Cardiovascular Risk In Essential Hypertension Research Articles

Statins benefit in androgen levels and target organ damage in hypertensive males with erectile dysfunction

Abstract Background Statins may benefit cardiovascular physiology by cholesterol independent or pleiotropic actions. Target organ damage (TOD) amplifies cardiovascular risk in essential hypertension and endogenous testosterone (TT) exhibit vasoprotective effects. Erectile dysfunction (ED) is frequent in hypertensive middle aged men when androgen levels typically fall, impairing thus quality of life. Purpose To investigate the effect of statins in TT and TOD in hypertensive middle aged men with ED, independently of cholesterol levels. Methods 248 hypertensive ED males (mean age: 57 yo) with no history of diabetes mellitus or overt cardiovascular disease enrolled the study. Of those 95 (38%) were on statin therapy for treatment of dyslipidemia. There were all screened for the presence of microalbuminuria, defined as urinary albumin loss 30–300 mg in a 24 h urine volume collection. TT, total cholesterol (Tchol) and low density lipoprotein (LDL) levels were measured on blood samples taken before 09:00 am. All individuals underwent a non invasive evaluation of the carotid-femoral pulse wave velocity (PWV), estimation of central pressures and augmentation index (AIx) a parameter of wave reflection amplification (Sphygmocor device). ED severity was assessed by the SHIM-5 score (range: 0–25) and higher values indicate a better erectile ability. Results In bivariate analysis statin use was positively related to TT (p<0.05 – Figure 1) and negatively to microalbuminuria, Tchol and LDL (p<0.005). Moreover TT was negatively related to PWV, AIx, microalbuminuria (all p<0.005) and positively to the SHIM-5 score (p: 0.003). By linear regression analysis association of TT to statins remained significant after correction for age, BMI, PWV, AIx, Tchol and LDL levels. Conclusions Statin therapy benefits endogenous testosterone in hypertensive middle aged men with ED and so lessens TOD and enhances erectile ability independently of cholesterol levels. In such population group pleiotropic effects of statins may help restoring androgen levels, decrease cardiovascular risk and ameliorate quality of life. Funding Acknowledgement Type of funding sources: None.

Target organ damage in relation to intensity of cigarette smoking, statin therapy and the endogenous testosterone in middle aged hypertensive men with erectile dysfunction

Abstract Background Target organ damage (TOD) amplifies cardiovascular risk in essential hypertension. Erectile dysfunction (ED) refers to microvascular disease and frequently accompanies the hypertensive middle aged male population. Endogenous testosterone (TT) and statins exhibit vasoprotective effects while cigarette smoking typically relates to an adverse cardiovascular outcome. Purpose To investigate TOD in relation to cigarette smoking, statin therapy and TT in essential hypertension middle aged males with ED. Methods 223 hypertensive ED males (mean age: 59 yo) with no history of diabetes mellitus or overt cardiovascular disease enrolled the study. There were all screened for the presence of microalbuminuria, defined as urinary albumin loss 30 – 300 mg in a 24 h urine volume collection. Among them 96 (43%) were current cigarette smokers. Intensity of smoking referred in terms of packs per year. The presence and severity of ED was assessed by the SHIM-5 score (range 0–25), higher values indicate better erectile ability. All underwent a non invasive evaluation of the carotid – femoral pulse wave velocity (PWV), estimation of central pressures and augmentation index (AIx) a parameter of wave reflection amplification (Sphygmocor device).Moreover left ventricular mass index (LVMI) was assessed by 2D echocardiography (Devereux formula) and intima-media thickness (cIMT) of the common carotid artery by vascular ultrasound imaging. cIMT is a marker of atheromatosis. Results Microalbuminuria detected in 89 (40%) patients was positively related to other parameters of TOD such as PWV, cIMT, LVMI (all p<0,005) and smoking habits (p=0,02) and negatively to the SHIM-5 score, TT and statin use (all p<0,01). A notably negative correlation to the intensity of smoking was the SHIM-5 score (p=0,013) and a positive the cIMT (p=0,001). Statins were positively related to TT (p=0,006).In linear regression analysis, relation of packs per year remained significant regarding microalbuminuria and the SHIM-5 after adjustment for age, body mass index, PWV, LVMI, central systolic, diastolic and pulse blood pressure. Similarly, relation of statins, TT and microalbuminuria remained significant after adjustment for age, LVMI, PWV, AIx and smoking status. Conclusion Intensive cigarette smoking accelerates silent kidney damage and sabotages erectile performance in hypertensive middle aged men with ED independently of the central hemodynamic load. Statins protect from microvascular kidney damage and the decline of testosterone probably by enhancing endothelial physiology. In such population group, simple and clinically oriented criteria may reveal early diagnosis of target organ damage and guide appropriate life-style modifications and further therapeutic judgments. Funding Acknowledgement Type of funding sources: None. Figure 1

HDL CHOLESTEROL LEVELS AND ENDOTHELIAL GLYCOCALYX INTEGRITY IN TREATED HYPERTENSIVE PATIENTS OVER 40 YEARS OLD

Abstract Objective: Endothelial dysfunction indicates target organ damage in hypertensive patients. The integrity of endothelial glycocalyx (EG) plays a vital role in vascular permeability, inflammation and elasticity and finally to cardiovascular disease. We aimed to investigate the role of increased HDL cholesterol levels (HDL-C), which usually are considered protective against cardiovascular disease, in EG integrity in middle aged hypertensive patients. Design and method: We studied 186 treated hypertensive patients, apparently healthy and older than 40 years. They were divided regarding sex distribution in two groups. In males’ group, HDL-C was 48 + 19 mg/dl (n = 77, mean age 51 + 11 years) while in females’ group, HDL-C was 67 + 16 mg/dl (n = 109, mean age 63 + 12 years). Increased perfusion boundary region (PBR) of the sublingual arterial microvessels (ranged from 5–9 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck) was measured as a non-invasive accurate index of reduced EG thickness. Results: Females were older (p = 0.04) with fewer smokers (p = 0.04), higher levels of office SBP (148 + 19 mmHg vs. 139 + 15 mmHg, p < 0.001) as well as higher HDL levels (p < 0.001). No differences were found within groups regarding BMI, DBP, total Cholestelol and PBR 5–9. In males, HDL-C was inversely related with PBR 5–9 (r = -0.29, p = 0.01). In a multiple linear regression analysis model, using smoking habit and office SBP levels, as independent variables, we found that HDL-C independently predicted PBR 5–9 (Beta = 0.25, p = 0.006) in male hypertensives. Conclusions: In middle-aged, apparently healthy, hypertensive patients, higher HDL-C levels protect EG and subsequently endothelial function. However, the role of EG as a novel index regarding cardiovascular risk in essential hypertension needs to be extensively investigated in future studies.

Tissue-Type Plasminogen Activator Release in Healthy Subjects and Hypertensive Patients

The relationship between adrenergic stimuli and NO in modulating tissue-type plasminogen activator (t-PA) release from endothelial cells was investigated in normotensive subjects and essential hypertensive patients. Sympathetic activation, a well-known stimulus for endogenous fibrinolysis, is also involved in the determination of cardiovascular risk in essential hypertension. However, the existence of cross-talk between adrenergic stimuli and NO availability in modulating t-PA release is not well established yet. We assessed the release of t-PA in the forearm microcirculation of 58 normotensive subjects (mean age: 47+/-9 years) and 44 essential hypertensive patients (mean age: 48+/-11 years) under specific intra-arterial adrenergic stimuli. Intrabrachial infusion of epinephrine (0.1 to 0.3 microg/100 mL per minute) induced greater t-PA release in normotensive subjects as compared with essential hypertensive patients (P<0.05). However, inhibition of NO synthase with N(G)-monomethyl-L-arginine (100 microg/100 mL per minute) infusion blunted epinephrine-induced t-PA release in normotensive subjects (P<0.05) but not in essential hypertensive patients. In normotensive subjects, t-PA release by epinephrine was not affected by phentolamine (8 microg/100 mL per minute) coinfusion and was abolished in the presence of propanolol (10 microg/100 mL per minute). Intrabrachial isoproterenol (0.03 microg/100 mL per minute) induced a significant increase in t-PA release (P<0.01), an effect blunted by N(G)-monomethyl-L-arginine (P<0.05). In essential hypertensive patients, the response to isoproterenol was impaired as compared with normotensive subjects and was unaffected by N(G)-monomethyl-L-arginine coinfusion. In conclusion, the results of the present study demonstrate that adrenergic-induced t-PA release is mediated by beta-adrenoreceptors via a mechanism involving the NO pathway. Our results show an impaired adrenergic-stimulated t-PA release among essential hypertensive patients, probably mediated via a reduced NO availability. This impaired fibrinolytic activity might contribute to the increased cardiovascular risk associated with hypertension.

Long-Term Effects of Angiotensin II Receptor Blockade with Valsartan on Carotid Arterial Stiffness and Hemodynamic Alterations in Patients with Essential Hypertension

Increased arterial stiffness and intima media thickness (IMT) in the common carotid artery (CCA) are related to cardiovascular risk in essential hypertension. Angiotensin II plays an important role in structural and functional changes in the vasculature. In this study, we evaluated the long-term effect of the angiotensin II receptor blocker, valsartan, on IMT, arterial stiffness, and hemodynamics in the CCA in patients with essential hypertension. A prospective 24 month study of treatment with valsartan (80–160mg/day) was performed in 24 hypertensive patients. An ultrasound of the CCA was carried out to determine IMT, the cross-sectional distensibility coefficient (CSDC), the carotid arterial stiffness index β, and diastolic flow velocity to systolic flow velocity ratio (Vd/Vs). Treatment with valsartan for 24 months reduced systolic and diastolic blood pressure significantly. Compared to baseline, the decrease in pulse pressure was greater after 24 months treatment than after 12 months treatment. Valsartan did not influence IMT; however, after 24 months, it caused a significant increase in CSDC and a decrease in stiffness index β compared to baseline. These changes were not observed after 12 months of treatment. In addition, Vd/Vs, a sensitive marker of relative diastolic blood flow, increased after 24 months' treatment with valsartan. These results suggest that long-term treatment with valsartan improves vascular wall function and hemodynamics in patients with essential hypertension.

The Many Possible Benefits of Natriuretic Peptides After Myocardial Infarction

Natriuretic peptides (NPs) are well-known markers of the ventricular hypertrophic response, as documented in many studies performed either in animals or with cultured cardiomyocytes. In recent years, evidence has been mounting that NPs are in fact negative regulators of the hypertrophic response, as reviewed recently.1 In this light, NPs appear as endogenous cardioprotective agents of which expression increases in reaction to myocardial pathological conditions, but it is still unclear to which extent these agents may actually decrease mortality. In this issue of Hypertension , Nakanashi et al2 show that when myocardial infarction (MI) is induced by permanent occlusion of the coronary artery, mortality by heart failure is increased in knockout mice with inactivation of the gene coding for the NP receptor guanylyl cyclase-A (GC-A). Beyond these short-term effects, inactivation of GC-A also worsens post-MI chronic ventricular remodeling. Although the present study does not show whether these chronic remodeling processes also increase mortality at a later stage, the remodeling is accompanied by ventricular enlargement and decreased fractional shortening, both of which usually associate with poor prognosis. The importance of these data is enhanced by the fact that increasing numbers of studies are investigating the utility of recombinant NPs in humans.3 However, several questions remain concerning the particular modes of action of NPs. One issue concerns the question of whether NPs work via peripheral mechanisms or via a direct action on the myocardium. Importantly, congestive heart failure is accompanied by volume expansion, and the present article shows that the natriuresis and diuresis are decreased in GC-A knockout animals during the 4 days that follow MI, thus possibly contributing to increased heart failure during …

Role of Microalbuminuria in the Assessment of Cardiovascular Risk in Essential Hypertension

Accurate cardiovascular risk evaluation is a prerequisite for devising cost-effective therapeutic strategies in patients with essential hypertension. In fact, the knowledge of concomitant risk factors, diabetes, target organ damage, or associated clinical conditions may be useful when deciding both treatment and BP goals. Thorough evaluation of target organ damage is the key to sensitive assessment of global risk, but cost-effective allocation of economic resources should also be taken into consideration. Thanks to its low cost and widespread availability, the search for microalbuminuria is a first-line tool for identifying hypertensive patients who are at higher cardiovascular risk.

Prognostic impact of low‐shear whole blood viscosity in hypertensive men

The role of blood viscosity as a marker for discriminating cardiovascular risk in essential hypertension remains uncertain. The aim of this study was to assess whether whole blood viscosity (WBV) could be useful in assessing cardiovascular risk in men with a first diagnosis of hypertension. A total of 331 middle-aged men with newly diagnosed essential hypertension (age at entry 40-64 years, average blood pressure 151/95 mmHg) underwent low-shear-rate (0.94 s(-1)) and high-shear-rate (94.5 s(-1)) WBV determination and were then followed for a mean of 4.8 +/- 3 years (range 0-12 years). Cardiovascular event rates in the bottom, middle and top tertiles of the distribution of low-shear WBV were 1.10, 2.13 and 4.43 per 100 patient-years, respectively (log-rank test, P < 0.001). After taking into account several established cardiovascular risk factors in a Cox survival analysis, a raised low-shear WBV conferred an increased risk for cardiovascular events (top vs. bottom tertile hazard ratio = 3.42, 95% confidence interval = 1.4-8.4, P = 0.006; middle vs. bottom tertile hazard ratio = 2.25, 95% confidence interval = 0.9-5.6, P = 0.09). The independent association between high-shear-rate WBV and cardiovascular events bordered statistical significance (P = 0.07). Inclusion in the survival model of low-shear-rate resulted in a significantly greater chi(2) improvement (P < 0.05) than inclusion of high-shear-rate WBV. In hypertensive men, an increased WBV at low shear rate is a predictor of cardiovascular events independently from the effect of several traditional risk factors. Low-shear WBV is a better discriminator of cardiovascular risk than high-shear WBV.

Effect of proteinuria and glomerular filtration rate on cardiovascular risk in essential hypertension

Changes in renal function related with essential hypertension are associated with an elevated cardiovascular morbidity and mortality. Indices of altered renal function (e.g., microalbuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance or GFR, and overt proteinuria) are independent predictors of cardiovascular morbidity and mortality. The Framingham Heart Study documented the relevance of proteinuria for cardiovascular prognosis in the community. The INSIGHT Study assessed the role of proteinuria as a risk factor in essential hypertension. The presence of proteinuria at baseline turned out to be a very potent predictor for the development of cardiovascular events and death in patients with essential hypertension and one or more associated cardiovascular risk factors. Recent data indicate that minor derangements of renal function, including proteinuria, are associated, both in the community and in the hypertensive population, with the clustering of cardiovascular risk factors observed in metabolic syndrome that promote progression of atherosclerosis. Renal function has to be routinely evaluated in every hypertensive patient, and the presence of minor alterations considered in the stratification of cardiovascular risk in hypertensive patients.

Angiotensin II Receptor Blocker Prevents Increased Arterial Stiffness in Patients With Essential Hypertension

High pulse wave velocity (PWV) is related to cardiovascular risk in essential hypertension (EHT). It is reported that short-term treatment with an angiotensin II receptor blocker (ARB) decreases PWV, as well as blood pressure (BP), and increases the serum adiponectin, known as an adipocytokine, which has an anti-atherosclerotic effect. However, it is not known whether long-term treatment with ARB prevents the increase in PWV independently of the reduction of BP, and whether adiponectin is related to the chronic effect of ARB on PWV. In order to examine the short-term effect of ARB on PWV, 9 subjects with EHT had PWV measured before and after treatment with an ARB for 1 month. The treatment significantly reduced PWV and BP. For evaluation of the long-term effect of ARB therapy, 56 consecutive subjects with EHT who were already taking anti-hypertensive drugs other than an angiotensin-converting enzyme inhibitor had their PWV measured. We divided the EHT subjects into 2 groups: (1) the ARB group (EHT treated with an ARB for at least 6 months) and (2) the control group (EHT treated with anti-hypertensive drugs other than an ARB). Although there was no significant difference between the 2 groups in BP, age or body mass index, the PWV value in the ARB group was significantly lower than that in the control group. Moreover, the serum adiponectin concentration in the ARB group was significantly higher than that in the control group. Long-term treatment with ARB inhibits the progression of arterial stiffness independent of BP reduction. One of the mechanisms may be related to the increased serum adiponectin concentration after treatment with an ARB.

Microalbuminuria

The capacity of microalbuminuria to predict an increased cardiovascular and renal risk is well established in diabetic patients, as well as in essential hypertensive patients and in general population. Detection of microalbuminuria could then be relevant to select specific therapeutic strategies for reducing or preventing cardiovascular events in patients with essential hypertension. Microalbuminuria is detectable in almost 40% of the population with established hypertension, particularly in those patients not controlled satisfactorily with medical therapy. Albuminuria may represent a marker of renal damage and cardiovascular risk in essential hypertension. Microalbuminuria seems to represent a simple and reproducible method to better define cardiovascular risk profile in the hypertensive patient and to stratify the prognosis in relation to renal and cardiovascular risk. ACE-inhibitors and more recently angiotensin II receptor antagonists seem to exhibit a more market capacity to reduce microalbuminuria in patients with essential hypertension or diabetes mellitus. Determination of this parameter in daily clinical practice could facilitate the stratification of risk as well as the choice of therapy in essential hypertensive patients.

The kidney as a sensor of cardiovascular risk in essential hypertension.

Renal damage as a consequence of uncontrolled arterial hypertension is well recognized. Antihypertensive therapy has come to very significantly decrease the vascular damage in the kidneys of hypertensive patients. However, prevalence of mild renal insufficiency remains present in a significant proportion of the hypertensive population. This is accompanied by a marked increase in cardiovascular risk, as a consequence of the clustering of other cardiovascular risk factors and of insufficiently controlled BP. Prevention and protection of renal and cardiovascular damage in these patients will be one of the most relevant tasks in the future.

Microalbuminuria identifies overall cardiovascular risk in essential hypertension: an artificial neural network-based approach.

Ultrasound (US) examination of heart and carotid arteries provides an accurate assessment of target organ damage (TOD) and may influence the stratification of the absolute cardiovascular risk profile. Microalbuminuria has recently proved to be a useful cost-effective marker of increased cardiovascular risk but is still too often neglected in clinical practice. To evaluate how well artificial neural networks (ANNs) predict cardiovascular risk stratification by means of routine data and urinary albumin excretion, as compared to prediction by the clinical work-up suggested by the International Society of Hypertension (ISH), with and without ultrasound-determined TOD. A group of 346 never previously treated essential hypertensives (212 men, 134 women, mean age 47 +/- 9 years) was studied. Risk was stratified according to the criteria suggested by the 1999 WHO/ISH guidelines; first, by routine procedures alone, and subsequently by reassessment, using data on cardiac and vascular structures obtained by US evaluation. The ANN was trained and tested to predict the overall cardiovascular risk on the basis of routine clinical data and urinary albumin excretion (UAE). The impact of these three approaches on the determination of cardiovascular risk profile was evaluated. According to the first classification, 5.5% (n = 19) of patients were considered at low risk, 47.3% (n = 164) at medium, 26.7% (n = 92) at high and 20.6% (n = 71) at very high risk. A marked change in risk stratification, namely an increase in the prevalence of high- and very-high-risk patients (2.3% low, 29.8% medium, 42.8% high and 25.2% very high risk; chi(2) 15.201, P < 0.0001), was obtained when US examination of TOD was taken into consideration. On the basis of routine clinical data and UAE, the artificial neural network successfully predicted overall cardiovascular risk and allocated patients in different classes as accurately as the US-based evaluation. The use of US techniques allows a more precise stratification of absolute cardiovascular risk in hypertensive patients as compared to routine clinical data. An ANN can accurately identify the patients' risk status by using low-cost routine data and UAE. These results further emphasize the value of UAE in the stratification of cardiovascular risk.

Microalbuminuria identifies overall cardiovascular risk in essential hypertension: an artificial neural network-based approach

Microalbuminuria identifies overall cardiovascular risk in essential hypertension: an artificial neural network-based approach

Microalbuminuria, an integrated marker of cardiovascular risk in essential hypertension.

This paper reviews the existing epidemiological and clinical evidence about the relationships of non-diabetic microalbuminuria with cardiovascular risk factors such as elevated blood pressure (BP), systolic particularly, cardiac hypertrophy, adverse metabolic status, smoking habits, elevated angiotensin II levels, endothelial dysfunction, acute and perhaps subclinical inflammation. Because of that unique property of reflecting the influence of so many clinically relevant parameters, microalbuminuria may legitimately be defined as an integrated marker of cardiovascular risk, an unique profile among the several prognostic predictors available to stratify risk in hypertensive patients. Recent cohort studies also showed associations with cardiovascular morbidity and mortality independently from conventional atherogenic factors. This behaviour, whose understanding still needs further elucidation, suggests to measure albuminuria and to screen patients at a higher absolute risk in whom preventive treatment is expected to be more beneficial than in those with a lower absolute risk.

High-normal serum creatinine concentration is a predictor of cardiovascular risk in essential hypertension.

Determination of serum creatinine concentration is recommended in all patients with hypertension as a marker of target organ damage. However, the possibility that creatinine values within the reference range might contribute to stratification of cardiovascular risk in essential hypertension has never been tested. In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale Study, for up to 11 years (mean, 4 years) we followed up 1829 white patients with hypertension (mean +/- SD age, 51 +/- 12 years; 53% men; office blood pressure, 157/98 mm Hg) free of cardiovascular events and with normal pretreatment creatinine levels (men, <136 micromol/L [<1.5 mg/dL]; women, <120 micromol/L [<1.4 mg/dL]) who also underwent 24-hour blood pressure monitoring and electrocardiography before therapy. During follow-up, there were 175 fatal or nonfatal major cardiovascular morbid events (2.4 per 100 patient-years). Event rate increased progressively from the first to the fourth sex-specific quartiles of creatinine distribution (1.5, 2.3, 2.3, and 3.5 per 100 patient-years; P =.003 by log-rank test). After adjustment (in a multivariate Cox model) for age, sex, diabetes, cholesterol, smoking, left ventricular hypertrophy, and 24-hour pulse and mean blood pressures (P<.05 for all), creatinine concentration was an independent adverse predictor of cardiovascular morbid events (P =.01). The observed excess risk was 1.30 (95% confidence interval, 1.07-1.59) for a 20-micromol/L (0.23-mg/dL) increase in creatinine concentration. A serum creatinine value within the reference range is a predictor of cardiovascular morbidity in white patients with essential hypertension. Its prognostic value persists after adjustment for several powerful confounders, including average 24-hour blood pressure and left ventricular hypertrophy.

Renal Participation in Cardiovascular Risk in Essential Hypertension

The possibility that the kidney plays a relevant role in the origin of essential hypertension in humans has been amply debated [1–3]. However, it has also been shown that the kidney suffers the consequences of sustained elevated blood pressure in the absence of therapy [4]. Nephrosclerosis together with diabetic nephropathy are the most common causes of end-stage renal disease [5]. A review of the literature published in the last decade transmits the picture that, with an "adequate" blood pressure control with standard antihypertensive therapy, the kidney is well protected and very few patients will suffer the consequences of blood pressure increments [6, 7]. The aim of this short review is to present the evidence supporting the existence of mild renal insufficiency in hypertensive patients, but also to show the association of this disorder with a very significant increment in global cardiovascular risk.

Genetic polymorphism of the renin-angiotensin system and organ damage in essential hypertension

The renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development of hypertensive cardiac and vascular remodeling. Recently, several genetic variants of its key components, which may be clinically relevant and thus prove to be useful in the evaluation of cardiovascular risk, have been described. We therefore investigated the association between ACE I/D, AGT M235T, and AT1 A1266C gene polymorphisms and early signs of target organ damage in 215 untreated patients with essential hypertension (EH). Genotyping was based on the polymerase chain reaction technique, with further restriction analysis when required. Albuminuria was measured as the albumin-to-creatinine ratio (ACR). The left ventricular mass index (LVMI) was assessed by echocardiography (LVH = LVMI > or = 125 g/m2), carotid wall thickness (IMT) by an ultrasonographic (US) scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of microalbuminuria (Mi), LVH, and retinal vascular changes was 14, 46, and 74%, respectively. ACE, AGT, and AT1 genotype distribution was in agreement with the Hardy-Weinberg equilibrium. There was no difference in age, duration of disease, body mass index (BMI), blood pressure, and lipid profile when data were analyzed on the basis of genotype. Serum levels of angiotensin-converting enzyme (ACE) were related to the ACE genotype (10.2 +/- 0.5, DD; 8.2 +/- 0.3, ID; 6.5 +/- 0.4 IU/mL, II; P < 0. 0001 by analysis of variance). The ACE genotype independently influences serum ACE levels and accounts for approximately 14% of its variations (F = 26.7, r2 = 0.1393, df 1 to 214, P < 0.0001). Patients with DD and ID genotypes showed higher levels of ACR (1.59 +/- 0.2, DD + ID; 0.8 +/- 0.2 mg/mmol, II; P < 0.006 by ANOVA) and bigger LVMI (124.1 +/- 2.3, DD + ID vs. 117.8 +/- 3.6 g/m2, II; P < 0.01 by ANOVA). No differences in the prevalence and degree of target organ damage (TOD) were found when data were analyzed on the basis of the AGT and AT1 genotypes, respectively. Potentially unfavorable combinations of genotypes were also investigated by K-means cluster analysis. Two subgroups of patients were identified (cluster 1, N = 70; cluster 2, N = 57), and each differed significantly with regards to the presence and degree of TOD and patterns of RAAS gene polymorphisms (F, 15.97 for ACR; F, 7.19 for IMT; F, 217.03 for LVMI; F, 3.91 for ACE; F, 4.06 for AGT; and F, 5. 22 for AT1; df 1 to 214, P < 0.02, for each one of the variables examined). The D allele of the ACE gene may be an independent risk factor for the development of target organ damage, and evaluating it could be useful for assessing cardiovascular risk in EH. Unfavorable patterns of RAAS genotypes seem to predispose patients to subclinical cardiovascular disease in EH.

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.