Guido Garavelli

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.

Cardiovascular Effects of Anabolic Steroids in Weight‐Trained Subjects

The effects of large doses of anabolic steroids on 24‐hour blood pressure, cardiac structure and function, and lipid profiles were studied in 10 body builders using anabolic steroids and 14 body builders who did not use steroids (control subjects). All subjects underwent noninvasive 24‐hour blood pressure monitoring, echocardiography, Doppler analysis of transmitral flow, and analysis for lipoprotein and gonadotropin levels. Anabolic steroid users were studied at the end of a steroid cycle and after a period of withdrawal. Average 24‐hour blood pressure was similar in the two groups, but anabolic steroid users exhibited a smaller pressure reduction during sleep than did nonusers. This finding was present both at the end of treatment and after the period of withdrawal. Echocardiographic dimensional and functional indexes did not differ substantially between anabolic steroid users and the nonusers, and were similar in anabolic steroid users during use and after withdrawal. Anabolic steroid users also had higher LDL and lower HDL cholesterol levels than nonusers; Lp(a) was higher in nonusers, although this difference did not attain the level of statistical significance. These differences were more striking at the end of the treatment period. The results of this study show that chronic anabolic steroid intake causes an abnormal 24‐hour blood pressure pattern, characterized by a flattening of the diurnal curve, and minor changes of the dimensional echocardiographic parameters.

The Effects of Alcohol Consumption on Ambulatory Blood Pressure and Target Organs in Subjects With Borderline to Mild Hypertension

The objective of this study was to examine the relationship of alcohol consumption to target organ involvement and ambulatory blood pressure (BP) in a population of young borderline to mild hypertensive subjects. Participants were 793 male subjects, aged 18-45 years, from the HARVEST Study. The analysis was performed in three age-matched groups with similar body mass index. Casual and 24-h ambulatory BP monitoring, routine biochemistry, echocardiography, and albumin excretion rate were measured. The men were divided into three groups: 1) nondrinkers, 2) drinkers of < 50 g/day, and 3) drinkers of > or = 50 g/day. Office systolic BP was not significantly different among the three groups, whereas 24-h and daytime BPs increased progressively from the first to the third group (group 1 v 3; P = .01 for 24-h systolic BP and P = .02 for daytime systolic BP). These differences remained significant even after adjusting for smoking. Left ventricular mass index, interventricular septum thickness, and wall thickness increased progressively from group 1 to group 3; this difference also remained significant after adjusting for smoking and 24-h BPs. The albumin excretion rate was much higher in group 3 than in group 1 (P = .003), but when 24-h BP was added to the model the difference was no longer significant. These results indicate that alcohol has a detrimental effect on the heart and the kidney. Alcohols effect on LV wall thickness appears to be direct, whereas its action on albumin excretion rate seems to be mediated mainly by its effect on BP.

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.

Structural Abnormalities and Not Diastolic Dysfunction Are the Earliest Left Ventricular Changes in Hypertension

It has been claimed that diastolic dysfunction is the earliest cardiac abnormality in hypertension, preceding the development of left ventricular (LV) structural abnormalities. To detect early signs of hypertensive cardiac involvement 722 subjects (533 men and 189 women), 18-45 years old, with stage I hypertension, were studied by M-mode and Doppler echocardiography. Blood pressure was measured by 24-h ambulatory monitoring. Ninety-five normotensive individuals of similar age and gender distributions were studied as controls. Significant, though modest, changes of LV mass and geometry were found in the participants in comparison with the normotensive controls. The increment was +10.4 g/m2 for LV mass index, +1.8 mm for LV wall thickness, and +0.032 for relative wall thickness. A slight increase in atrial filling peak velocity was found in the hypertensive subjects at Doppler analysis of transmitral flow, but the ratio of early to atrial velocity of LV diastolic filling did not differ between the two groups. In multiple regression analyses, which included age, body mass index, heart rate, smoking, and physical activity, 24-h mean blood pressure emerged as a significant predictor of LV mass index (men, P = .003; women, P = .04) and wall thickness (men, P = .03; women, P = .004) in the hypertensive subjects, whereas no index of diastolic filling was significantly associated with ambulatory blood pressure in either gender. The present data indicate that changes in LV anatomy are the earliest signs of hypertensive cardiac involvement. Left ventricular filling is affected only marginally in the initial phase of hypertension.

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.

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.

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.

3A.07: NIGHT-TIME HEART RATE IS A LONG-TERM PREDICTOR OF MICROALBUMINURIA IN SUBJECTS SCREENED FOR STAGE 1 HYPERTENSION

Objective: Heart rate (HR) has been found to be associated with target organ damage in hypertension but the predictive capacity of resting HR vs ambulatory HR in longitudinal studies is not well known. We did a prospective study to investigate whether clinic HR and ambulatory HR assessed at baseline were independent predictors of albumin excretion rate (AER) and microalbuminuria (MA) in the early stage of hypertension. Design and method: The study was conducted in a cohort of 621 white stage 1 hypertensive subjects from the HARVEST never treated for hypertension (mean age 33.8 ± 8.4 years, 449 men). Clinic HR was the average of 6 readings. Clinic HR, daytime HR and night-time HR were included separately in linear (for AER) and logistic (for MA) regressions and were adjusted for baseline logAER, age, gender, body mass index, blood pressure, physical activity, smoking, alcohol consumption, and follow-up time. Results: During a median follow-up of 8.5 years AER increased from a median value of 5.7 mg/24 h to 7.2 mg/24 h (p < 0.001 for log-transformed data), and 42 subjects developed MA (AER >  = 30 mg/24 h). In both linear and logistic regressions average night-time HR was an independent predictor of final AER (p = 0.014) and MA (p = 0.007), whereas clinic HR and daytime HR were not associated with these outcomes (p = NS for both). Night-time HR was 62.6 ± 8.3 bpm in the 579 subjects who did not develop MA and was 66.6 ± 7.7 bpm in the 42 subjects who developed MA (p = 0.002). Baseline BMI was another independent predictor of final AER (p = 0.007) and final MA (p = 0.001) and its inclusion into the models slightly attenuated the association of night-time HR with AER (p = 0.029) and MA (p = 0.016). Conclusions: HR is an independent predictor of microalbuminuria in young persons screened for stage 1 hypertension suggesting that the chronic hemodynamic stress related to tachycardia may play a role in the development of renal damage in hypertension. In agreement with previous results, HR measured during sleep seems to be more representative of the overall hemodynamic load on the arteries than HR measured during waking hours or in the doctors office.