Relationship between GFR and albuminuria in stage 1 hypertension.

BACKGROUND AND OBJECTIVES: Whether glomerular hyperfiltration is implicated in the development of microalbuminuria in hypertension is not well known. This prospective study investigated the relationship between changes in GFR and microalbuminuria in hypertension. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study assessed 534 stage 1 hypertensive participants from the Hypertension and Ambulatory Recording Venetia Study (n=386 men) without microalbuminuria at baseline, who were recruited from 1990 to 1995 and followed for a median of 8.5 years. Mean age was 33.9±8.6 years and mean BP was 146.6±10.5/94.0±5.0 mmHg. Creatinine clearance and 24-hour urinary albumin were measured at study entry and end. Participants were defined as normofilterers (normo) or hyperfilterers (hyper) according to whether GFR was <150 or ≥150 ml/min per 1.73 m(2), respectively. Participants were divided into four groups based on GFR changes from baseline to follow-up end: normo→normo (n=395), normo→hyper (n=31), hyper→hyper (n=61), and hyper→normo (n=47). RESULTS: Microalbuminuria progressively increased across the four groups and was 5.3% in normo→normo, 9.7% in normo→hyper, 16.4% in hyper→hyper, and 36.2% in hyper→normo (P<0.001). This association held true in a multivariable logistic regression in which several confounders, ambulatory BP, and other risk factors were taken into account (P<0.001). In particular, hyperfilterers whose GFR decreased to normal at study end had an adjusted odds ratio of 7.8 (95% confidence interval, 3.3-18.2) for development of microalbuminuria compared with participants with normal GFR throughout the study. CONCLUSIONS: These data support the hypothesis for a parabolic association between GFR and urinary albumin in the early stage of hypertension.

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.

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.

Regular physical activity prevents development of left ventricular hypertrophy in hypertension.

AIMS: The longitudinal relationship between aerobic exercise and left ventricular (LV) mass in hypertension is not well known. We did a prospective study to investigate the long-term effect of regular physical activity on development of LV hypertrophy (LVH) in a cohort of young subjects screened for Stage 1 hypertension. METHODS AND RESULTS: We assessed 454 subjects whose physical activity status was consistent during the follow-up. Echocardiographic LV mass was measured at entry, every 5 years, and/or at the time of hypertension development before starting treatment. LVH was defined as an LV mass >/=50 g/m(2.7) in men and >/=47 g/m(2.7) in women. During a median follow-up of 8.3 years, 32 subjects developed LVH (sedentary, 10.3%; active, 1.7%, P = 0.000). In a logistic regression, physically active groups combined (n = 173) were less likely to develop LVH than sedentary group with a crude OR = 0.15 (CI, 0.05-0.52). After controlling for sex, age, family history for hypertension, hypertension duration, body mass, blood pressure, baseline LV mass, lifestyle factors, and follow-up length, the OR was 0.24 (CI, 0.07-0.85). Blood pressure declined over time in physically active subjects (-5.1 +/- 17.0/-0.5 +/- 10.2 mmHg) and slightly increased in their sedentary peers (0.0 +/- 15.3/0.9 +/- 9.7 mmHg, adjusted P vs. active = 0.04/0.06). Inclusion of changes in blood pressure over time into the logistic model slightly decreased the strength of the association between physical activity status and LVH development (OR = 0.25, CI, 0.07-0.87). CONCLUSION: Regular physical activity prevents the development of LVH in young stage 1 hypertensive subjects. This effect is independent from the reduction in blood pressure caused by exercise.

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.

Setting up a multidisciplinary program for management of patent foramen ovale-mediated syndromes.

BACKGROUND: These days no codified multidisciplinary protocol has been reported to manage all the different patent foramen ovale (PFO)-mediated syndromes. We sought to propose a multidisciplinary program of diagnosis, treatment, and follow-up of all PFO-mediated syndromes based on an in-hospital multidisciplinary task force and to review the activities during the first year. METHODS: From September 2004, we organized in our hospital, a 600-bed tertiary hospital, a management program for PFO-mediated syndromes based on a task force composed of cardiologists, neurologists, and internists. Different levels of protocols were created in order to cover diagnosis, treatment, and follow-up of PFO-mediated syndromes. We reviewed the activity of our program in the first year up to September 2005. RESULTS: Thirty-five patients (23 female, mean age 65 +/- 24 years) were evaluated for suspected PFO-mediated syndromes: 20 for cryptogenic stroke, 2 for peripheral and coronary embolisms, 3 for platypnea-orthodeoxia, 9 for emicrania with aura, and 1 with hypoxiemia during neurosurgical intervention in the posterior cranial fossa. Diagnosis of PFO was confirmed in 25 patients. According to the multidisciplinary protocols, 15 patients failed to meet the requirements for transcatheter closure and were left in medical therapy whereas 11 patients (7 patients with PFO, 2 with multiperforated ASD, and 2 with a secundum ASD) underwent transcatheter closure. After a mean follow-up of 10.8 +/- 4.9 months, no recurrent PFO syndromes were noted in patients treated with devices. CONCLUSION: The first year of our multidisciplinary program allowed a reasonable and potentially successful approach for correctly identifying patients with PFO-mediated syndromes until randomized studies are completed.