Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes.

Importance: Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. Objective: To evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and Participants: Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). Exposures: Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and Measures: Multivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). Results: Among 11 135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P < .001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and Relevance: In this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.

Ambulatory hypertension subtypes and 24-hour systolic and diastolic blood pressure as distinct outcome predictors in 8341 untreated people recruited from 12 populations.

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). CONCLUSIONS: 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.

Risk stratification by self-measured home blood pressure across categories of conventional blood pressure: a participant-level meta-analysis.

BACKGROUND: The Global Burden of Diseases Study 2010 reported that hypertension is worldwide the leading risk factor for cardiovascular disease, causing 9.4 million deaths annually. We examined to what extent self-measurement of home blood pressure (HBP) refines risk stratification across increasing categories of conventional blood pressure (CBP). METHODS AND FINDINGS: This meta-analysis included 5,008 individuals randomly recruited from five populations (56.6% women; mean age, 57.1 y). All were not treated with antihypertensive drugs. In multivariable analyses, hazard ratios (HRs) associated with 10-mm Hg increases in systolic HBP were computed across CBP categories, using the following systolic/diastolic CBP thresholds (in mm Hg): optimal, <120/<80; normal, 120-129/80-84; high-normal, 130-139/85-89; mild hypertension, 140-159/90-99; and severe hypertension, ≥160/≥100. Over 8.3 y, 522 participants died, and 414, 225, and 194 had cardiovascular, cardiac, and cerebrovascular events, respectively. In participants with optimal or normal CBP, HRs for a composite cardiovascular end point associated with a 10-mm Hg higher systolic HBP were 1.28 (1.01-1.62) and 1.22 (1.00-1.49), respectively. At high-normal CBP and in mild hypertension, the HRs were 1.24 (1.03-1.49) and 1.20 (1.06-1.37), respectively, for all cardiovascular events and 1.33 (1.07-1.65) and 1.30 (1.09-1.56), respectively, for stroke. In severe hypertension, the HRs were not significant (p≥0.20). Among people with optimal, normal, and high-normal CBP, 67 (5.0%), 187 (18.4%), and 315 (30.3%), respectively, had masked hypertension (HBP≥130 mm Hg systolic or ≥85 mm Hg diastolic). Compared to true optimal CBP, masked hypertension was associated with a 2.3-fold (1.5-3.5) higher cardiovascular risk. A limitation was few data from low- and middle-income countries. CONCLUSIONS: HBP substantially refines risk stratification at CBP levels assumed to carry no or only mildly increased risk, in particular in the presence of masked hypertension. Randomized trials could help determine the best use of CBP vs. HBP in guiding BP management. Our study identified a novel indication for HBP, which, in view of its low cost and the increased availability of electronic communication, might be globally applicable, even in remote areas or in low-resource settings.

Hospital admissions for acute myocardial infarction before and after implementation of a comprehensive smoke-free policy in Uruguay: experience through 2010.

BACKGROUND: Comprehensive smoke-free laws have been followed by drops in hospitalisations for acute myocardial infarction (AMI), including in a study with 2 years follow-up for such a law in Uruguay. METHODS: Multiple linear and negative binomial regressions for AMI admissions (ICD-10 code 121) from 37 hospitals for 2 years before and 4 years after Uruguay implemented a 100% nationwide smoke-free law. RESULTS: Based on 11 135 cases, there was a significant drop of -30.9 AMI admissions/month (95% CI -49.8 to -11.8, p=0.002) following implementation of the smoke-free law. The effect of the law did not increase or decrease over time following implementation (p=0.234). This drop represented a 17% drop in AMI admissions following the law (IRR=0.829, 95% CI 0.743 to 0.925, p=0.001). CONCLUSIONS: Adding two more years of follow-up data confirmed that Uruguay's smoke-free law was followed by a substantial and sustained reduction in AMI hospitalisations.

Hospital admissions for acute myocardial infarction before and after implementation of a comprehensive smoke-free policy in Uruguay.

BACKGROUND: Stimulated by the WHO Framework Convention on Tobacco Control, many countries in Latin America adopted comprehensive smoke-free policies. In March 2006, Uruguay became the first Latin American country to adopt 100% smoke-free national legislation, which ended smoking in all indoor public places and workplaces, including restaurants and bars. The objective of this study was to evaluate trends in hospital admissions for cardiovascular disease 2 years before and 2 years after the policy was implemented in Uruguay. METHODS: Reports of hospital admissions for acute myocardial infarction (AMI) (International Classification of Disease-10 I21) from 37 hospitals (79% of all hospital admissions in the country), representing the period 2 years before and 2 years after the adoption of a nationwide smoke-free policy in Uruguay (between 1 March 2004 and 29 February 2008), were reviewed. A time series analysis was undertaken to compare the average monthly number of events of hospital admission for AMI before and after the smoke-free law. RESULTS: A total of 7949 hospital admissions for AMI were identified during the 4-year study period. Two years after the smoke-free policy was enacted, hospital admissions for AMI fell by 22%. The same pattern and roughly the same magnitude of reduction in AMI admissions were observed for patients seen in public and private hospitals, men, women and people aged 40-65 years and older than 65 years. CONCLUSIONS: The national smoke-free policy implemented in Uruguay in 2006 was associated with a significant reduction in hospital admissions for AMI.

Predictive power of 24-h ambulatory pulse pressure and its components for mortality and cardiovascular outcomes in 11 848 participants recruited from 13 populations.

BACKGROUND: The role of pulse pressure (PP) 'widening' at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: 'elastic PP' (elPP) and 'stiffening PP' (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP ('PP variables') with mortality and composite cardiovascular events in different age classes. METHOD: Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age classes were age 40 or less, 40-50, 50-60, 60-70, and over 70 years. Co-primary endpoints were total mortality and composite cardiovascular events. The relative risk expressed by hazard ratio per 1SD increase for each of the PP variables was calculated from multivariable-adjusted Cox regression models. RESULTS: The 11 848 participants from 13 cohorts (age 53 ±â€Š16 years, 50% men) were followed for up for 13.7 ±â€Š6.7 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or nonfatal cardiovascular event (12.9 per 1000 person-years). Mean PP, elPP, and stPP were, respectively, 49.7, 43.5, and 6.2 mmHg, and elPP and stPP were uncorrelated ( r  = -0.07). At age 50-60 years, all PP variables displayed association with risk for almost all outcomes. From age over 60 years to age over 70 years, hazard ratios of of PP and elPP were similar and decreased gradually but differently for pulse rate lower than or higher than 70 bpm, whereas stPP lacked predictive power in most cases. For age 40 years or less, elPP showed protective power for coronary events, whereas stPP and PP predicted stroke events. Adjusted and unadjusted hazard ratio variations were similar over the entire age range. CONCLUSION: This study provides a new basis for associating PP components with outcome and arterial properties in different age groups and at different pulse rates for both old and young age. The similarity between adjusted and unadjusted hazard ratios supports the clinical usefulness of PP components but further studies are needed to assess the prognostic significance of the PP components, especially at the young age.

[Impact of tobacco control on healthcare costs for acute myocardial infarction in Uruguay: costs based on Diagnosis-Related Groups]. / Impacto del control de tabaco en los costos asistenciales del infarto agudo de miocardio en Uruguay: costos en base a Grupos Relacionados por el Diagnóstico.

Tobacco is the leading modifiable cause of cardiovascular disease, cancer, and respiratory diseases and is thus a serious global public health problem. In 2006, Uruguay implemented the World Health Organization Framework Convention on Tobacco Control (WHO-FCTC) and achieved a decrease in the smoking rate and improvements in cardiovascular and respiratory health. We analyzed the clinical and economic impacts of tobacco control measures on the healthcare costs for acute myocardial infarction, which was reduced by 17%. The costs avoided for other diseases were not included. The study examined the trend in a healthcare institution and projected the result to the country's population. The cost analysis used the diagnosis-related groups (DRG) methodology, combined with the institution's accounting reports. Besides the hospitalization costs, the analysis included patient transportation, invasive cardiovascular procedures, and healthcare costs for the 12 months following the acute myocardial infarction. The cost per patient was USD 12,037. Considering a decrease of 500 acute myocardial infarctions per year, the estimated annual savings are USD 6 million in medical care costs for the averted acute myocardial infarctions, besides savings from averted work absenteeism, subsequent disability, and disability adjusted life years. This successful tobacco control policy has been the leading public health intervention in the last 30 years in Uruguay. The study aims to contribute to the guidelines determined by the World Health Organization (WHO).

El tabaco es la principal causa modificable de enfermedad cardiovascular, cáncer y enfermedades respiratorias, por lo que es un serio problema de salud pública universal. En 2006, Uruguay implementó el Convenio Marco para el Control del Tabaco de la Organización Mundial de la Salud (CMCT-OMS), y consiguió un descenso de la tasa de fumadores y mejoras en la salud cardiovascular y respiratoria. Se investigó el impacto clínico y económico de las medidas de control de tabaco sobre los costos asistenciales del infarto agudo de miocardio, que se redujo un 17%. No se incluyeron los costos evitados por otras patologías. Se investigó lo ocurrido en una institución sanitaria y se proyectó a toda la población del país. El análisis de costos se realizó usando la metodología del sistema de los Grupos Relacionados por el Diagnóstico (GRD), combinada con los informes contables de la institución. Además de los costos de internación, se incluyeron los relacionados con los traslados, los de los procedimientos cardiovasculares invasivos y los gastos sanitarios de los 12 meses posteriores al evento agudo. El costo por paciente fue de USD 12.037. Considerando un descenso de 500 infartos por año, el ahorro anual estimado es de USD 6.000.000 en costos asistenciales de los infartos evitados; a lo que debería agregarse otros ahorros de costos por pérdida laboral, discapacidad posterior y años de vida prematura perdidos por fallecimiento del paciente. La exitosa política de control del tabaco ha sido la principal medida de salud pública en los últimos 30 años en nuestro país. Esta investigación busca contribuir al camino trazado por la Organización Mundial de la Salud (OMS).

O tabaco é a principal causa modificável de doença cardiovascular, câncer e doenças respiratórias, o que faz dele um sério problema de saúde pública universal. Em 2006, Uruguai implementou a Convenção-Quadro para o Controle do Tabaco da Organização Mundial da Saúde (CQCT-OMS), registrando desde então uma queda na taxa de fumantes, além de melhoras na saúde cardiovascular e respiratória. Foi avaliado o impacto económico e clínico das medidas de controle do tabaco sobre os custos da atenção ao infarto agudo do miocárdio, que diminuíram 17%. Não foram computados os custos evitados de outras patologias. A pesquisa investigou os registros em uma unidade de saúde e operou uma projeção para toda a população do país. A análise de custos foi desenvolvida usando a metodologia do sistema de Grupos Relacionados pelo Diagnóstico (GRD), combinada com os relatórios contábeis da instituição. Além dos custos de internação, foram incluídos aqueles relativos aos traslados, aos procedimentos cardiovasculares invasivos e às despesas em saúde dos 12 meses posteriores ao evento agudo. O custo por paciente foi de USD 12.037. Considerando uma diminuição de 500 infartos por ano, a economia anual estimada representa USD 6.000.000 na atenção aos infartos evitados; devem ser acrescentadas outras economias de custos de licença médica, invalidez posterior e anos de vida prematura perdidos por óbito do paciente. A bem-sucedida política de controle de tabaco foi a principal medida de saúde pública nos últimos 30 anos, no nosso país. Esta pesquisa pretende contribuir com o caminho trilhado pela Organização Mundial da Saúde (OMS).

Isolated Diastolic Hypertension in the IDACO Study: An Age-Stratified Analysis Using 24-Hour Ambulatory Blood Pressure Measurements.

[Figure: see text].

Association of Fatal and Nonfatal Cardiovascular Outcomes With 24-Hour Mean Arterial Pressure.

Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R2 statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of <90 (normotension, n=6183), 90 to <92 (elevated MAP, n=909), 92 to <96 (stage-1 hypertension, n=1544), and ≥96 (stage-2 hypertension, n=2960) mm Hg yielded equivalent 10-year major adverse cardiovascular events risks as office MAP categorized using 2017 American thresholds for office SBP and DBP. Compared with 24-hour MAP normotension, hazard ratios were 0.96 (95% CI, 0.80-1.16), 1.32 (1.15-1.51), and 1.77 (1.59-1.97), for elevated and stage-1 and stage-2 hypertensive MAP. On top of 24-hour MAP, higher 24-hour SBP increased, whereas higher 24-hour DBP attenuated risk (P<0.001). Considering the 24-hour measurements, R2 statistics were similar for SBP (1.34) and MAP (1.28), lower for DBP than for MAP (0.47), and reduced to null, if the base model included SBP and DBP; if the ambulatory BP indexes were dichotomized according to the 2017 American guideline and the proposed 92 mm Hg for MAP, the R2 values were 0.71, 0.89, 0.32, and 0.10, respectively. In conclusion, the clinical application of 24-hour MAP thresholds in conjunction with SBP and DBP refines risk estimates.

Relative and Absolute Risk to Guide the Management of Pulse Pressure, an Age-Related Cardiovascular Risk Factor.

BACKGROUND: Pulse pressure (PP) reflects the age-related stiffening of the central arteries, but no study addressed the management of the PP-related risk over the human lifespan. METHODS: In 4,663 young (18-49 years) and 7,185 older adults (≥50 years), brachial PP was recorded over 24 hours. Total mortality and all major cardiovascular events (MACEs) combined were coprimary endpoints. Cardiovascular death, coronary events, and stroke were secondary endpoints. RESULTS: In young adults (median follow-up, 14.1 years; mean PP, 45.1 mm Hg), greater PP was not associated with absolute risk; the endpoint rates were ≤2.01 per 1,000 person-years. The adjusted hazard ratios expressed per 10-mm Hg PP increments were less than unity (P ≤ 0.027) for MACE (0.67; 95% confidence interval [CI], 0.47-0.96) and cardiovascular death (0.33; 95% CI, 0.11-0.75). In older adults (median follow-up, 13.1 years; mean PP, 52.7 mm Hg), the endpoint rates, expressing absolute risk, ranged from 22.5 to 45.4 per 1,000 person-years and the adjusted hazard ratios, reflecting relative risk, from 1.09 to 1.54 (P < 0.0001). The PP-related relative risks of death, MACE, and stroke decreased >3-fold from age 55 to 75 years, whereas absolute risk rose by a factor 3. CONCLUSIONS: From 50 years onwards, the PP-related relative risk decreases, whereas absolute risk increases. From a lifecourse perspective, young adulthood provides a window of opportunity to manage risk factors and prevent target organ damage as forerunner of premature death and MACE. In older adults, treatment should address absolute risk, thereby extending life in years and quality.

Outcome-Driven Thresholds for Ambulatory Blood Pressure Based on the New American College of Cardiology/American Heart Association Classification of Hypertension.

The new American College of Cardiology/American Heart Association guideline reclassified office blood pressure and proposed thresholds for ambulatory blood pressure (ABP). We derived outcome-driven ABP thresholds corresponding with the new office blood pressure categories. We performed 24-hour ABP monitoring in 11 152 participants (48.9% women; mean age, 53.0 years) representative of 13 populations. We determined ABP thresholds resulting in multivariable-adjusted 10-year risks similar to those associated with elevated office blood pressure (120/80 mm Hg) and stages 1 and 2 of office hypertension (130/80 and 140/90 mm Hg). Over 13.9 years (median), 2728 (rate per 1000 person-years, 17.9) people died, 1033 (6.8) from cardiovascular disease; furthermore, 1988 (13.8), 893 (6.0), and 795 (5.4) cardiovascular and coronary events and strokes occurred. Using a composite cardiovascular end point, systolic/diastolic outcome-driven thresholds indicating elevated 24-hour, daytime, and nighttime ABP were 117.9/75.2, 121.4/79.6, and 105.3/66.2 mm Hg. For stages 1 and 2 ambulatory hypertension, thresholds were 123.3/75.2 and 128.7/80.7 mm Hg for 24-hour ABP, 128.5/79.6 and 135.6/87.1 mm Hg for daytime ABP, and 111.7/66.2 and 118.1/72.5 mm Hg for nighttime ABP. ABP thresholds derived from other end points were similar. After rounding, approximate thresholds for elevated 24-hour, daytime, and nighttime ABP were 120/75, 120/80, and 105/65 mm Hg, and for stages 1 and 2, ambulatory hypertension 125/75 and 130/80 mm Hg, 130/80 and 135/85 mm Hg, and 110/65 and 120/70 mm Hg. Outcome-driven ABP thresholds corresponding to elevated blood pressure and stages 1 and 2 of hypertension are similar to those proposed by the current American College of Cardiology/American Heart Association guideline.

Opposing Age-Related Trends in Absolute and Relative Risk of Adverse Health Outcomes Associated With Out-of-Office Blood Pressure.

Participant-level meta-analyses assessed the age-specific relevance of office blood pressure to cardiovascular complications, but this information is lacking for out-of-office blood pressure. At baseline, daytime ambulatory (n=12 624) or home (n=5297) blood pressure were measured in 17 921 participants (51.3% women; mean age, 54.2 years) from 17 population cohorts. Subsequently, mortality and cardiovascular events were recorded. Using multivariable Cox regression, floating absolute risk was computed across 4 age bands (≤60, 61-70, 71-80, and >80 years). Over 236 491 person-years, 3855 people died and 2942 cardiovascular events occurred. From levels as low as 110/65 mm Hg, risk log-linearly increased with higher out-of-office systolic/diastolic blood pressure. From the youngest to the oldest age group, rates expressed per 1000 person-years increased (P<0.001) from 4.4 (95% CI, 4.0-4.7) to 86.3 (76.1-96.5) for all-cause mortality and from 4.1 (3.9-4.6) to 59.8 (51.0-68.7) for cardiovascular events, whereas hazard ratios per 20-mm Hg increment in systolic out-of-office blood pressure decreased (P≤0.0033) from 1.42 (1.19-1.69) to 1.09 (1.05-1.12) and from 1.70 (1.51-1.92) to 1.12 (1.07-1.17), respectively. These age-related trends were similar for out-of-office diastolic pressure and were generally consistent in both sexes and across ethnicities. In conclusion, adverse outcomes were directly associated with out-of-office blood pressure in adults. At young age, the absolute risk associated with out-of-office blood pressure was low, but relative risk high, whereas with advancing age relative risk decreased and absolute risk increased. These observations highlight the need of a lifecourse approach for the management of hypertension.

Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study.

BACKGROUND: Few studies have formally compared the predictive value of the blood pressure at night over and beyond the daytime value. We investigated the prognostic significance of the ambulatory blood pressure during night and day and of the night-to-day blood pressure ratio. METHODS: We did 24-h blood pressure monitoring in 7458 people (mean age 56.8 years [SD 13.9]) enrolled in prospective population studies in Denmark, Belgium, Japan, Sweden, Uruguay, and China. We calculated multivariate-adjusted hazard ratios for daytime and night-time blood pressure and the systolic night-to-day ratio, while adjusting for cohort and cardiovascular risk factors. FINDINGS: Median follow-up was 9.6 years (5th to 95th percentile 2.5-13.7). Adjusted for daytime blood pressure, night-time blood pressure predicted total (n=983; p<0.0001), cardiovascular (n=387; p<0.01), and non-cardiovascular (n=560; p<0.001) mortality. Conversely, adjusted for night-time blood pressure, daytime blood pressure predicted only non-cardiovascular mortality (p<0.05), with lower blood pressure levels being associated with increased risk. Both daytime and night-time blood pressure consistently predicted all cardiovascular events (n=943; p<0.05) and stroke (n=420; p<0.01). Adjusted for night-time blood pressure, daytime blood pressure lost prognostic significance only for cardiac events (n=525; p> or =0.07). Adjusted for the 24-h blood pressure, night-to-day ratio predicted mortality, but not fatal combined with non-fatal events. Antihypertensive drug treatment removed the significant association between cardiovascular events and the daytime blood pressure. Participants with systolic night-to-day ratio value of 1 or more were older, at higher risk of death, and died at an older age than those whose night-to-day ratio was normal (> or =0.80 to <0.90). INTERPRETATION: In contrast to commonly held views, daytime blood pressure adjusted for night-time blood pressure predicts fatal combined with non-fatal cardiovascular events, except in treated patients, in whom antihypertensive drugs might reduce blood pressure during the day, but not at night. The increased mortality in patients with higher night-time than daytime blood pressure probably indicates reverse causality. Our findings support recording the ambulatory blood pressure during the whole day.

Is blood pressure during the night more predictive of cardiovascular outcome than during the day?

The objective of this study was to investigate the prognostic significance of the ambulatory blood pressure (BP) during night and day and of the night-to-day BP ratio (NDR). We studied 7458 participants (mean age 56.8 years; 45.8% women) enrolled in the International Database on Ambulatory BP in relation to Cardiovascular Outcome. Using Cox models, we calculated hazard ratios (HR) adjusted for cohort and cardiovascular risk factors. Over 9.6 years (median), 983 deaths and 943 cardiovascular events occurred. Nighttime BP predicted mortality outcomes (HR, 1.18-1.24; P<0.01) independent of daytime BP. Conversely, daytime systolic (HR, 0.84; P<0.01) and diastolic BP (HR, 0.88; P<0.05) predicted only noncardiovascular mortality after adjustment for nighttime BP. Both daytime BP and nighttime BP consistently predicted all cardiovascular events (HR, 1.11-1.33; P<0.05) and stroke (HR, 1.21-1.47; P<0.01). Daytime BP lost its prognostic significance for cardiovascular events in patients on antihypertensive treatment. Adjusted for the 24-h BP, NDR predicted mortality (P<0.05), but not fatal combined with nonfatal events. Participants with systolic NDR of at least 1 compared with participants with normal NDR (> or = 0.80 to <0.90) were older, at higher risk of death, but died at higher age. The predictive accuracy of the daytime and nighttime BP and the NDR depended on the disease outcome under study. The increased mortality in patients with higher NDR probably indicates reverse causality. Our findings support recording the ambulatory BP during the whole day.

The International Database of Ambulatory Blood Pressure in relation to Cardiovascular Outcome (IDACO): protocol and research perspectives.

OBJECTIVES: The International Database on Ambulatory Blood Pressure Monitoring (1993-1994) lacked a prospective dimension. We are constructing a new resource of longitudinal population studies to investigate with great precision to what extent the ambulatory blood pressure improves risk stratification. METHODS: The acronym IDACO refers to the new International Database of Ambulatory blood pressure in relation to Cardiovascular Outcome. Eligible studies are population based, have fatal as well as nonfatal outcomes available for analysis, comply with ethical standards, and have been previously published in peer-reviewed journals. In a meta-analysis based on individual patient data, composite and cause-specific cardiovascular events will be related to various indexes derived by ambulatory blood pressure monitoring. The analyses will be stratified by cohort and adjusted for the conventional blood pressure and other cardiovascular risk factors. RESULTS: To date, the international database includes 7609 patients from four cohorts recruited in Copenhagen, Denmark (n=2311), Noorderkempen, Belgium (n=2542), Ohasama, Japan (n=1535), and Uppsala, Sweden (n=1221). In these four cohorts, during a total of 69,295 person-years of follow-up (median 9.3 years), 1026 patients died and 929 participants experienced a fatal or nonfatal cardiovascular event. Follow-up in five other eligible cohorts, involving a total of 4027 participants, is still in progress. We expect that this follow-up will be completed by the end of 2007. CONCLUSION: The international database of ambulatory blood pressure in relation to cardiovascular outcome will provide a shared resource to investigate risk stratification by ambulatory blood pressure monitoring to an extent not possible in any earlier individual study.

Impacto del control de tabaco en los costos asistenciales del infarto agudo de miocardio en Uruguay: costos en base a Grupos Relacionados por el Diagnóstico / Impact of tobacco control on healthcare costs for acute myocardial infarction in Uruguay: costs based on Diagnosis-Related Groups / Impacto do controle do tabaco sobre os custos da atenção ao infarto agudo do miocárdio no Uruguai: custos com base em Grupos Relacionados pelo Diagnóstico

El tabaco es la principal causa modificable de enfermedad cardiovascular, cáncer y enfermedades respiratorias, por lo que es un serio problema de salud pública universal. En 2006, Uruguay implementó el Convenio Marco para el Control del Tabaco de la Organización Mundial de la Salud (CMCT-OMS), y consiguió un descenso de la tasa de fumadores y mejoras en la salud cardiovascular y respiratoria. Se investigó el impacto clínico y económico de las medidas de control de tabaco sobre los costos asistenciales del infarto agudo de miocardio, que se redujo un 17%. No se incluyeron los costos evitados por otras patologías. Se investigó lo ocurrido en una institución sanitaria y se proyectó a toda la población del país. El análisis de costos se realizó usando la metodología del sistema de los Grupos Relacionados por el Diagnóstico (GRD), combinada con los informes contables de la institución. Además de los costos de internación, se incluyeron los relacionados con los traslados, los de los procedimientos cardiovasculares invasivos y los gastos sanitarios de los 12 meses posteriores al evento agudo. El costo por paciente fue de USD 12.037. Considerando un descenso de 500 infartos por año, el ahorro anual estimado es de USD 6.000.000 en costos asistenciales de los infartos evitados; a lo que debería agregarse otros ahorros de costos por pérdida laboral, discapacidad posterior y años de vida prematura perdidos por fallecimiento del paciente. La exitosa política de control del tabaco ha sido la principal medida de salud pública en los últimos 30 años en nuestro país. Esta investigación busca contribuir al camino trazado por la Organización Mundial de la Salud (OMS).

Tobacco is the leading modifiable cause of cardiovascular disease, cancer, and respiratory diseases and is thus a serious global public health problem. In 2006, Uruguay implemented the World Health Organization Framework Convention on Tobacco Control (WHO-FCTC) and achieved a decrease in the smoking rate and improvements in cardiovascular and respiratory health. We analyzed the clinical and economic impacts of tobacco control measures on the healthcare costs for acute myocardial infarction, which was reduced by 17%. The costs avoided for other diseases were not included. The study examined the trend in a healthcare institution and projected the result to the country's population. The cost analysis used the diagnosis-related groups (DRG) methodology, combined with the institution's accounting reports. Besides the hospitalization costs, the analysis included patient transportation, invasive cardiovascular procedures, and healthcare costs for the 12 months following the acute myocardial infarction. The cost per patient was USD 12,037. Considering a decrease of 500 acute myocardial infarctions per year, the estimated annual savings are USD 6 million in medical care costs for the averted acute myocardial infarctions, besides savings from averted work absenteeism, subsequent disability, and disability adjusted life years. This successful tobacco control policy has been the leading public health intervention in the last 30 years in Uruguay. The study aims to contribute to the guidelines determined by the World Health Organization (WHO).

O tabaco é a principal causa modificável de doença cardiovascular, câncer e doenças respiratórias, o que faz dele um sério problema de saúde pública universal. Em 2006, Uruguai implementou a Convenção-Quadro para o Controle do Tabaco da Organização Mundial da Saúde (CQCT-OMS), registrando desde então uma queda na taxa de fumantes, além de melhoras na saúde cardiovascular e respiratória. Foi avaliado o impacto económico e clínico das medidas de controle do tabaco sobre os custos da atenção ao infarto agudo do miocárdio, que diminuíram 17%. Não foram computados os custos evitados de outras patologias. A pesquisa investigou os registros em uma unidade de saúde e operou uma projeção para toda a população do país. A análise de custos foi desenvolvida usando a metodologia do sistema de Grupos Relacionados pelo Diagnóstico (GRD), combinada com os relatórios contábeis da instituição. Além dos custos de internação, foram incluídos aqueles relativos aos traslados, aos procedimentos cardiovasculares invasivos e às despesas em saúde dos 12 meses posteriores ao evento agudo. O custo por paciente foi de USD 12.037. Considerando uma diminuição de 500 infartos por ano, a economia anual estimada representa USD 6.000.000 na atenção aos infartos evitados; devem ser acrescentadas outras economias de custos de licença médica, invalidez posterior e anos de vida prematura perdidos por óbito do paciente. A bem-sucedida política de controle de tabaco foi a principal medida de saúde pública nos últimos 30 anos, no nosso país. Esta pesquisa pretende contribuir com o caminho trilhado pela Organização Mundial da Saúde (OMS).

The Cardiovascular Risk of White-Coat Hypertension.

BACKGROUND: The role of white-coat hypertension (WCH) and the white-coat-effect (WCE) in development of cardiovascular disease (CVD) risk remains poorly understood. OBJECTIVES: Using data from the population-based, 11-cohort IDACO (International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes), this study compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with WCH and 653 normotensive control subjects. METHODS: European Society Hypertension guidelines were used as a 5-stage risk score. Low risk was defined as 0 to 2 risk factors, and high risk was defined as ≥3 to 5 risk factors, diabetes, and/or history of prior CVD events. Age- and cohort-matching was done between 653 untreated subjects with WCH and 653 normotensive control subjects. RESULTS: In a stepwise linear regression model, systolic WCE increased by 3.8 mm Hg (95% confidence interval [CI]: 3.1 to 4.6 mm Hg) per 10-year increase in age, and was similar in low- and high-risk subjects with or without prior CVD events. Over a median 10.6-year follow-up, incidence of new CVD events was higher in 159 high-risk subjects with WCH compared with 159 cohort- and age-matched high-risk normotensive subjects (adjusted hazard ratio [HR]: 2.06; 95% CI: 1.10 to 3.84; p = 0.023). The HR was not significant for 494 participants with low-risk WCH and age-matched low-risk normotensive subjects. Subgroup analysis by age showed that an association between WCH and incident CVD events is limited to older (age ≥60 years) high-risk WCH subjects; the adjusted HR was 2.19 (95% CI: 1.09 to 4.37; p = 0.027) in the older high-risk group and 0.88 (95% CI: 0.51 to 1.53; p = 0.66) in the older low-risk group (p for interaction = 0.044). CONCLUSIONS: WCE size is related to aging, not to CVD risk. CVD risk in most persons with WCH is comparable to age- and risk-adjusted normotensive control subjects.

Effect of Uruguay's National 100% Smokefree Law on Emergency Visits for Bronchospasm.

INTRODUCTION: Implementation of smokefree laws is followed by drops in hospital admissions for cardiovascular diseases and asthma. The impact of smokefree laws on use of non-hospital medical services has not been assessed. The purpose of this study is to evaluate the impact of Uruguay's national 100% smokefree legislation on non-hospital emergency care visits, hospitalizations for bronchospasm, and bronchodilator use. METHODS: The monthly number of non-hospital emergency care visits and hospitalizations for bronchospasm, as well as monthly puffs of bronchodilators (total and per person), from 3 years prior to the adoption of the 100% smokefree policy on March 1, 2006, through 5 years after the policy were assessed using interrupted time series negative binomial regression. Data analysis was conducted in 2014. RESULTS: The incidence of non-hospital emergency visits for bronchospasm decreased by 15% (incidence rate ratio [IRR]=0.85, 95% CI=0.76, 0.94) following implementation of the law. Hospitalizations for bronchospasm did not change significantly (IRR=0.89, 95% CI=0.66, 1.21). Total monthly puffs of salbutamol and ipratropium administered in the non-hospital emergency setting decreased by 224 (95% CI=-372, -76) and 179 (95% CI=-340, -18.6), respectively, from means of 1,222 and 1,007 before the law. CONCLUSIONS: Uruguay's 100% smokefree law was followed by fewer emergency visits for bronchospasm and less need for treatment, supporting adoption of such policies in low- and middle-income countries to reduce the disease burden and healthcare costs associated with smoking.

Thresholds for conventional and home blood pressure by sex and age in 5018 participants from 5 populations.

Whether blood pressure thresholds for hypertension should differ according to sex or age remains debated. We did a subject-level meta-analysis of 5018 people untreated for hypertension and randomly recruited from 5 populations (women, 56.7%; ≥60 years, 42.3%). We used multivariable-adjusted Cox regression and a bootstrap procedure to determine home blood pressure (HBP) levels yielding 10-year cardiovascular risks similar to those associated with established systolic/diastolic thresholds (140-160/80-100 mm Hg) for the conventional blood pressure (CBP). Conversely, we estimated CBP thresholds providing 10-year cardiovascular risks similar to those associated established HBP levels (125-135/80-85 mm Hg). All analyses were stratified for sex and age (<60 versus ≥60 years). During 8.3 years (median), 414 participants experienced a cardiovascular event. The sex differences between HBP thresholds derived from CBP and between CBP thresholds derived from HBP were all nonsignificant (P≥0.24), ranging from -4.6 to 3.6 mm Hg systolic and from -4.3 to 2.1 mm Hg diastolic. The age differences between HBP thresholds derived from CBP and between CBP thresholds derived from HBP ranged from -6.7 to 8.4 mm Hg systolic and from -1.9 to 1.7 mm Hg diastolic and were nonsignificant (P≥0.08), except for HBP thresholds derived from CBP levels of 140 mm Hg systolic and 80 mm Hg diastolic (P≤0.04). Sensitivity analyses based on cardiac or cerebrovascular complications were confirmatory. In conclusion, our findings based on outcome-driven criteria support contemporary guidelines that propose single blood pressure thresholds that can be indiscriminately applied in both sexes and across the age range.

Reference frame for home pulse pressure based on cardiovascular risk in 6470 subjects from 5 populations.

The absence of an outcome-driven reference frame for self-measured pulse pressure (PP) limits its clinical applicability. In an attempt to derive an operational threshold for self-measured PP, we analyzed 6470 participants (mean age 59.3 years; 56.9% women; 22.5% on antihypertensive treatment) from 5 general population cohorts included in the International Database on HOme blood pressure in relation to Cardiovascular Outcome. During 8.3 years of follow-up (median), 294 cardiovascular deaths, 393 strokes and 336 cardiac events occurred. In 3285 younger subjects (<60 years), home PP only predicted all-cause and cardiovascular mortality (P⩽0.036), whereas in 3185 older subjects (⩾60 years) PP predicted total and cardiovascular mortality (P⩽0.0067) and all cardiovascular and coronary events (P⩽0.044). However, PP did not substantially refine risk prediction based on classical risk factors including mean blood pressure (generalized R(2) statistic ⩽0.20%). In older subjects, the adjusted hazard ratios expressing the risk in the upper decile of home PP (⩾76 mm Hg) versus the average risk in whole population were 1.41 (95% confidence interval, 1.09-1.81; P=0.0081) for all-cause mortality, 1.62 (1.11-2.35; P=0.012) for cardiovascular mortality and 1.31 (1.00-1.70; P=0.047) for all fatal and nonfatal cardiovascular end points combined. The low number of events precluded an analysis by tenths of the PP distribution in younger participants. In conclusion, a home PP of ⩾76 mm Hg predicted cardiovascular outcomes in the elderly with the exception of stroke, whereas in younger subjects no threshold could be established.