Post-traumatic stress disorder symptoms and risk of hypertension over 22 years in a large cohort of younger and middle-aged women.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been linked to hypertension, but most research on PTSD and hypertension is cross-sectional, and potential mediators have not been clearly identified. Moreover, PTSD is twice as common in women as in men, but understanding of the PTSD-hypertension relationship in women is limited. We examined trauma exposure and PTSD symptoms in relation to incident hypertension over 22 years in 47 514 civilian women in the Nurses' Health Study II. METHOD: We used proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for new-onset hypertension (N = 15 837). RESULTS: PTSD symptoms assessed with a screen were modestly associated with incident hypertension in a dose-response fashion after adjusting for potential confounders. Compared to women with no trauma exposure, women with 6-7 PTSD symptoms had the highest risk of developing hypertension (HR 1.20, 95% CI 1.12-1.30), followed by women with 4-5 symptoms (HR 1.17, 95% CI 1.10-1.25), women with 1-3 symptoms (HR 1.12, 95% CI 1.06-1.18), and trauma-exposed women with no symptoms (HR 1.04, 95% CI 1.00-1.09). Findings were maintained, although attenuated, adjusting for hypertension-relevant medications, medical risk factors, and health behaviors. Higher body mass index and antidepressant use accounted for 30% and 21% of the PTSD symptom-hypertension association, respectively. CONCLUSIONS: Screening for hypertension and reducing unhealthy lifestyle factors, particularly obesity, in women with PTSD may hold promise for offsetting cardiovascular risk.

Plasma uric acid concentrations and risk of ischaemic stroke in women.

BACKGROUND AND PURPOSE: Elevated plasma uric acid has been inconsistently associated with an increased risk of total stroke; however, data are sparse amongst women. The association between plasma uric acid concentrations and ischaemic stroke amongst women was examined and the effect modification by key cardiovascular risk factors was evaluated. METHODS: A nested case-control design with matching by age, race/ethnicity, smoking status, menopausal status, postmenopausal hormone therapy use, date of blood draw and fasting status was utilized amongst female participants of the Nurses' Health Study who provided blood samples between 1989 and 1990. Plasma uric acid was measured on stored blood samples. The National Survey of Stroke criteria were utilized to confirm 460 incident cases of ischaemic stroke by medical records from 1990 to 2006. Multivariable conditional logistic regression models were estimated. RESULTS: In matched analysis, risk of ischaemic stroke increased by 15% for each 1 mg/dl increase in plasma uric acid [95% confidence interval (CI) 3%-28%], but was no longer significant after adjustment for cardiovascular risk factors, particularly history of hypertension. The highest quartile of uric acid was significantly associated with greater risk of ischaemic stroke (relative risk 1.56; 95% CI 1.06-2.29, extreme quartiles) in matched analysis, but estimates were no longer significant after adjustment for cardiovascular risk factors (relative risk 1.43; 95% CI 0.93-2.18). Significant effect modification by key cardiovascular risk factors was not observed. CONCLUSIONS: Plasma uric acid levels were not independently associated with increased risk of ischaemic stroke in this cohort of women. Whilst plasma uric acid was associated with stroke risk factors, it was not independently associated with stroke risk.

Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma.

AIMS: Vascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG. METHODS: We used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG. RESULTS: The vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only. DISCUSSION: Although the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.

Vitamin D and the vascular sensitivity to angiotensin II in obese Caucasians with hypertension.

Obesity and vitamin D deficiency have both been linked to augmented activity of the tissue renin-angiotensin system (RAS). We investigated whether obesity status influenced the relationship between 25-hydroxyvitamin D (25(OH)D) and vascular RAS activity. The levels of 25(OH)D were measured in hypertensive obese (n=39) and non-obese (n=58) Caucasian individuals. RAS activity was assessed by plasma renin activity, and evaluation of the vascular sensitivity to angiotensin II (AngII) using the mean arterial pressure (MAP) response to an infusion of AngII. Among obese subjects, 25(OH)D was an independent positive predictor of the MAP response to AngII (ß=0.70, r=0.41, P<0.01); lower 25(OH)D concentrations were associated with a blunted MAP response to AngII. In contrast, 25(OH)D did not significantly predict the vascular sensitivity to AngII in non-obese subjects (ß=0.10, r=0.07, P=0.62). A multivariable-adjusted interaction model confirmed that the positive relationship between 25(OH)D and the vascular sensitivity to AngII strengthened with obesity (P-interaction=0.03). These findings demonstrate a positive association between 25(OH)D and the vascular sensitivity to AngII in obese hypertensives, and further suggest that vascular RAS activity may progressively increase when 25(OH)D deficiency occurs in obesity. Future studies to evaluate the effect of vitamin D supplementation on vascular RAS activity in obesity are needed.

Habitual intake of flavonoid subclasses and incident hypertension in adults.

BACKGROUND: Dietary flavonoids have beneficial effects on blood pressure in intervention settings, but there is limited information on habitual intake and risk of hypertension in population-based studies. OBJECTIVE: We examined the association between habitual flavonoid intake and incident hypertension in a prospective study in men and women. DESIGN: A total of 87,242 women from the Nurses' Health Study (NHS) II, 46,672 women from the NHS I, and 23,043 men from the Health Professionals Follow-Up Study (HPFS) participated in the study. Total flavonoid and subclass intakes were calculated from semiquantitative food-frequency questionnaires collected every 4 y by using an updated and extended US Department of Agriculture database. RESULTS: During 14 y of follow-up, 29,018 cases of hypertension in women and 5629 cases of hypertension in men were reported. In pooled multivariate-adjusted analyses, participants in the highest quintile of anthocyanin intake (predominantly from blueberries and strawberries) had an 8% reduction in risk of hypertension [relative risk (RR): 0.92; 95% CI: 0.86, 0.98; P < 0.03] compared with that for participants in the lowest quintile of anthocyanin intake; the risk reduction was 12% (RR: 0.88; 95% CI: 0.84, 0.93; P < 0.001) in participants ≤60 y of age and 0.96 (0.91, 1.02) in participants >60 y of age (P for age interaction = 0.02). Although intakes of other subclasses were not associated with hypertension, pooled analyses for individual compounds suggested a 5% (95% CI: 0.91, 0.99; P = 0.005) reduction in risk for the highest compared with the lowest quintiles of intake of the flavone apigenin. In participants ≤60 y of age, a 6% (95% CI: 0.88, 0.97; P = 0.002) reduction in risk was observed for the flavan-3-ol catechin when the highest and the lowest quintiles were compared. CONCLUSIONS: Anthocyanins and some flavone and flavan-3-ol compounds may contribute to the prevention of hypertension. These vasodilatory properties may result from specific structural similarities (including the B-ring hydroxylation and methyoxylation pattern).

Association between the serum anion gap and blood pressure among patients at Harvard Vanguard Medical Associates.

Animal and human data suggest a link between endogenous acid production with elevations in blood pressure and the development of hypertension; increases in endogenous organic acid production can lead to a higher anion gap. We studied the cross-sectional association between the serum anion gap and blood pressure among 1057 non-diabetic patients who were not taking antihypertensive drugs, and who received their care at a multisite, multispecialty group practice in eastern Massachusetts. Using linear regression controlling for age, sex, race, BMI, estimated GFR and presence of impaired fasting glucose, every 1 mEq l(-1) higher serum anion gap was associated with a 0.27 mm Hg (P=0.08) higher systolic, 0.20 mm Hg (P=0.05) higher diastolic and 0.22 mm Hg (P=0.04) higher mean arterial pressure; these results suggest that endogenous acid production may raise the risk of hypertension.

'Hypertension' and 'microalbuminuria': the bell tolls for thee.

Since the terms 'hypertension' and 'microalbuminuria' were first defined, data from numerous studies have documented the continuous, rather than dichotomous, relation between blood pressure, albumin excretion, and cardiovascular disease. Lower blood pressures, down to at least 115/75 mmHg, and lower albumin excretions, below an estimated 2 mg/day, are associated with less cardiovascular risk. We hypothesize that the abundances of modern civilization superimposed on the Paleolithic genotype of humans, which has not substantially changed in the last 10 000 years, have considerably shifted the 'normal' values for blood pressure and various biochemical indices such as albuminuria still found in today's stone-aged cultures to the 'neo-normal' values observed today in the rest of the modern world. Defining a large portion of the population as 'normal' based upon these dichotomous 'neo-normal' standards is not supported by the data, and therefore seems unjustifiable. We propose that the medical community consider abandoning the terms 'hypertension' and 'microalbuminuria' in favor of 'blood pressure-associated' and 'albuminuria-associated' disease.