The ß(2) -adrenergic receptor (ADRB2) is located on smooth muscle cells and is an important regulator of smooth muscle tone. The Thr164Ile polymorphism (rs1800888) in the ADRB2 gene is rare but has profound functional consequences on receptor function and could cause lifelong elevated smooth muscle tone. We tested the hypothesis that Thr164Ile is associated with increased blood pressure, increased frequency of hypertension and increased risk of cardiovascular disease (CVD).
A total of 66 750 individuals from two large Danish general population studies were genotyped, and 1943 Thr164Ile heterozygotes and 16 homozygotes were identified.
Thr164Ile genotype was associated with increased systolic and diastolic blood pressure in women (trend: P = 0.04 and 0.02): systolic and diastolic blood pressure increased by 5% and 2%, respectively, in female homozygotes compared with female noncarriers. All female Thr164Ile homozygotes had hypertension compared with 58% of female heterozygotes and 54% of female noncarriers (chi-square: P = 0.001). Female Thr164Ile homozygotes and heterozygotes had odds ratios for ischaemic heart disease (IHD) of 2.93 (0.56-15.5) and 1.28 (1.03-1.61), respectively, compared with female noncarriers (trend: P = 0.007). These differences were not observed in men. Furthermore, Gly16Arg (rs1042713) and Gln27Glu (rs1042714) in the ADRB2 gene were not associated with blood pressure, hypertension or CVD either in the population overall or in women and men separately.
ADRB2 Thr164Ile is associated with increased blood pressure, increased frequency of hypertension and increased risk of IHD amongst women in the general population. These findings, particularly for homozygotes, are novel.
OBJECTIVES: Previous studies have suggested that abnormal levels of cortisol and testosterone might increase the risk of serious somatic diseases. To test this hypothesis, we conducted a 5-year follow-up study in middle-aged men. METHODS: A population-based cohort study conducted in 1995 amongst 141 Swedish men born in 1944, in whom a clinical examination supplemented by medical history aimed to disclose the presence of cardiovascular disease (CVD) (myocardial infarction, angina pectoris, stroke), type 2 diabetes and hypertension were performed at baseline and at follow-up in the year 2000. In addition, salivary cortisol levels were measured repeatedly over the day. Serum testosterone concentrations were also determined. Using the baseline data, an algorithm was constructed, which classified the secretion pattern of cortisol and testosterone from each individual as being normal or abnormal. RESULTS: By the end of follow-up, men with an abnormal hormone secretion pattern (n = 73) had elevated mean arterial pressure (P = 0.003), fasting insulin (P = 0.009) and insulin : glucose ratio (P = 0.005) compared with men with a normal secretion pattern (n = 68). Body mass index, waist circumference, and waist : hip ratio were significantly elevated in both groups. However, the 5-year incidence of CVD, type 2 diabetes, and hypertension were significantly higher (P
The intraocular pressure reducing effect and side-effects of latanoprost, a phenyl-substituted prostaglandin analogue, were compared with those of timolol, in a group of 31 glaucomatous or ocular hypertensive patients, divided into three subgroups. The study was randomized and double masked. At the end of 6 month's treatment with latanoprost 0.005% once daily, either as a morning dose or as an evening dose, there was a reduction in intraocular pressure of 33% (p
The purpose of the study was to examine the 7-year stability of systolic (SBP) and diastolic (DBP) blood pressures in the Canadian population.
The sample included 1,503 participants 7-69 years of age from the 1981 Canada Fitness Survey who were remeasured in Campbell's Survey of 1988. Both SBP and DBP were adjusted for the effects of body mass index (BMI) using regression procedures.
Interage correlations from baseline to follow-up ranged from -0.17 to 0.61 for SBP and from -0.22 to 0. 51 for DBP. With few exceptions, correlations were positive and significant, and were highest and most consistent in adulthood. Further, between 27 and 39% of participants in the upper or lower quintiles in 1981 remained there in 1988. There were few differences in adiposity between those who remained in the upper or lower quintiles and those who did not. One exception was that males who remained in the upper quintile of SBP had greater values for BMI, sum of skinfolds, and waist circumference at baseline. Among adults, the best predictor of future blood pressure was baseline blood pressure, which accounted for between 12 and 34% of the variance in follow-up blood pressure, followed by age, follow-up BMI, and, in females, baseline physical activity levels.
Blood pressure demonstrated low to moderate stability over 7 years in Canada, and baseline level of adiposity was related to the stability of SBP in males.
The perioperative and long-term risks for living kidney donors are of concern. We have studied donors at the University of Minnesota 20 years or more (mean 23.7) after donation by comparing renal function, blood pressure, and proteinuria in donors with siblings. In 57 donors (mean age 61 [SE 1]), mean serum creatinine is 1.1 (0.01) mg/dl, blood urea nitrogen 17 (0.5) mg/dl, creatinine clearance 82 (2) ml/min, and blood pressure 134 (2)/80 (1) mm Hg. 32% of the donors are taking antihypertensive drugs and 23% have proteinuria. The 65 siblings (mean age 58 [1.3]) do not significantly differ from the donors in any of these variables: 1.1 (0.03) mg/dl, 17 (1.2) mg/dl, 89 (3.3) ml/min, and 130 (3)/80 (1.5) mm Hg, respectively. 44% of the siblings are taking antihypertensives and 22% have proteinuria. To assess perioperative mortality, we surveyed all members of the American Society of Transplant Surgeons about donor mortality at their institutions. We documented 17 perioperative deaths in the USA and Canada after living donation, and estimate mortality to be 0.03%. We conclude that perioperative mortality in the USA and Canada after living-donor nephrectomy is low. In long-term follow-up of our living donors, we found no evidence of progressive renal deterioration or other serious disorders.
Comment In: Lancet. 1992 Nov 28;340(8831):1354-51360068
Numerous linkage studies have indicated chromosome 18q21-22 as a locus of importance for blood pressure regulation. This locus harbors the neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) gene, which is instrumental for the regulation of the amiloride-sensitive epithelial sodium channel (ENaC). In a linkage study of 16 markers (including two single nucleotide polymorphism markers located within the NEDD4L gene) on chromosome 18 between 70-104 cM and ambulatory blood pressure (ABP), in 118 families, the strongest evidence of linkage was found for 24 h and day-time systolic ABP at the NEDD4L locus (82.25 cM) (P=0.0014). In a large population sample (n=4001), we subsequently showed that a NEDD4L gene variant (rs4149601), which by alternative splicing leads to varying expression of a functionally crucial C2 domain, was associated with diastolic blood pressure (DBP) (P=0.03) and DBP progression over time (P=0.04). A genotype combination of the rs4149601 and an intronic NEDD4L marker (rs2288774) was associated with systolic blood pressure (SBP) (P=0.01), DBP (P=0.04), and progression of both SBP (P=0.03) and DBP (P=0.05) over time. A quantitative transmission disequilibrium test in the family material of the rs4149601 supported this NEDD4L variant as being at least partially causative of the linkage result. In conclusion, our findings suggest that the chromosome 18 linkage peak at 82.25 cM is explained by genetic NEDD4L variation affecting cross-sectional and longitudinal blood pressure, possibly as a consequence of altered NEDD4L interaction with ENaC.
The objective of the study was to determine completeness of 24-hour urine collection in pregnancy.
This was a retrospective laboratory/chart review of 24-hour urine collections at British Columbia Women's Hospital. Completeness was assessed by 24-hour urinary creatinine excretion (UcreatV): expected according to maternal weight for single collections and between-measurement difference for serial collections.
For 198 randomly selected pregnant women with a hypertensive disorder (63% preeclampsia), 24-hour urine collections were frequently inaccurate (13-54%) on the basis of UcreatV of 97-220 micromol/kg per day (11.0-25.0 mg/kg per day) or 133-177 micromol/kg per day (15.1-20.1 mg/kg per day) of prepregnancy weight (respectively). Lean body weight resulted in more inaccurate collections (24-68%). The current weight was frequently unavailable (28%) and thus not used. For 161 women (81% proteinuric) with serial 24-hour urine levels, a median [interquartile range] of 11 [5-31] days apart, between-measurement difference in UcreatV was 14.4% [6.0-24.9]; 40 women (24.8%) had values 25% or greater, exceeding analytic and biologic variation.
Twenty-four hour urine collection is frequently inaccurate and not a precise measure of proteinuria or creatinine clearance.
AIM: To specify a 24-h profile of arterial pressure (AP) in hypertensive patients working in duty regime in the Far North (Tyumen Region). MATERIAL AND METHODS: AP parameters were studied in 155 males aged 25-59 with hypertension of stage I, II who were employed for duty work in the Far North areas and 38 control patients with hypertension stage I, II living in a moderate climatic zone (Tyumen). The groups were comparable by gender, age, duration of hypertension, office systolic and diastolic AP (SAP and DAP). All the patients have undergone 24-h monitoring of AP with assessment of basic mean parameters. RESULTS: The study group patients had scare symptoms and lower mean 24-h SAP, but high AP variability, high DAD as reflection of more significant structural changes of vessels and special functioning of the autonomic nervous system in the North. Mean 24-h AP showed more unfavourable changes in hypertensive subjects who had flight from Yamburg-Moscow-Yamburg. CONCLUSION: The data of the study dictate the necessity to develop a differentiated risk strategy for health promotion, prevention and treatment of hypertension in those who work in the North of Tyumen Region in duty regime.