Francesca Dorigatti

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.

Increase in Carotid Intima-Media Thickness in Grade I Hypertensive Subjects. White-Coat Versus Sustained Hypertension

We studied 74 never-treated grade I hypertensive subjects aged 18 to 45 years and 20 normotensive control subjects to define the rate of increase in carotid intima-media thickness (IMT) and the potential role played by the various risk factors. IMT was assessed as mean IMT and as maximum IMT in the right and left common carotid artery, carotid bulb, and internal carotid artery at baseline and at the 5-year follow-up. In grade I hypertensive subjects, both mean IMT and mean of maximum IMT were significantly higher compared with baseline values. Compared with normotensive subjects, both mean IMT and maximum IMT increased significantly (at least P<0.01) in each carotid artery segment. The increase in cumulative IMT was 3.4-fold for mean IMT and 3.2-fold for mean of maximum IMT. Levels of mean arterial pressure at 24-hour monitoring and total serum cholesterol were factors potentially linked to the increment in mean IMT and mean of maximum IMT. Age was also relevant for the increment in mean of maximum IMT, whereas body mass index played some role in the increment of mean IMT. During the follow-up, mean IMT and mean of maximum IMT increased to a greater degree in white-coat hypertensive subjects (n=35) and sustained hypertensive subjects (n=39) than in normotensive control subjects. No differences were found between white-coat hypertensive subjects and sustained hypertensive subjects for both mean IMT and maximum IMT. Levels of mean arterial pressure at 24-hour monitoring affected the increment in IMT in both white-coat hypertensive subjects and sustained hypertensive subjects. In conclusion, our findings indicate that carotid IMT is greater and grows faster in white-coat hypertensive subjects than in normotensive subjects without significant differences with sustained hypertensive patients.

Heart rate as a predictor of development of sustained hypertension in subjects screened for stage 1 hypertension: the HARVEST Study.

Objective Whether heart rate predicts the development of sustained hypertension in individuals with hypertension is not well known. We carried out a prospective study to investigate whether clinic and ambulatory heart rates assessed at baseline and changes in clinic heart rate during 6 months of follow-up were independent predictors of subsequent blood pressure (BP). Methods The study was conducted in a cohort of 1103 white, stage 1 hypertensive individuals from the HARVEST study, never treated for hypertension and followed-up for an average of 6.4 years. Data were adjusted for baseline BP, age, sex, body fatness, physical activity habits, parental hypertension, duration of hypertension, cigarette smoking, alcohol consumption, and change of body weight from baseline. Results Clinic heart rate and heart rate changes during the first 6 months of follow-up were independent predictors of subsequent systolic blood pressure (SBP) and diastolic blood pressure (DBP) regardless of initial BP and other confounders (all P < 0.01). A significant interaction was found between sex (male) and baseline resting heart rate on final SBP (P = 0.017) and DBP (P < 0.001). The ambulatory heart rate and the heart rate white-coat effect did not add prognostic information to that provided by the clinic heart rate. Patients whose heart rate was persistently elevated during the study had a doubled fully adjusted risk (95% confidence interval 1.4–2.9) of developing sustained hypertension in comparison with subjects with a normal heart rate. Conclusions Baseline clinic heart rate and heart rate changes during the first few months of follow-up are independent predictors of the development of sustained hypertension in young persons screened for stage 1 hypertension.

PREVALENCE AND CLINICAL CORRELATES OF MICROALBUMINURIA IN STAGE I HYPERTENSION. RESULTS FROM THE HYPERTENSION AND AMBULATORY RECORDING VENETIA STUDY (HARVEST STUDY)

The objective of the present study was to examine the association between albumin excretion rate (AER) and office and ambulatory blood pressures (BP), and other recognized cardiovascular risk factors in stage I hypertension. The study was carried out in 870 never-treated 18- to 45-year-old hypertensives (628 men, 242 women). Office and ambulatory BP, 24-h urinary collection for AER assessment, and echocardiographic left ventricular mass (n = 587) were obtained. AER was similar in men and women (12.3 v 12.5 mg/24 h) and was unrelated to age and body mass index. In 85.2% of the subjects, AER was < 16 mg/24 h, in 8.3% it was between 16 and 29 mg/24 h (borderline microalbuminuria), and in 6.1% it was >or= 30 mg/24 h (overt microalbuminuria). Office systolic BP was not different in the three groups, whereas 24-h systolic BP was higher in the subjects with microalbuminuria than in those with normal AER (P < .0001) and was similar in the two microalbuminuric groups. Office and 24-h diastolic BPs were higher in the subjects with overt microalbuminuria than in those with normal AER. Left ventricular mass was correlated to systolic (P < .0001) and diastolic (P = .01) 24-h BP, but was unrelated to AER. Family history for hypertension, smoking, coffee and alcohol intake, and physical activity habits did not influence AER. In a logistic regression analysis, 24-h systolic BP emerged as the only determinant of microalbuminuria (P < .0001). In conclusion, these results indicate that borderline levels of microalbuminuria may also be clinically relevant in stage I hypertension. Overweight and lifestyle factors do not appear to influence AER in these patients. Finally, the lack of correlation between AER and left ventricular mass suggests that renal and cardiac involvement do not occur in a parallel fashion in the initial phase of hypertension.

Interactive Action of the White-Coat Effect and the Blood Pressure Levels on Cardiovascular Complications in Hypertension

PURPOSE This study was undertaken to investigate whether there is a relationship between the white-coat effect and the cardiovascular complications of hypertension. PATIENTS AND METHODS In 1,013 consecutive borderline to severe hypertensive outpatients (889 men) with a mean age (+/-SE) of 33.6 +/- 0.5 years and a mean office blood pressure of 152.3 +/- 0.6/95.5 +/- 0.4 mm Hg, blood pressure was measured by noninvasive 24-hour ambulatory monitoring. Target organ damage was assessed by electrocardiogram, chest X-ray, echocardiography, and ophthalmoscopy. The degree of target organ damage and of left ventricular hypertrophy was assessed in the subjects divided according to the levels of their daytime blood pressure and the extent of their white-coat effect. RESULTS The subjects with a high white-coat effect showed a greater degree of hypertensive complications than those with intermediate or a low white-coat effect. The significant association between the white-coat phenomenon and the hypertensive complications was confirmed by the results of stepwise regression analyses, where sex, age, duration of hypertension, and ambulatory blood pressure were added to the model. A two-way ANOVA showed that both ambulatory blood pressure and the white-coat effect were related to the degree of target organ damage and to left ventricular hypertrophy. Moreover, daytime blood pressure and the white-coat effect showed an interactive effect on hypertensive complications, as the influence of the white-coat effect on end organs increased with increasing levels of ambulatory blood pressure. CONCLUSIONS The present results show that the white-coat effect is related to the degree of hypertensive complications and that this association is stronger in the subject with more severe hypertension.

Microalbuminuria, renal function and development of sustained hypertension: a longitudinal study in the early stage of hypertension.

Objective Microalbuminuria (MA) is a marker of adverse outcome in hypertension. The aim of this study was to investigate the association of MA with cardiovascular risk factors and glomerular hyperfiltration in the early stage of hypertension and to assess its predictive value for the development of sustained hypertension requiring antihypertensive treatment. Design and participants We studied 1041 young stage 1 hypertensive subjects. Study variables were 24-h ambulatory blood pressure and heart rate, anthropometric measures, metabolic variables, creatinine clearance and lifestyle factors analyzed as a function of ascending urinary albumin measured from 24-h collections. Subjects were followed until they developed sustained hypertension and were eligible for antihypertensive medication according to current guidelines. Setting Seventeen outpatient clinics in Italy. Results Eighty-five percent of the subjects were normoalbuminuric, 9% had borderline MA, and 6% had overt MA. No between-group differences were found for age, body mass index, heart rate, lifestyle factors and biochemistry in both genders. Creatinine clearance was greater in the subjects with overt MA and borderline MA than in the normoalbuminuric subjects (P = 0.003 and 0.011, respectively). In a two-way ANCOVA, microalbuminuric subjects both with hyperfiltration (P < 0.001) and with normal filtration (P = 0.04) had higher 24-h systolic blood pressure than subjects with normoalbuminuria and normal filtration. In a Cox analysis, neither MA nor hyperfiltration were significant predictors of development of sustained hypertension. Conclusion MA is not associated with an adverse metabolic risk profile in the early stage of hypertension. MA is associated with greater hemodynamic load and with glomerular hyperfiltration in this clinical setting, but does not help in predicting those subjects destined to develop sustained hypertension requiring antihypertensive therapy.

White-coat hypertension: a selection bias?

BACKGROUND Results of several studies have shown that subjects with white-coat hypertension (WCH) have more target-organ damage than do normotensive controls with similar ambulatory blood pressures. OBJECTIVE To investigate whether this is due to a selection bias. SETTING Seventeen hypertension clinics in northeast Italy. MAIN OUTCOME MEASURES Echocardiographic data in relation to WCH status. PATIENTS AND METHODS Mild hypertensive subjects from the HARVEST (n = 565) who underwent two ambulatory blood pressure monitorings 3 months apart and M-mode echocardiography, and 95 normotensive control subjects. RESULTS From first ambulatory monitoring, 90 hypertensive subjects were classified as having WCH (mean daytime blood pressure < 130/80 mmHg). Their 24 h blood pressure was similar to that of the normotensive subjects, but their left ventricular mass index was greater. From second ambulatory monitoring, only 38 of the 90 subjects still had WCH, whereas 24 h blood pressure in the other 52 had risen beyond the limit of WCH. Left ventricular mass index (89.2 +/- 2.4 g/m2), wall thickness (18.1 +/- 0.3 mm), and relative wall thickness (0.359 +/- 0.006%) of the 38 subjects with WCH at both recordings were still greater than those of the normotensive subjects (82.4 +/- 1.5 g/m2, P = 0.02; 17.2 +/- 0.2 mm, P = 0.002; and 0.337 +/- 0.004%, P = 0.025) and similar to those of the 52 subjects who no longer had WCH (88.5 +/- 2.0 g/m2, 18.7 +/- 0.2 mm, and 0.375 +/- 0.005%, all NS). CONCLUSIONS Owing to regression toward the mean, over 50% of the subjects with WCH could no longer be classified as such from repeated ambulatory monitoring, indicating that the current diagnosis of WCH is subject to selection bias. Cardiac remodeling was present also in the subjects confirmed to have WCH by repeated blood pressure recording, suggesting that the effect of WCH has an actual impact on target organs.

Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high-risk nondiabetic patients

Objective.  To investigate the association of plasma adiponectin levels with coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance (IR) in nondiabetic Caucasian patients.

Physical Activity and Angiotensin-Converting Enzyme Gene Polymorphism in Mild Hypertensives

It has been suggested that the insertion(I) allele of the I/deletion(D) polymorphism of the angiotensin converting enzyme (ACE) gene is associated with endurance exercise and increased physical conditioning in response to this type of exercise. To investigate the association between the ACE I/D polymorphism and physical activity status in 355 never treated, stage I hypertensives (265 men, 90 women, mean age: 33 ± 9 years), in whom power exercise is contraindicated, participants of the HARVEST study. Physical activity was assessed using a standardized questionnaire. BMI and age did not vary among genotypes. None of active subjects performed power oriented exercises. ACE I/D frequencies (II‐18%, ID‐55%, DD‐27%) were in Hardy–Weinberg equilibrium. Sedentary lifestyle was more common among DD than II hypertensives (76% in DD, and 48% in II, Chi2 = 13.9, P = 0.001). In stepwise MANOVA using age, marital status, profession, sex, and ACE genotype as predictors of physical activity, marital status (F = 24.4, P < 0.0001) and ACE genotype (F = 16.03, P < 0.0001) contributed to more than 50% of the variance in physical activity status of the population. Our results suggest that the ACE I/D polymorphism may be a specific genetic factor associated with physical activity levels in free‐living borderline and mild hypertensive subjects.

Association between coffee consumption and risk of hypertension

Background. The longitudinal relationship between coffee use and hypertension is not well known. Aim. We did a prospective study to investigate if there is a temporal relationship between coffee consumption and development of sustained hypertension. Method. We assessed 1107 white subjects with elevated blood pressure who were followed up for 6.4 years. Coffee intake and other life‐style factors were ascertained from regularly administered questionnaires. Incident physician‐diagnosed hypertension was the outcome measure. Results. During the follow‐up, 561 subjects developed sustained hypertension, whereas 546 subjects did not meet the criteria for treatment. Coffee drinkers developed sustained hypertension more frequently than abstainers (53.1% versus 43.9%, P = 0.007). The incidence of hypertension did not differ between moderate and heavy coffee drinkers. Kaplan‐Meier analysis confirmed that sustained hypertension was developed more frequently by coffee drinkers compared with nondrinkers (P<0.001). The adjusted relative risk of hypertension was greater in both categories of coffee drinking than in abstainers (hazard ratio, 95% confidence limit (CL) = 1.24, 1.06–1.44). The risk of hypertension associated with coffee drinking increased gradually with increasing level of alcohol use (adjusted P for interaction = 0.005). Conclusions. In subjects screened for stage 1 hypertension a nonlinear association was found between coffee consumption and development of sustained hypertension.