[Show abstract][Hide abstract] ABSTRACT: Several allometric methods for indexing cardiac structures to body size have been proposed but the optimal way for normalization of cardiac structures is still controversial. We aimed to estimate the allometric exponents that best describe the relationships between cardiac dimensions and body size and propose normative values. We also explored how different scaling metrics influence the associations of left heart size with cardiovascular risk factors and outcome in the general population.
We measured left ventricular end-diastolic dimension (LVEDD), end-diastolic volume (LVEDV), left ventricular mass (LVM) and left atrial volume (LAV) in randomly recruited population cohorts (n = 1509; 52.8% women; mean age, 47.8 years). After determining optimal scaling metrics in a healthy reference population (n = 656) and proposing normative values, we analyzed how the different scaling metrics influence predictive models for left ventricular hypertrophy (LVH) and left atrial enlargement (LAE) as well as cardiovascular outcome.
The allometric exponents that described the relationships between LVEDD and body size were 1, 0.5 and 0.33 for body height (BH), body surface area (BSA) and estimated lean body mass (eLBM), respectively. With regards to LVEDV, LVM and LAV the allometric exponents for BH were 2.9, 2.7 and 2.0, respectively; for BSA they ranged from 1.7 to 1.8; for eLBM all exponents were around 1. These exponents were used to appropriately scale the cardiac dimensions to body size and derived sex-specific cut-off limits for different indexed cardiac dimensions. Indexation of LVM to height2.7 better detected LVH in overweight and obese subjects. The hazard ratios of cardiovascular outcome were highest for LVH defined by LVM/height2.7.
Our current study resulted in a proposal for thresholds for various indexed cardiac dimensions. LVM indexed to height has the advantage of being more sensitive in detection of LVH associated with obesity and slightly better for prediction of outcome.
[Show abstract][Hide abstract] ABSTRACT: Background
Left ventricular (LV) function depends on the activity of transmembrane electrolyte transporters. Failing human myocardium has lower Na+/K+ ATPase expression and higher intracellular sodium concentrations. The ATP12A gene encodes a catalytic subunit of an ATPase that can function as a Na+/K+ pump. We, therefore, investigated the association between LV function and common genetic variants in ATP12A.MethodsA random sample of 1166 participants (53.7% women; mean age 49.5 years, 44.8% hypertensive) was recruited in Belgium, Poland, Italy and Russia. We measured transmitral early and late diastolic velocities (E and A) by pulsed wave Doppler, and mitral annular velocities (e¿ and a¿) by tissue Doppler. Using principal component analysis, we summarized 7 Doppler indexes ¿ namely, E, A, e¿ and a¿ velocities, and their ratios (E/A, e¿/a¿, and E/e¿) ¿ into a single diastolic score. We genotyped 5 tag SNPs (rs963984, rs9553395, rs10507337, rs12872010, rs2071490) in ATP12A. In our analysis we focused on rs10507337 because it is located within a transcription factor binding site.ResultsIn the population-based analyses while adjusting for covariables and accounting for family clusters and country, rs10507337 C allele carriers had significantly higher E/A (P¿=¿0.003), e¿ (P¿=¿5.8x10¿5), e¿/a¿ (P¿=¿0.003) and diastolic score (P¿=¿0.0001) compared to TT homozygotes. Our findings were confirmed in the haplotype analysis and in the family-based analyses in 74 informative offspring.ConclusionsLV diastolic function as assessed by conventional and tissue Doppler indexes including a composite diastolic score was associated with genetic variation in ATP12A. Further experimental studies are necessary to clarify the role of ATP12A in myocardial relaxation.
BMC Medical Genetics 11/2014; 15(1):121. DOI:10.1186/s12881-014-0121-6 · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001).The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged ≥70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P<0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.
[Show abstract][Hide abstract] ABSTRACT: Background:
Understanding to what extent genetic factors influence diastolic Doppler indexes is an important issue in view of the relation of left ventricular diastolic dysfunction with outcome. We, therefore, investigated the heritability of left ventricular diastolic traits and the composite diastolic score in nuclear families recruited from the general population.
In a random sample of 316 nuclear families (452 parents and 600 offspring, mean age, 58.5 and 33.3 years), we measured transmitral early and late diastolic velocities (E and A) by pulsed wave Doppler, and mitral annular velocities (e' and a') by tissue Doppler. Using principal component analysis, we summarized seven Doppler indexes - namely, E, A, e' and a' velocities, and their ratios - into a single diastolic score. To calculate the heritability of diastolic indexes, we used variance decomposition in nuclear families and offspring as implemented in SOLAR and SAS, and the regression slope of offspring on mid-parent residual values.
In variance decomposition analyses in nuclear families, the abovementioned traits with adjustment for covariables had moderate heritability ranging from 0.27 to 0.43 (P < 0.0001 for all). The parent-offspring concordances of all diastolic indexes were significant and ranged from 0.17 for A (P = 0.009) to 0.42 for e' (P < 0.0001). In nuclear families and offspring, the heritability estimates of the composite diastolic score were 0.42 and 0.64, respectively (P < 0.0001).
Our study demonstrated moderate heritability of various indexes reflecting left ventricular diastolic function in nuclear families. The observation highlights the necessity of further research into the genes that affect left ventricular diastolic function.
Journal of Hypertension 07/2014; 32(9). DOI:10.1097/HJH.0000000000000256 · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce.
Methods and results:
We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs≤1.54; P≥0.18), but was associated with a higher risk of fatal combined with nonfatal cardiovascular, cardiac, or coronary events (HRs≥1.75; P≤0.0054). Isolated systolic hypertension (SBP24≥130 mm Hg) and mixed diastolic plus systolic hypertension were associated with increased risks of all aforementioned end points (P≤0.0012). Below age 50, DBP24 was the main driver of risk, reaching significance for total (HR for 1-SD increase, 2.05; P=0.0039) and cardiovascular mortality (HR, 4.07; P=0.0032) and for all cardiovascular end points combined (HR, 1.74; P=0.039) with a nonsignificant contribution of SBP24 (HR≤0.92; P≥0.068); above age 50, SBP24 predicted all end points (HR≥1.19; P≤0.0002) with a nonsignificant contribution of DBP24 (0.96≤HR≤1.14; P≥0.10). The interactions of age with SBP24 and DBP24 were significant for all cardiovascular and coronary events (P≤0.043).
The risks conferred by DBP24 and SBP24 are age dependent. DBP24 and isolated diastolic hypertension drive coronary complications below age 50, whereas above age 50 SBP24 and isolated systolic and mixed hypertension are the predominant risk factors.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Previous studies testing the hypothesis that symptoms of anxiety and depression increase blood pressure (BP) levels show inconsistent and limited findings. We examined the association between those symptoms across adult life and BP in late middle age.
Using data from 1683 participants from the MRC NSHD, we investigated associations between affective symptoms at ages 36, 43, 53 and 60–64 years and SBP and DBP at age 60–64. Multivariable linear regression was used to examine the effect on BP of affective symptoms at each age separately and as a categorical cumulative score based on the number of times an individual was classified as a ‘case’. Models were adjusted for sex, BMI, educational attainment, socio-economic position, heart rate, lifestyle factors and antihypertensive treatment.
In fully adjusted models, we observed lower SBP in study members with case-level symptoms at one to two time-points [−1.83 mmHg; 95% confidence interval (CI) −3.74 to 0.01] and at three to four time-points (−3.93 mmHg; 95% CI −7.19 to −0.68) compared with those never meeting case criteria suggesting a cumulative inverse impact of affective symptoms on SBP across adulthood (P value for trend 0.022). Sex and BMI had a large impact on the estimates while not other confounders. Potential mediators such as heart rate and lifestyle behaviours had a little impact on the association. SBP at age 36 and behavioural changes across adulthood, as additional covariates, had a little impact on the association. A similar but weaker trend was observed for DBP.
A cumulative effect of symptoms of anxiety and depression across adulthood results in lower SBP in late middle age that is not explained by lifestyle factors and antihypertensive treatment. Mechanisms by which mood may impact BP should be investigated.
Journal of Hypertension 06/2014; 32(8). DOI:10.1097/HJH.0000000000000244 · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atherosclerosis begins early in life and obesity is a key determinant. We investigated the role of body mass index (BMI) and height from infancy to adulthood in presenting with high adulthood carotid intima-media thickness.
Odds ratios of BMI, and height Z scores at 2, 4, 6, 7, 11, 15, and 20 years, and changes between 2 and 4, 4 and 7, 7 and 15, and 15 and 20 years, for carotid intima-media thickness at 60 to 64 years in the upper quartile were estimated for 604 men and 669 women. Confounding by early-life environments, mediating by body size and cardiometabolic measures at 60 to 64 years, and effect modification were investigated. In men, there was positive association of BMI at 4 years (odds ratio, 1.256; 95% confidence interval, 1.026-1.538) and 20 years (1.282; 1.022-1.609), negative association of height at 4 years (0.780; 0.631-0.964), and negative association of height growth between 2 and 4 years (0.698; 0.534-0.913) with high carotid intima-media thickness. The childhood estimates were robust, but the estimate for BMI at 20 years was attenuated by adjustment for BMI at 60 to 64 years. The protective influence of greater early childhood height was strongest in those with the lowest systolic blood pressure at 60 to 64 years. In women, there was no pattern of association and all confidence intervals crossed 1.
Early childhood in men might be a sensitive developmental period for atherosclerosis, in which changes in BMI and height represent 2 distinct biological mechanisms. The maintenance of healthy weight in men from adolescence onward may be a useful strategy to avoid the atherosclerotic complications of adiposity tracking.
[Show abstract][Hide abstract] ABSTRACT: Guidelines propose classification of conventional blood pressure (CBP) into normotension (<120/<80mm Hg), prehypertension (120-139/80-89mm Hg), and hypertension (≥140/≥90mm Hg).
To assess the potential differential contribution of ambulatory blood pressure (ABP) in predicting risk across CBP strata, we analyzed outcomes in 7,826 untreated people recruited from 11 populations.
During an 11.3-year period, 809 participants died (276 cardiovascular deaths) and 639, 383, and 225 experienced a cardiovascular, cardiac, or cerebrovascular event. Compared with normotension (n = 2,639), prehypertension (n = 3,076) carried higher risk (P ≤ 0.015) of cardiovascular (+41%) and cerebrovascular (+92%) endpoints; compared with hypertension (n = 2,111) prehypertension entailed lower risk (P ≤ 0.005) of total mortality (-14%) and cardiovascular mortality (-29%) and of cardiovascular (-34%), cardiac (-33%), or cerebrovascular (-47%) events. Multivariable-adjusted hazard ratios (HRs) for stroke associated with 24-hour and daytime diastolic ABP (+5mm Hg) were higher (P ≤ 0.045) in normotension than in prehypertension and hypertension (1.98 vs.1.19 vs.1.28 and 1.73 vs.1.09 vs. 1.24, respectively) with similar trends (0.03 ≤ P ≤ 0.11) for systolic ABP (+10mm Hg). However, HRs for fatal endpoints and cardiac events associated with ABP did not differ significantly (P ≥ 0.13) across CBP categories. Of normotensive and prehypertensive participants, 7.5% and 29.3% had masked hypertension (daytime ABP ≥135/≥85mm Hg). Compared with true normotension (P ≤ 0.01), HRs for stroke were 3.02 in normotension and 2.97 in prehypertension associated with masked hypertension with no difference between the latter two conditions (P = 0.93).
ABP refines risk stratification in normotension and prehypertension mainly by enabling the diagnosis of masked hypertension.
American Journal of Hypertension 02/2014; 27(7). DOI:10.1093/ajh/hpu002 · 2.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract To evaluate the effect of hypnotically induced amusia for rhythm (a condition in which individuals are unable to recognize melodies or rhythms) on mismatch negativity (MMN), 5 highly (HH) and 5 poorly (LH) hypnotizable nonmusician volunteers underwent MMN recording before and during a hypnotic suggestion for amusia. MMN amplitude was recorded using a 19-channel montage and then processed using the low-resolution electromagnetic tomography (LORETA) to localize its sources. MMN amplitude was significantly decreased during hypnotic amusia (p < .04) only in HH, where the LORETA maps of MMN showed a decreased source amplitude in the left temporal lobe, suggesting a hypnotic top-down regulation of activity of these areas and that these changes can be assessed by neurophysiological investigations.
International Journal of Clinical and Experimental Hypnosis 02/2014; 62(2):129-44. DOI:10.1080/00207144.2014.869124 · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Experts proposed blood pressure (BP) load derived from 24-hour ambulatory BP recordings as a more accurate predictor of outcome than level, in particular in normotensive people. We analyzed 8711 subjects (mean age, 54.8 years; 47.0% women) randomly recruited from 10 populations. We expressed BP load as percentage (%) of systolic/diastolic readings ≥135/≥85 mm Hg and ≥120/≥70 mm Hg during day and night, respectively, or as the area under the BP curve (mm Hg×h) using the same ceiling values. During a period of 10.7 years (median), 1284 participants died and 1109 experienced a fatal or nonfatal cardiovascular end point. In multivariable-adjusted models, the risk of cardiovascular complications gradually increased across deciles of BP level and load (P<0.001), but BP load did not substantially refine risk prediction based on 24-hour systolic or diastolic BP level (generalized R(2) statistic ≤0.294%; net reclassification improvement ≤0.28%; integrated discrimination improvement ≤0.001%). Systolic/diastolic BP load of 40.0/42.3% or 91.8/73.6 mm Hg×h conferred a 10-year risk of a composite cardiovascular end point similar to a 24-hour systolic/diastolic BP of 130/80 mm Hg. In analyses dichotomized according to these thresholds, increased BP load did not refine risk prediction in the whole study population (R(2)≤0.051) or in untreated participants with 24-hour ambulatory normotension (R(2)≤0.034). In conclusion, BP load does not improve risk stratification based on 24-hour BP level. This also applies to subjects with normal 24-hour BP for whom BP load was proposed to be particularly useful in risk stratification.
[Show abstract][Hide abstract] ABSTRACT: Overweight clusters with high blood pressure (BP), but the independent contribution of both risk factors remains insufficiently documented. In a prospective population study involving 8467 participants (mean age 54.6 years; 47.0% women) randomly recruited from 10 populations, we studied the contribution of body mass index (BMI) to risk over and beyond BP, taking advantage of the superiority of ambulatory over conventional BP. Over 10.6 years (median), 1271 participants (15.0%) died and 1092 (12.9%), 637 (7.5%) and 443 (5.2%) experienced a fatal or nonfatal cardiovascular, cardiac or cerebrovascular event. Adjusted for sex and age, low BMI (<20.7 kg m(-2)) predicted death (hazard ratio (HR) vs average risk, 1.52; P<0.0001) and high BMI (30.9 kg m(-2)) predicted the cardiovascular end point (HR, 1.27; P=0.006). With adjustments including 24-h systolic BP, these HRs were 1.50 (P<0.001) and 0.98 (P=0.91), respectively. Across quartiles of the BMI distribution, 24-h and nighttime systolic BP predicted every end point (1.13standardized HR 1.67; 0.046 P<0.0001). The interaction between systolic BP and BMI was nonsignificant (P0.22). Excluding smokers removed the contribution of BMI categories to the prediction of mortality. In conclusion, BMI only adds to BP in risk stratification for mortality but not for cardiovascular outcomes. Smoking probably explains the association between increased mortality and low BMI.Journal of Human Hypertension advance online publication, 16 January 2014; doi:10.1038/jhh.2013.145.
Journal of human hypertension 01/2014; 28(9). DOI:10.1038/jhh.2013.145 · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evidence-based thresholds for risk stratification based on pulse pressure (PP) are currently unavailable. To derive outcome-driven thresholds for the 24-hour ambulatory PP, we analyzed 9938 participants randomly recruited from 11 populations (47.3% women). After age stratification (<60 versus ≥60 years) and using average risk as reference, we computed multivariable-adjusted hazard ratios (HRs) to assess risk by tenths of the PP distribution or risk associated with stepwise increasing (+1 mm Hg) PP levels. All adjustments included mean arterial pressure. Among 6028 younger participants (68 853 person-years), the risk of cardiovascular (HR, 1.58; P=0.011) or cardiac (HR, 1.52; P=0.056) events increased only in the top PP tenth (mean, 60.6 mm Hg). Using stepwise increasing PP levels, the lower boundary of the 95% confidence interval of the successive thresholds did not cross unity. Among 3910 older participants (39 923 person-years), risk increased (P≤0.028) in the top PP tenth (mean, 76.1 mm Hg). HRs were 1.30 and 1.62 for total and cardiovascular mortality, and 1.52, 1.69, and 1.40 for all cardiovascular, cardiac, and cerebrovascular events. The lower boundary of the 95% confidence interval of the HRs associated with stepwise increasing PP levels crossed unity at 64 mm Hg. While accounting for all covariables, the top tenth of PP contributed less than 0.3% (generalized R(2) statistic) to the overall risk among the elderly. Thus, in randomly recruited people, ambulatory PP does not add to risk stratification below age 60; in the elderly, PP is a weak risk factor with levels below 64 mm Hg probably being innocuous.
[Show abstract][Hide abstract] ABSTRACT: To verify whether the C825T polymorphism of the GNB3 influences the response to neuropsychological tests, mini-mental state examination, digit span (DS), immediate and delayed prose memory, memory with interference at 10 and 30 seconds (MI 10 and 30), trail making tests (TMTs) A and B, abstraction task, verbal fluency (VF) test, figure drawing and copying, overlapping figures test and clock test were performed in 220 elderly men and women free from clinical dementia and from neurological and psychiatric diseases randomly taken from the Italian general population and analysed across the C825T polymorphism. The performance of DS, immediate and delayed prose memory, VF, and TMTs was worse in subjects who were TT for the polymorphism in comparison to the C-carriers. The performance of all tests declined with age. In the case of DS, immediate and delayed prose memory, MI 10 and VF, this trend was maintained in the C-carriers but not in TT. In the case of prose memory, of memory with interference, and of VF, schooling reduced the detrimental interaction between age and genotype. The C825T polymorphism of GNB3 gene therefore influences memory and verbal fluency, being additive to the effects of age and partially mitigated by schooling.
Neurology Research International 10/2013; 2013(1):597034. DOI:10.1155/2013/597034
[Show abstract][Hide abstract] ABSTRACT: The general belief that orthostatic hypotension (OH) predisposes to cardiovascular events is based on sparse and contradictory data, rarely derived from population studies.
A total of 1,016 men and women aged ≥65 years was studied in a 12-year epidemiological population-based study. Cardiovascular events were detected in subjects with and without OH (blood pressure (BP) decrease ≥20mm Hg for systolic or ≥10mm Hg for diastolic), and Cox analysis was performed including OH as an independent variable.
In univariate analysis, coronary (20.2% vs. 13.1%, P = 0.05), cerebrovascular (13.1% vs. 8.4%, P = 0.05), and heart failure (HF) events (20.2% vs. 13.8%, P = 0.03) were apparently more incidental in subjects with OH than in those without OH. Nevertheless, after adjusting for age, gender, and systolic BP as confounders, OH did not act as a cardiovascular predictor (relative risk for cerebrovascular events 1.33, 95% confidence interval (CI), 0.78-2.2, for coronary events 1.25, CI 0.82-1.88, for HF 1.07, CI 0.71-1.62, for arrhythmias 0.82, CI 0.40-1.37, and for syncope 0.58, CI 0.13-2.71).
Although OH seems to be a predictor of coronary, cerebrovascular, and HF events, no predictive role was found in models that include biological confounders. Independent of the cause of OH, age and systolic BP, which are positively associated with OH, fully explain the greater incidence of cardiovascular events and the greater cardiovascular risk observed in subjects with OH.
American Journal of Hypertension 09/2013; 27(1). DOI:10.1093/ajh/hpt172 · 2.85 Impact Factor