Hypertriglyceridemia and omega-3 fatty acids: Their often overlooked role in cardiovascular disease prevention.

AIMS: This review aims to describe the pathogenic role of triglycerides in cardiometabolic risk, and the potential role of omega-3 fatty acids in the management of hypertriglyceridemia and cardiovascular disease. DATA SYNTHESIS: In epidemiological studies, hypertriglyceridemia correlates with an increased risk of cardiovascular disease, even after adjustment for low density lipoprotein cholesterol (LDL-C) levels. This has been further supported by Mendelian randomization studies where triglyceride-raising common single nucleotide polymorphisms confer an increased risk of developing cardiovascular disease. Although guidelines vary in their definition of hypertriglyceridemia, they consistently define a normal triglyceride level as <150 mg/dL (or <1.7 mmol/L). For patients with moderately elevated triglyceride levels, LDL-C remains the primary target for treatment in both European and US guidelines. However, since any triglyceride level in excess of normal increases the risk of cardiovascular disease, even in patients with optimally managed LDL-C levels, triglycerides are an important secondary target in both assessment and treatment. Dietary changes are a key element of first-line lifestyle intervention, but pharmacological treatment including omega-3 fatty acids may be indicated in people with persistently high triglyceride levels. Moreover, in patients with pre-existing cardiovascular disease, omega-3 supplements significantly reduce the risk of sudden death, cardiac death and myocardial infarction and are generally well tolerated. CONCLUSIONS: Targeting resistant hypertriglyceridemia should be considered as a part of clinical management of cardiovascular risk. Omega-3 fatty acids may represent a valuable resource to this aim.

Hyperuricemia is associated with increased hospitalization risk and healthcare costs: Evidence from an administrative database in Italy.

BACKGROUND AND AIM: Chronic hyperuricemia is responsible for a relevant burden of articular diseases and cardio-nephrometabolic disorders. We evaluated the effect of high serum uric acid (SUA) levels on hospitalization risk and mortality and on healthcare costs in a real-life setting. METHODS AND RESULTS: We conducted a retrospective analysis using a large administrative database and a clinical registry among 112,170 subjects from three Italian local health units. Individuals were divided into four groups according to their SUA levels: <6 mg/dL (66.5%), >6 mg/dL and ≤7 mg/dL (19.3%), >7 mg/dL and ≤8 mg/dL (8.7%), and >8 mg/dL (5.5%). Compared to those with SUA level of <6 mg/dL, the risk of hospitalization related to gout and/or nephrolithiasis was higher in the three groups of patients with higher SUA levels (1.51, P = 0.100; 2.21, P = 0.005; and 1.17, P = 0.703, respectively). A similar trend was also observed for hospitalization due to chronic kidney disease (CKD) (1.31, P < 0.001; 1.40, P < 0.001; and 2.18, P < 0.001, respectively) and cardiovascular disease (CVD) (1.08, P < 0.001; 1.23, P < 0.001; and 1.67, P < 0.001, respectively) and for all-cause mortality (0.97, P = 0.309; 1.21, P < 0.001; and 2.15, P < 0.001). The mean annual healthcare costs were higher in patients with higher SUA level (€2752, €2957, €3386, and €4607, respectively) mainly because of a progressive increase in hospitalization costs per patient (from € 1515 for SUA <6 mg/dL to € 3096 for SUA >8 mg/dL). CONCLUSIONS: Increased SUA levels are associated with an increased risk of hospitalizations related to hyperuricemia, CKD, and CVDs and total mortality, and consequently with higher total healthcare costs and hospitalization costs per patient.

Serum uric acid and its relationship with metabolic syndrome and cardiovascular risk profile in patients with hypertension: insights from the I-DEMAND study.

BACKGROUND AND AIMS: The independent role of serum uric acid (SUA) as a marker of cardio-renal risk is debated. The aim of this study was to assess the relationship between SUA, metabolic syndrome (MS), and other cardiovascular (CV) risk factors in an Italian population of hypertensive patients with a high prevalence of diabetes. METHODS AND RESULTS: A total of 2429 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were stratified on the basis of SUA gender specific quartiles. MS was defined according to the NCEP-ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi) <60 ml/min/1.73 m(2) or as the presence of microalbuminuria (albumin-to-creatinine ratio ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women). The prevalence of MS, CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA levels correlated with the presence of MS, its components, signs of renal damage and worse CV risk profile. Multivariate logistic regression analysis revealed that SUA was associated with a positive history of CV events and high Framingham risk score even after adjusting for MS and its components (OR 1.10, 95% CI 1.03-1.18; P = 0.0060; OR 1.28, 95% CI 1.15-1.42; P < 0.0001). These associations were stronger in patients without diabetes and with normal renal function. CONCLUSIONS: Mild hyperuricemia is a strong, independent marker of MS and high cardio-renal risk profile in hypertensive patients under specialist care. Intervention trials are needed to investigate whether the reduction of SUA levels favorably impacts outcome in patients at high CV risk.

Cardiovascular and renal effects of hyperuricaemia and gout.

A number of epidemiological studies have reported an association between serum uric acid levels and a wide variety of high-risk conditions including hypertension, insulin resistance, and kidney and cerebro-cardiovascular disease. All things considered, serum uric acid may induce cardiovascular and kidney events both directly and indirectly by promoting other well-known mechanisms of damage. While asymptomatic hyperuricemia is currently not considered to be an indication for urate lowering therapy, there is growing evidence indicating a linear relationship between pharmacological reduction in serum uric acid and incidence of cardiovascular and renal events.

Author Correction: Antihypertensive treatment with calcium channel blockers and renal protection: focus on lercanidipine and lercanidipine/enalapril.

Correction to: European Review for Medical and Pharmacological Sciences 2022; 26 (20): 7482-7492. DOI: 10.26355/eurrev_202210_30018-PMID: 36314318, published online on October 28, 2022. After publication, the authors applied some corrections to the text: - The section "Clinical Oharmacology of Lercanidipine" has been corrected into "Clinical Pharmacology of Lercanidipine" - The Legend of Figure 2 has been corrected as follows: Ca T-type channels vs. Ca L-type channels selectivity ratio. LAC, lacidipine, AML, amlodipine; MIB, mibefradil; LER, lercanidipine; *p<0.05, ** p<0.01 vs. LAC (low concentrations); †p<0.01 LAC vs. all other CCBs (high concentrations). Source: Modified from 25. - The reference 25 has been changed into: Hart P, Bakris GL. Calcium antagonists: Do they equally protect against kidney injury? Kidney Int 2008; 73: 795-796. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/30018.

Antihypertensive treatment with calcium channel blockers and renal protection: focus on lercanidipine and lercanidipine/enalapril.

OBJECTIVE: The aim of the study was to review the literature on clinical pharmacology of lercanidipine and experimental and clinical evidence and evaluate its ability to reduce proteinuria and preserve renal function when used as monotherapy or in combination with the angiotensin-converting enzyme (ACE) inhibitor enalapril. MATERIALS AND METHODS: MEDLINE/PubMed was searched for appropriate keywords. RESULTS: Lercanidipine, a third-generation calcium channel blocker, has been shown to have a unique pharmacological and clinical profile, which translates into favorable renal hemodynamic changes. The fixed-dose combination lercanidipine/enalapril has been proposed to overcome unmet therapeutic needs, often as the initial treatment in the high-risk patient. CONCLUSIONS: Lercanidipine may be regarded as an ideal antihypertensive drug for patients at renal risk and possibly the preferred choice among calcium channel blocker drugs.

A prediction model to assess the risk of egfr loss in patients with type 2 diabetes and preserved kidney function: The amd annals initiative.

OBJECTIVE: To develop and validate a model for predicting 5-year eGFR-loss in type 2 diabetes mellitus (T2DM) patients with preserved renal function at baseline. RESEARCH DESIGN AND METHODS: A cohort of 504.532 T2DM outpatients participating to the Medical Associations of Diabetologists (AMD) Annals Initiative was splitted into the Learning and Validation cohorts, in which the predictive model was respectively developed and validated. A multivariate Cox proportional hazard regression model including all baseline characteristics was performed to identify predictors of eGFR-loss. A weight derived from regression coefficients was assigned to each variable and the overall sum of weights determined the 0 to 8-risk score. RESULTS: A set of demographic, clinical and laboratory parameters entered the final model. The eGFR-loss score showed a good performance in the Validation cohort. Increasing score values progressively identified a higher risk of GFR loss: a score ≥ 8 was associated with a HR of 13.48 (12.96-14.01) in the Learning and a HR of 13.45 (12.93-13.99) in the Validation cohort. The 5 years-probability of developing the study outcome was 55.9% higher in subjects with a score ≥ 8. CONCLUSIONS: In the large AMD Annals Initiative cohort, we developed and validated an eGFR-loss prediction model to identify T2DM patients at risk of developing clinically meaningful renal complications within a 5-years time frame.

Sub-clinical organ damage in hypertension and obesity.

BACKGROUND: The development of sub-clinical organ damage precedes and predicts the occurrence of cardiovascular (CV) events in hypertensive as well as in obese patients. AIM AND METHODS: We investigated the prevalence and clinical correlates of organ damage (OD), namely carotid atherosclerosis (US scan) and urine albumin to creatinine ratio (three non-consecutive first morning samples) in a group of 164 obese patients and in an age- and gender-matched group of non-obese hypertensive patients. RESULTS: There was a significantly greater prevalence and severity of OD in obese patients as compared to non-obese hypertensive patients. In particular obese patients more frequently had microalbuminuria (16 vs 7%, χ(2) 5.8, P=0.0157) and carotid abnormalities (53 vs 10%, χ(2) 69.5, P<0.0001) as well as higher urinary albumin excretion rate (-0.05 ± 0.52 vs -0.28 ± 0.43log ACR, P<0.0001) and carotid intima-media thickness (0.955 ± 0.224 vs 0.681 ± 0.171, <0.0001). Notably, the coexistence of hypertension and obesity did not entail a greater prevalence and severity of OD. Moreover, after adjusting for potentially confounding factors including blood pressure levels, diagnosis of diabetes, and lipid profile, morbidly obese patients showed a 5-fold, and 22-fold higher risk of having microalbuminuria, and carotid atherosclerosis, respectively. CONCLUSIONS: Sub-clinical OD is highly prevalent in obese patients, even in the absence of high blood pressure. Hypertension and obesity seem to exert an independent, possibly non-additive role on the occurrence of organ damage.

Reduced glomerular filtration rate and prior cardiovascular event entail similar risk for coronary atherosclerotic burden.

OBJECTIVE: Prior cardiovascular event and kidney dysfunction are both strong risk factors for coronary artery disease. The aim of this study is to assess coronary atherosclerotic burden in a large population of patients undergoing coronary angiography, according to prior cardiovascular event or chronic kidney disease. PATIENTS AND METHODS: We evaluated 700 consecutive patients who underwent coronary angiography (CA). Serum creatinine to estimate glomerular filtration rate (eGFR) was measured. Clinically significant coronary artery disease (CAD) was defined by the presence of a coronary lesion resulting in a luminal stenosis >50%. For the purpose of the study, the whole population was divided into 4 subgroups according to the presence/absence of eGFR <60 ml/min/1.73 m2 or prior cardiovascular event: eGFR≥60/no event (Group A), eGFR≥60/yes event (Group B), eGFR<60/no event (Group C), eGFR<60/yes event (Group D). PATIENTS: As expected, patients in group D had the worst clinical and biochemical profile. These patients also presented the highest values of urinary albumin creatinine ratio (ACR, p<0.001) and the lowest values of eGFR (p<0.01). One-hundred-ninety-six patients had three-vessel disease. Patients who had undergone PCI procedure showed a lower eGFR as compared to patients who had not (p=0.009). Considering group A as reference, the risk of having three-vessel disease was increased in group B (OR= 2.09; 95% CI 1.37-3.19), in group C, (OR= 1.80; 95% CI 1.04-3.14), and finally in group D (OR= 3.35; 95% CI 2.01-5.58). The risk carried by group C was not significantly different from that carried by Group B: OR= 0.86; 95% CI 0.5-1.5. CONCLUSIONS: In our study, low eGFR seems to have the same excess risk of prior CV event.

Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project.

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

[Glomerular filtration rate and cardiovascular risk: prognostic and therapeutic implications]. / Filtrato glomerulare e rischio cardiovascolare: implicazioni prognostiche e terapeutiche.

The glomerular filtration rate is generally accepted as the best overall measure of kidney function and many scientific organizations recommend the use of equations that estimate this parameter to facilitate the diagnosis, evaluation and management of chronic kidney disease. Large-scale epidemiological studies have shown that a mild to moderate reduction in glomerular filtration rate is not an uncommon condition in the general population, and its prevalence further increases in patients at higher cardiovascular risk. Moreover, a large body of evidence has recently established that even minor renal dysfunction is an independent predictor of adverse cardiovascular prognosis. The excess cardiovascular risk related to renal damage is due in part to a higher prevalence of traditional atherosclerotic risk factors, in part to nontraditional, emerging risk factors peculiar to chronic kidney disease which enhance the atherogenic process at the systemic level. Therapeutic approaches in the presence of renal damage are aimed at providing simultaneous cardiovascular and renal protection. Optimal blood pressure control, as indicated by international guidelines, is of the utmost importance both to slow the progression of renal damage and to prevent cardiovascular events. Better outcomes of renal function can be obtained with inhibition of the renin-angiotensin system in both diabetic and nondiabetic renal disease, although the administration of a combination of antihypertensive drugs will be required in almost every patient to achieve the blood pressure target. Aggressive intervention on associated modifiable cardiovascular risk factors is also advisable in order to optimize the global risk profile of patients with chronic kidney disease.

Metabolic syndrome and ambulatory arterial stiffness index in non-diabetic patients with primary hypertension.

Increased arterial stiffness and the presence of metabolic syndrome (MS) have been shown to predict cardiovascular events in patients with primary hypertension. We investigated the relationship between a recently proposed index of arterial stiffness derived from ambulatory blood pressure (BP) monitoring and MS in 156 untreated, non-diabetic patients with primary hypertension. Ambulatory arterial stiffness index (AASI) was defined as 1 minus the regression slope of diastolic over systolic BP readings obtained from 24-h recordings. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The prevalence of MS was 23%. Patients with MS were more frequently male (0.0291) and had increased serum uric acid (P=0.0005), high-sensitivity C-reactive protein (P=0.0259), as well as total and low-density lipoprotein (LDL)-cholesterol (P=0.0374 and P=0.0350, respectively) as compared to those without MS. After adjusting for these confounders, the association between AASI and the presence of MS was statistically significant (P=0.0257). Moreover, the prevalence of increased AASI (upper tertile, that is >or=0.550) was greater in patients with MS (P=0.0156). After adjusting for age and 24-h mean BP, the presence of MS entailed a more than twofold greater risk for increased AASI (0.0280). MS is associated with increased AASI in non-diabetic patients with primary hypertension. These data support the role of this new index of arterial stiffness as a marker of risk and help to explain the high cardiovascular morbidity and mortality that is observed in hypertensive patients with MS.

[The role of microalbuminuria in the overall risk assessment of hypertensive patients]. / Ruolo della microalbuminuria nella valutazione del rischio globale nel paziente con ipertensione essenziale.

The cost-effectiveness of antihypertensive treatment increases in parallel with the global burden of risk in the individual patient. Therefore, there has been growing interest in developing sensitive and easy-to-perform clinical tools to accurately and inexpensively identify patients at high cardiovascular risk. Over the past several years a number of studies have provided evidence that microalbuminuria is an integrated marker of hypertensive organ damage and a strong, independent predictor of cardiovascular and cerebrovascular events. Recent data indicate that the risk is linearly related to the degree of urinary albumin excretion, with no identifiable threshold or plateau. Furthermore, changes in urinary albumin excretion parallel changes in risk. We propose the routine search for microalbuminuria in order to optimize cost-effectiveness in the diagnostic approach to patients with primary hypertension.

Metabolic syndrome is associated with left ventricular dilatation in primary hypertension.

Metabolic syndrome (MS) has been shown to predict cardiovascular events in hypertension. Recently, a new four-group left ventricular (LV) hypertrophy classification based on both LV dilatation and concentricity was proposed. This classification has been shown to provide a more accurate prediction of cardiovascular events, suggesting that the presence of LV dilatation may add prognostic information. We investigated the relationship between MS and the new classification of LV geometry in patients with primary hypertension. A total of 372 untreated hypertensive patients were studied. Four different patterns of LV hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The overall prevalence of MS and LV hypertrophy (LVH) was 29% and 61%, respectively. Patients with MS showed a higher prevalence of LVH (P=0.0281) and dilated LV geometries, namely eccentric dilated and concentric dilated hypertrophy (P=0.0075). Moreover, patients with MS showed higher LV end-diastolic volume (P=0.0005) and prevalence of increased LV end-diastolic volume (P=0.0068). The prevalence of LV chamber dilatation increased progressively with the number of components of MS (P=0.0191). Logistic regression analysis showed that the presence of MS entails a three times higher risk of having LV chamber dilatation even after adjusting for several potential confounding factors. MS is associated with LV dilatation in hypertension. These findings may, in part, explain the unfavourable prognosis observed in patients with MS.

The calpastatin defect in hypertension is possibly due to a specific degradation by calpain.

Calpastatin activity, significantly reduced in erythrocytes of patients affected by essential hypertension, is restored to normal values by appropriate therapeutical treatments in a time-dependent fashion and in parallel with the decline in blood pressure. Evidence is also presented indicating that red cell calpastatin is degraded in human and rat red cells by homologous calpain, and that the rate of degradation is approx. 5-times higher in rat erythrocytes. Thus, increased proteolytic degradation catalyzed by calpain could explain both the decrease in the amount of calpastatin activity and the profound difference between the intracellular level of the calpain inhibitor observed in erythrocytes from patients with essential hypertension and the genetically hypertensive rats.

Blood pressure levels and control in Italy: comprehensive analysis of clinical data from 2000-2005 and 2005-2011 hypertension surveys.

This analysis is aimed to determine blood pressure (BP) levels and BP control rates in a large population of hypertensive patients in Italy. Data were taken from two large and inclusive cross-sectional surveys, which covered two distinct and subsequent time periods (2000-2005 and 2005-2011, respectively). Observational clinical studies and surveys, which reported average systolic/diastolic clinic BP levels, proportions of treated/untreated and controlled/uncontrolled patients, and prevalence of cardiovascular risk factors in hypertensive patients followed in either outpatient clinics, hypertension centres or general practice, were considered for the analyses. The overall sample included 211 591 hypertensive patients (119 997 (56.7%) women, age 57.0±10.0 years, body mass index 26.9±4.0 kg m(-2), BP levels 146.9±16.7/88.7±9.6 mm Hg). BP levels were 148.2±15.4/87.5±9.3 mm Hg in patients followed by general practitioners (n=168 313, 79.5%), 148.1±17.3/90.1±9.7 mm Hg in those followed by hypertension centres (n=28 180, 13.3%), and 142.4±17.6/86.6±9.8 mm Hg in those followed by outpatient clinics and hospital divisions (n=15 098, 7.1%). Among treated hypertensive patients (n=128 079; 60.5%), 43 008 (33.6%) were reported to have controlled BP levels. Over one decade of observation, we reported that ~60% of hypertensive patients were treated and among these only 33% achieved effective BP control. These findings highlight the need for more effective interventions to improve management of hypertension in Italy.

Erythrocyte deficiency in calpain inhibitor activity in essential hypertension.

The calpain-calpain inhibitor system was evaluated in erythrocytes of patients with essential hypertension and normotensive controls, either with or without a family history of hypertension. Calpain levels were similar in the controls and hypertensive patients, whereas the inhibitor activity level was significantly reduced in the latter (301.8 +/- 26.4 vs 220 +/- 14 U/mg hemoglobin, p less than 0.001). Borderline hypertensive patients and a few controls with a history of hypertension showed low inhibitor activity. Similar results have recently been reported in genetically hypertensive rats of the Milan strain. A significant inverse correlation (r = -0.43, p less than 0.001) was found between mean arterial pressure and calpain inhibitor. Although the pathophysiological significance of these observations is not yet clear, they suggest a new area of investigation into the molecular mechanisms underlying essential hypertension and its complications.

Prevalence and clinical correlates of microalbuminuria in essential hypertension: the MAGIC Study. Microalbuminuria: A Genoa Investigation on Complications.

The prevalence of microalbuminuria and its relationship with several cardiovascular risk factors and target organ damage were evaluated in a cohort of 787 untreated patients with essential hypertension. Albuminuria was measured as the albumin-to-creatinine ratio in three nonconsecutive, first morning urine samples. The prevalence of microalbuminuria was 6.7%. Albuminuric patients were more likely to be men and to be characterized by higher blood pressure, body mass index, and uric acid levels and lower HDL cholesterol and HDL cholesterol-to-LDL cholesterol ratio. Piecewise linear regression analysis demonstrated that uric acid and diastolic blood pressure significantly influence albuminuria and together account for a large part of its variations. K-means cluster analysis performed on the entire cohort of patients confirmed that microalbuminuria is associated with a worse cardiovascular risk profile. Furthermore, microalbuminuria was associated with the presence of target organ damage (eg, electrocardiographic [ECG] abnormalities and retinal vascular changes). Age and the presence of microalbuminuria act as independent risk factors for the development of ECG abnormalities and retinal vascular changes. Cluster analysis allowed us to identify three subgroups of patients who differed in the presence or absence of microalbuminuria, retinopathy, and ECG abnormalities. We conclude that the prevalence of microalbuminuria in essential hypertension is lower than previously reported. Increased urinary albumin excretion is associated with a worse cardiovascular risk profile and is a concomitant indicator of early target organ damage.

Fibroblast Na+-Li+ countertransport rate is elevated in essential hypertension.

OBJECTIVES: Elevated erythrocyte Na+- Li+ countertransport (SLC) rates are commonly found in essential hypertension. We have recently shown that human skin fibroblasts functionally express a phloretin-sensitive Na+-H+ exchange (NHE) which may also be similar to erythrocyte SLC because of amiloride-insensitivity. DESIGN AND METHODS: We investigated whether elevations in fibroblast SLC parallel the known elevations in erythrocyte SLC and in cell NHE that characterize essential hypertension. RESULTS: Higher fibroblast SLC rates were found among hypertensive patients (n = 23, median 48.8 nmol Li+/ mg(protein) per min) than in 19 normotensive individuals of similar age and sex (median 14.8 nmol Li+/mg(protein) per min, P= 0.0002). As expected, erythrocyte SLC was elevated in patients with hypertension (median 411 versus 329 micromol/l(cell) per h, P= 0.0273), but was not quantitatively related to fibroblast SLC. Finally, fibroblast NHE exchange activity was higher in essential hypertension (median Vmax 14.2 versus 7.6 mmol H+/l(cell) per min, P= 0.002), but was unrelated to fibroblast SLC. CONCLUSIONS: These findings extend to human skin fibroblasts the notion of abnormal Li+ transport in essential hypertension, and appear to be in accordance with the hypothesis that fibroblast SLC may be independent of NHE. However, molecular studies will be required to understand whether distinct exchangers and/or regulation mechanisms underlie these dysregulations.

Left ventricular geometry and function in patients with essential hypertension and microalbuminuria.

BACKGROUND: Microalbuminuria has recently emerged as a strong, independent predictor of cardiovascular mortality in patients with essential hypertension, yet the pathophysiological mechanisms underlying this association remain to be elucidated. OBJECTIVE: To study the relationship between microalbuminuria and left ventricular geometry and function and extra-cardiac vascular changes in a group of 211 untreated hypertensive patients. METHODS: Albuminuria was evaluated as albumin-to-creatinine ratio in three non-consecutive first morning urine samples. Left ventricular mass index and function were assessed by M-B mode echocardiography and carotid wall thickness by high-resolution ultrasound scan. RESULTS: The prevalences of microalbuminuria and left ventricular hypertrophy were 14 and 47% respectively. Patients in the top quartile of albuminuria showed a higher left ventricular mass index (57 +/- 1.8, 55 +/- 2, 47 +/- 1.4 and 48 +/- 1.6 g/m2.7, respectively; P< 0.0001) as well as a higher prevalence of left ventricular hypertrophy (72, 65, 26 and 25%, respectively; P< 0.001) and especially concentric hypertrophy (56, 47, 17 and 21%, respectively; P< 0.0001) in the four quartiles of albuminuria. Microalbuminuric patients showed depressed left ventricular performance as indicated by a reduced midwall fractional shortening (15.7 +/- 0.3, 15.9 +/- 0.3, 16.7 +/- 0.4 and 16.8 +/- 0.3%, respectively; P< 0.02). Furthermore patients in the top quartile of albuminuria showed increased carotid wall thickness as compared to normoalbuminuric patients (0.78 +/- 0.03, 0.7 +/- 0.04, 0.65 +/- 0.03 and 0.6 +/- 0.03 mm, respectively; P < 0.001). CONCLUSIONS: Hypertensive patients with microalbuminuria show a higher prevalence of unfavourable left ventricular geometric patterns, depressed left ventricular function and early signs of extra-cardiac vascular damage. These findings strengthen the role of microalbuminuria as an indicator of subclinical cardiovascular disease and may account for the worse outcome that is usually associated with increased urinary albumin excretion in essential hypertension.