[show abstract][hide abstract] ABSTRACT: A recent genome wide association study in 1017 African Americans identified several single nucleotide polymorphisms that reached genome-wide significance for systolic blood pressure. We attempted to replicate these findings in an independent sample of 2474 unrelated African Americans in the Milwaukee metropolitan area; 53% were women and 47% were hypertensives.
We evaluated sixteen top associated SNPs from the above genome wide association study for hypertension as a binary trait or blood pressure as a continuous trait. In addition, we evaluated eight single nucleotide polymorphisms located in two genes (STK-39 and CDH-13) found to be associated with systolic and diastolic blood pressures by other genome wide association studies in European and Amish populations. TaqMan MGB-based chemistry with fluorescent probes was used for genotyping. We had an adequate sample size (80% power) to detect an effect size of 1.2-2.0 for all the single nucleotide polymorphisms for hypertension as a binary trait, and 1% variance in blood pressure as a continuous trait. Quantitative trait analyses were performed both by excluding and also by including subjects on anti-hypertensive therapy (after adjustments were made for anti-hypertensive medications).
For all 24 SNPs, no statistically significant differences were noted in the minor allele frequencies between cases and controls. One SNP (rs2146204) showed borderline association (p = 0.006) with hypertension status using recessive model and systolic blood pressure (p = 0.02), but was not significant after adjusting for multiple comparisons. In quantitative trait analyses, among normotensives only, rs12748299 was associated with SBP (p = 0.002). In addition, several nominally significant associations were noted with SBP and DBP among normotensives but none were statistically significant.
This study highlights the importance of replication to confirm the validity of genome wide association study results.
BMC Medical Genetics 04/2012; 13:27. · 2.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Insulin resistance (IR) is associated with obesity and predisposes to diabetes mellitus (DM) and cardiovascular disease. The purpose of this study is to determine if IR is related to cardiovascular function independent of DM or hypertension among African Americans (AA). Four hundred sixty-two nondiabetic AA (50% hypertensive and 51% women) were studied on an inpatient General Clinical Research Center. Measurements included anthropometrics and 24-hour blood pressure (BP), heart rate (HR), fasting blood glucose, plasma aldosterone, and insulin. Stroke volume (SV) and cardiac output (CO) were measured by impedance plethysmography; peripheral vascular resistance (PVRI) and vascular compliance indices (VCI) were computed. These measurements were also obtained in response to mental (computerized math testing) and pharmacologic (graded norepinephrine infusion) stress. Insulin resistance was calculated using the homeostasis model assessment (HOMA-IR). SV, CO, and VCI decreased with increasing HOMA-IR, whereas HR and PVRI increased. Overall, BP, HR, and PVRI were positively correlated with HOMA-IR (P < .01); and SV index, cardiac index, and VCI were negatively correlated with HOMA-IR (P < .0001). The correlations persisted after adjustment for BP, age, sex, plasma aldosterone, total cholesterol, or low-density lipoprotein and high-density lipoprotein cholesterol. In addition, multiple linear regression analyses showed that HOMA-IR contributes to the maximum variability of all the hemodynamic variables. Blood pressure responses to math stress and norepinephrine infusion did not correlate with HOMA-IR. Unrelated to DM and BP, IR is associated with increased PVRI and decreased CO in AA. These observations suggest that an exclusive focus on effects of IR on DM or BP may ignore independent pathophysiologic contributions of IR to cardiovascular disease.
Metabolism: clinical and experimental 06/2011; 60(6):835-42. · 2.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent studies demonstrated a key role of ubiquitous isoform of Na+,K+,2Cl- co-transport (NKCC1) in regulation of myogenic tone and peripheral resistance. We examined the impact of race, gender, and plasma lipid on NKCC1 activity in French Canadians and African Americans with hypertension and dyslipidemia.
NKCC and passive erythrocyte membrane permeability to K+, measured as ouabain-resistant, bumetanide-sensitive, and (ouabain+bumetanide)-resistant 86Rb influx, respectively, were compared in 111 French-Canadian men, 107 French-Canadian women, 26 African-American men, and 45 African-American women with essential hypertension and dyslipidemia.
The African-American men and women were 7 years younger and presented twofold decreased plasma triglycerides compared to their French-Canadian counterparts (P < 0.01) whereas body mass index (BMI), total cholesterol, low-density lipoprotein, and high-density lipoprotein (HDL) were not different. NKCC was respectively 50 and 38% lower in the African-American men and women than in the French Canadians (P < 0.005) without any differences in passive erythrocyte membrane permeability for K+. We did not observe any impact of age on NKCC in all groups under investigation, whereas plasma triglycerides correlated positively with the activity of this carrier in the French-Canadian men only.
NKCC1 activity is lower in erythrocytes of African Americans with essential hypertension and dyslipidemia than in Caucasian counterparts. We suggest that decreased NKCC1 may contribute to the feature of the pathogenesis of salt-sensitive hypertension seen in African Americans.
American Journal of Hypertension 03/2010; 23(3):321-6. · 3.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hypertension and obesity are highly prevalent among African Americans (AAs). We have previously reported that both plasma aldosterone (PA) and body mass index (BMI) are higher in hypertensive than in normotensive AAs. This study evaluates the relative contributions of adiposity and PA to hypertension in AAs.
A total of 466 AAs (50% hypertensive, 51% women) were evaluated in a Clinical Research Center by stratifying them into three subgroups based on BMI (normal weight, overweight, and obese). Anthropometric measurements, ambulatory blood pressure (BP), fasting glucose, insulin, 24-h urine sodium and potassium, creatinine clearance, standing PA and plasma renin activity (PRA) were measured. Insulin resistance was estimated by the homeostasis model assessment.
Compared to normotensives, hypertensives had higher BMI, waist circumference (WC), and were more insulin resistant (P < or = 0.01). When stratified by BMI, hypertensives in each BMI strata had higher PA (P < or = 0.05) and lower PRA (P < or = 0.01) compared to normotensives. Compared to normotensives, WC was greater in overweight and obese hypertensives, but not in normal-weight hypertensives. In the overall sample, age, WC, PA, and PRA were the major contributors to BP variance and to hypertension. Among normal-weight subjects, PA and PRA significantly predicted BP and the odds ratio for hypertension, whereas WC had no predictive value.
PA, but not WC, is associated with BP and likelihood of hypertension in normal-weight AAs, whereas both WC and PA are predictive of hypertension in overweight and obese individuals. This suggests that aldosterone antagonists may be useful for the treatment of hypertension among AAs, regardless of BMI.
American Journal of Hypertension 09/2009; 22(12):1303-8. · 3.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: : To determine the prevalence of cocaine use and associated risk factors in African Americans volunteering as research subjects for a hypertension study.
: African Americans recruited from Milwaukee's inner city received $25 for completing a blood pressure screening protocol with the potential to participate in an additional protocol for $200, contingent on a negative drug test for cocaine. This study is based on the characteristics of the participants who completed the drug screen for cocaine. The significance of differences in the frequencies of categorical variables between users and nonusers was determined by χ analysis or Fisher exact test.
: Of 389 drug-tested participants, 35% tested positive for cocaine. Cocaine positive volunteers were slightly older (P = 0.02), had a lower body mass index (P = 0.001), a smaller waist circumference (P = 0.005), and lower serum cholesterol levels (P = 0.04). Those testing positive were more likely to be tobacco smokers (P < 0.0001), unemployed (P = 0.001), and alcohol users (P < 0.0001), but less likely to use prescription medications (P = 0.01). Income and education did not differ between cocaine positive and negative subjects. Individuals employed full-time were less likely to test positive than the unemployed, whereas part-time employees were intermediate (P = 0.0003). Although those testing positive were slightly less likely to have a living mother (P = 0.07), there was no association with living fathers.Cigarette smokers were almost five times more likely to test positive for cocaine than nonsmokers (OR 4.88, 95% CI 2.73-8.71). Additional predictors of positive tests were alcohol consumption (OR 1.90, 95% CI 1.18-3.19), a reported history of substance abuse (OR 1.83, 95% CI 1.05-3.19), and a family history that included one or more deceased siblings (OR 1.82, 95% CI 1.03-3.21).
: A high prevalence of substance use was detected among inner city African Americans offered financial incentives for participating in a general medical research protocol. This information may be relevant for designing future clinical trials and drug use intervention programs.
Journal of Addiction Medicine 06/2009; 3(2):83-8. · 1.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: To test the accuracy of the Omron Elite 7300W home blood pressure monitor using the European Society of Hypertension (ESH) Protocol.
The device was tested using the European Society of Hypertension International Protocol in 33 women and then in 10 men to satisfy the ESH for both men and women.
The average error in all participants was 1.2+/-5.2 (SD) [(range -10 to 17)/3.29+/-5.5 (-6 to 17)] mmHg. This is the first device to have been tested using the ESH protocol for the special population of women only. The additional testing of men in the standard ESH protocol enables the validation of this device specifically in women but also in men. However, as with all automatic devices, it is important to validate its accuracy in each individual patient who uses it and to monitor its accuracy intermittently in each individual patient.
The Omron Elite 7300W home blood pressure monitor passed the ESH validation protocol and can be recommended for patient use.
[show abstract][hide abstract] ABSTRACT: African Americans, particularly men, have the highest morbidity and mortality rates from hypertension in the United States. The authors studied 527 African Americans in a general clinical research center to determine whether there are sex differences in the relationships between hypertension with insulin resistance (IR) and aldosterone, which are risk factors for cardiovascular disease. Measurements included ambulatory blood pressure (BP), anthropometric measures, plasma renin activity, plasma aldosterone (PA) concentration, and fasting serum lipids, glucose, and insulin. IR was estimated using the Homeostasis Model Assessment (HOMA) model. BP correlated with aldosterone in both sexes. However, both BP and PA correlated with IR in men, but not in women. Compared with men in the lower tertile of HOMA-IR, men in the upper tertile had higher mean systolic BP, a higher odds ratio of having hypertension, and higher levels of PA. The association of IR with both hypertension and PA in men, but not in women, may contribute to the high prevalence of cardiovascular disease in African American men.
Journal of Clinical Hypertension 04/2009; 11(3):130-7. · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: African Americans have a high prevalence of hypertension and hypertension-related vascular disease. We previously reported that plasma aldosterone concentrations are relatively high in hypertensive African Americans. This study evaluates the hypothesis that hypertension and hypertension-related alterations of peripheral vascular and renal vascular function are associated with aldosterone.
Twenty four-hour blood pressures, cardiac output, renal blood flow (RBF), plasma renin activity (PRA), and plasma aldosterone were measured in hypertensive and normotensive African Americans. Hemodynamic measurements were repeated in response to graded infusions of norepinephrine (NE).
Ambulatory blood pressures in hypertensives and normotensives were 142 +/- 1/86 +/- 1 and 117 +/- 1/70 +/- 1 mm Hg, respectively. Cardiac index (CI) was lower (P < 0.01), peripheral vascular resistance was higher (P < 0.0001), arterial compliance was lower (P < 0.0001), RBF was lower (P = 0.04), and renal vascular resistance (RVR) was higher (P < 0.0001) in the hypertensives. Overall, blood pressures were positively correlated with peripheral vascular resistance (P < 0.0001) and inversely correlated with vascular compliance (P < 0.0001). In response to NE, hypertensives had greater increases of systolic blood pressure (P < 0.004) and pulse pressure (P < 0.005). PRA was lower (P < 0.0001) and plasma aldosterone was higher (P < 0.0001) in the hypertensives. Overall, blood pressures and pulse pressure were correlated with aldosterone (P < or = 0.01). Vascular compliance, RVR, and the increment of RVR in response to NE were also correlated with aldosterone (P < or = 0.03).
Aldosterone may contribute to hypertension and to hypertension-related alterations of peripheral vascular and renal vascular function in African Americans.
American Journal of Hypertension 12/2008; 22(3):319-24. · 3.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: We have tested two home blood pressure monitors made by the HoMedics, Inc., 300 Pontiac Trail, Commerce Township, Michigan 48390, USA, using the European Society of Hypertension International Protocol. Both failed and we believe it is important to get this into the literature quickly to protect patients and practitioners.
[show abstract][hide abstract] ABSTRACT: The Omron HEM-711 DLX home Blood pressure monitor was tested using the European Society of Hypertension International Protocol in 33 patients. The average error was 0.9+/-5.2 (SD) (range: -12 to 10 mmHg)/-0.8+/-5.6 (-19 to 8). It can be recommended for use by patients. With all automatic devices it is, however, important to validate its accuracy in each individual patient who uses it.
[show abstract][hide abstract] ABSTRACT: Blood pressure levels and the prevalence of hypertension are related to adiposity. We evaluated the relationship of adiposity to blood pressure in normotensive and untreated hypertensive African Americans-an ethnic group with a high prevalence of hypertension and obesity.
Outpatient measurements were obtained in 1,858 normotensive and 1,998 hypertensive subjects (44% untreated) residing in Milwaukee. The blood pressure-adiposity relationship was also analyzed in non-Hispanic black (n = 908) and non-Hispanic white (n = 2182) National Health and Nutrition Examination Survey (NHANES) participants.
In Milwaukee subjects, body mass index (BMI), waist/hip ratio, waist/height ratio, and percent body fat were higher in hypertensives (P < 0.0001). Combining normotensive and untreated hypertensive subjects, each of the anthropometric indices was correlated with systolic and diastolic blood pressure (P <0.0001). In separate analyses, correlations of the indices with blood pressure were observed in normotensive subjects (P < 0.0001), but generally not in hypertensive subjects. Further, separating all subjects into quartiles based on systolic blood pressure, indices of adiposity correlated with blood pressure only in subjects in the lowest blood pressure quartile (blood pressure <120/78 mm Hg). Similarly, among NHANES participants, blood pressure correlated with anthropometric indices in normotensive (P < 0.0005), but not in untreated hypertensive blacks or whites.
Although indices of adiposity were greater in hypertensive than in normotensive subjects, blood pressures were significantly correlated with measures of adiposity in normotensive, but not in untreated hypertensive subjects. We hypothesize that the blood pressure-adiposity relationship in hypertensives is modulated by a combination of environmental and genetic factors.
American Journal of Hypertension 03/2008; 21(3):284-9. · 3.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hypertension control rates are low in inner-city African-Americans. This article describes the demographic and clinical characteristics of uncontrolled hypertension in this population. During a single outpatient visit, normotensive and hypertensive African-American volunteers (age 18 to 55) completed a questionnaire, and the following measurements were obtained: blood pressure (BP), anthropometric measures, and blood chemistries. Volunteers received a gift for participating. Of the 3,943 volunteers, 52% were hypertensive. Among the hypertensives, 75% were aware of hypertension, and of those aware, 76% were on antihypertensive drug therapy. BP was uncontrolled in 78% of all hypertensives and in 60% of those on drug therapy. Males were two times more likely than females to have uncontrolled hypertension. Compared to participants with controlled hypertension, those with uncontrolled hypertension were younger, had lower body mass index, and were more likely to report smoking cigarettes, drinking alcohol, and less likely to report restricting dietary salt. Lack of hypertension control was primarily related to the lack of antihypertensive drug therapy rather than to inadequate drug therapy. Uncontrolled hypertension was associated with several self-reported aversive health behaviors, including not taking antihypertensive medications. Strategies to improve hypertension control should be directed to patients and to health care providers.
Journal of the American Society of Hypertension 01/2008; 2(5):366-71. · 2.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: 52% of adults have uncontrolled hypertension in the Republic of Georgia. We incorporated a blood pressure control program into an existing primary healthcare system in an attempt to improve the rate of blood pressure control.
We conducted standardized trainings of rural primary care providers--doctors and nurses--in accurate measurement of blood pressure according to the Shared Care Method of Training and Certification. Our attention was focused especially on patient management based on Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) guidelines. Antihypertensive treatment was implemented by a stepped-care approach; hydrochlorothiazide and atenolol were given to patients at follow-up visits at no cost. The treatment goal was < 140/ 90 mm Hg based on the office blood pressure.
A total of 251 patients with uncontrolled hypertension were enrolled in the program; 32% had stage I hypertension, 41% had stage II hypertension, and 27% had stage III, as defined by JNC VI. During the first 30 months of followup, blood pressure decreased gradually from 170/95 to 140/ 82 mm Hg. The rate of high blood pressure control increased progressively up to 59%.
We conclude that hypertension control can be improved in all groups of patients, even in a healthcare system with limited resources. We emphasize that Georgia or any other healthcare system should not wait for universal health care to improve high blood pressure control. It can be incorporated into whatever system exists today.
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: The recent "epidemic" of primary aldosteronism reported in the literature is most likely related to the widespread acceptance that with easy access to accurate measurements of renin and aldosterone, it is no longer necessary to wait until hypokalemia has become profound before embarking on diagnostic testing to attempt to ferret out this most common cause of "essential" hypertension. This is especially true for those who are now classified as "drug resistant" using today's popular drugs, which are particularly ineffective in lowering blood pressure in primary aldosteronism and its variants. Understanding the physiologic consequences of a slowly increasing aldosterone production by autonomous cells will help both the family practitioner and the specialist understand the role of the aldosterone renin ratio (ARR) in the care of the hypertensive patient. In addition, the increasing number of specific genetic mutations that drive sodium retention and lead to low levels of renin activity and familial hypertension must be incorporated into the routine evaluation and care of hypertensive patients and their families.
Current Hypertension Reports 01/2005; 6(6):485-92. · 3.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: The authors tested the single and combined effects of nuclear and mitochondrial DNA genotypes on the phenotypes of systolic blood pressure (SBP) and weight, and their changes over 5 years in normotensive subjects living in Barbados. The nuclear genotypes were gender (Y chromosome), haptoglobin (HP), and group specific component (Gc). A mitochondrial genotype was chosen as a marker for maternal lineage. Baseline clinic SBP and weight (N=78), 24-hour SBP (N=28) were measured. Five years later, clinic SBP and weight were measured again in 28 participants. Male participants generally had higher pressures than female participants. The HP genotype was associated with 5 of the 8 SBP phenotypes. The haptoglobin-1 (HP1) allele was associated with higher clinic (P=.024) and evening SBP at baseline (P=.020). The effect of HP1 appears to be dominant. Haptoglobin-2 (HP2) was associated with the increase in weight over 5 years (P=.002). Group specific component (Gc) genotype was associated with 6 of the 8 SBP phenotypes. The Gc polymorphism 2 was associated with higher 24-hour SBP, sleep SBP (midnight-6 AM), afternoon SBP (noon-6 PM) and evening SBP (6 PM to midnight). Furthermore, we found a significant association between the haptoglobin/mt-DNA and Gc/mt-DNA polymorphisms with SBP between 6 PM and midnight (P=.009 and P=.011, respectively). The 5-year changes in SBP were significantly associated with the haptoglobin/mt-DNA and Gc/mt-DNA polymorphisms (P=.005 and P=.011, respectively). Multivariate analysis for genetic effects on change in weight and change in BP suggested the rise in BP, but was not suggestive of change in weight. Furthermore, multivariate analysis was associated with Gc, but not Haptoglobin genotype. In normotensive subjects of African descent living in Barbados, the increase in blood pressure with age is significantly influenced by both nuclear and mitochondrial genotypes that are more common in African derived populations.