Observational study of hypertension in Matelica, Italy (Matelica hypertension study).

This study summarizes the results of an epidemiological investigation carried out on the occasion of the Second World Hypertension Day (May 13, 2006) in the city of Matelica in the Region of the Marches, Central Italy. In all, 518 subjects (298 males, average age 52.3 years; 220 females, average age 55 years) with either diagnosed hypertension or who were thought to be normotensive had arterial blood pressure measured. Other cardiovascular risk factors and the costs of pharmacological treatment for hypertension were assessed as well. In 72.46% of examined subjects, arterial blood pressure levels averaged > or =140-90 mmHg if non-diabetic and > or =130-80 mmHg if diabetics. A total of 48.14% of individuals assumed in anamnesis to be normotensive had arterial blood pressure levels higher than the above values and were therefore found to have hypertensive values. The cost of anti-hypertensive treatment in the area of Matelica averages Euro 543.7/patient/year. The present data, which are in line with those of other epidemiological studies performed in Italy, confirm the view that arterial hypertension control in Italy is still largely unsatisfactory. This observation should stimulate both health and specific medical measures to counter the risk of complications of arterial hypertension in aged populations, such as those present in the territory examined.

Does the reduction in systolic blood pressure alone explain the regression of left ventricular hypertrophy?

Systolic blood pressure (SBP) is an important determinant of the development and regression of left ventricular hypertrophy (LVH) in hypertensive humans. However, comparative assessments with other BP components are scarce and generally limited in size. As part of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA), 743 hypertensive subjects underwent echocardiography and 24-h ambulatory BP monitoring before and after an average of 3.9 years of treatment. The changes in left ventricular mass showed a significant direct association with the changes in 24-h SBP (r=0.40), diastolic blood pressure (DBP) (r=0.33) and pulse pressure (PP) (r=0.35). Weaker associations were found with the changes in clinic BP (r=0.32, 0.31 and 0.16, respectively). In a multivariate linear regression analysis, the changes in 24-h SBP were the sole independent determinants of the changes in left ventricular mass (LVM) according to the following equation: percentage changes in LVM=0.73 x (percentage changes in 24-h SBP) -0.48 (P<0.0001). For any given reduction in 24-h SBP, the reduction in LVM did not show any association with the changes in DBP and PP, either clinic or ambulatory. These data indicate that SBP is the principal determinant of LVH regression in hypertensive humans.

Switch from ABCD pretreatment to A-II-A treatment: a multinational, open, centrally randomized, prospective parallel group comparison.

The aim of this trial was to evaluate the efficacy and safety of switching antihypertensive monotherapy from a non-angiotensin II receptor blocker treatment, i.e., angiotensin-converting enzyme (ACE) inhibitor, beta-blocker, calcium (Ca2+) channel blocker or diuretic, to monotherapy with candesartan cilexetil 8 or 16 mg once daily. Patients (age 18-74 years) with mild to moderate essential hypertension were enrolled in this multinational, open-label, centrally randomized, prospective parallel group study. Previous antihypertensive treatment, with either an ACE inhibitor, a beta-blocker, a Ca2+ channel blocker or a diuretic, was maintained for a run-in period of 4 weeks and was then substituted at the baseline visit where patients were randomized into two groups to receive either candesartan cilexetil 8 mg (n = 985) or 16 mg (n = 982) once daily for an 8-week treatment period. Blood pressure (BP) reduction was the primary endpoint after 4 weeks of therapy and the secondary endpoint after 8 weeks of therapy. Results of the first 4 weeks of therapy are presented here. A total of 1,967 patients were included: 985 received candesartan cilexetil 8 mg and 982 candesartan cilexetil 16 mg once daily; 1,879 patients were included in the intention-to-treat analysis. The percentages of patients receiving an ACE inhibitor, a beta-blocker, a Ca2+ channel blocker or a diuretic as previous antihypertensive treatment were 44.7, 18.8, 30.6 and 5.9%, respectively. After 4 weeks of treatment with candesartan cilexetil 8 and 16 mg, sitting diastolic and systolic BP were reduced (mean +/- SD): -7 +/- 10 and -14 +/- 17 mmHg, and -8 +/- 10 and -16 +/- 16 mmHg, respectively. The percentage of patients who were still borderline hypertensive or hypertensive after 4 weeks of substitute treatment was lower in the candesartan cilexetil 16 mg group than in the 8 mg group: 7.1 and 5.3%, respectively, versus 9 and 7.4%, respectively. Reported adverse events were mild or moderate in intensity and in accordance with those reported in the literature. Candesartan cilexetil can be considered an effective and safe alternative to other common antihypertensive monotherapies in a large spectrum of patients with mild and moderate hypertension.

Prevalent influence of systolic over pulse pressure on left ventricular mass in essential hypertension.

BACKGROUND: Elevated pulse pressure, an index of increased large artery stiffness, has been associated with increased left ventricular mass. It is unknown whether this relation is independent or mediated by other blood pressure components. METHODS AND RESULTS: We examined data in 2545 untreated hypertensive subjects (45% women) who underwent echocardiography and 24-h ambulatory blood pressure monitoring. Left ventricular mass increased with all blood pressure components and all associations were closer with ambulatory than with office blood pressure. In a multiple regression analysis, after adjustment for the significant association with age, gender, body weight and duration of hypertension, the proportion of variability of left ventricular mass explained by systolic blood pressure was greater than that explained by other blood pressure components. When different blood pressure components were forced into the same model, the same degree of left ventricular mass variability was accounted for by models including 24-h systolic blood pressure alone, or 24-h mean blood pressure plus 24-h pulse pressure, or 24-h diastolic blood pressure plus 24-h pulse pressure. When 24-h systolic blood pressure and 24-h pulse pressure were forced into the same model, 24-h pulse pressure lost statistical significance. CONCLUSIONS: The association between pulse pressure and left ventricular mass is explained by systolic blood pressure, which is the main pressure determinant of left ventricular mass in essential hypertension.

Left ventricular mass and systolic dysfunction in essential hypertension.

A relation between left ventricular (LV) hypertrophy and depressed midwall systolic function has been described in hypertensive subjects. However, a strong confounding factor in this relation is concentric geometry, which is both a powerful determinant of depressed midwall systolic function and a correlate of LV mass in hypertension. To evaluate the independent contribution of LV mass to depressed systolic function, 1827 patients with never-treated essential hypertension (age 48 +/- 12 years, men 58%) underwent M-mode echocardiography under two-dimensional guidance. Relative wall thickness was the strongest determinant of low midwall fractional shortening (r = -0.63, P < 0.0001). The significant inverse relation observed between LV mass and midwall fractional shortening (r = -0.43, P < 0.0001) persisted after taking into account the effect of relative wall thickness (partial r = -0.27, P < 0.0001). Within each sex-specific quintile of relative wall thickness, prevalence of subnormal afterload-corrected midwall systolic function was greater in subjects with, than in subjects without, LV hypertrophy (P < 0.05 for the first, third, fourth and fifth quintile). In a multiple linear regression analysis, both LV mass (P < 0.0001) and relative wall thickness (P < 0.0001) were independent predictors of a reduced midwall fractional shortening. In conclusion, the inverse association between LV mass and midwall systolic function is partly independent from the effect of relative wall thickness. LV hypertrophy is a determinant of subclinical LV dysfunction independently of the concomitant changes in chamber geometry.

High-density lipoprotein cholesterol and left ventricular hypertrophy in essential hypertension.

OBJECTIVE: The proportion of left ventricular (LV) mass variability explained by blood pressure in essential hypertension is small, and several non-haemodynamic determinants of LV mass have been identified or hypothesized. This study examines the possible relation between blood lipids and LV mass in hypertension. DESIGN: Never-treated non-diabetic hypertensive patients. SETTING: Hospital hypertension outpatient clinics in Umbria, Italy. PATIENTS: We investigated the association between high-density lipoprotein (HDL)-cholesterol and echocardiographic LV mass in 1306 never-treated subjects with essential hypertension. Subjects with previous cardiovascular events, diabetes and current or previous antihypertensive or lipid-lowering therapy were excluded. RESULTS: HDL-cholesterol showed an inverse association with LV mass (r = -0.30, P < 0.001). No association was found between LV mass and total or low-density lipoprotein cholesterol. With multiple linear regression analysis we tested the independent contribution of several potential determinants of LV mass in women and in men. Average 24 h blood pressure (both pulse and mean), body mass index, height, stroke volume, age (all P < 0.01) and low HDL-cholesterol (P < 0.0001 in women, P < 0.001 in men) were associated with a greater LV mass in both sexes. Triglycerides showed a weak univariate association with LV mass in women (r = 0.11, P < 0.02), which did not hold in a multivariate analysis. CONCLUSIONS: Low HDL-cholesterol is an independent predictor of LV mass in untreated hypertensive subjects. Common hormonal and metabolic mechanisms, including insulin resistance, could explain this association, which may contribute to the adverse prognostic significance of low HDL-cholesterol levels.

Left ventricular hypertrophy as an independent predictor of acute cerebrovascular events in essential hypertension.

BACKGROUND: It is uncertain whether left ventricular hypertrophy (LVH) confers an increased risk for cerebrovascular disease in apparently healthy patients with essential hypertension. METHODS AND RESULTS: A total of 2363 initially untreated hypertensive patients (mean age 51+/-12 years, 47% women) free of previous cardiovascular disease were followed up for up to 14 years (mean 5 years). At entry, all patients underwent diagnostic tests, including ECG, echocardiography, and 24-hour ambulatory blood pressure (BP) monitoring. At entry, the prevalence of LVH was 17.6% by ECG (Perugia score) and 23.7% by echocardiography (LVM >125 g/m(2)). Over the subsequent years, 105 patients experienced a first stroke or transient ischemic attack. The cerebrovascular event rate was higher among patients with LVH at entry, diagnosed by either ECG or echocardiography, than among those without hypertrophy (both P<0.01). After control for the significant influence of age, sex, diabetes, and 24-hour mean ambulatory BP, LVH by ECG conferred an increased risk for cerebrovascular events (relative risk [RR] 1.79; 95% CI 1.17 to 2.76). LVH by echocardiography also conferred a higher risk for cerebrovascular events (RR 1.64; 95% CI 1.07 to 2.68). For each increase in LV mass of 1 SD (29 g/m(2)), there was a significant independent increase in the risk for cerebrovascular events (RR 1.31; 95% CI 1.09 to 1.58). CONCLUSIONS: In apparently healthy patients with essential hypertension, LVH diagnosed by ECG or echocardiography confers an excess risk for stroke and transient ischemic attack independently of BP and other individual risk factors.

Independent predictors of isolated clinic ('white-coat') hypertension.

BACKGROUND: Hypertension guidelines recommend 24 h ambulatory blood pressure (ABP) monitoring in hypertensive subjects with suspected isolated clinic hypertension (ICH). However, the pre-test probability of ICH based on the distribution of its independent predictors has not yet been estimated in hypertensive subjects with mildly elevated blood pressure. OBJECTIVE: To ascertain the independent predictors of ICH in mildly hypertensive subjects. METHODS: In the setting of the HARVEST-PIUMA collaboration, we studied 1564 subjects with hypertension stage I. At entry, all subjects were untreated and all underwent ABP monitoring and echocardiography. Diabetes, hypertension grade > I, renal failure or previous cardiovascular morbid events were exclusion criteria. Clinic BP was 143/92 mmHg (SD 9/5) and 24 h ABP was 128/81 mmHg (SD 10/8). RESULTS: Prevalence of ICH (daytime ABP < 130 mmHg systolic and 80 mmHg diastolic) was 10.4%. In a multivariate logistic regression analysis, sex (P = 0.002), smoking (P = 0.038) and clinic diastolic BP (P = 0.0002) were the sole independent predictors of ICH according to the following equation: Y = 2.6438 + 0.5128 x sex (0 = men; 1 = women) + 0.4543 x current smoking (0 = yes; 1 = no) - 0.0531 x clinic diastolic BP (mmHg) and P (probability of ICH) = exp(Y)/[1 + (exp(Y)]. Left ventricular (LV) mass at echocardiography was a further independent predictor (P = 0.002) of ICH according to the following equation: Y= 3.4343 + 0.4603 x sex + 0.5989 x current smoking - 0.0482 x clinic diastolic BP - 0.0312 x LV mass [g/height (m)2.7]. LV mass was greater (P < 0.01) in the group with ambulatory hypertension [42.3 g/height (m)2.7] than in that with ICH [39.2 g/height (m)2.7] and not dissimilar between the ICH group and a control group of 370 healthy normotensive subjects [38.1 g/height (m)2.7]. CONCLUSIONS: In untreated subjects with stage I hypertension, ICH is most frequent among women, nonsmokers and subjects with low clinic BP and smaller LV mass. These findings allow identification of subjects with indication to ABP monitoring because of suspected ICH.

Different prognostic impact of 24-hour mean blood pressure and pulse pressure on stroke and coronary artery disease in essential hypertension.

BACKGROUND: We tested the hypothesis that the steady and pulsatile components of blood pressure (BP) exert a different influence on coronary artery disease and stroke in subjects with hypertension. METHODS AND RESULTS: We analyzed data on 2311 subjects with essential hypertension. All subjects (mean age 51 years, 47% women) underwent off-therapy 24-hour ambulatory BP monitoring. Over a follow-up period of up to 14 years (mean 4.7 years), there were 132 major cardiac events (1.20 per 100 person-years) and 105 cerebrovascular events (0.90 per 100 person-years). After adjustment for age, sex, diabetes, serum cholesterol, and cigarette smoking (all P<0.01), for each 10 mm Hg increase in 24-hour pulse pressure (PP), there was an independent 35% increase in the risk of cardiac events (95% CI 17% to 55%). Twenty-four-hour mean BP was not a significant predictor of cardiac events after controlling for PP. After adjustment for age, sex, and diabetes (all P<0.05), for every 10 mm Hg increase in 24-hour mean BP, the risk of cerebrovascular events increased by 42% (95% CI 19% to 69%), and 24-hour PP did not yield significance after controlling for 24-hour mean BP. Twenty-four-hour PP was also an independent predictor of fatal cardiac events, and 24-hour mean BP was an independent predictor of fatal cerebrovascular events. CONCLUSIONS: In subjects with predominantly systolic and diastolic hypertension, ambulatory mean BP and PP exert a different predictive effect on the cardiac and cerebrovascular complications. Although PP is the dominant predictor of cardiac events, mean BP is the major independent predictor of cerebrovascular events.

Original articles prognostic value of combined echocardiography and ambulatory blood pressure monitoring in hypertensive patients at low or medium cardiovascular risk.

BACKGROUND: The clinical value of echocardiography and ambulatory blood pressure monitoring (ABPM) in hypertensive patients at low immediate risk of cardiovascular disease is still unknown. METHODS: Echocardiography and ABPM were performed in 715 untreated subjects with essential hypertension World Health Organization/International Society of Hypertension stage I or II and low or medium cardiovascular risk defined by the absence of diabetes, previous cardiovascular events, left ventricular (LV) hypertrophy at electrocardiography, proteinuria, stages III-IV retinopathy and creatinine levels > 106.08 mmoll (1.2 mg/dl) and the presence of one or two traditional risk factors. RESULTS: The LV mass was increased in 26.5% of these subjects. Subjects with a limited blood pressure reduction from day to night (non-dippers) were 11.3%. Over 1-13 years of follow-up, 31 subjects developed a first major cardiovascular event. The event rate (per 100 person-years) was 0.60 in the subgroup with a normal LV mass vs 1.63 in that with an increased LV mass (p < 0.017), and 0.74 in dippers vs 3.75 in non-dippers (p < 0.001). On multivariate analysis, the relative risk of cardiovascular events was 1.70 (95% confidence interval-CI 1.23-2.36) for each 11 g/m(2.7) increment in LV mass (p < 0.01), and 2.77 (95% CI 1.12-6.83) in non-dippers vs dippers (p < 0.05). Overall, on the basis of results of combined echocardiography and ABPM, 33% of subjects were at increased risk of future cardiovascular events. CONCLUSIONS: At standard first-line work-up performed on hypertensive subjects at low or medium cardiovascular risk, combined echocardiography and ABPM identify an increase in the risk of subsequent cardiovascular disease in one third of subjects.

Prognostic value of midwall shortening fraction and its relation with left ventricular mass in systemic hypertension.

We followed 1,778 subjects (up to 12 years) with essential hypertension who underwent echocardiography at the time of their initial diagnostic workup. There were 166 major cardiovascular events during follow-up and the prognostic value of the midwall shortening fraction did not remain significant after controlling for left ventricular mass.

Subclinical left ventricular dysfunction in systemic hypertension and the role of 24-hour blood pressure.

The relation between blood pressure (BP) and left ventricular (LV) systolic function in systemic hypertension is controversial. We assessed the relation of LV midwall fractional shortening (FS) to 24-hour BP in 1,702 never-treated hypertensive subjects (age 48 +/- 12 years), who underwent 24-hour BP monitoring and echocardiography. Stress-corrected endocardial and midwall FS (the latter calculated taking into account the epicardial migration of midwall during systole) were predicted in hypertensives on the basis of the values observed in 130 healthy normotensives (age 43 +/- 13 years, office BP 126/78 mm Hg). Subjects below the fifth percentile of observed-to-predicted FS had depressed LV function. The use of midwall FS resulted in an increase from 3.5% to 17.5% in the proportion of patients with depressed chamber function. Compared with the group with normal function, subjects with low midwall LV function had similar office systolic BP (155 +/- 21 vs 154 +/- 17 mm Hg), but increased 24-hour systolic BP (140 +/- 17 vs 133 +/- 12 mm Hg, p <0.001). Midwall FS had a closer negative relation to 24-hour systolic BP than to office systolic BP (r = -0.27 vs -0.08, p <0.001), whereas this difference was not apparent for diastolic BP (r = -0.23 vs -0.20). Compared with endocardial FS, midwall FS had a stronger inverse association to LV mass (r = -0.45 vs -0.16, p <0.001). Thus, an increased 24-hour BP load may chronically lead to depressed myocardial function in systemic hypertension in the absence of clinically overt heart disease.

Long-term effects of losartan and enalapril, alone or with a diuretic, on ambulatory blood pressure and cardiac performance in hypertension: a case-control study.

BACKGROUND: The long-term effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on ambulatory blood pressure and cardiac performance have never been examined comparatively. OBJECTIVE: We compared losartan and enalapril in their long-term effects on office and ambulatory blood pressure, cardiac structure and function, and routine biochemical tests. DESIGN: In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, 22 hypertensive subjects were studied with ambulatory blood pressure monitoring and echocardiography before and after an average of 3.3 years of treatment with losartan 50mg daily. These subjects were matched in a 1:3 ratio with a group of 66 subjects treated with enalapril 20mg daily. Case-control sampling was based on age (+/-5years), sex, pre-treatment office blood pressure (+/-5mmHg) and ambulatory blood pressure (+/-5mmHg), and duration of treatment (+/-6months). An additional group of subjects who interrupted their treatment with enalapril (n=18) or losartan (n =2) because of unwanted effects before execution of the follow-up study was not included in the analysis. RESULTS: Hydrochlorothiazide was added during follow-up in order to optimize blood pressure control (office blood pressure <140mmHg systolic and 90mmHg diastolic) in 10 subjects (45%) in the losartan group and 34 subjects (52%) in the enalapril group. Office and ambulatory blood pressures were lowered to a similar extent by losartan and enalapril. Left ventricular mass decreased from 98 to 87g/m(2) with losartan (P <0.01) and from 98 to 89 g/m(2) with enalapril (P <0.01). The change in left ventricular mass over time was more closely associated with the change in ambulatory blood pressure than with office blood pressure in both groups. Left ventricular internal diameter did not change with either drug. The endocardial shortening fraction, mid-wall shortening fraction and Doppler indexes of active diastolic relaxation did not change with either drug. None of the biochemical parameters showed a significant change. Serum uric acid showed a slight and non-significant reduction only in the losartan group. CONCLUSION: In this case-control study in uncomplicated subjects with essential hypertension, losartan and enalapril, alone or combined with a diuretic, effectively and equally lowered office and ambulatory blood pressure and induced a significant reduction in left ventricular mass during long-term treatment. Left ventricular systolic and diastolic function remained unchanged with either regimen.

Persistence of increased left ventricular mass despite optimal blood pressure control in hypertension.

BACKGROUND: Left ventricular hypertrophy is an adverse risk marker in essential hypertension and its regression has a favorable effect on prognosis. It is unclear whether blood pressure normalization induced by long-term therapy is able to normalize left ventricular mass completely. METHODS: In the setting of a prospective cohort study, 107 consecutive hypertensive patients who achieved blood pressure normalization (clinic blood pressure < 140/90 mmHg on > or = 3 consecutive visits) under long-term (1-10 years, average 2.9) drug treatment were individually matched with 107 healthy normotensive controls by gender, age (+/- 5 years), body mass index (+/- 3 kg/m2), and clinic systolic blood pressure (+/- 5 mmHg) in a case-control design. All subjects underwent 24-hour blood pressure monitoring and M-mode echocardiography. RESULTS: Treated hypertensive patients and normotensive controls did not differ by age, body mass index, clinic blood pressure (128/82 vs 128/81 mmHg), and 24-hour blood pressure (120/77 vs 120/76 mmHg). Left ventricular mass and relative wall thickness were greater in the hypertensive than in the normotensive group (97 +/- 24 vs 86 +/- 17 g/m2 and 0.40 +/- 0.08 vs 0.37 +/- 0.08, both p < 0.001). CONCLUSIONS: Left ventricular mass is greater in well-controlled hypertensive patients than in normotensive controls matched by age, obesity, gender, and clinic and 24-hour blood pressure. This finding is consistent with the lower than epidemiologically expected reduction in coronary heart disease risk during antihypertensive therapy and might reflect the persistent effect on left ventricular mass of hemodynamic and/or non-hemodynamic factors other than blood pressure in treated patients with essential hypertension.

Clinical relevance of office underestimation of usual blood pressure in treated hypertension.

Average 24-h blood pressure (BP) is more representative of usual BP than office BP. However, the clinical relevance of 24-h BP in treated hypertensive subjects is incompletely known. Thus, we studied 395 uncomplicated hypertensive subjects (209 men, 53+/-10 years) who were receiving antihypertensive drug therapy from >1 year. All subjects underwent 24-h ambulatory BP monitoring and M-mode echocardiography. Subjects were classified by tertile of the difference between observed and predicted 24-h systolic BP (the latter determined by regressing 24-h systolic BP on office systolic BP): higher-than-predicted (III tertile), around the regression line (II tertile), and lower-that-predicted (I tertile) 24-h BP. Despite similar office BP (144/89, 141/88, and 144/89 mm Hg in the III, II, and I tertile, P = not significant), age, body mass index, and duration of hypertension, left ventricular mass was greater in the subjects with higher-than-predicted 24-h systolic BP (50+/-14 g x m(-2.7)) than in the other two groups (46+/-13 g x m(-2.7) and 42+/-10 g x m(-2.7), both P < .05). The III tertile also showed a more concentric left ventricular geometric pattern (relative wall thickness was 0.42+/-0.08, 0.40+/-0.07, and 0.38+/-0.07 in the III, II, and I tertile, P < .001) and a reduced systolic function at the midwall level (16.8+/-3, 17.7+/-3, and 18.2+/-3, P < .001). In conclusion, treated hypertensive subjects whose 24-h BP is notably higher than one would predict from office BP are more likely to develop left ventricular hypertrophy, a strong adverse prognostic marker. In a sizable subset of treated hypertensive subjects, BP measured in the physician's office underestimates usual BP and its impact on left ventricular structure.

Continuous relation between left ventricular mass and cardiovascular risk in essential hypertension.

The detection of left ventricular (LV) hypertrophy on echocardiography is a powerful risk indicator in essential hypertension. However, the prognostic impact of LV mass values within the "normal" range and the shape of the relation between LV mass and prognosis remain unclear. Thus, 1925 white subjects with uncomplicated essential hypertension underwent off-therapy 24-hour blood pressure monitoring and M-mode echocardiography. During 4. 0+/-2 years of follow-up, there were 181 major cardiovascular events (2.4/100 patient-years) and 49 deaths from all causes. In the 5 gender-specific quintiles of LV mass distribution (partition values: 92, 105, 120, and 138 g/m(2) in men and 79, 91, 102, and 116 g/m(2) in women), cardiovascular event rates were 0.8, 1.7, 2.2, 2.9, and 4. 3 per 100 patient-years. After adjustment for several risk factors, including 24-hour ambulatory blood pressure, the relative risk (RR) of developing a cardiovascular event increased progressively from the first quintile (RR 1) to the second (RR 1.6, 95% CI 0.8 to 3.1), third (RR 1.9, 95% CI 1.01 to 4.0), fourth (RR 3.0, 95% CI 1.5 to 5. 8), and fifth (RR 3.5, 95% CI 1.8 to 6.8) quintile. For all-cause death, the RR in the fifth quintile compared with the first quintile was 4.3 (95% CI 1.2 to 13.4). In conclusion, the powerful relation between LV mass and risk of cardiovascular disease in subjects with uncomplicated essential hypertension is continuous over a wide range of LV mass values, even below the current "upper normal" limits. The relation remains significant after control for traditional risk factors, including ambulatory blood pressure.

Relation between serum uric acid and risk of cardiovascular disease in essential hypertension. The PIUMA study.

The question of serum uric acid as an independent risk factor in subjects with essential hypertension remains controversial. For up to 12 years (mean, 4.0) we followed 1720 subjects with essential hypertension. At entry, all subjects were untreated and all were carefully screened for absence of cardiovascular disease, renal disease, cancer, and other important disease. Outcome measures included total cardiovascular events, fatal cardiovascular events, and all-cause mortality. During 6841 person-years of follow-up there were 184 cardiovascular events (42 fatal) and 80 deaths from all causes. In the 4 quartiles of serum uric acid (division points: 0.268, 0.309, and 0.369 mmol/L [4.5, 5.2, and 6.2 mg/dL] in men; 0.190, 0.232, and 0.274 mmol/L [3.2, 3.9, and 4.6 mg/dL] in women), the rate (per 100 person-years) of cardiovascular events was 2.51, 1.48, 2.66, and 4.27, that of fatal cardiovascular events was 0.41, 0.33, 0.38, and 1.23, and that of all-cause deaths was 1.01, 0.55, 0.93, and 2.01, respectively. The relation between uric acid and event rate was J-shaped in both genders. After adjustment for age, gender, diabetes, total cholesterol/HDL cholesterol ratio, serum creatinine, left ventricular hypertrophy, ambulatory blood pressure, and use of diuretics during follow-up, uric acid levels in the highest quartile were associated with increased risk for cardiovascular events (relative risk, 1.73; 95% CI, 1.01 to 3.00), fatal cardiovascular events (relative risk, 1.96; 95% CI, 1.02 to 3.79), and all-cause mortality (relative risk, 1.63; 95% CI, 1.02 to 2.57) in relation to the second quartile. In untreated subjects with essential hypertension, raised uric acid is a powerful risk marker for subsequent cardiovascular disease and all-cause mortality.

Value of a simple echocardiographic linear predictor of left ventricular mass in systemic hypertension.

The need for calculations limits the clinical use of left ventricular (LV) mass. Because LV mass is strictly dependent on wall thickness for every given value of LV external dimension, we tested the clinical value of the sum of LV external dimension plus ventricular septal thickness plus posterior wall thickness as predictors of standard LV mass. We studied 295 healthy normotensive subjects and 1,686 subjects with systemic hypertension, followed up for 1 to 9 years. In the normotensive group, the predictor of LV mass showed a very close association with standard LV mass according to an allometric model (LV mass [g] = 0.230 x LV mass predictor [cm]3.01), with 99.7% of LV mass variability explained by the model. Also, in the hypertensive group, the LV mass predictor showed a very close allometric relation to standard LV mass (R2 = 0.998). During follow-up there were 154 cardiovascular morbid events and 50 deaths from all causes. The risk of cardiovascular morbid events and that of death increased to a similar extent with LV mass normalized by body surface area, height or height2.7, as well as with the LV mass predictor. The risk estimates for cardiovascular morbidity and all-cause mortality provided by models including either LV mass predictor or LV mass uncorrected or corrected by height, body surface area, or height2.7 did not show any statistical differences between the different models. In conclusion, the sum of LV external dimension plus ventricular septum thickness plus posterior wall thickness, easily measurable from the M-mode echocardiographic tracing, very closely predicts standard LV mass in adult hypertensive subjects. The prognostic value of this measure does not differ from that of standard LV mass.

Circulating insulin and insulin growth factor-1 are independent determinants of left ventricular mass and geometry in essential hypertension.

BACKGROUND: It is unclear whether insulin and insulin-like growth factor-1 (IGF-1) are independent determinants of left ventricular (LV) mass in essential hypertension. METHODS AND RESULTS: We studied 101 never-treated nondiabetic subjects with essential hypertension. All had 24-hour noninvasive ambulatory blood pressure (ABP) monitoring and a 75-g oral glucose tolerance test. We determined fasting glucose, insulin, and IGF-1 and postload glucose and insulin 2 hours after glucose. Insulin resistance was estimated by the homeostasis model assessment (HOMA(IR)) formula. LV mass showed an association with body mass index (BMI) (r=0.47; P<0.01), postload insulin (r=0.54; P<0.01), HOMA(IR) (r=0.39; P<0.01), and IGF-1 (r=0. 43; P<0.01) and a weaker association with average 24-hour systolic and diastolic ABPs (r=0.29 and r=0.26; P<0.05) and basal insulin (r=0.31; P<0.05). Relative wall thickness was positively related to IGF-1 (r=0.39; P<0.01) but not to fasting or 2-hour postload insulin, HOMA(IR), and glucose. In a multiple regression analysis, the final LV mass model (R(2)=0.64) included IGF-1, postload insulin, average 24-hour systolic ABP, sex, and BMI. IGF-1 and postload insulin accounted for >40% of variability of LV mass. The final model (R(2)=0.36) for relative wall thickness included IGF-1 (16% total explained variability), average 24-hour systolic ABP, sex, BMI, and age but not insulin and HOMA(IR). CONCLUSIONS: These data indicate that insulin and IGF-1 are powerful independent determinants of LV mass and geometry in untreated subjects with essential hypertension and normal glucose tolerance.