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.

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.

Cystatin C as predictor of microalbuminuria in the early stage of hypertension.

BACKGROUND/AIMS: Predictors of microalbuminuria in the early stage of hypertension are not well known. We did a prospective study to investigate whether glomerular hyperfiltration assessed from serum cystatin C predicts development of microalbuminuria in hypertension. METHODS: We assessed 101 treatment-naive subjects screened for stage 1 hypertension and followed-up for a median 3.1 years. Cystatin C was measured at entry and glomerular filtration rate was estimated using the Hoek formula (CystGFR). Urinary albumin and ambulatory blood pressure were measured at entry and during the follow-up. RESULTS: Subjects in the top CystGFR tertile (>115 ml/min/1.73 m(2)) were leaner (p = 0.002) and developed microalbuminuria more frequently (p = 0.02) than the rest of the group. In univariate Cox regression, CystGFR was associated with future microalbuminuria (hazard ratio, 1.06, 95% confidence interval (CI), 1.02-1.10, p = 0.001). After controlling for baseline albumin excretion rate and several confounders, CystGFR remained a significant predictor of microalbuminuria development (hazard ratio, 1.19, 95% CI, 1.03-1.37, p = 0.019). The association between future microalbuminuria and creatinine clearance or glomerular filtration rate estimated with the Cockroft-Gault or the Modification of Diet in Renal Disease formula did not attain the level of statistical significance in this sample. CONCLUSIONS: The present findings indicate that CystGFR is more sensitive than creatinine clearance or estimated glomerular filtration rate for predicting microalbuminuria development in the early stage of hypertension and confirm that hyperfiltration precedes microalbuminuria in this clinical entity.

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 x 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.

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.