↗

PubMed2005

Aortic pulse wave velocity is associated with the presence and quantity of coronary artery calcium: a community-based study.

We investigated the relationship of aortic pulse wave velocity (aPWV), a measure of central arterial stiffness, with the presence and quantity of coronary artery calcium (CAC) in a community-based sample of adults without prior history of heart attack or stroke (n=401, mean age 59.8 years, 53% men). ECG-gated waveforms of the right carotid and right femoral artery were obtained by applanation tonometry, and aPWV was calculated using established methods. CAC was measured noninvasively by electron beam computed tomography, and CAC score was calculated. aPWV was significantly correlated with log(CAC +1; r=0.41; P<0.0001) and pulse pressure (r=0.47; P<0.0001). Multivariable logistic and linear regression models were used to identify independent predictors of the presence and quantity of CAC, respectively. In multivariable logistic regression analyses, aPWV was associated with the presence of CAC (P=0.011) after adjustment for age, male sex, total cholesterol, high-density lipoprotein cholesterol, diabetes, history of smoking, systolic blood pressure, body mass index, and use of hypertension and statin medications. In multivariable linear regression analyses, aPWV was significantly associated with log(CAC +1) after adjustment for the covariates enumerated above (P<0.0001). aPWV remained significantly associated with both the presence and quantity of CAC even after the additional adjustment for diastolic blood pressure. We conclude that aPWV is related to subclinical coronary atherosclerosis independent of conventional risk factors (including indices of blood pressure) and may be a biomarker of cardiovascular risk in asymptomatic individuals.

Adult↗

PubMed2005

Arg16Gly polymorphism of the beta2-adrenergic receptor is associated with differences in cardiovascular function at rest and during exercise in humans.

In humans, subjects homozygous for arginine (ArgArg) at codon 16 of the beta2-adrenergic receptor (beta2AR) have been shown to have greater agonist-mediated desensitization than subjects homozygous for glycine (GlyGly). We sought to determine if this substitution differentially influenced cardiovascular function during short duration (9 min) low and high intensity exercise (40 and 75% of peak work). Healthy Caucasian ArgArg (n = 16), GlyGly (n = 31) and ArgGly (n = 17) subjects matched for age, sex and peak oxygen uptake were studied. There were no differences in adrenaline (ADR) at rest or with heavy exercise, but the ArgArg group had lower ADR with light exercise (P = 0.04). Resting heart rate (HR) was higher in ArgArg (P < 0.01), while cardiac output (Q), stroke volume (SV), and mean arterial pressure (MAP) were lower than the other groups (HR = 86+/-2, 78+/-2, 80+/-1 beats min(-1); Q = 5.7+/-0.81, 6.1+/-0.18, 6.7+/-0.22 l min(-1); SV = 68+/-3, 82+/-3, 89+/-4 ml beat(-1); MAP = 92+/-1, 103+/-2, 98+/-1 mmHg-- for ArgArg, ArgGly and GlyGly, respectively, means +/-s.e.m., P < 0.01), however, no differences were observed in systemic vascular resistance (SVR). With low intensity exercise and high intensity exercise the ArgArg group continued to have a lower , SV and MAP compared to the other groups (P < 0.05), with no differences observed in SVR. During recovery, the ArgArg subjects continued to have a lower MAP but there were no differences in HR, , or SVR. These data suggest that subjects homozygous for Arg at codon 16 of the beta2AR have reduced and MAP at rest that persist during exercise with no evidence for differential changes over the course of exercise despite large changes in catecholamines. This may suggest possible genotype-related differences in baseline receptor function or density which causes phenotypic differences at rest that are sustained during short-term exercise.

Adult↗

PubMed2005

Genome-wide linkage analysis for loci affecting pulse pressure: the Family Blood Pressure Program.

Pulse pressure, the difference between systolic and diastolic blood pressure, is an independent risk factor for cardiovascular disease. Increased pulse pressure reflects reduced compliance of arteries and is a marker of atherosclerosis. To locate genes that affect pulse pressure, a genome-wide linkage scan for quantitative trait loci influencing pulse pressure was performed using variance components methods as implemented in sequential oligogenic linkage analysis routines. The analysis sample included 10 798 participants in 3320 families who were recruited as part of the Family Blood Pressure Program and were phenotyped with an oscillometric blood pressure measurement device using a consistent protocol across centers. Pulse pressure was adjusted for the effects of sex, age, age2, age-by-sex interaction, age2-by-sex interaction, body mass index, and field center to remove sources of variation other than the genetic effects related to pulse pressure. Significant linkage was observed on chromosome 18 (logarithm of odds [LOD]=3.2) in a combined racial sample, chromosome 20 (LOD=4.4), and 17 (LOD=3.6) in Hispanics, chromosome 21 (LOD=4.3) in whites, chromosome 19 (LOD=3.1) in a combined sample of blacks and whites, and chromosome 7 (logarithm of odds [LOD]=3.1) in blacks from the GenNet Network. Our genome scan shows significant evidence for linkage for pulse pressure in multiple areas of the genome, supporting previous published linkage studies. The identification of these loci for pulse pressure and the apparent congruence with other blood pressure phenotypes provide increased support that these regions contain genes influencing blood pressure phenotypes.

Adult↗

PubMed2005

A genome-wide linkage scan for ankle-brachial index in African American and non-Hispanic white subjects participating in the GENOA study.

Little is known about the genetics of peripheral arterial disease (PAD). We performed linkage analyses to identify genomic regions that influence ankle-brachial index (ABI), a measure of PAD, in 1310 African Americans (AA) (mean age 62+/-9 years) and 796 non-Hispanic whites (NHW) (mean age 58+/-9 years) belonging to hypertensive sibships. ABI was determined at two sites in each lower extremity and the lower of the two average ABIs was used in the analyses after adjustment for age, age(2), sex, weight, total cholesterol, HDL cholesterol, and ever-smoking. Genotypes were measured at microsatellite marker loci spaced approximately 10cM apart across the 22 autosomes. Heritability was assessed by SOLAR and linkage analyses performed using a variance components approach. Modest heritability (h(2)) was noted for the fully adjusted ABI in each ethnic group (h(2)=0.195, P=0.002 in AA; h(2)=0.212, P=0.006 in NHW). Univariate linkage analyses demonstrated tentative evidence of linkage (multipoint LOD=1.3-2.0) for ABI on chromosomes 1p, 6q, 7q, 10p, and 16p in AA and on chromosome 3p and 3q in NHW. In conclusion, ABI is a modestly heritable trait in AA and NHW hypertensive sibships. Quantitative trait linkage analyses identified several chromosomal regions that may harbor genes influencing ABI.

Black or African American↗

PubMed2005

Two major QTLs and several others relate to factors of metabolic syndrome in the family blood pressure program.

Genome-wide variance components linkage analysis was performed on 4 latent factors underlying metabolic syndrome derived from 10 risk factors. The latent factors represent obesity and insulin, blood pressure, lipids and insulin, and central obesity. The metabolic syndrome factor scores were derived in 4 ethnic groups recruited in 3 Networks of the Family Blood Pressure Program: GENOA (blacks, Hispanics, and whites), HyperGEN (blacks and whites), SAPPHIRe (Asians). Heritabilities of metabolic syndrome factors ranged from 66% for obesity and insulin to 11% for blood pressure factor. We observed higher heritabilities for obesity and insulin, and lipids and insulin, whereas those for blood pressure and central obesity were smaller. Linkage analysis detected two major quantitative trait loci. One of them linked to the obesity and insulin factor with a lod score of 3.94 (P=0.00001, marker GATA11A06, D18S53, 41.24 cM) at marker positions linkage (lod 4.71, at 46.84 cM at 1-cM-apart distances linkage), located on chromosome 18p11.21 in GENOA black. The other linked to the blood pressure factor with a lod score of 3.22 (P=0.000059, marker GATA49C09, D17S1290, 82 cM) at marker positions linkage (lod 3.56, at 84.63 cM for 1 cM apart distances linkage) located on chromosome 17q23.1 in Hispanics. These quantitative trait loci, together with 4 additional ones with lod scores >2.5, and 30 additional ones with lod score >1.7, offer hope for dissecting the genetic architecture of metabolic syndrome with beneficial implications for molecular diagnosis, prognosis, and in potential medical intervention.

Asian People↗

PubMed2005

WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic.

Single nucleotide polymorphisms (SNPs) in genes encoding or influencing renal sodium transport systems were investigated as potential predictors of blood pressure (BP) response to a thiazide diuretic. A sample of 585 adults with essential hypertension (30 to 59.9 years of age; 50% blacks; 47% women) were treated with hydrochlorothiazide for 4 weeks (25 mg daily, orally) to determine office BP responses. Ambulatory BP responses were measured in a subset of 228 subjects. After adjustment for ethnicity, sex, age, and waist-to-hip ratio, 3 SNPs in WNK1 (rs2107614, rs2277869, and rs1159744), encoding a lysine-deficient protein kinase that regulates thiazide-sensitive sodium-potassium cotransport, made statistically significant contributions to predicting ambulatory BP responses, accounting for 2% to 4% of variation in systolic and diastolic responses (P<0.05). SNPs in the beta2-adrenoceptor (rs2400707) and the epithelial sodium channel gamma-subunit (rs5723 and rs5729) were associated with similar magnitude of variation in ambulatory systolic BP response (P=0.028) or office diastolic BP response (P<0.05), respectively. However, SNPs evaluated in the furosemide-sensitive sodium-potassium chloride cotransporter, potassium inwardly rectifying channel, chloride channel, thiazide-sensitive sodium chloride cotransporter, epithelial sodium channel beta-subunit, and the mineralocorticoid receptor were not associated with significant variation in ambulatory or office BP responses. Polymorphisms in genes regulating renal sodium transport, in particular WNK1, predict interindividual differences in antihypertensive responses to hydrochlorothiazide.

Adult↗

PubMed2005

An evaluation of the metabolic syndrome in a large multi-ethnic study: the Family Blood Pressure Program.

BACKGROUND: The Family Blood Pressure Program is an ongoing, NHLBI-sponsored, multi-center program to study the genetic determinants of high blood pressure. The goal of this particular study was to study patterns of metabolic syndrome (MetS) in four ethnic groups: African Americans, Caucasians, Hispanics, and Asians. METHODS: A major part of participants in three networks GENOA, HyperGEN and SAPPHIRe were recruited mainly through hypertensive probands. MetS was defined as a categorical trait following the National Cholesterol Education Program definition (c-MetS). MetS was also characterized quantitatively through multivariate factor analyses (FA) of 10 risk variables (q-MetS). Logistic regression and frequency tables were used for studying associations among traits. RESULTS: Using the NCEP definition, the Hispanic sample, which by design was enriched for type 2 diabetes (T2D), had a very high prevalence of MetS (73%). In contrast, its prevalence in Chinese was the lowest (17%). In African Americans and Hispanics, c-MetS was more prevalent in women than in men. Association of c-MetS with type 2 diabetes (T2D) was prominent in the Hispanics and African Americans, less pronounced in the Whites and Japanese, (although still significant), and weakest in the Chinese sample. Using FA without rotation, we found that the main factor loaded obesity (OBS) and blood pressure (BP) in African Americans; OBS and insulin (INS) in Hispanics, in Japanese, and in Whites; and OBS alone in Chinese. In Hispanics, Whites, and Japanese, BP loaded as a separate factor. Lipids in combination with INS also loaded in a separate factor. Using FA with Varimax rotation, 4 independent factors were identified: "Obesity-INS," "Blood pressure," "Lipids-INS," and "Central obesity." They explained about 60% of the variance present in the original risk variables. CONCLUSION: MetS ethnic differences were identified. Ascertaining for hypertension or T2D increased the MetS prevalence in networks compared with the one in the US general population. Obesity was the most prominent risk factor contributing to both c-MetS and q-MetS. INS contributed in two important factors (obesity and lipids). The information imbedded into c-MetS trait /q-MetS factors scores can contribute in future research of the MetS, especially its utilization in the genetic analysis.

Journal Article↗

PubMed2005

Genomic loci with pleiotropic effects on coronary artery calcification.

We measured 381 genomewide markers and performed genetic linkage analyses in search of loci influencing coronary artery calcification (CAC), a measure of atherosclerosis determined by electron beam computed tomography, in 948 non-Hispanic white siblings (mean age [+/-standard deviation] = 59.6 +/- 9.9 years; 73.7% hypertensive). Measured risk factors for atherosclerosis included body mass index, pulse pressure, and high-density lipoprotein (HDL)-cholesterol. After adjustment for sex and age, the logarithm transformed measure of CAC was heritable (0.40 +/- 0.08, P < 0.0001) and genetically correlated with body mass index (0.28, P < 0.001), pulse pressure (0.36, P < 0.001), and HDL-cholesterol (-0.19, P < 0.001). Univariate linkage analysis demonstrated evidence of linkage for CAC, defined by maximum LOD scores (MLS) >or= 1.30, on chromosomes 1p, 4p, 5q, 7p, 13q, and 14q. Bivariate linkage analyses of CAC with each risk factor provided evidence of two regions with pleiotropic effects on CAC and HDL-cholesterol on chromosomes 4p16 (MLS=3.03, P = 0.00084) and 9q12 (MLS = 3.21, P = 0.00056), and of a region with pleiotropic effects on CAC and body mass index on chromosome 17p11 (MLS = 3.04, P = 0.00082). Inasmuch as the chromosome 9 and 17 regions were not detected in the univariate linkage analysis for CAC, multivariate linkage analyses of CAC and genetically correlated risk factors may help localize genes for coronary atherosclerosis.

Blood Pressure↗

PubMed2005

Arg16/Gly beta2-adrenergic receptor polymorphism alters the cardiac output response to isometric exercise.

Normotensive adults homozygous for glycine (Gly) of the Arg16/Gly beta2-adrenergic-receptor polymorphism have 1) greater forearm beta2-receptor mediated vasodilation and 2) a higher heart rate (HR) response to isometric handgrip than arginine (Arg) homozygotes. To test the hypothesis that the higher HR response in Gly16 subjects serves to maintain the pressor response [increased cardiac output (CO)] in the setting of augmented peripheral vasodilation to endogenous catecholamines, we measured continuous HR (ECG), arterial pressure (Finapres), and CO (transthoracic echocardiography) during isometric, 40% submaximal handgrip to fatigue in healthy subjects homozygous for Gly (n = 30; mean age +/- SE: 30 +/- 1.2, 13 women) and Arg (n = 17, age 30 +/- 1.6, 11 women). Resting data were similar between groups. Handgrip produced similar increases in arterial pressure and venous norepinephrine and epinephrine concentrations; however, HR increased more in the Gly group (60.1 +/- 4.3% increase from baseline vs. 45.5 +/- 3.9%, P = 0.03), and this caused CO to be higher (Gly: 7.6 +/- 0.3 l/m vs. Arg: 6.5 +/- 0.3 l/m, P = 0.03), whereas the decrease in systemic vascular resistance in the Gly group did not reach significance (P = 0.09). We conclude that Gly16 homozygotes generate a higher CO to maintain the pressor response to handgrip. The influence of polymorphic variants in the beta2-adrenergic receptor gene on the cardiovascular response to sympathoexcitation may have important implications in the development of hypertension and heart failure.

Adult↗

PubMed2005

Progression of subclinical coronary atherosclerosis: does obesity make a difference?

BACKGROUND: Obesity is associated with coronary artery calcification (CAC), a marker of the presence and extent of subclinical coronary atherosclerosis. Obesity adds incremental information in identifying those at higher risk of coronary heart disease to traditional risk factor assessment. The present study examined associations between obesity measures and progression of CAC in those at higher (> or =10%) and lower (<10%) 10-year coronary heart disease risk according to the Framingham risk equation. METHODS AND RESULTS: In this study, 443 asymptomatic white individuals >30 years of age (243 men) had baseline and follow-up CAC measurements an average of 8.9 years apart. Multivariable linear regression models were fit to determine associations of obesity measures at baseline with progression of CAC defined as log(e) of the difference between follow-up and baseline CAC area plus 1 divided by time (in years) between examinations, adjusting for baseline CAC quantity, age, sex, baseline hypertension status, and baseline cholesterol level. Among 329 participants (74.3%) in the lower-risk group, waist circumference (P=0.024), waist-to-hip ratio (P<0.001), body mass index (P=0.036), and being overweight compared with being underweight or of normal weight (P=0.008) were each significantly positively associated with progression of CAC. Among those at higher coronary heart disease risk, no baseline obesity measures were associated with CAC progression. CONCLUSIONS: Various measures of obesity were associated with increased progression of CAC in those at lower risk of coronary heart disease. Future studies examining the effectiveness of weight reduction strategies in reducing CAC progression among those with an otherwise favorable risk factor profile may be warranted.

Adult↗

PubMed2005

Genomic susceptibility loci for brain atrophy in hypertensive sibships from the GENOA study.

We measured 366 microsatellite markers genome-wide to search for loci contributing to subcortical white matter ischemic damage (leukoariosis) and brain atrophy in 488 non-Hispanic white subjects (193 men, 295 women; mean age+/-SD=64.1+/-7.7 years; 79% hypertensive) from 223 sibships recruited through > or =2 members with essential hypertension diagnosed before age 60. Leukoariosis was quantitated by magnetic resonance imaging (MRI), brain atrophy by the difference between intracranial and brain volumes, and calculated mean arterial pressure and pulse pressure provided measures of steady-state level and pulsatile components of blood pressure. After adjustment for sex and age, variance components models estimated significant heritability of leukoariosis (0.72), brain atrophy (0.52), mean arterial pressure (0.084), and pulse pressure (0.294) (P<0.0001 for each trait). Univariate maximum logarithm of odds scores (MLS) were observed for leukoariosis on chromosome 5 (MLS=1.91; P=0.00150); for brain atrophy on 1q and 17p (MLS=2.76, P=0.00018); for mean arterial pressure on 11p (MLS=1.57; P=0.00354); and for pulse pressure on 11p (MLS=3.02; P=0.00070). Bivariate linkage analyses provided evidence of loci with pleiotropic effects on brain atrophy and pulse pressure on chromosomes 11p (MLS = 5.07 at 16 cM; P=0.00001) and 16q (MLS of 4.56 at 124 cM; P=0.00003). These results demonstrate usefulness of multivariate linkage analyses to detect loci with pleiotropic effects on genetically correlated traits and suggest overlap between the genes influencing blood pressure and those contributing to brain atrophy.

Aged↗

PubMed2005

Gene markers and antihypertensive therapy.

Increasingly, detailed characterization of human molecular genetic variation will facilitate the use of genetic information in preventing, diagnosing, and treating common diseases. One promising application is the identification of genetic variants influencing responses to drugs used to lower blood pressure (BP) and prevent target-organ complications of hypertension. This update on gene markers to guide antihypertensive therapy highlights polymorphisms recently reported to predict interindividual differences in response to antihypertensive medications. However, single-site variation in most genes makes only a small contribution to differences in BP response, and, after all known genetic and environmental predictors have been considered, most variation in responses still remains unexplained. Advancing beyond our current "trial-and-error" approach to selecting drug therapy in individual patients will undoubtedly require whole-genome approaches to discover additional, novel genetic pathways influencing drug response. In addition, larger samples will be required to more fully characterize genetic variation within candidate genes and to consider the joint effects of gene-gene and gene-environment interactions. Eventually, knowledge of genetic variants that influence BP responses may allow more individualized tailoring of therapy to optimally reduce BP and target-organ damage.

Adrenergic beta-Antagonists↗

PubMed2005

Treatment of leukoaraiosis.

Altered signal intensity in the subcortical white matter on magnetic resonance imaging of the brain, referred to as leukoaraiosis, is frequently observed on imaging studies in elderly persons and was previously considered a benign accompaniment of aging. However, recent studies have found a clear association between the presence of leukoaraiosis and an increased risk for stroke, cognitive decline, and dementia. Moreover, epidemiologic studies have shown an association of leukoaraiosis with age, and several risk factors that are amenable to treatment, including smoking, hypertension, diabetes, homocysteinemia, hyperlipidemia, and excess alcohol use. Although results from prospective trials are not available, current evidence suggests that vigorous treatment of cardiovascular disease risk factors may prevent the development or progression of leukoaraiosis and the attendant risks of stroke and dementia.

Journal Article↗

PubMed2005

Pleiotropic genetic effects contribute to the correlation between HDL cholesterol, triglycerides, and LDL particle size in hypertensive sibships.

OBJECTIVE: Abnormalities of HDL cholesterol (HDL-C), triglycerides, and LDL particle size are present in familial dyslipidemic hypertension. We investigated heritability of these three lipid traits and the extent to which shared effects of genes (pleiotropy) contribute to the additive genetic variation in each trait in hypertensive sibships. METHODS: Subjects included 788 individuals (60% women) ascertained through sibships with >/=2 members diagnosed with hypertension before age 60 years. The LDL particle size was measured by polyacrylamide gel electrophoresis. Triglycerides were log transformed to reduce skewness, and age- and sex-adjusted lipid traits were used in the analyses. Heritability and pairwise genetic correlations were computed using a variance components approach. The genetic correlation between a pair of traits was squared to yield genetic covariance, a measure of pleiotropic effects of genes influencing both traits concomitantly. RESULTS: Heritability estimates indicated significant genetic effects on HDL-C (0.58), log triglycerides (0.47), and LDL particle size (0.71). Genetic correlation was strongest between HDL-C and log triglycerides (-0.642), followed by log triglycerides and LDL particle size (-0.493), and HDL-C and LDL particle size (0.334). HDL-C and log triglycerides showed the strongest genetic covariance (41%), followed by LDL particle size and log triglycerides (24%), and HDL-C and LDL particle size (11%). CONCLUSIONS: Multivariate quantitative genetic analyses in hypertensive sibships reveal that pleiotropy contributes to the additive genetic variation in HDL-C, triglycerides, and LDL particle size. These findings provide the rationale for multivariate linkage analyses to identify novel genetic loci with pleiotropic effects on the traits.

Aged↗

PubMed2005

Lack of agreement between office and ambulatory blood pressure responses to hydrochlorothiazide.

BACKGROUND: Differences between the antihypertensive responses to drug therapy measured by office blood pressure (OBP) and ambulatory blood pressure monitoring (ABPM) techniques have been noted but rarely analyzed. We studied whether the OBP and 24-h ABPM responses to hydrochlorothiazide differ and, if so, the relevance of these differences. METHODS: The OBP and ABPM responses to hydrochlorothiazide (25 mg/d, for 4 weeks) were measured in 228 subjects with essential hypertension, and mean responses were compared between methods using the Student paired t test. To assess variation in the agreement between OBP and ABPM responses among subjects, the limits of agreement were calculated as the mean difference between OBP and ABPM responses +/-2 standard deviations. RESULTS: The mean systolic OBP response was 4.8 mm Hg greater than the response measured by ABPM (-14.3 v -9.5 mm Hg, P < .001), and the mean diastolic OBP response was 2.1 mm Hg greater than the response measured by ABPM (-7.5 v -5.5, P < .001). The limits of agreement between the OBP and ABPM responses ranged from -18.7 to +28.2 mm Hg for systolic response and from -12.9 to +17.1 mm Hg for diastolic response. The systolic and diastolic OBP and ABPM responses were in opposite directions in 22.8% and 23.7% of the subjects, respectively. CONCLUSIONS: Compared to ABPM, OBP overestimates the mean systolic and mean diastolic blood pressure responses to hydrochlorothiazide. Variation among subjects in the magnitude and direction of responses renders OBP an unreliable predictor of ABPM responses.

Adult↗

PubMed2005

Genome-wide linkage study of erythrocyte sodium-lithium countertransport.

BACKGROUND: Increased erythrocyte sodium-lithium countertransport (SLC) has been observed in patients with essential hypertension. An analytic strategy for identification of genetic variation contributing to hypertension is the evaluation of appropriate intermediate phenotypes for hypertension, such as SLC. Thus, in this study, genome-wide linkage scans for SLC were performed in two independent samples of pedigrees from the Rochester Family Heart Study (RFHS). METHODS: Genome-wide linkage scans for SLC were performed in independent samples of 232 and 252 non-Hispanic white families from the RFHS. Multipoint variance-component linkage analysis was performed using MERLIN. RESULTS: Chromosomes 8, 9, 10, 19, and 20 contained evidence for linkage (log of the odds [LOD] > or =2) in at least one sample of RFHS pedigrees. Consistent evidence of linkage for SLC between the two samples was observed on chromosome 10 (LOD = 2.02 at 64 cM in the first sample and LOD = 2.27 at 55 cM in the second sample). CONCLUSIONS: Consistent evidence of linkage (LOD > or =2) for SLC was observed in two independent samples of non-Hispanic white families on chromosome 10. Concordance of linkage evidence between the two samples provides confidence that a region on chromosome 10 contains genetic variation influencing SLC, which may potentially influence susceptibility to hypertension.

Antiporters↗

PubMed2005

A summary of the effects of antihypertensive medications on measured blood pressure.

BACKGROUND: Epidemiologic analysis of family data on blood pressure (BP) is often compromised by the effects of antihypertensive medications. A review of numerous clinical trials that investigated the effects of BP-lowering medications is summarized here. METHODS: Published clinical trials, including 137 clinical trials with monodrug therapies and 28 clinical trials of combination drug therapies with a total of 11,739 participants, were reviewed from PubMed. Six major classes/groups of antihypertensive medications were categorized by ethnicity, including angiotensin-converting enzyme (ACE) inhibitors, alpha1-blockers, cardioselective beta-blockers (beta1-blockers), calcium channel blockers, thiazide and thiazide-like diuretics, and loop diuretics. RESULTS: Using sitting or supine BP, for ethnic groups combined, monodrug therapy with ACE inhibitors showed a weighted average effect of lowering the systolic and diastolic BP by 12.5/9.5 mm Hg; alpha1-blockers by 15.5/11.7 mm Hg; beta1-blockers by 14.8/12.2 mm Hg; calcium channel blockers by 15.3/10.5 mm Hg; thiazide diuretics by 15.3/9.8 mm Hg; and loop diuretics by 15.8/8.2 mm Hg. However, ACE inhibitors, alpha1-blockers, and beta1-blockers were less effective in African Americans than in non-African Americans, whereas calcium channel blockers, thiazide diuretics, and loop diuretics were more effective in African Americans than in non-African Americans. For two-drug combination therapy with ethnic groups combined, the BP-lowering effect of the second medication, when compared to its effect as monodrug therapy, was 84% and 65% for systolic and diastolic BP, respectively. CONCLUSIONS: The BP-lowering effects reported here may be used to impute the pretreatment BP levels, which can improve the information content and hence the power of epidemiologic analysis in studies where use of antihypertensive medications is a confounding factor in the BP measurements.

Adult↗