The deletion polymorphism of the angiotensin I-converting enzyme gene is associated with target organ damage in essential hypertension

The activity of the renin-angiotensin-aldosterone system is thought to play a significant role in the development of target organ damage in essential hypertension. An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has recently been associated with increased risk for left ventricular hypertrophy and coronary heart disease in the general population. The D allele is associated with higher levels of circulating ACE and therefore may predispose to cardiovascular damage. The study presented here was performed to investigate the association between the ACE genotype, microalbuminuria, retinopathy, and left ventricular hypertrophy in 106 patients with essential hypertension. ACE gene polymorphism was determined by polymerase chain reaction technique. Microalbuminuria was evaluated as albumin-to-creatinine ratio (A/C) in three nonconsecutive first morning urine samples (negative urine culture) after a 4-wk washout period. Microalbuminuria was defined as A/C between 2.38 to 19 (men) and 2.96 to 20 (women). Hypertensive retinopathy was evaluated by direct funduscopic examination (keith-Wagener-Barker classification) and left ventricular hypertrophy by M-B mode echocardiography. The distribution of the DD, ID, and II genotypes was 27, 50, and 23%, respectively. The prevalence of microalbuminuria, retinopathy, and left ventricular hypertrophy was 19, 74, and 72% respectively. There were no differences among the three genotypes for age, known duration of disease, body mass index, blood pressure, serum glucose, uric acid, and lipid profile. DD and ID genotypes were significantly associated with the presence of microalbuminuria (odds ratio, 8.51; 95% confidence interval, 1.07 to 67.85; P = 0.019), retinopathy (odds ratio, 5.19; 95% confidence interval, 1.71 to 15.75; P = 0.005) and left ventricular hypertrophy (odds ratio, 5.22; 95% confidence interval, 1.52 to 17.94; P = 0.016). Furthermore, patients with DD and ID genotypes showed higher levels of A/C (3.6 +/- 0.9, DD; 2.6 +/- 0.7, ID; 0.9 +/- 0.2 mg/mmol, II; P = 0.0015 by analysis of variance) and increased left ventricular mass index (152 +/- 4.7, DD + ID versus 133 +/- 5.7 g/m2, II; P = 0.01) compared with II patients. The D allele was significantly more frequent in patients with microalbuminuria (odds ratio, 2.59; 95% confidence interval, 1.24 to 5.41; P = 0.013) and in those with retinopathy (odds ratio, 2.44; 95% confidence interval, 1.21 to 4.90; P = 0.015). Multiple regression analyses performed among the entire cohort of patients demonstrated that ACE genotype significantly and independently influences the presence of retinopathy, left ventricular hypertrophy, and microalbuminuria. In conclusion, the D allele of the ACE gene is associated with microalbuminuria as well as with retinopathy and left ventricular hypertrophy, and seems to be an independent risk factor for target organ damage in essential hypertension.     

Left ventricular geometry as an independent predictor for extracardiac target organ damage in essential hypertension

Left ventricular hypertrophy (LVH) is an independent cardiovascular risk factor. It has not been established, however, whether left ventricular geometry is an independent predictor of extracardiac target organ damage in essential hypertension. Study groups were classified according to relative wall thickness: 27 patients with concentric LVH and 50 patients with eccentric LVH. Age and left ventricular mass indexes of two groups were matched. As indexes of extracardiac target organ damage, retinal funduscopic grade, and serum creatinine level were measured. The severity of hypertensive retinopathy and the renal involvement were more severe in patients with concentric LVH than in patients with eccentric LVH. Extracardiac target organ damage was consistently higher in patients with concentric LVH than in those with eccentric LVH. Systemic hemodynamics paralleled ventricular geometric patterns, with higher peripheral resistance and lower aortic compliance in patients with concentric LVH, whereas end-diastolic volumes and stroke volumes were higher in patients with eccentric LVH than in patients with concentric LVH. In addition, total peripheral resistance was related to retinal fundoscopic grade (r = 0.41, P < .01), and serum creatinine level (r = 0.28, P < .05). Even in the presence of an identical degree of LVH, echocardiographically determined left ventricular geometry may provide a further independent stratification of extracardiac target organ damage in essential hypertension.     

The effect of attention on phenomenal length

Family history of atherosclerosis has been recognised as an nonmodifiable cardiovascular risk factor. Lipid levels, together with hypertension and diabetes, appear to have an inheritable component. The aim of the study was to ascertain whether lipoprotein abnormalities of 169 adult patients with non-coronary atherosclerosis were associated with a family history of atherosclerosis. Besides intermediate density lipopoprotein composition and Lp(a) levels, we focused on apo(a) and apo E phenotypes, LDL cholesterol/apo B ratio, VLDL triglyceride/HDL cholesterol ratio, and environmental factors. We found that patients with a family history of atherosclerosis had a higher prevalence of VLDL triglyceride/HDL cholesterol ratio above 1.8 (51.3% vs 34.7%) than patients without. Similarly, there was a significant inverse correlation between both considered ratios (r = -0.24, p < 0.05). The odds ratio of the presence of both abnormal ratios (4.60, 95% CI, 1.41-15.00) and low molecular weight apo(a) isoforms (3.30, 95% CI, 1.05-10.30 and family history of atherosclerosis was independent of smoking and hypertension. Apo(a) isoform size seems to be more important than Lp(a) concentrations in the family history of atherosclerosis risk determination. Subsequent analysis showed that patients with a family history of atherosclerosis had a greater-than-fourfold increased risk of having one or both abnormal ratios reflecting metabolic disturbances which probably constitute a combined trait. Family history of atherosclerosis may constitute a specific lipoprotein-related marker of atherosclerosis. Such a marker often precedes the onset of overt disease and may contribute to identifying patients with an atherogenic lipoprotein profile even in the absence of classical lipid risk factors.     

Hyperperfusion syndrome following carotid endarterectomy: evaluation using diffusion-weighted magnetic resonance imaging--case report

OBJECTIVE: Epidemiological evidence suggests that resistance to insulin is the common nexus of the accumulation of factors in patients at high cardiovascular risk. To find a test which enables resistance to insulin to be identified in large populations will allow preventive and therapeutic measures to be taken. DESIGN: Crossover. SETTING: Carrascosa del Campo and Cuenca Health Centres. PARTICIPANTS: 408 patients (154 men and 254 women), all the non-diabetic obese patients at the two health centres, were studied. MEASUREMENTS AND MAIN RESULTS: Levels of cholesterol, triglycerides and uric acid were measured. Patients were medically examined, and blood pressure, waist and hip measurements, toxic habits and cardiovascular history were found. They were classified by pathology and normograms. The O'Sullivan and microalbuminuria tests were performed, and all the statistical associations with biochemical and medical characteristics were studied. The O'Sullivan test was significantly associated (p < 0.01) with cardiovascular risk and insulin-resistance factors such as hypercholesterolaemia (RR 1.63), hypertension (RR 1.92), hypertriglyceridaemia (RR 2.47), hyperuricaemia (RR 1.80), with the Berglund resistance index (RR 1.52) and the microalbuminuria test (RR 1.83). The association was more consistent when there were a number of factors combining. There was no relationship with the waist/hip index found. CONCLUSION: The O'Sullivan test, on its own or with the microalbuminuria test, seems very useful for identifying obese subjects with resistance to insulin.     

Syndrome X and mortality: a population-based study. Risk Factor and Life Expectancy Research Group

The present report analyzes the prevalence of the cluster of metabolic abnormalities defined as syndrome X (high blood glucose, high blood pressure, low high density lipoprotein (HDL) cholesterol, and high triglycerides) and its impact on cardiovascular disease mortality in a large cohort of men and women (22,561 men and 18,495 women). These individuals were participants in a series of epidemiologic investigations of cardiovascular disease conducted in Italy between 1978 and 1987. They were followed for an average of 7 years, during which time a total of 1,218 deaths occurred (1,003 in men and 215 in women). Deaths were coded according to the International Classification of Diseases, 9th Revision (ICD-9). The prevalence of the full cluster of metabolic abnormalities (syndrome X) was low in the population as a whole, with only 3.0 percent of men and 3.4 percent of women exhibiting the full cluster of abnormalities that comprise syndrome X. The risk of death from all causes and cardiovascular disease increased with increased numbers of metabolic abnormalities in both men and women. Mortality from cancer was significantly increased in women (but not in men) with syndrome X, compared with women with no metabolic abnormalities. Population attributable risks for all cause mortality and cardiovascular disease mortality were 0.06 and 0.09 in men and 0.04 and 0.48 in women when assessed by population cutpoints. These data from a large population-based epidemiologic investigation indicate that the presence of a full cluster of metabolic abnormalities from syndrome X is an important risk factor for cardiovascular disease and all-cause mortality in both men and women, but that the low prevalence of such a cluster in the population reduces the public health impact of syndrome X. The majority of individuals who die from cardiovascular disease present elevations in any one, two, or three of the metabolic abnormalities. The notion of the cluster of metabolic abnormalities (syndrome X) should not distract our attention from established individual risk factors that have been proven to be major causes of cardiovascular disease death and disability in our society.     

Microalbuminuria in essential hypertension

The prevalence of microalbuminuria in patients with essential hypertension ranges between 10 and 25%. The level of albuminuria is highly correlated with arterial pressure and more closely ambulatory arterial pressure. The interaction between albuminuria and arterial pressure is enhanced by overweight and smoking. The renal mechanisms of microalbuminuria are not well elucidated; however, an increase in filtration fraction suggestive of intraglomerular hypertension was observed in patients with hyperfiltration. The significance of microalbuminuria as a marker of cardiovascular risk or hypertensive renal damage needs to be confirmed through long-term follow-up studies. Antihypertensive treatment has variable influence on albuminuria; and angiotensin-converting enzyme inhibitors and to a lesser extent other agents, tend to partially correct this abnormality.     

High triglyceride, low HDL-cholesterol and risk of coronary heart disease

Hypercholesterolaemia is a strong risk factor of coronary artery disease (CAD). The importance of high triglyceride and low HDL cholesterol in predicting risk of CAD is less well-established. This review presents data showing that high triglyceride and low HDL cholesterol are important risk factors of CAD and suggests that combined lipid profiles of triglyceride, HDL cholesterol, and total cholesterol provide more information about risk of CAD than total cholesterol alone. High triglyceride and low HDL cholesterol is the characteristic dyslipidaemia seen in subjects with insulin resistance, a basic abnormality in glucose- and insulin metabolism. Since insulin resistance and raised triglyceride and decreased HDL cholesterol can be identified in children of patients with NIDDM, essential hypertension, and CAD, we suggest that efforts to prevent CAD should include interventions against all these associated abnormalities in glucose-, insulin-, and lipid metabolism and not only high cholesterol.     

Antibodies of the anti-Yo and anti-Ri type in the absence of paraneoplastic neurological syndromes: a long-term survey of ovarian cancer patients

PURPOSE: To determine the association between lipids, microalbuminuria and systemic blood pressure. Urinary albumin excretion rate (AER) was determined in timed overnight urine samples by radioimmunoassay. Microalbuminuria was defined when two out of three urine samples had AER ranging 20-200 micrograms/min. Lipids were determined by colorimetric methods (total cholesterol, HDL cholesterol and triglycerides). METHODS: Fifty patients with insulin dependent diabetes mellitus (28 females, 22 males) aged 21.9 +/- 7 years and with diabetes duration of 6.8 +/- 5.8 years attending the outpatients diabetes clinic were studied cross-sectionally. RESULTS: Microalbuminuria was present in 12% of our patients. A high systolic blood pressure (SBP) was found in microalbuminuric patients (p = 0.003). No difference concerning serum lipids were found in comparison between normo and microalbuminuric patients, although 20% of all patients had increased cholesterol and LDL cholesterol and 4% had high HDL cholesterol and triglycerides levels. Stepwise multiple regression analysis showed that SBP was the only significant independent variable to influence AER (r = 0.42 r2 = 0.18 p = 0.002). CONCLUSION: Although in our study, microalbuminuria was associated only with SBP, the independent alteration of lipids in young IDDM patients must be considered as a possible additional risk factor for cardiovascular disease.     

Heart protection: controlling risk factors for cardiovascular disease

Cardiovascular disease is the leading cause of illness and death in the United States. Clinical data continue to support primary prevention through the aggressive treatment of well-defined cardiovascular risk factors. Three risk factors that can be modified to lower the risk of cardiovascular disease and death are hypercholesterolemia, hypertension, and cigarette smoking. Even patients with asymptomatic cardiovascular disease have been shown to benefit from aggressive cholesterol-lowering therapy. New JNC-VI guidelines for managing hypertensive disease recommend that treatment decisions be based on level of blood pressure plus presence or absence of target organ damage or other risk factors. The risk of myocardial infarction in former smokers approaches that of nonsmokers after 3 years.     

Primary adenomatous tumor of the middle ear: a case report

This study was aimed at evaluating the level of metabolic control and cardiovascular risk factors in a population of Type 2 diabetic patients with coronary artery disease. We used myocardial thallium-201 scintigraphy as a measure of coronary perfusion integrity. One hundred and forty six diabetic patients presenting with chest pain, ischaemic ECG changes or a positive exercise test underwent myocardial thallium-201 imaging perfusion in conjunction with exercise stress. Scintigrams were assessed by a computer assisted image analysis. The cardiovascular risk factors considered were sex, age, BMI and waist-hip ratio, smoking, systolic and diastolic blood pressure, serum lipids (total cholesterol and triglycerides), glycated haemoglobin A1, urinary albumin excretion, white blood cell count, and diabetes duration. The proportion of male diabetic subjects with a positive scintigraphy was 63% while that of diabetic women was 45% (p < 0.05). Mean age, anthropometric measures and diabetes indices were similar when diabetic patients with positive or negative scintigraphy were compared. The prevalence of patients with microalbuminuria and retinopathy (both non-proliferative and proliferative) was higher in positive (26% and 27%, respectively) than in negative (10% and 11%, respectively, p = 0.01) diabetic patients. Total cholesterol and white blood cell counts were also higher in positive diabetics (p < 0.05-0.01). These findings suggest that a cluster of risk factors (cholesterol, white blood cells, microalbuminuria) may be implicated in the development of coronary artery disease in Type 2 diabetes mellitus.     

3-Hydroxy-3-methylglutaryl-CoA reductase gene of Gibberella fujikuroi: isolation and characterization

PURPOSE: Cardiovascular disease is a major cause of morbidity and death in non-insulin-dependent diabetes mellitus (NIDDM). While hyperglycemia is clearly related to diabetic microvascular complications, it contribution to large-vessel atherosclerosis is controversial. PATIENTS AND METHODS: We performed an analysis of the association between glycemic control and prevalent cardiovascular disease in 1,539 participants in the NIDDM Patient Outcomes Research Team study who were under usual care in a health maintenance organization. Prevalent cardiovascular disease and its risk factors were identified by self-administered questionnaire. Cardiovascular disease was defined by the presence of coronary heart disease, peripheral vascular disease, and/or cerebrovascular disease. Glycohemoglobin and lipid levels were obtained from a computerized laboratory database. RESULTS: The mean age of participants was 63 years (range 31 to 91); 51% were women. The mean duration of NIDDM was 9 years (range < 1 to 50), 35% took insulin, and 48% took sulfonylureas. Mean glycohemoglobin was 10.6%. Sixty percent had hypertension, 16% currently smoked cigarettes, and the mean total high-density lipoprotein (HDL) cholesterol ratio was 5.7. Fifty-one percent had cardiovascular disease. Cardiovascular disease prevalence remained constant across increasing quartiles of glycohemoglobin for both men and women. In contrast, prevalent cardiovascular disease was associated with established cardiovascular disease risk factors including age (67 versus 59 years, P < 0.0001), hypertension (66% versus 54%, P < 0.0001), current cigarette smoking (17% versus 13%, P < 0.005), and total/HDL cholesterol ratio (5.9 versus 5.6, P < 0.005). Cardiovascular disease was also associated with duration of NIDDM (11 versus 8 years, P < 0.0001). In multiple logistic regression analysis controlling for established cardiovascular disease risk factors and diabetes duration and therapy, glycohemoglobin remained unassociated with cardiovascular disease. CONCLUSIONS: Glycemic control is not associated with prevalent cardiovascular disease in this large population of individuals with NIDDM. Conventional cardiovascular disease risk factors are independently associated with cardiovascular disease and be a more promising focus for clinical intervention to reduce atherosclerotic complications in NIDDM.     

Drug clinics. How I treat a patient with a low concentration of HDL cholesterol

The decision to treat an individual with low HDL cholesterol level depends on his overall cardiovascular risk profile and the therapeutic strategy is based upon the characteristics of the lipid profile (isolated abnormality, associated hypertriglyceridaemia or combined elevation of LDL cholesterol). The treatment must favour diet and exercise, before considering a possible pharmacological approach. Results are usually acceptable with better life habits and appropriate diet when low HDL cholesterol level is associated to hypertriglyceridaemia. From a pharmacological point of view, the best results are obtained with fibrates or nicotinic acid. However, results are often disappointing when low HDL cholesterol level is isolated.     

Increased left ventricular mass in salt-sensitive hypertensive patients

Clinical, biochemical and echocardiographic characteristics were evaluated from 50 essential hypertensive patients classified asccording to their salt-sensitivity status. Salt-sensitive hypertension was diagnosed by means of ambulatory blood pressure monitoring (ABPM) in 22 (44%) patients showing a significant increase in mean BP (P < 0.05) from a 7-day period of low salt (20 mmol NaCl/day) intake, to a 7-day period of high salt (260 mmol NaCl/day) intake. The remaining 28 (56%) patients were considered as having salt-resistant hypertension. Compared with salt-resistant patients, salt-sensitive ones showed an increased left ventricular mass index (P = 0.0118), septal (P = 0.0021) and posterior wall thickness (P = 0.0026), without differences in the internal diastolic diameter. Decreased values of HDL-cholesterol (P = 0.0475) and increased total cholesterol/HDL-cholesterol ratio (P = 0.0098) were also observed in the salt-sensitive, compared with the salt-resistant hypertensive patients. Age, gender, body mass index, systolic and diastolic BP, fasting plasma glucose, creatinine and uric acid did not differ between salt-sensitive and salt-resistant patients. We conclude that, at the same level of BP, salt-sensitive patients exhibit an increased prevalence of left ventricular hypertrophy and a worse lipid profile. These two aspects may confer to salt-sensitive patients an increased risk in terms of cardiovascular morbidity and mortality.     

Inositolphosphoglycans and diacyglycerol are possible mediators in the glycogenic effect of GLP-1(7-36)amide in BC3H-1 myocytes

The objective of this study is to examine the influence of lipid profiles and blood pressure on the development of microvascular complications in adolescents with insulin-dependent diabetes mellitus (IDDM) in a matched pairs study. Patients with early background retinopathy (n = 21) or microalbuminuria (n = 15) and their respective statistical twins participated in the study. Serum total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting triglycerides, glycosylated haemoglobin A1c (HbA1c), and systolic and diastolic blood pressure during 3 years prior to the development of early background retinopathy or incipient nephropathy were examined. The multivariate discriminant analysis demonstrated glycaemic control and HDL cholesterol to be the most important variables related to the development of retinal lesions (84% correctness), and diastolic blood pressure to be associated with microalbuminuria (57% correctness). In addition to poor glycaemic control, different factors seem to be important for the early retinal or renal lesions of juvenile IDDM.     

Bursts of high-frequency synchronized electrical activity in the dog neocortex during food-related operant conditioning

BACKGROUND: Many studies have shown that estrogen replacement with oral micronized 17 beta-estradiol reduces the risk of cardiovascular disease. The aim of the present study was to evaluate the efficacy of transdermal estrogen replacement therapy in improving the risk profile of cardiovascular disease in postmenopausal women. METHODS: Two hundred and fifty postmenopausal women were enrolled from the "Bene Essere Donna" Center and grouped according to the absence (Group I, n = 175; mean age 54.6 +/- 3.5) or presence of mild to moderate hypertension (Group II, n = 75; mean age 54.1 +/- 4.5). Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glucose and fibrinogen levels were tested in all women. The total study population was treated with estrogen replacement therapy for 12 months: hysterectomized women received 17 beta-estradiol (0.05 mg/die), while non-hysterectomized women received 17 beta-estradiol 0.05 mg/die plus 5 mg/die of medroxyprogesterone acetate for 12 days during every 28-day cycle. After 12 months, blood pressure and blood chemistry were measured as baseline. RESULTS: Total cholesterol, LDL cholesterol and glucose levels decreased in both groups. HDL cholesterol levels increased significantly only in the sub-group of Group II treated with estrogen plus progesterone. Triglycerides glucose and fibrinogen blood levels decreased in both groups. No cardiovascular events were recorded during the first year of follow-up. CONCLUSION: Transdermal estrogen replacement therapy should be considered as a therapeutic support in order to contrast the elevated cardiovascular risk in postmenopausal women.     

A longitudinal study of work load and variations in psychological well-being, cortisol, smoking, and alcohol consumption

PURPOSE: Although public health interventions have not specifically targeted high density lipoprotein (HDL) cholesterol, observed changes in the prevalence of other cardiovascular risk factors would be expected to have differential effects on HDL. This study examined secular trends in HDL in relation to changes in other cardiovascular risk factors for the years 1981 through 1993 in the Pawtucket Heart Health Program (PHHP) study communities. METHODS: Nonfasting HDL levels were assessed in 12,223 respondents to six biennial population random sample surveys. RESULTS: Between 1981 and 1993, mean HDL cholesterol declined by 0.08 mmol/L in both men and women after adjustment for age, city, education, hormone use, medications, recent alcohol use, smoking, regular exercise, body mass index (BMI), and total cholesterol, (p for trend < 0.001). There was no apparent laboratory explanation for the trend which occurred concurrent with decreased smoking prevalence, increasing BMI and decreased prevalence of recent alcohol use. Decreasing HDL cholesterol was observed consistently across subgroups defined by smoking, alcohol use and BMI. CONCLUSIONS: Although several favorable cardiovascular risk factor trends have been observed in recent decades, declining HDL cholesterol is also of interest, particularly in conjunction with population increases in BMI.     

Secondary prevention in the elderly

A decrease in plasma HDL cholesterol concentration is considered as a major cardiovascular risk factor and is a prevalent lipid abnormality among patients with coronary heart disease. This condition is most often observed in the presence of hypertriglyceridaemia, generally linked to the insulin resistance syndrome, but may also be associated to elevated LDL cholesterol level or even be present alone (hypoalphalipoproteinaemia). The decision to treat a patient with low HDL level depends on the individual overall cardiovascular risk which should be evaluated as carefully as possible. The investigation should look for causes which may favour this metabolic condition, such as bad life habits or possible pharmacological interferences.     

Ureteral occlusion prosthesis

The improving survival rate of patients with childhood cancer has led to a growing awareness of the long-term effects of malignant disease and its treatment. Various endocrine abnormalities have been reported as frequent long-term adverse effects of cancer treatment in childhood, and among these growth hormone (GH) deficiency is the most common one, especially after cranial irradiation. Besides promoting growth, GH has well-established metabolic effects. Patients with GH deficiency tend to be obese, and obesity per se is also associated with insulin resistance which plays a key role in a cluster of metabolic derangements including glucose intolerance, hypertension, lipid abnormalities and atherosclerotic cardiovascular disease. This condition is known as the metabolic syndrome. Our recent observations indicate that a combination of obesity, glucose intolerance, hyperinsulinaemia and an abnormal lipid profile can be observed in long-term survivors of childhood cancer. Every sixth patient had the triad of obesity, hyperinsulinaemia and low HDL cholesterol, whereas this combination was not seen in any of the controls. The survivors with such a high-risk profile for cardiovascular disease had markedly reduced spontaneous GH secretion, and also additional features of the metabolic syndrome, such as higher systolic blood pressure and higher plasma glucose and serum triglyceride levels. Accordingly, decreased GH secretion, or alternatively some other disturbance in the hypothalamic-pituitary axis, emerging as a consequence of cranial radiation, may expose long-term survivors of childhood cancer to premature evolution of the metabolic syndrome. This can have an important impact on the long-term prognosis in these patients, because the syndrome as such results in an increased risk of cardiovascular morbidity and mortality.     

Phosphatidylinositol 4-kinase of Torpedo californica electrocytes: physico-chemical characterization and regulation by calcium and vicinal molecules of phosphatidylinositol

The kidney is an important target of hypertension-induced organ damage. Recent long-term observation studies have documented that in individuals, without primary chronic renal disease, a very significant relationship exists between hypertension and impaired renal function, elderly hypertensives having a particularly worse prognosis. The hallmark of hypertensive renal injury is thought to be a progressive increase in intrarenal vascular resistance. The alterations in renal hemodynamics are accentuated in elderly patients with essential hypertension, pointing to a greater vulnerability of the senescent kidney to superimposed injury such as high blood pressure. Treatment of elevated blood pressure in the elderly therefore not only reduces cardiovascular morbidity and mortality, but also reduces the incidence of renal failure as a consequence of hypertension-induced damage.     

Angiotensin converting enzyme gene I/D polymorphism in essential hypertension and nephroangiosclerosis

An insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene significantly influences circulating ACE levels and plays a role in the development of target organ damage, that is, left ventricular hypertrophy in essential hypertension (EH), and microalbuminuria in diabetes mellitus. We have examined the role of the I/D polymorphism in essential hypertensive patients with renal involvement. The study was divided in two independent protocols. In protocol 1, we retrospectively analyzed the ACE genotypes in 37 essential hypertensive patients with a clinical and histopathological diagnosis of nephroangiosclerosis. In protocol 2, ACE genotypes as well as microalbuminuria and renal hemodynamic parameters were investigated in 75 patients with EH with normal renal function and a strong family history of hypertension. As control group, 75 healthy subjects with BP < 130/85 mm Hg and no family history of cardiovascular diseases were studied. The ACE variants were determined by PCR and the genotypes were classified as DD, DI and II. In protocol 1, patients with nephroangiosclerosis displayed a significant difference in the genotype distribution (57% DD, 27% DI, 16% II) when compared to the control population (25% DD, 64% DI, 11% II; P < 0.001). There was no significant difference in genotype distribution between hypertensive patients with normal renal function (protocol 2; 33% DD, 59% DI, 8% II) and the control group. There were no differences in age, blood pressure, microalbuminuria and duration of the disease among the three genotypes in the EH group from protocol 2. Taken together, these findings suggest that the DD genotype of ACE is associated with histopathologic-proven kidney involvement in patients with EH and that this polymorphism could be a potential genetic marker in hypertensives at risk of renal complications.