Epidemiology of masked and white-coat hypertension: the family-based SKIPOGH study

Objective We investigated factors associated with masked and white-coat hypertension in a Swiss population-based sample. Methods The Swiss Kidney Project on Genes in Hypertension is a family-based cross-sectional study. Office and 24-hour ambulatory blood pressure were measured using validated devices. Masked hypertension was defined as office blood pressure<140/90 mmHg and daytime ambulatory blood pressure≥135/85 mmHg. White-coat hypertension was defined as office blood pressure≥140/90 mmHg and daytime ambulatory blood pressure<135/85 mmHg. Mixed-effect logistic regression was used to examine the relationship of masked and white-coat hypertension with associated factors, while taking familial correlations into account. High-normal office blood pressure was defined as systolic/diastolic blood pressure within the 130–139/85–89 mmHg range. Results Among the 652 participants included in this analysis, 51% were female. Mean age (±SD) was 48 (±18) years. The proportion of participants with masked and white coat hypertension was respectively 15.8% and 2.6%. Masked hypertension was associated with age (odds ratio (OR) = 1.02, p = 0.012), high-normal office blood pressure (OR = 6.68, p<0.001), and obesity (OR = 3.63, p = 0.001). White-coat hypertension was significantly associated with age (OR = 1.07, p<0.001) but not with education, family history of hypertension, or physical activity. Conclusions Our findings suggest that physicians should consider ambulatory blood pressure monitoring for older individuals with high-normal office blood pressure and/or who are obese.

Changes in left ventricular structure and function in patients with white coat hypertension: cross sectional survey

Objectives: To assess the relation between white coat hypertension and alterations of left ventricular structure and function.

Altered cardiovascular rhythmicity in children with white coat and ambulatory hypertension

Adults with ambulatory hypertension or white coat hypertension (WCH) display abnormal cardiovascular rhythms. We studied cardiovascular rhythms by Fourier analysis of 24-h ambulatory blood pressure (BP) measurement profiles in 129 hypertensive children, 54 children with WCH, and 146 age-, height-, and gender-matched healthy subjects. The day/night mean arterial pressure ratio was lower in hypertensive and patients with WCH compared with controls (1.13 versus 1.16 versus 1.21, respectively; p < 0.0001). Eighty-five percent of controls were dippers compared with 74% of WCH (n.s.) and 64% of patients with ambulatory hypertension (p < 0.0001). The prevalence of 24-h rhythms was similar among the groups, but prevalence of 12-h BP rhythms was increased in hypertensive (67%) and WCH (72%) compared with controls (51%, p < 0.0001). The amplitudes of the 24-, 8-, and 6-h BP rhythms were reduced in hypertensive and WCH compared with controls (p < 0.05). Hypertensive and patients with WCH displayed delayed 24-, 12-, 8-, 6-h acrophases in comparison with controls (p < 0.05). In conclusion, hypertensive children exhibit abnormal cardiovascular rhythmicity compared with controls, especially a higher prevalence of nondipping compared with normotensive children. Abnormalities in patients with WCH are intermediate between healthy children and patients with ambulatory hypertension.

Association between white-coat effect and blunted dipping of nocturnal blood pressure.

In this study, we assessed whether the white-coat effect (difference between office and daytime blood pressure (BP)) is associated with nondipping (absence of BP decrease at night). Data were available in 371 individuals of African descent from 74 families selected from a population-based hypertension register in the Seychelles Islands and in 295 Caucasian individuals randomly selected from a population-based study in Switzerland. We used standard multiple linear regression in the Swiss data and generalized estimating equations to account for familial correlations in the Seychelles data. The prevalence of systolic and diastolic nondipping (<10% nocturnal BP decrease) and white-coat hypertension (WCH) was respectively 51, 46, and 4% in blacks and 33, 37, and 7% in whites. When white coat effect and nocturnal dipping were taken as continuous variables (mm Hg), systolic (SBP) and diastolic BP (DBP) dipping were associated inversely and independently with white-coat effect (P < 0.05) in both populations. Analogously, the difference between office and daytime heart rate was inversely associated with the difference between daytime and night-time heart rate in the two populations. These results did not change after adjustment for potential confounders. The white-coat effect is associated with BP nondipping. The similar associations between office-daytime values and daytime-night-time values for both BP and heart rate suggest that the sympathetic nervous system might play a role. Our findings also further stress the interest, for clinicians, of assessing the presence of a white-coat effect as a means to further identify patients at increased cardiovascular risk and guide treatment accordingly.

Seven novel KIT mutations in horses with white coat colour phenotypes

White coat colour in horses is inherited as a monogenic autosomal dominant trait showing a variable expression of coat depigmentation. Mutations in the KIT gene have previously been shown to cause white coat colour phenotypes in pigs, mice and humans. We recently also demonstrated that four independent mutations in the equine KIT gene are responsible for the dominant white coat colour phenotype in various horse breeds. We have now analysed additional horse families segregating for white coat colour phenotypes and report seven new KIT mutations in independent Thoroughbred, Icelandic Horse, German Holstein, Quarter Horse and South German Draft Horse families. In four of the seven families, only one single white horse, presumably representing the founder for each of the four respective mutations, was available for genotyping. The newly reported mutations comprise two frameshift mutations (c.1126_1129delGAAC; c.2193delG), two missense mutations (c.856G>A; c.1789G>A) and three splice site mutations (c.338-1G>C; c.2222-1G>A; c.2684+1G>A). White phenotypes in horses show a remarkable allelic heterogeneity. In fact, a higher number of alleles are molecularly characterized at the equine KIT gene than for any other known gene in livestock species.

Association of left ventricular hypertrophy and stage of hypertension by ambulatory blood pressure monitor

Hypertension in adults is defined by risk for cardiovascular morbidity and mortality, but in children, hypertension is defined using population norms. The diagnosis of hypertension in children and adolescents requires only casual blood pressure measurements, but the use of ambulatory blood pressure monitoring to further evaluate patients with elevated blood pressure has been recommended in the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. The aim of this study is to assess the association between stage of hypertension (using both casual and 24 hour ambulatory blood pressure measurements) and target organ damage defined by left ventricular hypertrophy (LVH) in a sample of children and adolescents in Houston, TX. A retrospective analysis was performed on the primary de-identified data from the combination of participants in two, IRB approved, cross-sectional studies. The studies collected basic demographic data, height, weight, casual blood pressures, ambulatory blood pressures, and left ventricular measurements by echocardiography on children age 8 to 18 years old. Hypertension was defined and staged using the criteria for ambulatory blood pressure reported by Lurbe et al. [1] with some modification. Left ventricular hypertrophy was defined using left ventricular mass index (LVMI) criteria specific for children and adults. The pediatric criterion was LVMI2.7 > 95th percentile for gender and the adult criterion was LVMI2.7 > 51g/m2.7. Participants from the original studies were included in this analysis if they had complete demographic information, anthropometric measures, casual blood pressures, ambulatory blood pressures, and echocardiography data. There were 241 children and adolescents included: 19.1% were normotensive, 17.0% had white coat hypertension, 11.6% had masked hypertension, and 52.4% had confirmed hypertension. Of those with hypertension, 22.4% had stage 1 hypertension, 5.8% had stage 2 hypertension, and 24.1% had stage 3 hypertension. Participants with confirmed hypertension were more likely to have LVH by pediatric criterion than those who were normotensive [OR 2.19, 95% CI (1.04–4.63)]; LVH defined by adult criterion did not differ significantly in normotensives compared with hypertensives [OR 2.08, 95% CI (0.58–7.52)]. However, there was a significant trend in the increased prevalence of LVH across the six blood pressure categories for LVH defined by both pediatric and adult criteria (p < 0.001 and p = 0.02, respectively). Additionally, the mean LVM indexed by height 2.7 had a significantly increased trend across blood pressure stages from normal to stage 3 hypertension (p < 0.02). Pediatric hypertension is defined using population norms, and although children with mild hypertension are not at increased odds of having target organ damage defined by LVH, those with severe hypertension are more likely to have LVH. Staging hypertension by ambulatory blood pressure further describes an individual's risk for LVH target organ damage. ^

Null mutation of endothelin receptor type B gene in spotting lethal rats causes aganglionic megacolon and white coat color.

Mutations in the gene encoding the endothelin receptor type B (EDNRB) produce congenital aganglionic megacolon and pigment abnormalities in mice and humans. Here we report a naturally occurring null mutation of the EDNRB gene in spotting lethal (sl) rats, which exhibit aganglionic megacolon associated with white coat color. We found a 301-bp deletion spanning the exon 1-intron 1 junction of the EDNRB gene in sl rats. A restriction fragment length polymorphism caused by this deletion perfectly cosegregates with the sl phenotype. The deletion leads to production of an aberrantly spliced EDNRB mRNA that lacks the coding sequence for the first and second putative transmembrane domains of the G-protein-coupled receptor. Radioligand binding assays revealed undetectable levels of functional EDNRB in tissues from homozygous sl/sl rats. We conclude that EDNRB plays an essential role in the normal development of two neural crest-derived cell lineages, epidermal melanocytes and enteric neurons, in three mammalian species--humans, mice, and rats. The EDNRB-deficient rat may also prove valuable in defining the postnatal physiologic role of this receptor.