Healthy overweight and obesity in the young: Prevalence and risk of major adverse cardiovascular events.

AIMS: To investigate the prevalence of metabolically healthy overweight/obesity and to study its longitudinal association with major adverse cardiovascular and renal events (MARCE). METHODS AND RESULTS: The study was conducted in 1210 young-to-middle-age subjects grouped according to their BMI and metabolic status. The risk of MARCE was evaluated during 17.4 years of follow-up. Forty-eight-percent of the participants had normal weight, 41.9% had overweight, and 9.3% had obesity. Metabolically healthy status was found in 31.1% of subjects with normal weight and in 20.0% of those with overweight/obesity. During the follow-up, there were 108 MARCE. In multivariate Cox analysis adjusted for confounders and risk factors, no association was found between MARCE and overweight/obesity (p = 0.49). In contrast, metabolic status considered as a two-class variable (0 versus at least one metabolic abnormality) was a significant predictor of MARCE (HR, 2.11; 95%CI, 1.21-3.70, p = 0.009). Exclusion of atrial fibrillation from MARCE (N = 87) provided similar results (HR, 2.11; 95%CI, 1.07-4.16, p = 0.030). Inclusion of average 24 h BP in the regression model attenuated the strength of the associations. Compared to the group with healthy metabolic status, the metabolically unhealthy overweight/obesity participants had an increased risk of MARCE with an adjusted HR of 2.33 (95%CI, 1.05-5.19, p = 0.038). Among the metabolically healthy individuals, the CV risk did not differ according to BMI group (p = 0.53). CONCLUSION: The present data show that the risk of MARCE is not increased in young metabolically healthy overweight/obesity suggesting that the clinical approach to people with high BMI should focus on parameters of metabolic health rather than on BMI.

Hyperuricemia increases the risk of cardiovascular mortality associated with very high HdL-cholesterol level.

BACKGROUND AND AIMS: Whether the association between very high HDL-cholesterol levels and cardiovascular mortality (CVM) is modulated by some facilitating factors is unclear. Aim of the study was to investigate whether the risk of CVM associated with very high HDL-cholesterol is increased in subjects with hyperuricemia. METHODS AND RESULTS: Multivariable Cox analyses were made in 18,072 participants from the multicentre URRAH study stratified by sex and HDL-cholesterol category. During a median follow-up of 11.4 years there were 1307 cases of CVM. In multivariable Cox models a J-shaped association was found in the whole population, with the highest risk being present in the high HDL-cholesterol group [>80 mg/dL, adjusted hazard ratio (HR), 1.28; 95%CI, 1.02-1.61; p = 0.031)]. However, a sex-specific analysis revealed that this association was present only in women (HR, 1.34; 95%CI, 1.02-1.77; p = 0.034) but not in men. The risk of CVM related to high HDL-cholesterol was much greater in the women with high uric acid (>0.30 mmol/L, HR 1.61; 95%CI, 1.08-2.39) than in those with low uric acid (HR, 1.17; 95%CI, 0.80-1.72, p for interaction = 0.016). In women older than 70 years with hyperuricemia the risk related to high HDL-cholesterol was 1.83 (95%CI, 1.19-2.80, p < 0.005). Inclusion of BMI in the models weakened the strength of the associations. CONCLUSION: Our data indicate that very high HDL-cholesterol levels in women are associated with CVM in a J-shaped fashion. The risk of CVM is increased by concomitant hyperuricemia suggesting that a proinflammatory/oxidative state can enhance the detrimental cardiovascular effects associated with high HDL-cholesterol.

Exaggerated blood pressure response to standing in young-to-middle-age subjects: prevalence and factors involved.

PURPOSE: To investigate the prevalence of orthostatic hypertension and the association of the blood pressure (BP) level, supine BP decline, and white-coat effect with the orthostatic pressor response. METHODS: We studied 1275 young-to-middle-age individuals with stage-1 hypertension. Orthostatic response was assessed three times over a 3 month period. The white-coat effect was assessed at baseline and after 3 months, and was calculated as the difference between office and average 24 h BP. In 660 participants, urinary epinephrine and norepinephrine were also measured. RESULTS: An orthostatic systolic BP increase ≥ 20 mmHg was observed in 0.6-1.2% of the subjects during the three visits. Using the 20 mmHg cut-off, the prevalence of orthostatic hypertension was 0.6%. An orthostatic BP increase of ≥ 5 mmHg was found in 14.4% of participants. At baseline, the orthostatic response to standing showed an independent negative association with the supine BP level (p < 0.001), the supine BP change from the first to third measurement (p < 0.001), and the white-coat effect (p < 0.001). Similar results were obtained in the 1080 participants assessed at the third visit. Urinary epinephrine showed higher values in the top BP response decile (systolic BP increase ≥ 6 mmHg, p = 0.002 versus rest of the group). CONCLUSION: An orthostatic systolic BP reaction ≥ 20 mmHg is rare in young adults. However, even lower BP increases may be clinically relevant. The BP level, the supine BP decline over repeated measurement, and the white-coat effect can influence the estimate of the BP response to standing and should be considered in clinical and pathogenetic studies.

Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project.

BACKGROUND AND AIM: The URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes. METHODS AND RESULTS: The URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up. A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ≥5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04-1.47) and CV mortality (HR:1.31, 95%CI:1.03-1.66), than those with SUA <5.6 mg/dl. Increased all-cause mortality risk was shown in participants with SUA ≥4.7 mg/dl vs SUA below 4.7 mg/dl, but not statistically significant after adjustment for all confounders. CONCLUSIONS: SUA thresholds previously proposed by the URRAH study group are predictive of total and CV mortality also in people with diabetes. The threshold of 5.6 mg/dl can predict both total and CV mortality, and so is candidate to be a clinical cut-off for the definition of hyperuricemia in patients with diabetes.

Effect of the shape of the cuff on blood pressure measurement in people with large arms.

Purpose: Previous data suggest that tronco-conical cuffs should be used for accurate blood pressure (BP) measurement in the obese. However, not only arm size but also its shape may affect the accuracy of BP measurement when a cylindrical cuff is used.Methods: In 197 subjects with arm circumference >32 cm, and 157 subjects with arm circumference ≤ 32 cm, the upper-arm was considered as formed from two truncated cones and the frustum slant angles of the proximal (upper angle) and distal (middle angle) truncated cones were measured. Five cylindrical and five tronco-conical cuffs of appropriate size in relation to arm circumference were used.Results: In the group with large arm, the upper slant angle was greater than the middle angle (86.5 ± 1.7° versus 84.7 ± 2.3°), whereas in the group with normal arm the two angles were similar. In the former group, the cylindrical cuff overestimated BP by 2.5 ± 5.4/1.7 ± 4.7 mmHg, whereas in the latter negligible between-cuff BP discrepancies were found. In the whole sample, BP discrepancies between the cylindrical and the tronco-conical cuffs correlated with both arm size and shape, considered as the difference between the upper and middle slant angles (all p < 0.0001). Among the participants with large arm, the between-cuff BP discrepancies increased progressively with increasing upper-middle angle difference (3.75 ± 0.38/2.78 ± 0.32 mmHg for the top tertile, p < 0.001/<0.001).Conclusions: These data indicate that in people with large upper arms, the tronco-conical shape of the arm is more pronounced on the lower than the upper half, a feature that amplifies the BP measurement error when cylindrical cuffs are used.

[Lancet Commission on Hypertension Group position statement on the global improvement of accuracy standards for devices that measure blood pressurePosicionamento do Grupo da Lancet Commission on Hypertension sobre a melhoria global dos padrões de acurácia para aparelhos que medem a pressão arterial]. / 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.

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.

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.

Local carotid arterial stiffness is an independent determinant of left ventricular remodeling in never-treated hypertensive patients.

PURPOSE: The aim was to investigate the association between blood pressure (BP), carotid stiffness, carotid-femoral pulse wave velocity (cfPWV) and left ventricular (LV) remodeling in never-treated hypertensive patients. MATERIAL AND METHODS: 178 never-treated hypertensive underwent transthoracic echocardiography, 24-hour ambulatory BP monitoring (ABPM), local carotid stiffness and regional cfPWV assessed using a high-definition echo-tracking ultrasound system and a tonometric transducer, respectively. LV parameters and arterial stiffness were also considered in dippers and non-dippers. RESULTS: Mean night-time BP best correlated with carotid and LV parameters. Carotid stiffness parameters (ß-index, pressure-strain elastic modulus, one-point PWV) correlated with LV mass, relative wall thickness, and E/A ratio while cfPWV correlated only with E/A ratio. In multiple regression analysis, age and mean night-time ABPM had a stroger relation with carotid stiffness than cfPWV. In a second multiple regression analysis, day and night ABPM and carotid stiffness were independently related with LV remodeling and left atrial volume. In non-dippers, local carotid stiffness parameters were significantly higher than in dippers, whereas cfPWV was not significantly different. CONCLUSIONS: Carotid stiffness parameters are independently associated with LV remodeling and have an additive effect to BP and over cfPWV moreover local arterial stiffness is higher in non-dippers.

Recommendations for participation in competitive sports of athletes with arterial hypertension: a position statement from the sports cardiology section of the European Association of Preventive Cardiology (EAPC).

Current guidelines of the European Society of Cardiology advocate regular physical activity as a Class IA recommendation for the prevention and treatment of cardiovascular disease. Despite its undisputed multitude of beneficial effects, competitive athletes with arterial hypertension may be exposed to an increased risk of cardiovascular events. This document is an update of the 2005 recommendations and will give guidance to physicians who have to decide on the risk of an athlete during sport participation.

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.

Arterial Distensibility, Physical Activity, and the Metabolic Syndrome.

PURPOSE OF REVIEW: Metabolic syndrome (MetS), a cluster of risk factors including central obesity, metabolic abnormalities, and arterial hypertension, is a well-known determinant of arterial wall remodeling and stiffening. The mechanisms whereby MetS promotes arterial stiffening include increased sympathetic activity with the associated fast heart rate, enhanced activity of the renin-angiotensin-aldosterone system, increased production of inflammatory cytokines and reactive oxygen species, and reduction of nitric oxide availability. These adverse effects can explain why aerobic physical activity can retard the age-related decline in arterial elasticity in subjects with MetS. RECENT FINDINGS: A large number of studies have shown that in patients with MetS, exercise can reduce body weight and blood pressure and improve the metabolic profile. In addition, regular exercise training can counterbalance the detrimental effects of MetS by reducing sympathetic activity and improving endothelial function with a beneficial effect on arterial elasticity. Indeed, the majority of published data have shown a favorable effect of aerobic exercise on pulse wave velocity, augmentation index, central blood pressure, and small artery compliance. Special attention should be paid by clinicians to people with MetS in whom the adverse effect of metabolic disturbances on arterial structure and function can be offset by a program of physical training.

Low night-time heart rate is longitudinally associated with lower augmentation index and central systolic blood pressure in hypertension.

PURPOSE: Several studies have shown that the augmentation index (AIx) is negatively correlated with heart rate (HR). This led some authors to claim that the use of HR-lowering drugs may be detrimental in hypertension. The aim of this study was to assess the longitudinal and cross-sectional relationships of HR with AIx and central blood pressure (BP) in 346 subjects from the HARVEST (mean age 30.7 ± 8.5 years). METHODS: At baseline, HR was measured with 24-h ambulatory recording. Central hemodynamics were evaluated with Specaway DAT system after a median of 8.0 years from baseline. In multivariate linear regression analyses, AIx and central systolic BP were used as dependent variables and night-time HR or office HR as predictors adjusting for several risk factors and confounders. RESULTS: In fully adjusted models, baseline night-time HR was a significant positive predictor of AIx (p < 0.001) and central BP (p = 0.014) measured 8 years later. Adjusted office HR measured at the time of arterial distensibility assessment was inversely correlated with AIx (p = 0.001) a relationship which was attenuated after physical activity (p = 0.004) and left ventricular ejection time (p = 0.015) were taken into account. In addition, office HR was inversely correlated with central BP (p = 0.039) a relationship which was no longer significant after physical activity and ejection time were accounted for. CONCLUSIONS: These data show that HR measured during sleep is longitudinally associated with AIx and central BP. Thus, low HR in the long term may have beneficial effects on central hemodynamics and the wall properties of the large arteries in hypertension.

Aortic Diameters and Mild Functional Aortic Regurgitation in Hypertensive and Normotensive People: Do They Carry the Same Meaning?

OBJECTIVES: The association between the aortic root diameter and aortic regurgitation in hypertensive and normotensive people is still disputed, and the underlying mechanisms remain to be clearly elucidated. We aimed to investigate the relationship between the aortic root diameter and trivial to mild functional aortic regurgitation in never-treated hypertensive patients with a new diagnosis compared with healthy normotensive participants. METHODS: A total of 182 hypertensives and 232 age-matched normotensives were included in the study. Anthropometric and office blood pressure (BP) measurements, echocardiography, and a carotid stiffness assessment were performed in all of the participants. Aortic measures for the annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta were taken in late diastole according to the leading-edge method. RESULTS: The mean age of all participants was 52 years. Hypertensive patients had a significantly higher body surface area, mean arterial pressure, and pulse pressure (P < .0001) than normotensive participants. Annulus and sinotubular junction diameters adjusted for confounders and indexed to the body surface area were significantly higher in normotensives than in hypertensives. The prevalence of functional aortic regurgitation was higher in hypertensives (34.8% versus 15.4%; P < .0001). Among the hypertensives, no difference in aortic diameters was found between patients with or without functional aortic regurgitation, whereas normotensives with functional aortic regurgitation had larger aortic root diameters. Aging and BP among the hypertensives were the main determinants of functional aortic regurgitation. CONCLUSIONS: Hypertensive patients had a smaller indexed aortic root diameter than normotensive participants but had a higher prevalence of trivial to mild functional aortic regurgitation. The aging process is the main determinant of functional aortic regurgitation in both groups, but high BP also plays an important role in hypertensives.

Intima-media thickness remodelling in hypertensive subjects with long-term well-controlled blood pressure levels.

Aim of this study was to evaluate in a long follow-up the carotid artery remodelling in a cohort of young hypertensive subjects having good blood pressure (BP) control. We studied 20 grade I hypertensives (HT) by assessing the B-mode ultrasound of mean carotid intima-media thickness (mean-IMT) and maximum IMT (M-MAX) in each carotid artery segment (common, bulb, internal), bilaterally. We compared their ultrasound measurements with those recorded 5 and 10 years earlier. While the first 5-year follow-up was observational, in the second 5-year follow-up, lifestyle modifications and/or pharmacological therapy were started to obtain well-controlled BP levels. Office BP was measured at the time of the ultrasound studies and every 6 months during the follow-up. BP levels were: 10 years 144/91 mmHg, 5 years 143/90 mmHg and 129 ± 79 mmHg at the time of the study. In the first 5-year observational follow-up, both mean-IMT and M-MAX increased (Δ 0.116 and Δ 0.165 mm, respectively, p < 0.0005). In the 5-year intervention follow-up, characterized by well-controlled BP, mean-IMT slightly but significantly increased (Δ 0.084 mm, p = 0.004), whereas M-MAX remained stable (Δ 0.026 mm). In our HT, well-controlled BP levels were able to prevent pro-atherogenic remodelling (expressed by M-MAX). Conversely, good BP control slightly decreased but did not stop the progression in mean-IMT, which is likely to reflect some hypertrophy of the arterial media layer.

Left Ventricular Function Assessed by One-Point Carotid Wave Intensity in Newly Diagnosed Untreated Hypertensive Patients.

OBJECTIVES: To investigate whether newly diagnosed untreated hypertensive patients show higher left ventricular (LV) contractility, as assessed by traditional echocardiographic indices and carotid wave intensity (WI) parameters, including amplitude of the peak during early (W1 ) and late systole (W2 ). METHODS: A total of 145 untreated hypertensive patients were compared with 145 age- and sex-matched normotensive subjects. They underwent comprehensive echocardiography and WI analysis. WI analysis was performed at the level of the common carotid artery. The diameter changes were the difference between the displacement of the anterior and posterior walls, with the cursors set to track the media-adventitia boundaries 2 cm proximal to the carotid bulb and calibrated by systolic and diastolic BP. Peak acceleration was derived from blood flow velocity measured by Doppler sonography with the range-gate positioned at the center of the vessel diameter. WI was based on the calculation of (dP/dt)×(dU/dt), where dP/dt and dU/dt were the derivatives of BP (P) and velocity (U) with respect to time. One-point pulse wave velocity (PWVß) and the interval between the R wave on ECG and the first peak of WI (R-W1 ), using a high definition echo-tracking system implemented in the ultrasound machine (Aloka), were also derived. RESULTS: After adjustment for body weight, heart rate, and physical activity, the two groups had similar general characteristics and diastolic function. However, hypertensives showed significantly higher LV mass, LV ejection fraction (LVEF), circumferential and LV end-systolic stress, and one-point PWV as well as W1 (13.646 ± 7.368 vs 9.308 ± 4.675 mmHg m/s3 , P =.001) and W2 (4.289 ± 2.017 vs 2.995 ± 1.868 mmHg m/s3 , P =.001). Hypertensives were divided into tertiles according to LVEF: W1 (11.934 ± 5.836 vs 11.576 ± 5.857 vs 17.227 ± 8.889 mmHg m/s3 , P <.0001) was higher in the highest LVEF tertile along with relative wall thickness, midwall fractional shortening, endocardial fractional shortening, and R-W1 . CONCLUSIONS: Newly diagnosed hypertensives show increased LVM and LV contractility, including carotid WI parameters and R-W1 values, as compared with normotensive subjects, but no differences in LV diastolic function.

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.

Association of coffee consumption and CYP1A2 polymorphism with risk of impaired fasting glucose in hypertensive patients.

Whether and how coffee use influences glucose metabolism is still a matter for debate. We investigated whether baseline coffee consumption is longitudinally associated with risk of impaired fasting glucose in a cohort of 18-to-45 year old subjects screened for stage 1 hypertension and whether CYP1A2 polymorphism modulates this association. A total of 1,180 nondiabetic patients attending 17 hospital centers were included. Seventy-four percent of our subjects drank coffee. Among the coffee drinkers, 87% drank 1-3 cups/day (moderate drinkers), and 13% drank over 3 cups/day (heavy drinkers). Genotyping of CYP1A2 SNP was performed by real time PCR in 639 subjects. At the end of a median follow-up of 6.1 years, impaired fasting glucose was found in 24.0% of the subjects. In a multivariable Cox regression coffee use was a predictor of impaired fasting glucose at study end, with a hazard ratio (HR) of 1.3 (95% CI 0.97-1.8) in moderate coffee drinkers and of 2.3 (1.5-3.5) in heavy drinkers compared to abstainers. Among the subjects stratified by CYP1A2 genotype, heavy coffee drinkers carriers of the slow *1F allele (59%) had a higher adjusted risk of impaired fasting glucose (HR 2.8, 95% CI 1.3-5.9) compared to abstainers whereas this association was of borderline statistical significance among the homozygous for the A allele (HR 1.7, 95% CI 0.8-3.8). These data show that coffee consumption increases the risk of impaired fasting glucose in hypertension particularly among carriers of the slow CYP1A2 *1F allele.

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.