Clustering Of Several Risk Factors Research Articles

Association of detrusor underactivity with aging and metabolic syndrome: suggestions from animal models.

Detrusor underactivity, a condition in which the bladder muscle does not contract strongly or long enough to empty the bladder completely or within the normal time frame, is a common cause of lower urinary tract symptoms in older individuals of both sexes. Although aging is a known risk factor for detrusor underactivity, its pathophysiological mechanisms are not fully understood. Therefore, establishing animal models that closely mimic the pathophysiology of detrusor underactivity in humans is necessary to elucidate these mechanisms. Metabolic syndrome is a cluster of several risk factors, including obesity, hyperlipidemia, hyperglycemia, and hypertension, which are associated with the development of diabetes, cardiovascular disease, and lower urinary tract dysfunction in both sexes. Notably, bladder dysfunction resulting from detrusor underactivity is observed at an earlier age in animal models with diabetes mellitus than in those without. Recently, detrusor underactivity-like phenotypes have been observed at a relatively early age in animal models with metabolic syndrome, involving obesity, hyperlipidemia, and hypertension, compared with those without. Therefore, this review introduces the association of detrusor underactivity with aging and metabolic syndrome, as well as possible pathophysiological mechanisms for detrusor underactivity from reports of various animal models. Notably, metabolic syndrome may accelerate the onset of age-related detrusor underactivity, and further analysis of old animal models with metabolic syndrome may help elucidate the pathogenesis of detrusor underactivity in humans.

Features of myocardial damage indexes in patients with metabolic syndrome and nonalcoholic fatty liver disease

Background: Metabolic syndrome (MetS) is a cluster of several risk factors and is considered major risk for the development of cardiovascular disease. Metabolic syndrome patients often have concomitant nonalcoholic fatty liver disease (NAFLD), and two coming together of these two conditions increases the risk of myocardial damage.

Assessment of occurrence of metabolic syndrome among post-menopausal women

Background: Metabolic syndrome is described by the clustering of several risk factors for cardiovascular disease such as hypertension, dyslipidemia, obesity, Insulin resistance, and high fasting plasma glucose. Objective of this study was to determine the frequency and evaluate the components of metabolic syndrome in post-menopausal women.Methods: This Descriptive study was conducted in OPD as well as IPD of Department of Medicine, Sri Siddhartha Medical college Hospital and Research Centre, Tumkur After obtaining written informed consent. Period of study was 24 months. Purposive sampling was used.Results: Mean age of post-menopausal women was 54.19±8.454 years. Mean age of menopause was 45.41±2.428. Majority of patients between were between 45-50 years (33.7%). There were high number of women (34.6%) whose postmenopausal duration ranged between 6-10 years. In our study 10(9.6%) postmenopausal women had type 2 DM and 15(14.4%) postmenopausal women had HTN. Metabolic syndrome was present in 65(62.5%) postmenopausal women and absent in 39(37.5%) postmenopausal women. Waist circumference >80 cm (68.3) was the most prevalent component of metabolic syndrome followed by HDL <50 mg/dl (53.8%), BP>130/80 mmHg (51%) triglycerides >150 mg/dl (44.2%)/ and FBS>100 mg/dl (39.4%). There was statistical significance observed between the components of metabolic syndrome and metabolic syndrome in postmenopausal women.Conclusions: The prevalence of metabolic syndrome was high in our study. The components of metabolic syndrome such as waist circumference, FBS, blood pressure, triglycerides were significantly raised and HDL levels were significantly reduced in post-menopausal women with metabolic syndrome.

Subgrouping of Iranian children and adolescents based on cardiometabolic risk factors using latent class analysis: The CASPIAN-V study.

Background:Cardiometabolic syndrome indicates the clustering of several risk factors. The aims of this study were to identify the subgroups of the Iranian children and adolescents on the basis of the components of the cardio-metabolic syndrome and assess the role of demographic characteristics, socioeconomic status and lifestyle-related behaviors on the membership of participants in each latent class.Methods:This cross-sectional study was performed on 3730 Iranian students in 2015 using stratified cluster. All students in each class completed anonymous and structured questionnaires. Abdominal obesity, high triglyceride (TG), low high-density lipoprotein (HDL), high blood pressure (BP), high fasting blood sugar (FBS), high low-density lipoprotein (LDL), high cholesterol and obesity were used for assessing the pattern of cardio metabolic risk as a latent variable. Data analysis was performed using PROC LCA in SAS software.Results:Four latent classes were identified in this study; namely 1) healthy (59.6%), 2) low risk (20.4%), 3) moderate risk (13.7%) and 4) high risk (6.4%). Being a female (OR=0.59, 95% CI: 0.46-0.74), living in a rural area (OR=0.45, 95% CI;0.33-0.60), high screen time (OR=1.56, 95% CI:1.09-2.24), and parental obesity (OR=1.52, 95% CI: 1.18-1.95) were associated with moderate risk class. Only living in rural areas (OR=0.71, 95% CI; 0.51-0.99) was associated with high risk class.Conclusion:About 20% of the students are in the moderate risk and high risk classes. Design and implement interventions according to risk-based class that seem necessary by considering probably risk and protective factors for the prevention of complications of cardiometabolic syndrome.

Circulating MicroRNAs to Predict the Risk for Metabolic Diseases in the General Population?

Metabolic syndrome (MetS) results from the cluster of several risk factors, including central obesity, insulin resistance, dyslipidemia, and hypertension. Around 20%–25% of the world’s adult population is estimated to have MetS (1). MetS has been estimated to confer a fivefold increase in the risk of type 2 diabetes (T2D) over the next 5–10 years (2). Both MetS and T2D increase the risk of cardiovascular disease (CVD) (3). MetS diagnosis is cumbersome. A simple noninvasive and inexpensive test that risk stratifies the general population before MetS onset would allow for primary prevention strategies, especially aggressive lifestyle modifications, and the more stringent monitoring of those individuals positive to the predictor. This may have an enormous impact on our national health systems, ultimately slowing down the diabetes epidemics. MicroRNAs (miRNAs, or miRs) are small noncoding RNA regulatory molecules that inhibit the expression of a plethora of mRNAs, which they target within their parent cells but also in other cells that they reach via different shuttling mechanisms (4). Such shuttles, including lipoproteins and extracellular vesicles, protect their cargos from degradation and deliver active miRNAs from cells to cells contributing to cell-to-cell communication. Moreover, by conferring resilience to miRNAs, the shuttles incidentally increase our possibilities to develop miRNAs in extracellular biomarkers. Among many different actions, miRNAs are now recognized as regulators of lipid and glucose metabolism and as involved in the development of metabolic and cardiovascular diseases (5,6). The liver-enriched miR-122 (now identified as miR-122-5p) was the first miRNA to be recognized functionally associated with a metabolic phenotype, and in particularly to regulate …

Novel Association of the R230C Variant of the ABCA1 Gene with High Triglyceride Levels and Low High-density Lipoprotein Cholesterol Levels in Mexican School-age Children with High Prevalence of Obesity

Metabolic syndrome (MetS) is a disorder that includes a cluster of several risk factors for the development of type 2 diabetes and cardiovascular disease. The R230C variant of the ABCA1 gene has been associated with low HDL-cholesterol in several studies, but its association with MetS in children remains to be determined. The aim of this study was to analyze the association of the R230C variant with MetS and other metabolic traits in school-aged Mexican children. The study was performed in seven urban primary schools in the State of Mexico. Four hundred thirty-two Mexican school-age children 6-13years old were recruited. MetS was identified using the International Diabetes Federation definition. The R230C variant of the ABCA1 gene was genotyped to seek associations with MetS and other metabolic traits. The prevalence of MetS was 29% in children aged 10-13years. The R230C variant was not associated with MetS (OR=1.65; p=0.139). Furthermore, in the whole population, the R230C variant was associated with low HDL-cholesterol levels (βcoefficient=-3.28, p <0.001). Interestingly, in the total population we found a novel association of this variant with high triglyceride levels (β coefficient=14.34; p=0.027). We found a new association of the R230C variant of the ABCA1 gene with high triglyceride levels. Our findings also replicate the association of this variant with low HDL-cholesterol levels in Mexican school-age children.

Do all components of the metabolic syndrome cluster together in U.S. Hispanics/Latinos? Results from the Hispanic Community Health study/Study of Latinos

PurposeMetabolic syndrome (MetS), the clustering of several risk factors for cardiovascular disease, is highly prevalent in Hispanics/Latinos. We tested whether all components significantly loaded on the syndrome in Hispanics/Latinos and whether their contribution differed by sex and Hispanic ancestry. We also examined associations of MetS with prevalent diabetes and coronary heart disease in Hispanics/Latinos. MethodsData were obtained from a population-based cohort of n = 15,823 participants in the HCHS/SOL study who self-identified as being of Central American, Cuban, Dominican, Mexican American, Puerto Rican, or South American ancestry and were aged 18 to 74 years at screening. ResultsA latent variable model of waist circumference, systolic and diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol (HDL-C), and fasting glucose fit the data in men and women, but the contribution of HDL-C was weak. No difference in the latent model of MetS was detected across Hispanic/Latino ancestry groups. MetS was significantly associated with diabetes and coronary heart disease. ConclusionsOur results indicate that similar criteria for MetS may be applied across Hispanic/Latino ancestry groups but call into question the role of HDL-C in classifying the MetS in Hispanics/Latinos.

A Review on Metabolic Syndrome

The metabolic syndrome is described by the clustering of several risk factors for Type 2 diabetes and cardiovascular disease. Lipid disorder, obesity, diabetes in general and high blood pressure are collectively defined as risk factors for cardiovascular disease triggered by metabolic syndrome. The metabolic syndromes have a correlation with the variations in genetic susceptibility, nutritional regiment, physical exercise, chronological age and gender which play direct role in the incidence of metabolic syndrome and its side effects. There are several definitions of Metabolic Syndrome in the World: World Health Organization's (WHO), The NCEP Adult Treatment Panel (ATP) III and the International Diabetes Federation (IDF). It appears that the female type 2 diabetic patients need to change their life style to halt the burden of cardiovascular complications in type 2 diabetic patients . Clinicians should significantly consider screening all people regardless of age for abnormalities in glucose level. Early treatment in people with abnormal glucose level constitutes a strategy of preventing type 2 diabetes mellitus and metabolic syndrome. Studies about metabolic syndrome have shown that females were more affected than males. This may be due to the specific characteristics in the lifestyle changes between females and males diabetic patients. Postmenopausal status might be a predictor of metabolic syndrome. Some related factors of metabolic syndrome among postmenopausal women may increase cardiovascular risk in postmenopausal women. doi: http://dx.doi.org/10.4021/jem118e

A Review on Metabolic Syndrome

The metabolic syndrome is described by the clustering of several risk factors for Type 2 diabetes and cardiovascular disease. Lipid disorder, obesity, diabetes in general and high blood pressure are collectively defined as risk factors for cardiovascular disease triggered by metabolic syndrome. The metabolic syndromes have a correlation with the variations in genetic susceptibility, nutritional regiment, physical exercise, chronological age and gender which play direct role in the incidence of metabolic syndrome and its side effects. There are several definitions of Metabolic Syndrome in the World: World Health Organization's (WHO), The NCEP Adult Treatment Panel (ATP) III and the International Diabetes Federation (IDF). It appears that the female type 2 diabetic patients need to change their life style to halt the burden of cardiovascular complications in type 2 diabetic patients . Clinicians should significantly consider screening all people regardless of age for abnormalities in glucose level. Early treatment in people with abnormal glucose level constitutes a strategy of preventing type 2 diabetes mellitus and metabolic syndrome. Studies about metabolic syndrome have shown that females were more affected than males. This may be due to the specific characteristics in the lifestyle changes between females and males diabetic patients. Postmenopausal status might be a predictor of metabolic syndrome. Some related factors of metabolic syndrome among postmenopausal women may increase cardiovascular risk in postmenopausal women. J Endocrinol Metab. 2012;2(4-5):166-170 doi: https://doi.org/10.4021/jem118e

Prevalence of metabolic syndrome and associated socioeconomic and demographic factors among Palestinian adults (20–65 years) at the Gaza Strip

ObjectivesMetabolic syndrome (MetS) is a multifaceted syndrome and has been described as a clustering of several risk factors for cardiovascular disease. This study was conducted to estimate the prevalence of MetS and its individual components among Palestinian adults, 20–65 years old in Gaza Strip. In addition to find any possible associations with socioeconomic and demographic factors. Material and methodsThe study sample included 230 adults aged 20–65 years. Data were collected by questionnaire interviews, anthropometrics, and biochemical analysis that included: serum glucose, total cholesterol, triglyceride, HDL, and LDL. MetS was defined according to the NCEP/ATP III diagnostic criteria. ResultsOverall prevalence of MetS was 23.0% among the study subjects, with no significant differences between males (18.1%) and females (28.1%). The prevalence of MetS increased significantly with age and was associated significantly with physical activity and martial status, while no significant associations were found with household income; geographical locality; smoking; watching TV; or family history. ConclusionsAge, sex, physical activity and marital status are risk factors independently associated with MetS in the Palestinian population at the Gaza Strip. National health awareness and preventive programs should be established aiming at decreasing of MetS trends in the Palestinian population at Gaza Strip.

Pleiotropic Effects of ARB in Metabolic Syndrome

Metabolic syndrome comprises of a cluster of several risk factors including abdominal obesity, dyslipidemia, elevated blood pressure, and insulin resistance. Many manifestations occur in sequence which is also referred to as the metabolic domino. Because the renin-angiotensin system (RAS) seems to be involved in this domino effect, RAS blockade by angiotensin II receptor blockers (ARB) offers a therapeutic tool for treating hypertension and ultimately the metabolic syndrome itself. In this paper, I describe the effects of ARBs on adiponectin, blood pressure, and fatty liver. Several clinical studies have reported that ARBs elevate adiponectin. ARBs that activate the PPARγ may be more effective than others. In terms of blood pressure, transient ARB administration may prevent the development of hypertension and high doses of ARB may regress mild hypertension. In terms of fatty liver, several research studies have indicated that ARBs may prevent triglyceride accumulation in liver. Again, ARBs that activate PPARγ may be more effective than others. Thus, PPARγ-activating ARBs offer the most hopeful treatment for metabolic syndrome. Further studies are needed to confirm this hypothesis.

Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats

BackgroundThe metabolic syndrome, known also as the insulin resistance syndrome, refers to the clustering of several risk factors for atherosclerotic cardiovascular disease. Dyslipidaemia is a hallmark of the syndrome and is associated with a whole body reduction in the activity of lipoprotein lipase (LPL), an enzyme under the regulation of the class of nuclear receptors known as peroxisome proliferator-activated receptor (PPAR). Glycyrrhizic acid (GA), a triterpenoid saponin, is the primary bioactive constituent of the roots of the shrub Glycyrrhiza glabra. Studies have indicated that triterpenoids could act as PPAR agonists and GA is therefore postulated to restore LPL expression in the insulin resistant state.ResultsOral administration of 100 mg/kg of GA to high-fat diet-induced obese rats for 28 days led to significant reduction in blood glucose concentration and improvement in insulin sensitivity as indicated by the homeostasis model assessment of insulin resistance (HOMA-IR) (p < 0.05). LPL expression was up-regulated in the kidney, heart, quadriceps femoris, abdominal muscle and the visceral and subcutaneous adipose tissues but down-regulated in the liver - a condition in reverse to that seen in high-fat diet-induced obese rats without GA. With regard to lipid metabolism, GA administration led to significant hypotriglyceridemic and HDL-raising effects (p < 0.05), with a consistent reduction in serum free fatty acid, total cholesterol and LDL cholesterol and significant decrease in tissue lipid deposition across all studied tissue (p < 0.01).ConclusionIn conclusion, GA may be a potential compound in improving dyslipidaemia by selectively inducing LPL expression in non-hepatic tissues. Such up-regulation was accompanied by a GA-mediated improvement in insulin sensitivity, which may be associated with a decrease in tissue lipid deposition. The HDL-raising effect of GA suggests the antiatherosclerotic properties of GA.

Oxidative stress in the metabolic syndrome

The metabolic syndrome represents a cluster of several risk factors for atherosclerosis that increases the risk of future cardiovascular events. In this study, we evaluated whether oxidative stress is increased in subjects with the metabolic syndrome. We studied 100 subjects (50 men and 50 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III, and 50 (25 men and 25 women) matched subjects without the syndrome. Insulin sensitivity was assessed with the homeostasis model assessment (HOMA) methods; endothelium-dependent flow-mediated vasodilation (FMD) was evaluated in the right brachial artery with a high-resolution ultrasound machine; oxidative stress was assessed by measuring the circulating levels of nitrotyrosine (NT), considered a good marker for the formation of endogenous peroxynitrite. Compared with control subjects, patients with the metabolic syndrome had greater waist circumference, higher HOMA and systolic pressure values, higher triglyceride and lower HDL-cholesterol levels. NT levels were higher (0.44+/-0.12 micromol/l, mean+/-SD) while FMD was lower [7.3 (4.4/9.6), median and interquartile range] in subjects with the metabolic syndrome as compared with control subjects [0.27+/-0.08 and 11.8 (8.6/14.9), respectively, p<0.001]. There was an increase in NT levels and HOMA score as the number of components of the metabolic syndrome increased. NT levels were associated with waist circumference (r=0.38, p=0.01), triglycerides (r=0.32, p<0.02), systolic blood pressure (r=0.21, p<0.05) and fasting glucose (r=0.24, p<0.05). The oxidative stress that accompanies the metabolic syndrome is associated with both insulin resistance and endothelial dysfunction, providing a connection which is highly deleterious for vascular functions.

Treatment of Tachycardia in Hypertension: Where Do We Stand Now?

Mounting evidence shows that elevated heart rate is associated with a greater risk of developing hypertension and atherosclerosis and that it is a potent predictor of cardiovascular morbidity and mortality. These relationships have been shown not only in general populations but also among hypertensive individuals, with important implications for the treatment of hypertension. Recent evidence suggests that the predictive power of resting heart rate for cardiovascular mortality is even greater than indices derived from analysis of heart rate variability. In spite of this evidence heart rate is still overlooked as a risk factor, but the fact that in most studies the risk related to fast heart rate remained highly significant after controlling for major risk factors for atherosclerosis suggests that it plays a direct role in the induction of the risk. The clustering of several risk factors for coronary artery disease in subjects with fast heart rate suggests that sympathetic overactivity accounts for the increased cardiovascular morbidity in subjects with tachycardia. Moreover, experimental studies both in animals and human beings suggest that the heamodynamic disturbances related to high heart rate have a direct impact on the arterial wall promoting the development and the rupture of atherosclerotic plaques. Data obtained in the experimental animal and pooled data from intervention studies in patients with myocardial infarction or congestive heart failure suggest that drug-induced reduction of heart rate may be beneficial in several clinical conditions. Tachycardia (heart rate ≥ 80 bpm) has been found in over 30% of the hypertensive patients and thus reduction of high heart rate appears as a desirable additional therapeutic goal in a large proportion of the hypertensive population. Several antihypertensive agents have shown good potential for decreasing the fast heart rate in hypertension. In the future, goal of antihypertensive treatment in patients with tachycardia will be to prevent or reverse those functional abnormalities of the autonomic nervous system which accompany the hypertensive condition.

The metabolic basis of atherogenic dyslipidemia

Atherogenic dyslipidemia is one of the major components of the metabolic syndrome, a complex cluster of several risk factors within a single patient that according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III includes at least 3 of the following: large waist circumference, elevated triglyceride levels, low levels of high-density lipoprotein cholesterol (HDL-C), hypertension, and elevated fasting glucose levels, which are directly related to the incidence of coronary heart disease. Atherogenic dyslipidemia clinically presents as elevated serum triglyceride levels, increased levels of small dense low-density lipoprotein (sdLDL) particles, and decreased levels of HDL-C. An important component of atherogenic dyslipidemia is central obesity, which is defined as increased waist circumference and has recently been identified as a chief predictor of the metabolic syndrome in certain patients. Another recent study found that both body mass index and waist circumference were highly predictive of eventual development of the metabolic syndrome. Because atherogenic dyslipidemia usually precedes the clinical manifestation of the metabolic syndrome, strategies to treat it are the focus of pharmacologic intervention. For example, the 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors, commonly known as statins, benefit hypercholesterolemic patients who have atherogenic dyslipidemia that is associated with the metabolic syndrome. Pioglitazone, an antidiabetic agent that acts primarily by decreasing insulin resistance, improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Pioglitazone improves glycemic control while reducing circulating insulin levels. The investigational agent, rimonabant--a centrally and peripherally acting, selective cannabinoid type-1 receptor blocker--is the first therapy developed for managing several cardiovascular risk factors at one time. Rimonabant has shown promise in attacking atherogenic dyslipidemia from several vantage points by affecting glucose, HDL-C, triglycerides, and waist circumference in patients who are prone to atherogenic dyslipidemia.

Elevated Heart Rate: A Major Risk Factor for Cardiovascular Disease

Mounting evidence shows that elevated heart rate is associated with a greater risk of developing hypertension and atherosclerosis and that it is a potent predictor of cardiovafsscular morbidity and mortality. These relationships have been shown not only in general populations but also among hypertensive individuals, with important implications for the treatment of hypertension. In spite of this evidence heart rate has been overlooked as a risk factor, but the fact that in most studies the risk related to fast heart rate remained highly significant after controlling for major risk factors for atherosclerosis suggests that it plays a direct role in the induction of the risk. The clustering of several risk factors for coronary artery disease in subjects with fast heart rate suggests that sympathetic overactivity accounts for the increased cardiovascular morbidity in subjects with tachycardia. In fact, experimental studies have shown that a heightened sympathetic tone can cause obesity, hyperinsulinemia, and insulin resistance which in the long run can promote the development of atherosclerosis. Moreover, experimental studies in the animal suggest that the heamodynamic disturbances related to high heart rate have a direct impact on the arterial wall promoting the development of atherosclerotic plaques. Preliminary results in the experimental animal and pooled data from intervention studies in patients with myocardial infarction or congestive heart failure suggest that drug‐induced reduction of heart rate may be beneficial in several clinical conditions.

Sympathetic overactivity in hypertension: a risk factor for cardiovascular disease.

Numerous prospective studies have shown that high heart rate is related to the development of hypertension, atherosclerosis, and incidence of cardiovascular events. Experimental studies in monkeys have shown that high heart rate has direct atherogenic effects on the arteries as a result of increased wall stress. However, clustering of several risk factors for coronary artery disease in persons with high heart rate suggests that sympathetic overactivity also accounts for part of the increased cardiovascular morbidity that is observed in persons with tachycardia. Indeed, experimental studies have shown that heightened sympathetic tone can cause obesity, hyperinsulinemia, and insulin resistance, which in the long term can promote the development of atherosclerosis. Through its interaction with plasma insulin, sympathetic overactivity can promote the development of left ventricular hypertrophy. Sympathetic activation can also increase hematocrit and precipitate a procoagulant state. Angiotensin II has an effect both on the central nervous system, enhancing sympathetic outflow, and on the peripheral sympathetic nerves. Among the angiotensin II receptor antagonists, eprosartan showed a particular ability to block presynaptic angiotensin II receptor 1 (AT(1)) receptors at neuro-effector junctions in the sympathetic nervous system, as well as AT(1) receptors in blood vessels. This dual action may represent an important advance in treatment of elevated blood pressure.

Heart rate as a risk factor for atherosclerosis and cardiovascular mortality: the effect of antihypertensive drugs.

The aim of this review is to highlight the importance of heart rate (HR) as a risk factor for cardiovascular disease, and to discuss the classes of drugs which can be potentially useful in clinical conditions in which an elevated HR may be present. Numerous studies have shown that high resting HR is prospectively related to the development of atherosclerosis and of cardiovascular events. This relationship was independent of other major risk factors for atherosclerosis and was observed in the general population, in elderly people, in hypertensive cohorts and in patients with myocardial infarction or heart failure. The clustering of several risk factors in individuals with fast heart rate may explain why cardiovascular morbidity is higher in individuals with tachycardia. Sympathetic overactivity seems to be responsible for both the increase in HR, blood pressure and the metabolic abnormalities. Experimental studies in monkeys have shown that HR can also exert a direct atherogenetic action on the arteries through increased wall stress. Moreover, tachycardia can favour the occurrence of ventricular arrhythmias and sudden death. Reduction of HR appears as an additional goal of antihypertensive therapy. If fast HR in hypertension is a marker of increased sympathetic tone, agents which decrease HR through a decline of sympathetic outflow should be particularly efficacious. Beta-blockers retard the development of coronary atherosclerosis in cholesterol-fed monkeys and have proven to be beneficial in patients with myocardial infarction or with heart failure, but their efficacy appear limited in hypertension, probably on account of their unfavourable metabolic profile. Phenylalkylamines are devoid of this untoward effect, and seem to act also through inhibition of sympathetic discharge from the CNS. Mibefradil, a more recent calcium antagonist that selectively blocks voltage-dependent T-type calcium channels decreases HR without affecting left ventricular contractility. New drugs with agonistic properties at the I1-imidazoline receptors of the rostral ventrolateral medulla are effective in reducing blood pressure and HR by inhibiting the sympathetic outflow and improved metabolic parameters in obese or fructose-fed rats. The goal of antihypertensive therapy in the future will be to prevent or reverse those functional abnormalities which accompany the hypertensive condition. In patients with tachycardia the reduction of HR appears a desirable additional goal of therapy.