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.

Short-term blood pressure variability outweighs average 24-h blood pressure in the prediction of cardiovascular events in hypertension of the young.

OBJECTIVE: The association of short-term blood pressure (BP) variability (BPV) with cardiovascular events (CVEs) is controversial. Aim of this study was to investigate whether BPV measured as weighted 24-h SD was associated with CVE in a prospective cohort study of young patients screened for stage 1 hypertension. METHODS: We performed 24-h ambulatory BP monitoring in 1206 participants aged 33.1 ±â€Š8.5 years, untreated at baseline examination. Participants were divided into two categories with low (<12.8 mmHg) or high (≥12.8 mmHg) SBPV. Hazard ratios for CVE associated with BPV expressed either as continuous or categorical variable were computed from multivariable Cox models. RESULTS: During 15.4 ±â€Š7.4 years of follow-up there were 69 fatal and nonfatal CVE. In multivariable Cox models, high SBPV was an independent predictors of CVE [2.75 (1.65-4.58); P = 0.0001] and of coronary events [3.84 (2.01-7.35), P < 0.0001]. Inclusion in the model of development of hypertension requiring treatment during the follow-up, did not reduce the strength of the associations. Addition of SBPV to fully adjusted models had significant impact on risk reclassification and integrated discrimination (relative integrated discrimination improvement for BPV as continuous variable: 13.5%, P = 0.045, and for BPV as categorical variable: 26.6%, P = 0.001). When the coefficient of variation was used as BPV metric similar results were obtained. Of note, in all Cox models average 24-h BP was no longer an independent predictor of outcome after BPV was included. CONCLUSION: Short-term BPV adds to the risk stratification for cardiovascular events in young-to-middle-age patients screened for stage 1 hypertension over and above traditional 24-h ambulatory monitoring indexes.

Regular physical activity prevents development of hypertension in young people with hyperuricemia.

OBJECTIVE: The association of serum uric acid (SUA) with risk of hypertension is controversial and may be modulated by lifestyle factors. We did a prospective study to investigate whether SUA was an independent predictor of hypertension in the young and whether physical activity influences this association. METHODS: The study was conducted in a cohort of 1156 young to middle-age participants screened for stage 1 hypertension and followed for a median of 11.4 years. In multivariable Cox analyses, participants were stratified by tertiles of uric acid and physical activity habits. RESULTS: At follow-up end, 63.3% of the study participants developed hypertension needing treatment. In the whole group, SUA was an independent predictor of future hypertension (P = 0.005). Participants with SUA more than 5.60 mg/dl (top tertile) had a 31% increase in risk compared with those of the bottom tertile. However, the risk of hypertension related to SUA was increased only among the sedentary participants with a hazard ratio of 1.44 (95% confidence interval, 1.11-1.88) for the participants of the top SUA tertile. In contrast, among the active participants no association was found between SUA and risk of hypertension. Alcohol intake was another modulator of the SUA-hypertension relationship (hazard ratio, 95% confidence interval: 1.38, 1.02-1.87). Plasma renin activity, office and ambulatory heart rates, and metabolic variables were proportional to SUA level and were lower in active than sedentary participants. CONCLUSION: These data confirm that SUA is a predictor of hypertension and suggest that exercise may counteract the pathophysiological mechanisms involved in the association between hyperuricemia and future hypertension.

Coffee consumption and risk of cardiovascular events in hypertensive patients. Results from the HARVEST.

BACKGROUND: Controversy still exists about the long-term cardiovascular effects of coffee consumption in hypertension. METHODS: The predictive capacity of coffee use for cardiovascular events (CVEs) was investigated in 1204 participants from the HARVEST, a prospective cohort study of non-diabetic subjects aged 18-45years, screened for stage 1 hypertension. Subjects were grouped into three categories of coffee drinking, non-drinkers (none), moderate drinkers (1 to 3cups/day) and heavy drinkers (4or more cups/day). Multivariate Cox proportional hazards models were developed adjusting for possible confounding variables and risk factors. RESULTS: During a median follow-up of 12.6years, CVEs were developed by 60 participants. CVEs were more common among coffee drinkers than abstainers (abstainers, 2.2%; moderate drinkers, 7.0%; heavy drinkers, 14.0%; p for trend=0.0003). In a multivariable Cox regression model, coffee use was a significant predictor of CVE in both coffee categories, with a hazard ratio of 2.8 (95% CI, 1.0-7.9) in moderate coffee drinkers and of 4.5 (1.4-14.2) in heavy drinkers compared to abstainers. After inclusion of change in body weight (p=ns), incident hypertension (p=0.027) and presence of diabetes/prediabetes (p=ns) at follow-up end, the association with CVE was attenuated but remained significant in heavy coffee drinkers (HR, 95% CI, 3.4, 1.04-11.3). CONCLUSIONS: These data show that coffee consumption increases the risk of CVE in a linear fashion in hypertension. This association may be explained in part by the association between coffee and development of hypertension. Hypertensive patients should be discouraged from drinking coffee.

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.

Factors associated with glomerular hyperfiltration in the early stage of hypertension.

BACKGROUND: Glomerular hyperfiltration predicts development of nephropathy in hypertension but the factors responsible for increased glomerular filtration rate (GFR) are not well known. Aim of this study was to examine which clinical variables influence GFR in the early stage of hypertension. METHODS: Participants were 1,106 young-to-middle-age hypertensive adults with creatinine clearance >60 ml/min/1.73 m(2). Clinic and ambulatory blood pressures (BPs) were measured and the difference between clinic and 24-h systolic BP was defined as the white-coat effect (WCE). In 606 participants, 24-h urinary epinephrine and norepinephrine were also measured. Glomerular hyperfiltration, defined as a GFR ≥150 ml/min/1.73 m(2), was present in 201 subjects. RESULTS: Patients' mean age was 33.1 ± 8.5 years and office BP was 146 ± 10.5/94 ± 5.0 mm Hg. In multivariable linear regression, significant predictors of GFR were younger age (P < 0.0001), male gender (P < 0.0001), 24-h systolic BP (P = 0.0001), body mass (P < 0.0001), WCE (P = 0.02), log-epinephrine (P = 0.01), and coffee use (P < 0.01). In a logistic model, independent predictors of glomerular hyperfiltration were obesity (odds ratio, 95% confidence interval = 6.1, 3.8-9.8), male gender (2.9, 1.8-4.9), age <33 years (2.1, 1.5-3.1), ambulatory hypertension (2.0, 1.4-3.0), WCE >15 mm Hg (1.6, 1.1-2.3), heavy coffee use (2.0, 1.1-3.8), and epinephrine >25 mcg/24 h (1.9, 1.2-3.1). CONCLUSIONS: The novel finding of this study is that hyper-reactivity to stress, as determined by urinary epinephrine level and WCE, and coffee use contribute to determining glomerular hyperfiltration in the early stage of hypertension. Our data may help to identify a subset of patients with glomerular hyperfiltration, who may be at increased risk of chronic kidney disease and may benefit from antihypertensive treatment.

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.

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.

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.

Prevalence of home blood pressure measurement among selected hypertensive patients: results of a multicenter survey from six hospital outpatient hypertension clinics in Italy.

AIM: The purpose of this study was to evaluate the prevalence of home blood pressure (BP) measurement, the type of devices and accuracy in a large sample of hypertensive patients referred to hospital outpatient hypertension clinics. METHODS: Eight hundred and fifty-five consecutive treated hypertensive patients who attended six specialized centers during a period of 4 months were included. They underwent the following procedures: (i) detailed medical interview by a structured questionnaire; (ii) physical examination; (iii) standard 12-lead electrocardiogram; (iv) BP measurements taken by a validated mercury sphygmomanometer and patient's devices. RESULTS: A total of 640 (74.7%) of 855 patients were regularly performing home BP measurement. These patients were on average younger than those not practising it (58 vs 60 years, p<0.01); men were more numerous than women (58 vs 44%, p=0.03) and had higher educational level. Electronic arm-cuff instruments were the most frequently used devices (58%) followed by wrist devices (19%) and mercury or aneroid sphygmomanometers (23%). Significant correlations were found between BPs measured by validated mercury sphygmomanometers and patients' devices [r=0.85, p<0.0001 for systolic BP (SBP) and r=0.78, p<0.0001 for diastolic BP (DBP)]. Differences 5 mmHg in SBP or DBP were found in 50 and 60% of patients, respectively. CONCLUSIONS: Our findings indicate that: (i) home BP measurement is performed by a majority of treated hypertensives seen in specialized centers; (ii) male gender, age and educational level seem to influence the adoption of home BP monitoring; (iii) electronic arm-cuff devices are the most used instruments; (iv) a notable fraction of patient's devices do not meet the accuracy criteria recommended by US Association for the Advancement of Medical Instrumentation.

Structural changes in small resistance arteries and left ventricular geometry in patients with primary and secondary hypertension.

OBJECTIVE: To prospectively evaluate the interrelationships between left ventricular (LV) geometry and structural characteristics of the vessel wall in small resistance arteries in patients with consecutive primary and secondary hypertension. METHODS: In 14 patients with phaeochromocytoma, 12 with primary aldosteronism, 25 with renovascular, 25 with essential hypertension and 12 normotensive controls, an echocardiographic study for the measurement of LV mass index and relative wall thickness (RWT) was performed. Morphological characteristics of small resistance arteries (relaxed diameter < 300 microm) were directly evaluated by a micromyographic technique. RESULTS: A total of 25 patients had normal LV mass and geometry, 28 patients had normal RWT (< 0.45) and 23 patients had a RWT >or= 0.45; all normotensive subjects had normal LV mass and geometry. Media to lumen ratio (M/L) in subcutaneous small arteries was greater in hypertensive patients with concentric LV hypertrophy in respect to normotensives (ANOVA P = 0.01) and hypertensives with normal LV geometry (ANOVA P = 0.05). In the whole group of hypertensive patients the correlation coefficient between M/L and LV mass index was 0.33 (P < 0.05); the correlation coefficient between M/L and RWT was 0.46 (P < 0.01) and it was higher in primary aldosteronism (r = 0.67) and renovascular hypertension patients (r = 0.46). CONCLUSIONS: A close relation between morphology of subcutaneous small resistance arteries and LV geometric patterns may be observed in hypertensive patients; this relationship is more evident when the renin-angiotensin-aldosterone system is activated.