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.

Follow-up of Antihypertensive Therapy Improves Blood Pressure Control: Results of HYT (HYperTension survey) Follow-up.

INTRODUCTION: Although improved during the past few years, blood pressure control remains sub optimal. AIM: The impact of follow-up assessment on blood pressure control was evaluated in a group of patients of the HYT (HYperTension survey), treated with a combination of different dihydropyridine calcium-channel blockers (CCBs regimen) and inhibitors of renin-angiotensin-aldosterone system (RAAS) and with uncontrolled blood pressure. This was obtained assessing (a) the rate of blood pressure control at 3 and 6 months of follow-up in the whole group of patients, (b) the rate of blood pressure control and the average blood pressure values in subjects treated with different DHP-CCBs regimen. METHODS: From the 4993 patients with uncontrolled blood pressure, (BP ≥ 140/90 or ≥140/85 in patients with diabetes), 3729 (mean age 61.2 ± 11.5 years), maintained CCBs regimen combined wih RAAS blockers and were evaluated at 3 and 6 months follow-up. At each visit BP (semiautomatic device, Omron-M6, 3 measurements), heart rate, adverse events and treatment persistence were collected. RESULTS: At 1st and 2nd follow-up the rate of controlled BP was 63.5 and 72.8% respectively (p < 0.05 vs 35.3% at baseline), whereas in diabetes was 32.5 and 37.9% respectively (p < 0.05 vs 20% at baseline). No differences in heart rate were observed. No differences in control rate were observed between the different CCBs regimen. The incidence of drugs related adverse events was 3.6%. CONCLUSIONS: These findings provide evidence that: (a) the follow-up of hypertensive patients under therapy increase the rate of blood pressure control; (b) there is no significant difference in the antihypertensive effect between different CCBs regimen;

Protective effects of renin-angiotensin blockade beyond blood pressure control.

Antihypertensive drugs exert a number of blood pressure-independent benefits. However, demonstrating the clinical significance of these effects may be difficult for a number of reasons. First, blood pressure can be measured in the clinic, at home and over the 24-h period by ambulatory monitoring. Second, differences between these measures mean that achieving equivalent blood pressure reductions in two treatment arms may be difficult, if not impossible. Furthermore, even small differences in blood pressure can translate into significant effects on cardiovascular risk, especially in the later stages of the cardiovascular continuum. In large clinical trials, other errors limiting the sensitivity to treatment differences include high patient dropouts and unplanned crossover. In addition, as so many patients fail to achieve blood pressure goals even in clinical trials where patient's and physician's motivation is high, the need for cardiovascular protection beyond blood pressure control is unequivocal. Clinical trials of angiotensin II receptor blockers have suggested significant effects beyond blood pressure control, which are observed throughout and with greater consistency in the early phases of the cardiovascular continuum. There may also be differences between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors. Conclusive demonstration that these blood pressure-independent effects do exist will require, however, a much more accurate and extended assessment of the blood pressure effects of the drugs.

Blood pressure lowering effects of rimonabant in obesity-related hypertension.

Obesity-related hypertension represents a common clinical condition characterised by complex pathophysiological and therapeutic features. From a pathophysiological view point, results of experimental and animal studies have led to the hypothesis that neurogenic mechanisms participate in the development and progression of the disease. The hypothesis is based on the evidence that metabolic (i.e. insulin-resistance) and neural (sympathetic activation) alterations frequently co-exist in the obese hypertensive patient and that they reciprocally potentiate each other. From a therapeutic view point, the 2007 European Society of Hypertension/European Society of Cardiology emphasised the importance in this clinical condition of treatment not only through antihypertensive drugs but also via lifestyle changes and drug-induced interventions that reduce body weight. The four Rimonabant In Obesity (RIO) studies have shown that rimonabant can decrease body weight. A recent meta-analysis, based on the RIO results, showed that rimonabant, particularly in obese hypertensive patients, can also decrease - although modestly (2.8 mmHg for systolic and 2.2 mmHg for diastolic) - blood pressure. These effects, which appear to be triggered by the weight reduction induced by the drug, are clinically relevant because they contribute favourably to lower the elevated cardiovascular risk profile of the obese hypertensive patient.

Neuroadrenergic and reflex abnormalities in patients with metabolic syndrome.

AIMS/HYPOTHESIS: Previous studies have shown that alterations in vascular, metabolic, inflammatory and haemocoagulative functions characterise the metabolic syndrome. Whether this is also the case for sympathetic function is not clear. We therefore aimed to clarify this issue and to determine whether metabolic or reflex mechanisms might be responsible for the possible adrenergic dysfunction. METHODS: In 43 healthy control subjects (age 48.2+/-1.0 years, mean+/-SEM) and in 48 untreated age-matched subjects with metabolic syndrome (National Cholesterol Education Program's Adult Treatment Panel III Report criteria) we measured, along with anthropometric and metabolic variables, blood pressure (Finapres), heart rate (ECG) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor manipulation (vasoactive drug infusion technique). RESULTS: Compared with control subjects, subjects with metabolic syndrome had higher BMI, waist circumference, blood pressure, cholesterol, triglycerides, insulin and homeostasis model assessment (HOMA) index values but lower HDL cholesterol values. Sympathetic nerve traffic was significantly greater in subjects with metabolic syndrome than in control subjects (61.1+/-2.6 vs 43.8+/-2.8 bursts/100 heartbeats, p<0.01), the presence of sympathetic activation also being detectable when the metabolic syndrome did not include hypertension as a component. Muscle sympathetic nerve traffic correlated directly and significantly with waist circumference (r=0.46, p<0.001) and HOMA index (r=0.49, p<0.001) and was inversely related to baroreflex sensitivity (r=-0.44, p<0.001), which was impaired in the metabolic syndrome. CONCLUSIONS/INTERPRETATION: These data provide evidence that the metabolic syndrome is characterised by sympathetic activation and that this abnormality (1) is also detectable when blood pressure is normal and (2) depends on insulin resistance as well as on reflex alterations.