Blood pressure changes during 22-year of follow-up in large general population - the HUNT Study, Norway.

BACKGROUND: While hypertension still is a major health problem worldwide, some studies have indicated that the blood pressure level has decreased in some populations. This population based cohort study aims at analysing blood pressure changes in a large Norwegian population over a 22 year period. METHODS: Data is acquired from three comprehensive health surveys of the HUNT Study conducted from 1984-86 to 2006-08. All citizens of Nord-Trøndelag County, Norway, >20 years were invited: 74,549 individuals participated in 1984-86; 64,523 in 1995-97; and 43,905 in 2006-08. RESULTS: Both systolic and diastolic blood pressure levels decreased substantially from mid 1980s to mid 2000s, with the most pronounced decrease from 1995-97 to 2006-08 (from 136.0/78.9 to 128.3/70.9 mmHg in women and from 140.1/82.1 to 133.7/76.5 mmHg in men). Although the use of blood pressure lowering medication increased, there was a considerable decrease even in those who reported never use of medication (mean decrease 6.8/7.2 mmHg in women and 6.3/5.3 mmHg in men), and the decrease was most pronounced in the elderly (mean decrease 16.1/12.4 mmHg in women and 14.7/10.4 mmHg in men aged 80+). Mean heart rate, total cholesterol and daily smoking decreased, self-reported hard physical activity increased, while body weight and the prevalence of diabetes increased during the same period. CONCLUSIONS: The BP decrease might seem paradoxically, as body weight and prevalence of diabetes increased during the same period. Salt consumption might have decreased, but no salt data is available. The parallel decrease in mean heart rate might indicate reduction in the white-coat phenomenon, or increased use of beta blockers or calcium channel blockers for other diagnosis than hypertension. Additionally, the data could support the "healthy obese" hypothesis, i.e., that subgroups in the population can sustain obesity without serious health consequences.

Ultralow amounts of DNA from long-term archived serum samples produce quality genotypes.

While genotyping studies are scavenging for suitable samples to analyze, large serum collections are currently left unused as they are assumed to provide insufficient amounts of DNA for array-based genotyping. Long-term stored serum is considered to be difficult to genotype since preanalytical treatments and storage effects on DNA yields are not well understood. Successful genotyping of such samples has the potential to activate large biobanks for future genome-wide association studies (GWAS). We aimed to evaluate genotyping of ultralow amounts of DNA from samples stored up to 45 years in the Janus Serum Bank with two commercially available platforms. 64 samples, with various preanalytical treatments, were genotyped on the Axiom Array from Thermo Fisher Scientific and a subset of 24 samples with slightly higher yield were genotyped on the HumanCoreExome array from Illumina. Our results showed that about 80% of the serum samples produced call rates with the Axiom arrays that would be satisfactory in GWAS. The mean DNA yield was 5.8 ng as measured with PicoGreen, 3-6% of recommended yield. The failed samples had on average lower input amounts of DNA. All serum samples genotyped on the HumanCoreExome with a standard and FFPE protocol produced GWAS satisfactory call rates, with mean 97.57% and 98.35% call rates, respectively. The mean yield was 10.65 ng, 6% of the recommendations. Successful array-based genotyping of ultralow DNA yields from serum samples stored up to 45 years is possible. These results demonstrate the potential to activate large serum biobank collections for future studies.

PP084. Hypertension after preeclampsia in women with C1114G polymorphism in rgs2 (the regulator of g protein signaling 2).

INTRODUCTION: Women with preeclampsia have increased risk of developing hypertension later in life. We recently demonstrated an association between preeclampsia and the CG or GG genotype of the rs4606 in the regulator of G protein signaling 2 (RGS2) gene. RGS2 negatively regulates several vasoconstrictors. OBJECTIVES: To explore the potential association between the rs4606 and hypertension after pregnancy in women with previous preeclampsia or controls. METHODS: DNA from 933 women with a history of preeclampsia and 2010 women without a history of preeclampsia was analyzed for the rs4606 in RGS2. RESULTS: Preeclampsia, but not the rs4606, was significantly associated with hypertension (systolic blood pressure ⩾140mmHg and/or diastolic blood pressure ⩾90mmHg and/or taking antihypertensive drugs) in both univariate and multivariate analyses, including adjustment for classical cardiovascular risk factors. For women with hypertension defined as blood pressure above 160/100mmHg and/or taking antihypertensive drugs, the rs4606 was significantly associated with hypertension in multivariate analysis. Our data further suggested an association between the rs4606 and physical activity in relation to hypertension. CONCLUSIONS: Women with the rs4606 CG or GG genotype may be at elevated risk for severe hypertension. However, a history of preeclampsia remained an independent predictor of hypertension after accounting for this polymorphism and classical cardiovascular risk factors.

Single nucleotide polymorphisms in G protein signaling pathway genes in preeclampsia.

Preeclampsia is a pregnancy specific disorder and a risk factor for later cardiovascular disease. The cause and detailed pathophysiology remains unknown. G protein signaling is involved in a variety of physiological processes, including blood pressure regulation. We assessed whether distributions of 3 single nucleotide polymorphisms in genes coding for components of G protein signaling pathways that have been associated with hypertension differ between women with preeclampsia and normotensive pregnant women; the G protein ß3 subunit gene (GNB3) C825T polymorphism (rs5443), the angiotensin II type 1 receptor gene (AGTR1) 3'UTR A1166C polymorphism (rs5186), and the regulator of G protein signaling 2 gene (RGS2) 3'UTR C1114G polymorphism (rs4606). Two separate Norwegian study populations were used; a large population based study and a smaller, but clinically well-described pregnancy biobank. A descriptive study of 43 women with eclampsia was additionally included. In the population-based study, an increased odds of preeclampsia (odds ratio, 1.21; [95% confidence interval, 1.05-1.40]; P=0.009) and recurrent preeclampsia (odds ratio, 1.43; [95% confidence interval, 1.06-1.92];, P=0.017) was found in women carrying the rs4606 CG or GG genotype. In early-onset preeclamptic patients with decidual spiral artery biopsies available (n=24), the rs4606 CG or GG genotype was more frequent in those with acute atherosis (resembling early stage of atherosclerosis) compared with those without: odds ratio, 15.0; (95% confidence interval, 2.02-111.2); P=0.004. No association was found between preeclampsia and the rs5443 or the rs5186. The genotype distribution in eclamptic women was not different from preeclamptic women. In conclusion, RGS2 rs4606 may affect the risk and progression of preeclampsia.