Instability of Healthy Overweight and Obesity Phenotypes over the Long Term in Young Participants in the HARVEST Study: Influence of Sex.

BACKGROUND: Whether healthy metabolic status is stable or only temporary is still controversial. The aim of the present study was to determine the frequency of the transition from metabolically healthy to metabolically unhealthy status, or vice versa, over the long term. METHODS: We examined 970 individuals of 18 to 45 years of age. The participants' mean age was 33.1 ± 8.6 years and mean BP was 145.5 ± 10.6/93.5 ± 5.7 mmHg. Participants were classified into four groups according to whether they had normal weight or overweight/obesity (OwOb) and were metabolically healthy or unhealthy. After 7.5 years, 24.3% of men and 41.9% of women in the metabolically healthy normal-weight group remained metabolically healthy (p < 0.0001). Among the metabolically healthy OwOb participants, 31.9% remained metabolically healthy, with a similar frequency in men and women. However, more OwOb women (19.1%) than men (5.7%) achieved normal weight (p < 0.0001). Among the metabolically unhealthy OwOb subjects, 81.8% of men and 69.3% of women remained metabolically unhealthy, 7.4% of men and 12.0% of women transitioned to OwOb healthy status, and 10.7% of men and 18.7% of women achieved normal weight (men versus women, p < 0.0001). Predictors of transition to unhealthy status were high BP, high BMI, and smoking. Male sex was a borderline predictor of progression to unhealthy status in OwOb participants (p = 0.073). CONCLUSION: These data show that metabolically healthy status is a highly unstable condition in both normal-weight and OwOb individuals. The impairment of metabolic status was more frequent in men than in women. Lifestyle counseling produced beneficial effects in almost one-third of metabolically unhealthy OwOb women and in less than one-fifth of men.

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

BACKGROUND: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort. METHODS AND RESULTS: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P<0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P=0.004) and 1.150 (95% CI, 1.021-1.295, P=0.02), respectively. CONCLUSIONS: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

Both Moderate and Heavy Alcohol Use Amplify the Adverse Cardiovascular Effects of Smoking in Young Patients with Hypertension.

AIM: To evaluate the association of alcohol and smoking combined with cardiovascular and renal events and investigate whether moderate and heavy alcohol consumption have a different impact on this association. METHODS: The study was conducted in 1208 young-to-middle-age stage 1 hypertensive patients. Subjects were classified into three categories of cigarette smoking and alcohol use, and the risk of adverse outcomes was assessed over a 17.4-year follow-up. RESULTS: In multivariable Cox models, smoking showed a different prognostic impact on alcohol drinkers and abstainers. In the former, an increase in the risk of cardiovascular and renal events was observed compared to nonsmokers (hazard ratio, 2.6, 95% CI, 1.5-4.3, p < 0.001), whereas in the latter, the risk did not achieve the level of statistical significance (p = 0.27) with a significant interaction between smoking and alcohol use (p < 0.001). Among the heavy smokers who also drank alcoholic beverages, the hazard ratio from the fully adjusted model was 4.3 (95% CI, 2.3-8.0, p < 0.0001). In the subjects with moderate alcohol consumption, the risk of smoking and alcohol combined was similar to that found in the whole population (hazard ratio, 2.7; 95% CI, 1.5-3.9, p < 0.001). Among the subjects with heavy alcohol consumption, the hazard ratio was 3.4 (95% CI, 1.3-8.6, p = 0.011). CONCLUSION: These findings indicate that the detrimental cardiovascular effects of smoking can be worsened by concomitant alcohol use. This synergistic effect occurs not only for heavy alcohol consumption but also for moderate use. Smokers should be aware of the increased risk associated with concomitant alcohol consumption.

Microcirculation and Physical Exercise In Hypertension.

Hypertension is associated with important alterations in the morphology of small arteries and arterioles. Vascular-specific manifestations are changes in the structure and function of vascular smooth muscle cells, extracellular matrix, perivascular tissues, and endothelial cells. Arteriole and capillary remodeling and capillary rarefaction have been observed in hypertensive animals and human beings which contribute to increased vascular resistance. An impairment of different angiogenetic factors, such as VEGF (vascular endothelial growth factor), VEGFR-2 (vascular endothelial growth factor receptor-2), TIMP-1 (tissue inhibitor matrix metalloproteinases-1), and TSP-1 (thrombospondin-1), seems to be responsible for the reduction of the microvascular network. Exercise training has been shown to improve vascular structure and function in hypertension not only in the large arteries but also in the peripheral circulation. Exercise training may regress microvascular remodeling and normalize capillary density, leading to capillary growth possibly by increasing proangiogenic stimuli such as VEGF. Exercise enhances endothelium-dependent vascular relaxation through nitric oxide release increase and oxidative stress reduction. Other mechanisms include improved balance between prostacyclin and thromboxane levels, lower circulating levels of endothelin-1, attenuation of infiltration of immune cells into perivascular adipose tissue, and increase of local adiponectin secretion. In addition, exercise training favorably modulates the expression of several microRNAs leading to a positive modification in muscle fiber composition. Identifying the bioactive molecules and biological mechanisms that mediate exercise benefits through pathways that differ from those used by antihypertensive drugs may help to improve our knowledge of hypertension pathophysiology and facilitate the development of new therapeutic strategies.

Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project.

BACKGROUND: Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database. METHODS: Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m2 and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol. RESULTS: Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m22with a prevalence of eGFR < 60 and micro- or macroalbuminuria of 16, 15 and 4%, respectively. Serum uric acid showed a trend towards higher values along with decreasing renal function. Both the prevalence of gout and the frequency of allopurinol use increased significantly with the reduction of eGFR and the increase in albuminuria. Hyperuricemia was independently related to male gender, eGFR strata, and signs of insulin resistance such as body mass index (BMI) and triglycerides. CONCLUSIONS: The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR < 60 ml/min the occurrence of hyperuricemia is about 10 times higher than in those with eGFR > 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria.

Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study.

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.

Augmentation index predicts mortality in patients with aortic stenosis: an echo-tracking study.

Aortic valve stenosis (AS) shares similarities with the atherosclerotic process but little is known about the effect of the mechanical properties of large arteries on outcome in patients with AS. The aims of this study were (1) to determine the relationship between indexes of carotid stiffness/compliance and the severity of AS and (2) to identify whether local arterial stiffness is independently associated with mortality. 133 patients with moderate to severe isolated AS and preserved LV ejection fraction (LVEF) were included. All underwent transthoracic echocardiography and local carotid stiffness evaluation by means of high-definition echo-tracking ultrasound with the calculation of stiffness/compliance parameters included augmentation index (AIx). None of the carotid stiffness parameters were significantly associated with AS severity parameters. During a mean follow-up of 51.6 ± 39.4 months, 70 patients received aortic valve replacement, 45 died and 18 were alive with no surgery. Who died were older (79.2 ± 6.9 vs. 73 ± 8.8 years, p < 0.0001), had higher carotid AIx (21.3 ± 14 vs. 16 ± 12%, p = 0.028). In multivariate Cox regression analysis AIx was independently associated with mortality (HR 1.048, 95% CI 1.01-1.07, p = 0.001), also after inclusion of age and creatinine. There was a significant association between the level of AIx and mortality in those patients who did not have surgery (p = 0.016). In severe AS and a normal LVEF, carotid AIx measured by echo-tracking system was independently associated with death. No relationship between AS severity and local carotid stiffness was found. These data emphasize the importance of arterial stiffness has a hallmark of long-term atherosclerotic burden and impaired prognosis.

Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the URic acid Right for heArt Health study.

OBJECTIVE: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension. METHODS: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ±â€Š65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders. RESULTS: A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole database: SUA more than 5.34 mg/dl (confidence interval 4.37-5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78-5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284-2.109, P < 0.0001) for all heart failure and 1.645 (1.284-2.109, P < 0.0001) for fatal heart failure, respectively. CONCLUSION: The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).

Short-Term but not Long-Term Blood Pressure Variability Is a Predictor of Adverse Cardiovascular Outcomes in Young Untreated Hypertensives.

BACKGROUND: Whether blood pressure variability (BPV) measured with ambulatory monitoring (short-term BPV) or computed from office visits (long-term BPV) are related to each other and carry similar prognostic information is not well known. We investigated the independent determinants of short-term and long-term BPVs and their predictive capacity for the development of major adverse cardiovascular and renal events (MACEs) in a cohort of young hypertensive participants. METHODS: Long-term BPV was calculated as visit-to-visit SD and average real variability from office blood pressure (BP) measured during 7 visits, within 1 year. Short-term BPV was calculated as weighted 24-hour SD and coefficient of variation. Hazard ratios (HRs) for risk of MACE were computed from multivariable Cox regressions. RESULTS: 1,167 participants were examined; mean age was 33.1 ± 8.5 years. Variables independently associated with 24-hour systolic SD were 24-hour systolic BP, low physical activity, smoking, baseline office pulse pressure, systolic BP dipping, and diastolic white coat effect, while those associated with long-term BPV were mean systolic BP, age, female gender, and baseline office heart rate. During a median follow-up of 17.4 years 75 MACEs occurred. In Cox analysis only short-term BPV resulted a significant predictor of MACE (HR, 1.31 (1.07-1.59); P = 0.0086), while no index of long-term BPV was independently associated with outcome. CONCLUSIONS: In young hypertensive subjects only short-term BPV resulted a significant predictor of MACE on top of traditional ambulatory BP monitoring parameters. Whether reduction of short-term BPV with therapy may reduce the cardiovascular risk independently from the effects on 24-hour BP is a matter for future research.

Serum uric acid and fatal myocardial infarction: detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study.

OBJECTIVE: The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men. METHODS: The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ±â€Š66.9 months. RESULTS: A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P < 0.01), but not in men. CONCLUSION: The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.

Declaración de posición del Grupo de la Comisión Lancet de Hipertensión con respecto a la mejora mundial de las normas de exactitud para los dispositivos de medición de la presión arterial / Lancet Commission on Hypertension Group position statement on the global improvement of accuracy standards for devices that measure blood pressure / Posicionamento do Grupo da Lancet Commission on Hypertension sobre a melhoria global dos padrões de acurácia para aparelhos que medem a pressão arterial

Objetivos. El boletín de notas de México correspondiente al 2018 evalúa las oportunidades a disposición de la población infantil y joven mexicana para que puedan desarrollar niveles adecuados de actividad física y sueño, y disminuyan el sedentarismo.Métodos. El boletín es un sistema de vigilancia que recopila los datos obtenidos en las encuestas nacionales, censos, documentos gubernamentales, sitios web, literatura gris y estudios publicados con respecto al análisis de 16 indicadores en 4 categorías: comportamientos diarios, estado físico, entornos y fuentes influyentes, y estrategias e inversión. Los datos fueron cotejados con los puntos de referencia establecidos. A cada indicador se le asignó una calificación entre 1 y 10 (< 6 significa reprobado) o fue marcado como "incompleto" si los datos eran nulos o insuficientes. Resultados. Las calificaciones obtenidas para los comportamientos diarios fueron: actividad física en general: 4; participación en actividades deportivas organizadas: 5; juego activo: 3; modalidades de transporte activas: 5; sueño: 7; y sedentarismo: 3. El estado físico obtuvo un 7. Las calificaciones para los entornos y fuentes influyentes fueron: familiares y pares: "incompleto"; escuela: 3; comunidad y entorno: 4. Para las estrategias e inversión: estrategias gubernamentales: 6; entidades no gubernamentales: 2.Conclusiones. Las bajas calificaciones obtenidas en 11 de los 16 indicadores demuestran que las escuelas, las familias, las comunidades y el gobierno tienen que aunar esfuerzos para mejorar las oportunidades que tiene la población infantil y joven en México para desarrollar niveles de actividad física satisfactorios.(AU)

ABSTRACT The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.(AU)

RESUMO A Comissão Lancet sobre Hipertensão Arterial identificou que uma iniciativa central para enfrentar a carga mundial da hipertensão arterial seria a melhoria na qualidade da mensuração da pressão arterial pelo uso aparelhos de pressão arterial validados quanto à acurácia. Atualmente, existem mais de 3 000 aparelhos de pressão arterial disponíveis comercialmente; entretanto, muitos não têm dados publicados sobre testes de acurácia realizados de acordo com padrões científicos estabelecidos. Este problema resulta de regulamentação fraca ou inexistente, o que permite a aprovação para uso comercial de dispositivos sem validação formal. Além disso, surgiram novas tecnologias de mensuração da pressão arterial (por exemplo, sensores sem algemas) sem consenso científico quanto aos padrões de acurácia. No conjunto, essas questões contribuem para a oferta generalizada de dispositivos de pressão arterial clínica e domiciliar com acurácia limitada ou incerta, levando a diagnóstico, gerenciamento e tratamento inadequados da hipertensão em escala global. Os problemas mais significativos relacionados com a acurácia dos dispositivos de pressão arterial podem ser resolvidos por regulamentação que imponha a obrigatoriedade de validação independente dos aparelhos de pressão arterial, de acordo com a norma universalmente aceita pela Organização Internacional de Normalização. Esta é uma recomendação fundamental para a qual existe uma necessidade internacional urgente. Outras recomendações essenciais incluem o desenvolvimento de padrões de validação especificamente para novas tecnologias de mensuração da pressão arterial e listas on-line de aparelhos com acurácia adequada que sejam acessíveis aos consumidores e profissionais de saúde. As recomendações estão alinhadas com as políticas da Organização Mundial da Saúde (OMS) sobre dispositivos médicos e atenção universal à saúde. A adesão às recomendações aumentaria a oferta global de dispositivos de pressão arterial com acurácia adequada e resultaria em melhor diagnóstico e tratamento da hipertensão arterial, diminuindo assim a carga mundial dessa doença.(AU)

Glomerular hyperfiltration is a predictor of adverse cardiovascular outcomes.

The association between glomerular hyperfiltration and cardiovascular events is not well known. To investigate whether glomerular hyperfiltration is independently associated with risk of adverse outcome we analyzed 8794 participants, average age 52 years enrolled in 8 prospective studies. Of these, 89% had hypertension. Using the 5th and 95th percentiles of the age- and sex-specific quintiles of CKD-EPI-calculated estimated glomerular filtration rate (eGFR), we identified three participant groups with low, high and normal eGFR. The ambulatory pulse pressure interval was wider and nighttime blood pressure fall was smaller in both the low and high than in the normal eGFR participants. During a mean follow-up of 6.2 years, there were 722 cardiovascular events. Crude event rates were significantly higher for both high (1.8 per 100-person-year) and low eGFR groups (2.1 per 100 person-year) as compared with group with normal eGFR (1.2 per 100 person-year). In multivariable Cox models including age, sex, average 24-hour blood pressure, smoking, diabetes, and cholesterol, both high eGFR (hazard ratio 1.5 (95% confidence interval 1.2-2.1) and low eGFR (2.0 [1.5-2.6]) participants had a significantly higher risk of cardiovascular events as compared to those with normal eGFR. Addition of body mass index to the multivariable survival model did not change the magnitude of hazard estimates. Thus, glomerular hyperfiltration is a strong and independent predictor of cardiovascular events in a large multiethnic population of predominantly hypertensive individuals. Our findings support a U-shaped relationship between eGFR and adverse outcome.

Caffeine intake and abstract reasoning among 1374 unselected men and women from general population. Role of the -163C>A polymorphism of CYP1A2 gene.

BACKGROUND AND AIMS: The possible effect of caffeine as an enhancer of cognitive performance, particularly that on abstract reasoning, has never been studied in an epidemiological setting, especially in relation to -163C>A polymorphism of CYP1A2 gene, largely controlling caffeine metabolism. Aim of this study was to ascertain whether in general population free chronic caffeine intake modifies abstract reasoning, and if this effect is influenced by the above mentioned genotype, by age, schooling, ethanol intake and smoking habits. METHODS: We studied 1374 unselected men and women aged 51 ± 15 years (range 18-89) from a general population. Daily caffeine intake deriving from coffee, tea, chocolate or cola was calculated from an anamnestic questionnaire and from a 7-day dietary diary. Abstract reasoning was measured in the frame of a neuropsychological assessment as the ability to find a concept linking two words indicating objects or actions and explaining how they were connected. RESULTS: In age-schooling-adjusted linear regression, the higher the caffeine intake, the better the abstraction score. Abstract reasoning depended on caffeine in the -163C>A CC homozygous only (so-called slow metabolizers), where it was higher in the 3rd tertile of caffeine intake. Age and ethanol reduced while smoking and schooling enhanced this association. The interaction term between caffeine and the -163C>A polymorphism was accepted in linear regressions. Caffeine consumption resulted innocuous for the A-carriers (so-called fast metabolizers). CONCLUSIONS: In general population, a positive association between caffeine intake and abstract reasoning exists in the CC homozygous of the -163C>A polymorphism of CYP1A2 gene.

Alcohol Intake More than Doubles the Risk of Early Cardiovascular Events in Young Hypertensive Smokers.

PURPOSE: An interactive effect of tobacco and alcohol use has been described for cancer. The aim of this study was to investigate the joint effect of smoking and alcohol intake on major adverse cardiovascular and renal events (MACE) in young subjects screened for stage 1 hypertension. METHODS: A total of 1204 untreated patients aged from 18 to 45 years (mean 33.1) were included in this prospective cohort study. Subjects were classified into 4 categories of cigarette smoking and 3 classes of alcohol use. Main outcome variable was risk for MACE. RESULTS: During a 12.6-year follow-up, there were 74 fatal and nonfatal MACE. In multivariable Cox models, current smoking and alcohol drinking were associated with risk of MACE. In a multivariable model also including follow-up changes in blood pressure and body weight, hazard ratio (HR) was 1.48 (95% confidence interval [CI], 1.20-1.83) for smoking and was 1.82 (95% CI, 1.05-3.15) for alcohol use. In addition, an interactive effect was found between smoking and alcohol on risk of MACE (P <.001). Among the 142 smokers who also drank alcoholic beverages, the risk of MACE (HR 4.02; 95% CI, 1.98-8.15) was more than doubled compared with the 112 smokers who abstained from drinking (HR 1.64; 95% CI, 0.63-4.27). In the group of heavy smokers who also were alcohol drinkers (n = 51), the risk of MACE was even quadrupled (HR 7.79; 95% CI, 4.22-14.37). CONCLUSION: Alcohol use potentiates the deleterious cardiovascular effects of heavy smoking in stage 1 hypertensive subjects younger than 45 years. These results call for prompt intervention addressed to improve unhealthy behaviors in these subjects.

Hypertension types defined by clinic and ambulatory blood pressure in 14 143 patients referred to hypertension clinics worldwide. Data from the ARTEMIS study.

OBJECTIVE: The Ambulatory blood pressure Registry TEleMonitoring of hypertension and cardiovascular rISk project was designed to set up an international registry including clinic blood pressure (CBP) and ambulatory blood pressure (ABP) measurements in patients attending hypertension clinics in all five continents, aiming to assess different daily life hypertension types. METHODS: Cross-sectional ABP, CBP and demographic data, medical history and cardiovascular risk profile were provided from existing databases by hypertension clinics. Hypertension types were evaluated considering CBP (≥140/90 mmHg) and 24-h ABP (≥130/80 mmHg). RESULTS: Overall, 14 143 patients from 27 countries across all five continents were analyzed (Europe 73%, Africa 3%, America 9%, Asia 14% and Australia 2%). Mean age was 57 ±â€Š14 years, men 51%, treated for hypertension 46%, cardiovascular disease 14%, people with diabetes 14%, dyslipidemia 33% and smokers 19%. The prevalence of hypertension was higher by CBP than by ABP monitoring (72 vs. 60%, P < 0.0001). Sustained hypertension (elevated CBP and ABP) was detected in 49% of patients. White-coat hypertension (WCH, elevated CBP with normal ABP) was more common than masked hypertension (elevated ABP with normal CBP) (23 vs. 10%; P < 0.0001). Sustained hypertension was more common in Europe and America and in elderly, men, obese patients with cardiovascular comorbidities. WCH was less common in Australia, America and Africa, and more common in elderly, obese women. Masked hypertension was more common in Asia and in men with diabetes. Smoking was a determinant for sustained hypertension and masked hypertension. CONCLUSION: Our analysis showed an unbalanced distribution of WCH and masked hypertension patterns among different continents, suggesting an interplay of genetic and environmental factors, and likely also different healthcare administrative and practice patterns.

Effects of smoking on central blood pressure and pressure amplification in hypertension of the young.

The aim of this study was to investigate the effect of cigarette smoking on peripheral and central blood pressure (BP) in a group of young stage I hypertensives. A total of 344 untreated subjects from the HARVEST study were examined (mean age 37±10 years). Patients were divided into three groups based on smoking status: non-smokers, light smokers (⩽5 cigarettes/day) and moderate-to-heavy smokers (>5 cigarettes/day); and into three groups by age: 18-29, 30-39 and ⩾40 years. Central BP measurements and augmentation index (AIx) were calculated from brachial pressure waveform, with applanation tonometry, by means of the Specaway DAT System plus a Millar tonometer. The central waveform was derived from peripheral BP using the same software system of the SphygmoCor System pulse wave analysis. In addition, two indirect measurements of arterial stiffness were calculated: pulse pressure (PP) and systolic BP amplification. Central systolic BP and PP were higher in smokers than in non-smokers (systolic BP: 121.9±13.1 mmHg in non-smokers, 127.2±16.5 mmHg in light smokers, 126.7±15.3 mmHg in those who smoked >5 cigarettes/day, p=0.009; PP: 37.7±9.8 mmHg, 41.5±13.1 mmHg, 41.9±10.5 mmHg, respectively, p=0.005). Lower systolic BP amplification (p<0.001) and PP amplification (p=0.001) were observed in smokers compared to non-smokers. In a two-way ANCOVA analysis, systolic BP amplification markedly declined across the three age groups (p=0.0002) and from non-smokers to smokers (p=0.0001), with a significant interaction between smoking and age group (p=0.05). The AIx was higher in smokers compared to non-smokers (p=0.024). In young hypertensives, smoking has a detrimental effect on central BP, accelerating the age-related decline in BP amplification.

Regular physical activity is associated with improved small artery distensibility in young to middle-age stage 1 hypertensives.

The aim of the present study was to investigate the association of physical activity with small artery elasticity in the early stage of hypertension. We examined 366 young-to-middle-age stage 1 hypertensives (mean blood pressure 145.6±10.3/92.5±5.8 mmHg), divided into two categories of physical activity, sedentary (n=264) and non-sedentary (n=102) subjects. The augmentation index was measured using the Specaway DAT System. Small artery compliance (C2) was measured by applanation tonometry, at the radial artery, with an HDI CR2000 device. After 6 years of follow-up, arterial distensibility assessment was repeated in 151 subjects. Heart rate was lower in active than in sedentary subjects (71.2±8.9 vs 76.6±9.7 bpm, p<0.001). After adjusting for age, sex, heart rate, smoking, and blood pressure, C2 was higher (8.0±2.6 vs 6.4±3.0 ml/mmHg × 100, p=0.008) in non-sedentary than in sedentary patients. The augmentation index was smaller in the former (8.8±20.1 vs 16.8±26.5%, p=0.044) but the difference lost statistical significance after further adjustment for blood pressure. After 6 years, C2 was still higher in the non-sedentary than sedentary subjects. In addition, an improvement in the augmentation index accompanied by a decline in total peripheral resistance was found in the former. These data show that regular physical activity is associated with improved small artery elasticity in the early phase of hypertension. This association persists over time and is independent of blood pressure and heart rate.

Added predictive value of night-time blood pressure variability for cardiovascular events and mortality: the Ambulatory Blood Pressure-International Study.

The association of ambulatory blood pressure (BP) variability with mortality and cardiovascular events is controversial. To investigate whether BP variability predicts cardiovascular events and mortality in hypertension, we analyzed 7112 untreated hypertensive participants (3996 men) aged 52±15 years enrolled in 6 prospective studies. Median follow-up was 5.5 years. SD of night-time BP was positively associated with age, body mass index, smoking, diabetes mellitus, and average night-time BP (all P<0.001). In a multivariable Cox model, night-time BP variability was an independent predictor of all-cause mortality (systolic, P<0.001/diastolic, P<0.0001), cardiovascular mortality (P=0.008/<0.0001), and cardiovascular events (P<0.001/<0.0001). In contrast, daytime BP variability was not an independent predictor of outcomes in any model. In fully adjusted models, a night-time systolic BP SD of ≥12.2 mm Hg was associated with a 41% greater risk of cardiovascular events, a 55% greater risk of cardiovascular death, and a 59% increased risk of all-cause mortality compared with an SD of <12.2 mm Hg. The corresponding values for a diastolic BP SD of ≥7.9 mm Hg were 48%, 132%, and 77%. The addition of night-time BP variability to fully adjusted models had a significant impact on risk reclassification and integrated discrimination for all outcomes (relative integrated discrimination improvement for systolic BP variability: 9% cardiovascular events, 14.5% all-cause death, 8.5% cardiovascular death, and for diastolic BP variability: 10% cardiovascular events, 19.1% all-cause death, 23% cardiovascular death, all P<0.01). Thus, addition of BP variability to models of long-term outcomes improved the ability to stratify appropriately patients with hypertension among risk categories defined by standard clinical and laboratory variables.

Predictive value of night-time heart rate for cardiovascular events in hypertension. The ABP-International study.

BACKGROUND: Data from prospective cohort studies regarding the association between ambulatory heart rate (HR) and cardiovascular events (CVE) are conflicting. METHODS: To investigate whether ambulatory HR predicts CVE in hypertension, we performed 24-hour ambulatory blood pressure and HR monitoring in 7600 hypertensive patients aged 52 ± 16 years from Italy, U.S.A., Japan, and Australia, included in the 'ABP-International' registry. All were untreated at baseline examination. Standardized hazard ratios for ambulatory HRs were computed, stratifying for cohort, and adjusting for age, gender, blood pressure, smoking, diabetes, serum total cholesterol and serum creatinine. RESULTS: During a median follow-up of 5.0 years there were 639 fatal and nonfatal CVE. In a multivariable Cox model, night-time HR predicted fatal combined with nonfatal CVE more closely than 24h HR (p=0.007 and =0.03, respectively). Daytime HR and the night:day HR ratio were not associated with CVE (p=0.07 and =0.18, respectively). The hazard ratio of the fatal combined with nonfatal CVE for a 10-beats/min increment of the night-time HR was 1.13 (95% CI, 1.04-1.22). This relationship remained significant when subjects taking beta-blockers during the follow-up (hazard ratio, 1.15; 95% CI, 1.05-1.25) or subjects who had an event within 5 years after enrollment (hazard ratio, 1.23; 95% CI, 1.05-1.45) were excluded from analysis. CONCLUSIONS: At variance with previous data obtained from general populations, ambulatory HR added to the risk stratification for fatal combined with nonfatal CVE in the hypertensive patients from the ABP-International study. Night-time HR was a better predictor of CVE than daytime HR.