Francesca Saladini

CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension.

Objectives The longitudinal relationship between coffee use and hypertension is still controversial. Cytochrome P450 1A2 (CYP1A2) is the main responsible enzyme for the metabolism of caffeine. The aim of the present study was to investigate the effect of coffee intake on the risk of developing hypertension needing antihypertensive treatment in individuals stratified by CYP1A2 genotype. Design We assessed prospectively 553 young White individuals screened for stage 1 hypertension. Coffee intake was ascertained from regularly administered questionnaires. Incident physician-diagnosed hypertension was the outcome measure. Genotyping of CYP1A2 SNP was performed by real time PCR. Results During a median follow-up of 8.2 years, 323 individuals developed hypertension. For carriers of the slow *1F allele (59%), hazard ratios of hypertension from multivariable Cox analysis were 1.00 in abstainers (reference), 1.72 (95%CI, 1.21–2.44) in moderate coffee drinkers (P = 0.03), and 3.00 (1.53–5.90) in heavy drinkers (P = 0.001). In contrast, hazard ratios for coffee drinkers with the rapid *1A/*1A genotype were 0.80 (0.52–1.23, P = 0.29) for moderate drinkers and 0.36 (0.14–0.89, P = 0.026) for heavy drinkers. In a two-way ANCOVA, a gene × coffee interactive effect was found on follow-up changes in systolic (P = 0.000) and diastolic (P = 0.007) blood pressure. Urinary epinephrine was higher in coffee drinkers than abstainers but only among individuals with slow *1F allele (P = 0.001). Conclusion These data show that the risk of hypertension associated with coffee intake varies according to CYP1A2 genotype. Carriers of slow *1F allele are at increased risk and should thus abstain from coffee, whereas individuals with *1A/*1A genotype can safely drink coffee.

Arterial stiffness, central hemodynamics, and cardiovascular risk in hypertension.

This review summarizes several scientific contributions at the recent Satellite Symposium of the European Society of Hypertension, held in Milan, Italy. Arterial stiffening and its hemodynamic consequences can be easily and reliably measured using a range of noninvasive techniques. However, like blood pressure (BP) measurements, arterial stiffness should be measured carefully under standardized patient conditions. Carotid-femoral pulse wave velocity has been proposed as the gold standard for arterial stiffness measurement and is a well recognized predictor of adverse cardiovascular outcome. Systolic BP and pulse pressure in the ascending aorta may be lower than pressures measured in the upper limb, especially in young individuals. A number of studies suggest closer correlation of end-organ damage with central BP than with peripheral BP, and central BP may provide additional prognostic information regarding cardiovascular risk. Moreover, BP-lowering drugs can have differential effects on central aortic pressures and hemodynamics compared with brachial BP. This may explain the greater beneficial effect provided by newer antihypertensive drugs beyond peripheral BP reduction. Although many methodological problems still hinder the wide clinical application of parameters of arterial stiffness, these will likely contribute to cardiovascular assessment and management in future clinical practice. Each of the abovementioned parameters reflects a different characteristic of the atherosclerotic process, involving functional and/or morphological changes in the vessel wall. Therefore, acquiring simultaneous measurements of different parameters of vascular function and structure could theoretically enhance the power to improve risk stratification. Continuous technological effort is necessary to refine our methods of investigation in order to detect early arterial abnormalities. Arterial stiffness and its consequences represent the great challenge of the twenty-first century for affluent countries, and “de-stiffening” will be the goal of the next decades.

Validation of the Microlife WatchBP O3 device for clinic, home, and ambulatory blood pressure measurement, according to the International Protocol.

To determine the accuracy of the Microlife WatchBP O3 blood pressure measuring device tested according to the requirements of the International Protocol of the European Society of Hypertension. The WatchBP O3 is designed to provide clinic, ambulatory, and self blood pressure (BP) measurements. Device evaluation was performed in 33 participants with a mean ± standard deviation age of 56.1±20.7 years (range 30–95 years). Their systolic BP (SBP) was 144.7±24.1 mmHg (range 90–180 mmHg), diastolic BP (DBP) was 86.8±18.3 mmHg (range 50–120 mmHg), and arm circumference was 28.1±2.9 cm (range 22.0–34.0 cm). Blood pressure measurements were performed in the sitting position. The WatchBP O3 passed all three phases of the European Society of Hypertension protocol for SBP and DBP. Mean blood pressure differences for the WatchBP O3 (device observer) were −1.7±6.9 mmHg for SBP and −1.1±4.3 mmHg for DBP. In conclusion, these results indicate that the Microlife WatchBP O3 monitor can be recommended for clinical use in the adult population.

Premenopausal Women Have Increased Risk of Hypertensive Target Organ Damage Compared with Men of Similar Age

BACKGROUND The impact of high blood pressure (BP) on target organs (TO) in premenopausal women is not well known. The purpose of this study was to describe gender differences in TO involvement in a cohort of young-to-middle-aged subjects screened for stage 1 hypertension and followed for 8.2 years. METHODS Participants were 175 women and 451 men with similar age (range 18-45 years). Ambulatory BP at entry was 127.5±12.5/83.7±7.2 mm Hg in women and 131.9±10.3/81.0±7.9 mm Hg in men. Ambulatory BP, albumin excretion rate (AER), and echocardiographic data (n=489) were obtained at entry, every 5 years, and before starting antihypertensive treatment. RESULTS Female gender was an independent predictor of final AER (p=0.01) and left ventricular mass index (LVMI) (p<0.001). At follow-up end, both microalbuminuria (13.7% vs. 6.2%, p=0.002) and left ventricular hypertrophy (LVH) (26.4% vs. 8.8%, p<0.0001) were more common among women than men. In a multivariable Cox analysis, after adjusting for age, lifestyle factors, body mass, ambulatory BP, heart rate, and parental hypertension, female gender was a significant predictor of time to development of microalbuminuria (p=0.002), with a hazard ratio (HR) of 3.06, (95% confidence interval [CI] 1.48-6.34) and of LVH (p=0.004), with an HR of 2.50 (1.33-4.70). Inclusion of systolic and diastolic BP changes over time in the models only marginally affected these associations, with HRs of 3.13 (1.50-6.55) and 3.43 (1.75-6.70), respectively. CONCLUSIONS These data indicate that premenopausal women have an increased risk of hypertensive TO damage (TOD) and raise the question about whether early antihypertensive treatment should be considered in these patients.

Isolated systolic hypertension of young-to-middle-age individuals implies a relatively low risk of developing hypertension needing treatment when central blood pressure is low.

Objectives The clinical significance of isolated systolic hypertension (ISH) in the young is still controversial. Aim of the present study was to investigate whether prognosis of ISH in young-to-middle-age individuals differs according to central blood pressure (BP). Design We studied 354 participants screened for stage 1 hypertension and 34 normotensive controls to determine which individuals developed hypertension needing drug therapy. Among the hypertensive patients, 67 had ISH and were divided according to whether their central SBP, measured with applanation tonometry, was above (ISH-high) or below (ISH-low) the median (120.5 mmHg). Large artery (C1) and small artery (C2) compliance were also measured. Results Compared to normotensive individuals, ISH-high had decreased C1 (P = 0.02) and C2 (P = 0.01), and higher peripheral resistance (P = 0.01). In contrast, in ISH-low, all these variables were similar to those in normotensive individuals. During 9.5 years of follow-up, incident hypertension was more common among participants with systolic-diastolic hypertension (SDH) and ISH-high than the other two groups [odds ratio (OR) = 6.2, 95% confidence interval (CI) = 1.8–21.1, P = 0.003 for SDH; OR = 6.0, 95% CI = 1.5–24.0, P = 0.01 for ISH-high, versus normotensive individuals]. Among ISH-low, incidence of hypertension was only slightly higher than that in normotensive individuals (OR = 1.1, 95% CI 0.2–5.3, P = 0.90) and lower than that in ISH-high (P = 0.03). These associations remained significant when ambulatory BP was included in the models or when the 125 mmHg cut-off for central BP was used to identify ISH subgroups. Conclusion These data show that young-to-middle-age ISH individuals with low central BP have a lower risk of hypertension needing treatment than those with high central BP. These results are applicable mainly to male individuals.

Resting Heart Rate as a Predictor of Body Weight Gain in the Early Stage of Hypertension

We did a prospective study to investigate whether clinic heart rate (HR) and 24‐h ambulatory HR were independent predictors of subsequent increase in body weight (BW) in young subjects screened for stage 1 hypertension. The study was conducted in 1,008 subjects from the Hypertension and Ambulatory Recording Venetia Study (HARVEST) followed for an average of 7 years. Ambulatory HR was obtained in 701 subjects. Data were adjusted for lifestyle factors and several confounders. During the follow‐up BW increased by 2.1 ± 7.2 kg in the whole cohort. Both baseline clinic HR (P = 0.007) and 24‐h HR (P = 0.013) were independent predictors of BMI at study end. In addition, changes in HR during the follow‐up either measured in the clinic (P = 0.036) or with 24‐h recording (P = 0.009) were independent associates of final BMI. In a multivariable Cox regression, baseline BMI (P < 0.001), male gender (P < 0.001), systolic blood pressure (BP) (P = 0.01), baseline clinic HR (P = 0.02), and follow‐up changes in clinic HR (P < 0.001) were independent predictors of overweight (Ov) or obesity (Ob) at the end of the follow‐up. Follow‐up changes in ambulatory HR (P = 0.01) were also independent predictors of Ov or Ob. However, when both clinic and ambulatory HRs were included in the same Cox model, only baseline clinic HR and its change during the follow‐up were independent predictors of outcome. In conclusion, baseline clinic HR and HR changes during the follow‐up are independent predictors of BW gain in young persons screened for stage 1 hypertension suggesting that sympathetic nervous system activity may play a role in the development of Ob in hypertension.

Accuracy of a single rigid conical cuff with standard-size bladder coupled to an automatic oscillometric device over a wide range of arm circumferences

Although the upper arm has the shape of a truncated cone, cylindrical cuffs and bladders are currently used for blood pressure (BP) measurement. The aims of this study were to describe upper arm characteristics and to test the accuracy of a standard adult-size conical cuff coupled to an oscillometric device over a wide range of arm circumferences. Arm characteristics were studied in 142 subjects with arm circumferences ranging from 22 to 45 cm (study 1). In a subset of 33 subjects with the same range of arm circumferences, a rigid conical cuff with standard-size bladder (12.6 × 24.0 cm) and a rigid cylindrical cuff (13.3 × 24.0 cm), both coupled to a Microlife BP A100 device, were tested according to the requirements of the protocol of the European Society of Hypertension (ESH; study 2). Study 1. In all subjects, upper-arm shape was tronco-conical with slant angles ranging from 89.5° to 82.2°. In a multiple linear regression analysis, only arm circumference was an independent predictor of conicity (P<0.001). Study 2. The rigid conical cuff passed all three phases of the ESH protocol for systolic and diastolic BPs. Mean device-observer BP differences obtained with the conical cuff were unrelated to arm circumference. When the rigid cylindrical cuff was used, ESH criteria were not satisfied, and the cuff overestimated systolic BPs in subjects with large arms. BP can be measured accurately with the use of a standard-size rigid conical cuff coupled to a BP A100 device for a wide range of arm circumferences.

Rectangular cuffs may overestimate blood pressure in individuals with large conical arms

Objectives: Although the upper arm has the shape of a truncated cone, cylindrical cuffs and bladders are currently used for blood pressure (BP) measurement. The aim of this study was to ascertain whether cylindrical and tronco-conical cuffs provide different readings according to arm size and shape. Design: We studied 220 individuals with arm circumference ranging from 22 to 42.5 cm. Four different cylindrical and four different tronco-conical bladders of appropriate size were used. Sequential same-arm measurements were performed in triplicate by two observers using the two cuffs in a random order. In 100 individuals, the actual pressure transmitted to the arm surface by the two cuffs at the central point was also measured. Results: Upper arm shape was tronco-conical in all of the individuals. In a multiple regression, conicity was related to arm circumference (P < 0.001) and length (P = 0.001). Arm conicity and size were independently related to the between-cuff SBP (P = 0.001 and 0.002, respectively) and DBP (P = 0.001 and <0.001, respectively) discrepancies. In the group with arm circumference of 37.5–42.5 cm, the cylindrical cuff overestimated BP measured with the tronco-conical cuff by 2.0 ± 0.4/1.8 ± 0.3 mmHg (P = 0.001 and <0.001). In this group, 15% of individuals found hypertensive with the cylindrical cuff were normotensive when assessed with the conical cuff. Differences as great as 9.7/7.8 mmHg were found in individuals with large arms and slant angle equal to or less than 83°. Conclusion: In obese people, the upper arm may have a pronounced tronco-conical shape and cylindrical cuffs may overestimate BP. Tronco-conical cuffs should be used for BP measurement in individuals with large arms.

Natural History of Hypertension Subtypes in Young and Middle-Age Adults

BACKGROUND The evolution of hypertension (HT) subtypes in young-to-middle-age subjects is unclear. METHODS We did a prospective study in 1,141 participants aged 18-45 years from the HARVEST study screened for stage 1 HT, and 101 nonhypertensive subjects of control during a median follow-up of 72.9 months. RESULTS At baseline, 13.8% of the subjects were classified as having isolated systolic HT (ISH), 24.8% as having isolated diastolic HT (IDH), and 61.4% as having systolic-diastolic HT (SDH). All hypertensive groups developed sustained HT (clinic blood pressure > or =140/90 mm Hg from two consecutive visits occurring at least after > or =6 months of observation) more frequently than nonhypertensive subjects (P < 0.001 for all) with adjusted odds ratio of 5.2 (95%CI 2.9-9.2) among the SDH subjects, 2.6 (95%CI 1.5-4.5) among the IDH subjects, and 2.2 (95%CI 1.2-4.5) among the ISH subjects. When the definition of HT was based on ambulatory blood pressure (mean daytime blood pressure > or =135/85 mm Hg, n = 798), odds ratios were 5.1 (95%CI 3.1-8.2), 5.6 (95%CI 3.2-9.8), and 3.3 (95%CI 1.7-6.3), respectively. In the fully adjusted logistic model, the risk of ambulatory HT was smaller for the ISH than the IDH (P = 0.049) or SDH (P = 0.053) individuals. CONCLUSIONS The present results indicate that young-to-middle-age subjects with ISH have a smaller risk of developing ambulatory HT than either subjects with SDH or IDH. Whether antihypertensive treatment can be postponed for long periods of time in young subjects with mild elevations of clinic systolic BP and low global cardiovascular risk should be examined in further studies.

Regular physical activity attenuates the blood pressure response to public speaking and delays the development of hypertension

Objectives The objective of this study was to investigate the effect of regular physical activity on the haemodynamic response to public speaking and to evaluate the long-term effect of exercise on development of hypertension. Participants We assessed 75 sedentary and 44 active participants screened for stage 1 hypertension with consistent activity habits and 63 normotensive individuals as control. Methods The blood pressure (BP) response to public speaking was assessed with beat-to-beat noninvasive recording. Definition of incident hypertension was based either on clinic or 24-h BP measurement. Results The BP response to public speaking was greater in the hypertensive than the normotensive participants (P = 0.018/0.009). Among the former, sedentary participants showed increased BP reactivity to the speech test (45.2 ± 22.6/22.2 ± 11.5 mmHg, P < 0.01/<0.001 versus controls), whereas physically active participants had a response similar to that of controls (35.4 ± 18.5/18.5 ± 11.5 mmHg, P = not significant). During a median follow-up of 71 months, ambulatory BP did not virtually change in the active participants (−0.9 ± 7.8/−0.0 ± 4.7 mmHg) and increased in their sedentary peers (2.8 ± 9.8/3.2 ± 7.4 mmHg, P = 0.08/0.003 versus active). Active participants were less likely to develop incident hypertension than sedentary ones. After controlling for several confounders including baseline heart rate, the hazard ratio was 0.53 [95% confidence interval (CI) 0.31–0.94] for clinic hypertension and 0.60 (95% CI 0.37–0.99) for ambulatory hypertension. Inclusion of BP response to public speaking into the Cox model influenced the strength of the association only marginally [hazard ratio = 0.55 (95% CI 0.30–0.97) and hazard ratio = 0.59 (95% CI 0.36–0.99), respectively]. Conclusion Regular physical activity attenuates the BP reaction to psychosocial stressors. However, this mechanism seems to be only partially responsible for the long-term effect of exercise on BP.