Family History Of Essential Hypertension Research Articles

Genetic Markers Regulating Blood Pressure in Extreme Discordant Sib Pairs.

Genome-wide scans performed in affected sib pairs have revealed small and often inconsistent clues to the loci responsible for the inherited components of hypertension. Since blood pressure is a quantitative trait regulated by many loci, two siblings at opposite extremes of the blood pressure distribution are more likely to have inherited different alleles at any given locus. Hence, we investigated an extreme discordant sib pair strategy to analyse markers from two previous loci of interest: (1) the Gordons syndrome locus that includes the WNK4 gene and (2) the ROMK locus identified in our first genome-wide scan. For this study, 24 sib pairs with strong family histories of essential hypertension were selected from the top and bottom 10% of the blood pressure distribution and genotyped for highly polymorphic microsatellite markers on chromosomes 11 and 17. The mean age of the population was 39.8 ± 7.8 years. A significant inverse correlation was found between the squared difference in pulse pressure and the number of alleles shared by IBD between the siblings for the DS11925 marker (r = -0.44, p = 0.031), systolic pressure and chromosome 17 markers (D17S250: r = -0.42, p = 0.040; D17S799 (r = -0.51, p = 0.011), and this relationship persisted after correcting for age and gender. Markers on chromosome 17 (D17S250, D17S928 and D17S1301) and 11 (D11S1999) also correlated with diastolic pressure. These results illustrate the successful use of discordant sib pair analysis to detect linkage within relatively small numbers of pedigrees with hypertension. Further analysis of this cohort may be valuable in complementing findings from the large genome wide scans in affected sib pairs.

Case Report: Diagnosis and Management of Long-Standing Essential Hypertension on a Teenager

Background: Hypertension affects about one third of the worldwide adult population, in patients aged 18 to 39, prevalence of hypertension is 7.3%. The risk factors for primary hypertension in young adults are the same as in older adults, which include family history of hypertension, poor diet with excess intake of sodium, lack of physical activity, obesity and excess intake of alcohol or tobacco smoking. The treatment of choice for essential hypertension in young adult are lifestyle changes but there is no consensus on the role pharmacological treatment in young hypertensives. The Case: A 19–year–old patient present with a worsening five–year history of palpitations felt in the abdominal region, tachycardia and high blood pressure. He had a body mass index of 31.3 kg/m2, suboptimal diet and level of physical activity (though he was previously very active) and a family history of essential hypertension. Possible secondary causes of hypertension were ruled out and a diagnosis of essential hypertension was reached through 24–hour ambulatory blood pressure monitoring. The patient was treated with a combination of 5mg amlodipine and 5mg bisoprolol per day as well as lifestyle changes. Conclusion: This case highlights the increasingly young age of presentation of essential hypertension, especially since the patient refers presence of symptoms as early as 14 years old when he had a relative lack of risk factors. It is important to rule out other potential causes of hypertension in young adults before making a diagnosis of essential hypertension.

Catestatin in patients with essential hypertension of different cardiovascular risk

Abstract Maximum association of arterial hypertension is found with sympathetic overactivity which is involved in different mechanisms including RAAS, OSA, obesity, etc. It is not overt sympathetic activity but disturbed basal sympathetic tone. However, the factors that indicate the beginning of the regulation system impairment in hypertensive patients haven't been studied enough. Catestatin is considered by some studies as a part of the “catecholamines-catestatin buffer system” because of its inhibitory effect on excess catecholamine release. The purpose of the study was to assess the concentrations of catestatin and to analyze its relationships with cardiovascular continuum in patients with essential hypertension (EH) of different cardiovascular risk (CVR). The methods of the research. The study included 180 men in age from 30 to 50 years old, the patients were divided into groups: group 1 (n=28) – EH of moderate CVR, group 2 (n=76) – EH of high CVR, group 3 (n=31) – EH of very high CVR. The control group (n=45) included almost healthy men with optimal and normal blood pressure (BP). All included in the study were examined, anamnesis and complaints were collected, daily monitoring of BP and ECG, TTE were performed, carotid intima–media thickness (IMT) was measured. Catestatin (ng/ml) was determined by the ELISA method using RayBiotech kits. Results Patients with moderate and very high CVR and a history of inherited EH had statistically significantly higher (p<0,05) catestatin concentrations compared to those in the control group who has a family history of EH. Catestatin correlations with a history of inherited EH were revealed in groups of patients with EH of moderate (r=0,555; p=0,049) and high (r=−0,285; p=0,027) CVR. The participation of catestatin in cardiovascular remodeling mediated by hypertension was proved: in a group of patients with EH of high CVR catestatin correlations with carotid IMT were received (r=−0,246; p=0,040). The relationships between catestatin concentrations and left ventricular posterior wall thickness (r=−0,523; p=0,045) and the interventricular septum (r=−0,523, p=0,045) in group 2 in diastole were discovered. Catestatin concentrations in patients with normal heart geometry were higher (p=0,04) comparing to the patients with cardiac remodeling (9,05±5,12 vs 7,49±3,62 ng/ml respectively). Catestatin concentrations correlated with indicators characterizing the CVR: diastolic BP variability in all included in the study patients with EH (r=0,218; p=0,022), group 2 (r=0,326; p=0,006), and the value of the morning surge (r=−0,745; p=0,002). Conclusion Catestatin concentrations change at all stages of the cardiovascular continuum of arterial hypertension, which is proved by the obtained correlations, so all of the above allows us to consider catestatin as a new factor in the regulation of blood pressure in patients with essential hypertension of different cardiovascular risk. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Samara Region Provincial Grant

The influence of family history, aggravate by essential hypertension and metabolic disorders, on some cardiovascular risk factors in patients with essential hypertension

Objective — to clarify the effects of family history (FH), aggravate by essential hypertension (EH) and metabolic disorders (MD) (excessive body mass, obesity, diabetes mellitus) on some cardiovascular risk factors (arterial blood pressure (ABP), characteristics of visceral obesity (VO), a state of lipid, carbohydrate and purine exchange) in patients (pts) with EH.Materials and methods. The retrospective study has been performed with the data of clinical examination of 114 pts (46 (40.3 %) females and 68 (59.6 %) males) aged to 23 — 74 years old (average age is 60.7 ± 1.84 years old) with EH of I — III stage. FH with EH and MD was revealed in 82 (71.9 %) of cases. The following data were extracted from the case histories: levels of systolic and diastolic blood pressure (SBP and DBP) measured by S. N. Korotkov’s method, body mass index (BMI) total fat mass (TFM) and fat mass index (FMI), serum levels of glucose and uric acid (UA), measured by glucosooxidase and phosphovolframic methods, respectively. Blood lipid spectrum included levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) assessed by enzyme method with autoanalyser. Very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C) and non-HDL cholesterol (non-HDL-C), lipid ratios such as LDL-C/HDL-C, TC/HDL-C, non-HDL-C/TC, TG/HDL-C and ln (TG/HDL-C) were calculated by known formulas. Triglyceride-glucose index (TGGI) was calculated by known formula and used to reveal muscular insulin resistance (IR).Results. It has been established that FH, aggravated with EH and MD from mother’s or in both of parents’ side, was associated with higher SBP elevation in proband compared with heredity without such history. In men with FH, aggravated from both of parents’ side, the MD presence in mothers in the grater degrees was associated with DBP elevation in proband. The FH, aggravated by MD from both of parents’ side, in women in more extant vs men contributed to the elevation of TFM and FMI. In this case a considerable elevation of FMI in proband was associated with a presence of MD in mother. In pts with EH and FH included MD compared with an absence of such history was found to be associated with hypercholesterolemia (HC) and dysfunction of reverse cholesterol transport evidenced by elevation of such lipid ratios as TC/HDL-C and LDL-C/HDL-C due to a growth of serum TC, LDL-C and non-HDL-C levels in persons with MD in FH. In female probands compared with male with FH of EH and MD there was an association of more significant HC with serum UA levels elevation. The genetic factor determined a significance of HC in female probands was a FH of MD in both parents. Among the pts with EH included in the investigation there was also an association of FH with MD in mother and HC combined with serum UA elevation in proband.Conclusions. The history family aggravated with essential hypertension and metabolic disorders, was associated with such cardiovascular risk factors as increased blood pressure, elevated total fat mass and fat mass index in combination with hypercholesterolemia, reverse cholesterol transport dysfunction and increased serum uric acid levels in probands with essential hypertension and insulin resistance.

Epidemiology of Childhood Onset Essential Hypertension.

The knowledge of epidemiology of a disease is paramount in identifying preventive measures. Currently there is a paucity of literature on the epidemiologic determinants of childhood onset essential hypertension (EH). We evaluated children with EH, ascertained in a rigorous manner, in a large multiethnic population in a tertiary pediatric hypertension clinic. We enrolled children with and without EH and obtained data by in-person interview of their parents and by direct anthropometric measurements including blood pressures. A total of 148 children (76 hypertension probands, 72 control probands, and males 53%, mean age 12.2 ± 4.3 years) were enrolled. Of these 148 children, 51 pairs were matched 1:1 on ethnicity, gender and age (± 2.5 years). In this study we evaluated the demographics, genetic predisposition and a variety of exposures including, socioeconomic, perinatal, lifestyle and environmental, between cases and controls. All measures were similar between cases and controls other than a significantly higher BMI (p = 0.01) and rates of obesity (p = 0.03), and a difference of near-significance in any family history of EH (p = 0.05) higher in cases compared to controls. The odds of obesity was 3.5 times higher among cases than controls. In this study we evaluated a variety of prenatal and postnatal exposures that could potentially contributed to the EH phenotype in childhood. The findings of the study elucidate the epidemiology of EH in children and two important associated risk factors, any family history of hypertension and a higher body weight.

OP.5C.05] SERUM URIC ACID IS INCREASED IN NORMOTENSIVE OBESE CHILDREN WITH A PARENTAL HYSTORY OF HYPERTENSION

Objective: Increased uric acid levels are closely associated with new-onset hypertension in children, and pilot studies showed that pharmacological lowering of uric acid may reduce blood pressure (BP) in obese pediatric patients. Nevertheless, controversy remains concerning a direct causative role of serum uric acid (SUA) in the pathogenesis of essential hypertension (EH). Our study was aimed to determine if normotensive obese children and adolescent offspring of adults with EH show SUA levels different than those of pediatric subjects in whom there is non family history of EH. Design and method: Fifty-nine obese normotensive children and adolescents, attending for metabolic assessment the Pediatric Diabetes Unit, Children's Hospital “G. Di Cristina”, and for cardiovascular evaluation the ESH Hypertension excellence center of the University of Palermo, were studied. All the subjects, aged between 8 and 17 years, underwent routine blood chemistry and oral glucose tolerance test with glucose and insulin determinations. All subjects had blood pressure determinations below the 90th percentile and had no previous history of elevated blood pressure. Results: There were 14 subjects whose parents were both normotensive (FH—), and the remaining 45 subjects whose one or both parents were hypertensive. FH + did not differ regarding age, sex distribution, blood pressure values, body mass index, waist circumference, serum glucose levels when compared to FH-. Among the metabolic parameters assessed, only SUA was significantly higher in FH+ than in FH - (p = 0.007; figure 1).This difference held after adjusting for age, gender and BMI (p = 0.01). Conclusions: Our results, showing higher values of SUA in normotensive obese children and adolescents with parental history of EH, seem to support the hypothesis that increased uric acid may precede and determine the development of hypertension.

Polymorphisms of APLN-APLNR system are associated with essential hypertension in Mexican-Mestizo individuals

The aim of this study was to evaluate if polymorphisms of APLN and APLNR genes may play a role as susceptibility markers for hypertension in a group of Mexican-Mestizo patients. A case-control study was carried out including normotensive and hypertensive individuals. For these, two polymorphisms of APLN (rs3761581 and rs56204867) and two of APLNR () genes were genotyped by 5′ exonuclease TaqMan assay in 400 normotensive individuals and 383 patients. The results showed that, under an additive model adjusted by BMI, HDL, triglycerides, glucose and family history of essential hypertension, the rs7119375 and rs10501367 polymorphisms of APLNR gene were associated significantly with a decreased risk of essential hypertension (P=0.039 and P=0.029, respectively). Besides, the haplotypes analysis of these polymorphisms showed that H1 haplotype was associated with an increased risk of essential hypertension (P=0.026), while the H2 haplotype was associated with a decreased risk (P=0.032). Contrary, the rs3761581 and rs56204867 polymorphisms of APLN gene were not associated with essential hypertension (P=0.1707 and P=0.0769, respectively). The data suggest that APLNR rs7119375 and rs10501367 are associated with a decreased risk of essential hypertension in our Mexican-Mestizo studied group, but further studies are warranted.

Insertion/deletion gene variants of angiotensin converting enzyme do not predispose cameroonians of the Bantu ethnic group to essential hypertension

The insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene has been reported to be implicated in the predisposition to essential hypertension (EH). This association may depend on ethnic and genetic backgrounds. The objective of this study was to determine if the possible I/D polymorphism in the Bantu ethnic group of Cameroon is associated with EH. Data were analyzed from 60 patients and 50 healthy controls in order to access the risk factors of EH in this ethnic group. Comparison of gene and allele frequency distributions between the two populations revealed that systolic and diastolic blood pressures, age, family history and lack of physical exercise were risk factors of EH in this ethnic group. Comparison of means of age, systolic and diastolic blood pressures as well as the proportions of individuals with a family history of EH and lack of physical exercise were higher in the hypertensive than the normotensive group (p 0.05). Moreover, analyses of relationship between ACE I/D gene variants and EH did not reveal any association (p > 0.05). Consistently, the two groups also did not present with differences in I and D allele distribution (p > 0.05). These results suggest that EH is not associated with ACE I/D polymorphism. © 2016 International Formulae Group. All rights reserved. Keywords: ACE, Gene polymorphism, SWR, Cameroon

PP.23.17

Objective: Essential hypertension is associated with bioumoral abnormalities that might be related to poor hypertension control. Identification of these abnormalities might be useful in tailoring antihypertensive treatment, in order to reach blood pressure targets. Design and method: We examined 600 patients with essential hypertension diagnosed for more than 4 years. We initiated or adjusted antihypertensive treatment at first visit and evaluated response to treatment at 1 month. In patients not reaching blood pressure target, we measured plasma levels of aldosterone, cortisol, catecholamines, glucose, uric acid and lipid profile. We recorded the association of obesity, dyslipidemia, type 2 diabetes mellitus, ischemic heart disease and chronic kidney disease. Results: 97 patients (62 males and 35 females), aged 27 to 76 years, were found to be above blood pressure target at the second visit. All these patients had a family history of essential hypertension. 35 patients (36.1%) were obese, 24 (24.7%) had type 2 diabetes mellitus, 30 (30.9%) had ischemic heart disease and 18 (18.6%) had both diabetes mellitus and ischemic heart disease. Kidney function was mildly reduced (eGFR 60 – 89 ml/min/1.73 m2) in 50 patients (51.5%), whereas 3 patients (3.1%) had moderate chronic kidney disease (eGFR 30 – 59 ml/min/1.73 m2) and none had severe chronic kidney disease. Hyperuricemia was encountered in 11 patients (11.3%). High plasma cholesterol levels were found in 49 patients (50.5%). 39 patients (40.2%) had high LDL-C levels, 19 (19.6%) had low HDL-C levels and 34 (35.1%) had high plasma triglycerides. 15 patients (15.5%) had high plasma aldosterone levels, 3 (3.1%) had high basal cortisol and 5 (5.2%) had high plasma noradrenaline. All patients had normal thyroid function. Patients having abnormal plasma levels of aldosterone, cortisol or catecholamines were examined by an endocrinologist and secondary hypertension of endocrine origin was ruled out. Conclusions: Obesity, dyslipidemia, type 2 diabetes mellitus, ischemic heart disease and mild chronic kidney disease are frequently encountered in patients with uncontrolled essential hypertension. Plasma levels of aldosterone, cortisol and catecholamines may be high in these patients in the absence of endocrine disease and might be regarded as potential treatment targets.

The potential role of short-term heart rate variability tests in identifying risk of hypertension in normotensive offspring of hypertensive parents

Background: Hypertension is one of the leading causes of cardiovascular death and is primarily silent as there is hardly any symptom before target organ damage. Heredity and autonomic nervous system play pivotal roles in pathogenesis of essential hypertension. Aims: To detect early cardiovascular autonomic changes by heart rate variability (HRV) before overt hypertension, among the offspring having family history of essential hypertension. Materials and Methods: 34 normotensive offspring aged 19-24 years with parental history of essential hypertension were included as study group and the control group included 32 age, sex, and body mass index (BMI) matched normotensive offspring having normotensive parents. Resting pulse, blood pressure, and short-term supine HRV was recorded initially followed by standing HRV. Results: A statistically significant increase in resting diastolic blood pressure in study group indicated increased sympathetic tone. Postural stress in the study group revealed a greater increase (P

Prevalence and Predictors of hypertension, at Sriganganagar city of Rajasthan India.

Objective: The objective of this study is to determine the prevalence of essential hypertension among the population of Sriganganagar city of Rajasthan in north India and as well as to investigating the diseases and risk factors involved it its etiology. Methods: An hospital based retrospective study was carried out to investigating the demographic details of disease and history of patients during the period Jan 2006 to December 2008 at the hospitals of Sriganganagar city of Rajasthan. Results: From a total of 613400 patients involved in retrospective study 29072 were identified as having essential hypertension. The overall prevalence of essential hypertension was 4.73%. The hypertensive prevalence was 60.1% and 39.87% among males and females, respectively. Study revealed that the risk of essential hypertension was significantly associated with body mass index, smoking status and a family history of essential hypertension. Conclusion: As the prevalence of hypertension is high (4.73%), an appropriate intervention program shall be launched considering the modifiable risk factors in the area of Sriganganagar

A Cross Sectional Study of the Role of Family Biosocial Variables in Metabolic Syndrome among Adult Nigerians at a Primary Care Clinic in Eastern Nigeria

A Cross Sectional Study of the Role of Family Biosocial Variables in Metabolic Syndrome among Adult Nigerians at a Primary Care Clinic in Eastern Nigeria Background: Metabolic syndrome (Met-S) is a family health problem. In Nigeria, family lifestyles are changing rapidly, an alteration that is favourable to the early emergence of Met-S. It is vital that family centred interventions be proactively done before the clustering of Met-S in the family. .Aim: This study was aimed at determining the role of family biosocial variables in metabolic syndrome among adult Nigerians at a primary care clinic in Eastern Nigeria. Materials and Methods: A hospital-based cross sectional study carried out between February 2012 and May 2012 on 210 adult National Health Insurance Scheme primary care clinic patients using International Diabetes Federation(IDF) criteria: An Individual was considered to have Met-S in the presence of waist circumference(WC) ≥94 cm for men and ≥80 cm for women plus any two or more of the following: fasting blood glucose ≥ 100mg/dL and/or diabetes mellitus on treatment; systolic and/or diastolic blood pressure ≥130/85 mmHg and/or hypertension on treatment; triglyceride level ≥150 mg/dL and/or hypertriglyceridaemia on treatment and high density lipoprotein(HDL-C) cholesterol <40mg/dL for men or <50 mg/dL for women on treatment. Collection of data was done using pretested, structured and researcher administered questionnaire. Results: Met-S was significantly associated with family history of essential hypertension (p=.036) and family history of generalized obesity (p=.029). The most significant predictor of Met-S was family history of generalized obesity (OR=2.02, p=.011). The patient with family history of generalized obesity was one and half times more likely to have Met-S compared to those without family history of generalized obesity. Conclusion: This study has shown that Met-S was significantly associated with family history of hypertension and generalized obesity. The most significant predictor variable was family history of generalized obesity. Adult Nigerians with family history of hypertension and generalized obesity should be the focus of family oriented primary prevention interventions for Met-S in the study area.

Angiotensin‐converting enzyme gene insertion/deletion polymorphism frequency in normotensive children with a positive family history of essential hypertension

To evaluate the possible relationship between blood pressure (BP) and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in normotensive children with a positive family history of essential hypertension (EHT). Three hundred seventy-six randomly selected normotensive schoolchildren (147 boys, 229 girls) between the ages of seven and 17 years were enrolled. Children were subdivided into a 'first-degree relative group' and a 'second-degree relative group' according to the presence of EHT in parents or grandparents, respectively. BP was measured twice from the right arm and the systolic BP, diastolic BP and mean BP were recorded. ACE gene I/D polymorphism was performed from all studied children and frequency od DD, ID and ID allele were analysed in each study group. Allelic frequencies of the DD genotype of the ACE gene were higher in children with a positive history in the first- (36.2%) and second-degree (38.3%) relatives for EHT than the controls (30.7%) (P < 0.05 for both). Children with a positive family history of EHT and a DD genotype, had significantly higher SBP, DBP and MBP levels (P < 0.05) than the children with ID or II genotypes. We found that the ACE gene DD genotype was common and that BP levels were higher in Turkish children with a positive family history of EHT and DD genotype. Because the presence of DD allele might be the one of the potential contributor of EHT pathogenesis, further studies needed in large cohort for long term follow-up for EHT in children with DD allele.

Family history of hypertension, anthropometric parameters and markers of early atherosclerosis in young healthy individuals

The predisposition to thrombogenesis is increased in essential hypertension, and hypertensive patients are prone to develop more vulnerable atherosclerotic plaques. To evaluate the possible influence of family history of hypertension on some indicators of early atherosclerosis, we studied eighty-five healthy normotensive individuals with (FH+) or without (FH-) family history of essential hypertension by measuring metabolic profile and concentrations of P-selectin, interleukin 6 and matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1. In a subset of individuals, MMP-9 activity was assessed in monocytes by zymography, and TIMP-1 expression by western blot. As compared with FH- individuals, FH+ individuals had significantly higher P-selectin but similar interleukin-6 levels. Although no difference was observed in MMP-2 levels between the two groups, MMP-9 and TIMP-1 were higher in FH+ individuals, who also had higher intracellular MMP-9 levels and TIMP-1 protein expression. P-selectin (r=-0.32; P<0.01), MMP-9 (r=-0.37; P<0.001) and TIMP-1 (r=-0.23; P<0.05) levels were inversely related to high density lipoprotein (HDL) cholesterol. P-selectin was also directly related to serum triglycerides (r=0.30; P<0.01). We conclude that a positive family history of hypertension is associated with an initial increase in markers of inflammation and plaque instability in otherwise healthy young normotensive individuals, likely conveying a predisposition to develop early atherothrombosis.

Cardiovascular Characteristics in American Youth With Prehypertension

Cardiovascular structure and function in youth with prehypertension have been incompletely investigated. Casual and ambulatory blood pressure (BP) measurement, arterial stiffness, noninvasive hemodynamic profiles, and cardiac structure were studied in a twin cohort of American black and white youth (n = 942; mean age, 17.6 +/- 3.3 years SD). A family history of essential hypertension was used as a proxy to study genetic susceptibility to prehypertension. The occurrence of prehypertension was approximately 12% in the entire sample. Body mass index and waist circumference were significantly greater in prehypertensive subjects than in normotensive subjects. The 24-h ambulatory systolic BP (SBP), 24-h ambulatory diastolic BP (DBP), nighttime ambulatory SBP, and nighttime ambulatory DBP were significantly elevated in prehypertensive subjects compared with normotensive subjects. In whites, prehypertensive subjects compared with normotensive subjects showed increased radial (6.8 +/- 0.1 v 6.2 +/- 0.1 m/sec, P < .001) and foot pulse-wave velocity (PWV) (7.4 +/- 0.1 v 7.0 +/- 0.1 m/sec, P = .001). In whites, the total peripheral resistance index was greater in prehypertensive subjects than in normotensive subjects (P = .005). White prehypertensive subjects had a significantly greater heart rate than white normotensive subjects (69.0 +/- 1.4 v 64.0 +/- 0.6 bpm). In contrast, in blacks, the cardiac index was higher in prehypertensive subjects than in normotensive subjects (3.3 +/- 0.1 v 3.0 +/- 0.1 L/min/m2, P = .004). In blacks and whites, there were no statistical differences in the parameters of left-ventricular structure between normotensive subjects and prehypertensive subjects. Finally, prehypertensive subjects were more likely to have a positive family history of essential hypertension, especially in blacks. Prehypertension compared with normotension exhibited unfavorable cardiovascular phenotypes. Cardiovascular characteristics of prehypertension appear to be race-dependent.

Cardiovascular Function in Normotensive Offspring of Persons With Essential Hypertension and Black Race

Prior investigations have shown impaired endothelial function in hypertensive blacks when compared with whites. It is not clear, however, whether the difference in vascular responsiveness predates or follows the development of hypertension. Thirty-nine young black adults with a family history of essential hypertension and 41 control participants were studied for brachial artery reactivity and carotid intima-media thickness via ultrasonography, cardiac muscle mass and diastolic function by echocardiography, and biochemical analysis. There was no significant difference in brachial artery reactivity between the study groups, although women had greater reactivity than men (P=.05). Carotid intima-media thickness, left ventricular geometry, and biomarkers were equivalent between the study groups (P=not significant). Vascular imaging and biomarkers were unable to identify early evidence of endothelial dysfunction in offspring of African Americans with essential hypertension. These same studies demonstrated some early changes in vascular function based on sex.

Ethnic and Gender Differences in Ambulatory Blood Pressure Trajectories

Cross-sectional studies demonstrated ethnic and gender differences in ambulatory blood pressure patterns, but little is known about the longitudinal development of these differences. Twenty-four-hour ambulatory blood pressure was measured up to 12 times (5 times on average) over a 15-year period in 312 African Americans (AAs) and 351 European Americans aged 7 to 30 years. Multivariate individual growth curves across age were created for daytime and nighttime blood pressure jointly. For both daytime and nighttime systolic blood pressure (SBP), AAs and males had higher levels (P<0.001) than European Americans and females. Males also showed a greater increase with age (P<0.001) than females. For nighttime SBP, a faster increase of SBP with age (P<0.01) in AAs was additionally observed. The ethnic difference in nighttime SBP levels and its increase with age were significantly larger than in daytime SBP. For daytime and nighttime diastolic blood pressure, AAs had higher levels than European Americans (P<0.001), and this difference was significantly larger at night. From late adolescence onward, males showed a greater increase in diastolic blood pressure with age than females. Ethnic and gender differences persisted after adjustment for height, body mass index, socioeconomic status, and stress-related coping styles. Family history of essential hypertension explained ethnic differences in daytime SBP. We observed significant ethnic and gender differences in longitudinal trajectories of ambulatory blood pressure in youth and young adults. The blunted nocturnal decline and its exacerbation with age in AAs corroborate and extend findings of cross-sectional studies.

Incident Renal Events and Risk Factors in Autosomal Dominant Polycystic Kidney Disease

For determination of the incidence of renal events in autosomal dominant polycystic kidney disease (ADPKD) all patients who had ADPKD and attended nephrology/urology clinics in Newfoundland in 1981 were identified, and members of 18 families who were at 50% risk for inheriting ADPKD were followed prospectively for 22 yr, including research clinics at 6-yr intervals. Time to hypertension treatment, stage 3 chronic kidney disease (CKD), ESRD, and death was measured, and the impact of genotype, gender, gender of parent who transmitted PKD, family, family history of essential hypertension, parity, and oral contraceptive pill was assessed. Nine (50%) families had PKD1, four (22%) had PKD2, and one had both PKD1 and PKD2. The number of family members with PKD1 was 136 and with PKD2 was 60. In PKD1 median age to hypertension treatment was 46 yr, to CKD stage 3 was 50 yr, to ESRD was 53 yr, and to death was 67 yr. In PKD2, median age to hypertension treatment was 51 yr, to CKD stage 3 was 66 yr, to death was 71 yr, and ESRD was infrequent. Although the incidence of CKD was later and ESRD occurred infrequently in PKD2 compared with PKD1, early onset of hypertension occurred and life expectancy was compromised. Genotype, family, and proteinuria were identified as risk factors for incident renal events. Gender, gender of parent who transmitted PKD, family history of essential hypertension, multiparity, and use of the oral contraceptive pill were not identified as risk factors for renal events in ADPKD.

Alpha- and beta-adrenergic receptor polymorphisms in hypertensive and normotensive offspring

The offspring of hypertensive families are characterized by higher arterial blood pressure values and a depressed autonomic control of heart rate. The present study aimed to verify whether these differences are associated with a different genotype distribution of functionally relevant polymorphisms of the alpha- and beta-adrenergic receptor (AR) genes. We selected 109 age- and sex-matched young normotensive subjects with (FH+, n = 56) and without (FH-, n = 53) a family history of hypertension who underwent evaluation of arterial pressure; 24-h electrocardiogram monitoring to assess time-domain parameters of autonomic heart rate control [i.e. mean RR interval (NN), SD of RR intervals (SDNN) and mean square root of the differences of consecutive RR intervals (rMSSD)]; spectral baroreflex sensitivity measurement; and echo-Doppler to assess diastolic function and left ventricular mass. They were also characterized for the following polymorphisms by means of polymerase chain reaction-restriction fragment polymorphism analysis: Arg492Cys in the alpha1a-AR; Del301-303 in the alpha2b-AR; Ser49Gly and Arg389Gly in the beta1-AR; and the 5' leader cistron Arg19Cys, Arg16Gly and Gln27Glu in the beta2-AR. FH+ individuals showed a higher systolic pressure, a lower SDNN and a greater isovolumic relaxation time compared to normotensive offspring. No differences were found between the two groups when genotype distribution of the studied polymorphisms was considered. Subjects carrying alpha1a-AR Cys492 allelic variant showed lower values of NN, SDNN and rMSSD, independent of age, gender and body mass index. The functionally relevant polymorphisms of alpha2b-, beta1- and beta2-AR genes are not associated with a family history of essential hypertension. The Arg492Cys polymorphism of the alpha1a-AR gene, although not associated with a family history of hypertension, was strongly related to autonomic control of heart rate.

Low Adiponectin Level in Young Normotensive Men with a Family History of Essential Hypertension

Circulating level of adiponectin, an adipocyte-derived protein, is reduced in states of insulin resistance such as obesity and type 2 diabetes. We have previously shown that hypoadiponectinemia is related to insulin resistance in essential hypertension. Recent studies have shown that normotensive subjects with a positive family history of essential hypertension (FH+) have decreased insulin sensitivity compared to subjects with a negative family history of essential hypertension (FH-). We here examined the association between adiponectin concentration and insulin sensitivity in FH+ and FH-. Thirty young, non-obese and normotensive men without a family history of diabetes mellitus were enrolled. A total of 15 subjects were FH+, and the remaining 15 subjects were FH-. Insulin sensitivity index (ISI) was evaluated by the euglycemic hyperinsulinemic glucose clamp technique. Concentrations of adiponectin and other metabolic variables were measured. The FH+ group had significantly lower levels of ISI and adiponectin than did the FH- group. In all of the subjects, ISI was positively correlated with adiponectin concentration and high-density lipoprotein (HDL) cholesterol level and was negatively correlated with insulin level. Adiponectin concentration was the only independent determinant of ISI in a multiple regression analysis. Our results showed that adiponectin level was significantly decreased and that this was accompanied by reduced insulin sensitivity in young, nonobese and normotensive men with a family history of essential hypertension. Phenotype of reduced adiponectin level as an earlier penetrance may be especially useful in genetic analyses of insulin resistance and essential hypertension.