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.

Predictors of vascular remodelling in hypertensive subjects with well-controlled blood pressure levels.

We evaluated the structural/functional characteristics of the arterial wall in a cohort of hypertensives with well-controlled blood pressure (BP) levels. We studied 40 hypertensives with well-controlled BP. We assessed by B-mode ultrasound the mean intima-media thickness (mean-IMT) and maximum-IMT (M-MAX) of carotid artery (common, bulb, internal) bilaterally. Endothelial function was evaluated by post-occlusion flow-mediated dilation (FMD) of the brachial artery. Along with traditional risk factors, we studied the impact of serum high-sensitivity C-reactive protein (hs-CRP) and osteoprotegerin (OPG). Forty normotensive subjects served as controls. In the hypertensives, the BP levels were well controlled (office BP: 129/79 mm Hg, ambulatory BP monitoring: 121/75 mm Hg). Compared with controls, higher BP levels and body mass index were present in hypertensives, whereas age and metabolic parameters were similar. In hypertensives, the IMT (mean-IMT 0.68 mm, M-MAX 0.81 mm) was significantly higher than in controls (mean-IMT 0.60 mm, M-MAX 0.71 mm). FMD was impaired in hypertensives (5.9%) compared with controls (9.2%). In multivariate analyses, it turned out that in hypertensives IMT parameters were related to age, hs-CRP and OPG. Low-density lipoprotein (LDL) cholesterol was the only factor related to FMD. IMT and FMD had no relationship with BP levels. In conclusion, in hypertensives with well-controlled BP, the pro-atherogenic remodelling (IMT) is mainly dependent on age and the inflammatory cytokines, OPG in particular. The functional impairment of the arterial wall (FMD) was related to the levels of LDL cholesterol. Under these conditions, when the impact of BP is minimized, the role of inflammatory cytokines and lipids on structural/functional remodelling becomes predominant.

Obesity is a strong determinant of hypertensive target organ damage in young-to-middle-age patients.

OBJECTIVE: To examine the impact of overweight and obesity on development of target organ damage in the early stage of hypertension. SUBJECTS: Participants were 727 young-to-middle-age subjects screened for stage 1 hypertension and followed for 8 years. MEASUREMENTS: Ambulatory blood pressure (BP), albumin excretion rate and echocardiographic data were obtained at entry, every 5 years and/or before starting antihypertensive treatment. RESULTS: During the follow-up, hypertension needing treatment was developed by 54.7% of the subjects with normal weight, 66.6% of those with overweight and 73.0% of those with obesity (P<0.001). Kaplan-Meier curves showed that patients with obesity or overweight progressed to sustained hypertension earlier than those with normal weight (P<0.001). At study end, rate of organ damage was 10.7% in the normal weight, 16.4% in the overweight and 30.1% in the obese subjects (P<0.001). In a multivariable logistic regression analysis, overweight (P=0.008) and obesity (P<0.001) were significant predictors of final organ damage. Inclusion of changes in 24-h BP and body mass index, and of baseline organ damage did not virtually modify these associations (P=0.002 and <0.001, respectively). Obesity was a significant predictor of both left ventricular hypertrophy (P<0.001) and microalbuminuria (P=0.015) with an odds ratio (95% confidence interval) of 8.5 (2.7-26.8) and 3.5 (1.3-9.6), respectively. CONCLUSION: These data indicate that in hypertensive subjects obesity has deleterious effects on the cardiovascular system already at an early age. Preventive strategies addressed to achieve weight reduction should be implemented at a very early stage in young people with excess adiposity and high BP.

Phosducin rs12402521 polymorphism predicts development of hypertension in young subjects with overweight or obesity.

BACKGROUND AND AIMS: The G-protein regulator phosducin has been shown to be associated with stress-dependent blood pressure, but whether obesity is a modulator of the relationship between phosducin and risk of hypertension is unknown. We studied the effect of two phosducin polymorphisms on risk of hypertension in 273 overweight or obese (Ov-Ob) young-to-middle-age participants from the HARVEST and 287 normal weight (NW) participants. METHODS AND RESULTS: Genotyping of phosducin SNPs rs12402521 and rs6672836 was performed by real time PCR. For rs12402521, 64.6% of the participants were homozygous for the G allele, 27.9% heterozygous, and 7.5% homozygous for the A allele. During 7.7 years of follow-up, 339 subjects developed hypertension. In a Cox multivariable model, carriers of the A allele had a 1.28 (95% CI,1.00-1.63, p = 0.046) increased risk of hypertension. However, increased incidence of hypertension associated with A allele (AA + AG, 79% and GG, 59%, p = 0.001) was observed only among Ov-Ob individuals with a hazard ratio of 1.60 (95% CI, 1.13-2.21, p = 0.007) whereas in NW subjects the incidence of hypertension did not differ by genotype (56% in both groups). In the whole cohort, there was a significant interaction of phosducin genotype with body mass index on the risk of hypertension (p = 0.012). For SNP rs6672836 no association was found with incident hypertension. No haplotype effect was detected on the risk of hypertension. CONCLUSION: These data suggest that phosducin rs12402521 polymorphism is an important genetic predictor of obesity-related hypertension. In Ov-Ob carriers of the A allele aggressive nonpharmacological measures should be implemented.

Cardiovascular effects of exercise in young hypertensives.

Sedentary habits are largely responsible for the alarming rise in the prevalence of hypertension among young individuals. Regular aerobic exercise has been shown to reduce not only blood pressure (BP) in resting conditions but also BP reactivity to stressors. Much less is known about the long-term effects of physical activity on target organ damage in hypertension. Some studies have documented that exercise is able to decrease rather than increase left ventricular mass and that even competitive athletics have beneficial effects on the heart. In addition, physical activity during leisure has been found to be inversely associated with the progression of subclinical atherosclerosis and to delay aging dependent arterial stiffness. Isolated systolic hypertension in physically active young people is often an innocent clinical condition caused by an elevated pulse pressure amplification and low wave arterial reflection from peripheral sites, due to increased arterial elasticity. The above findings support a strategy of exercise training as an initial approach in the management of young sedentary patients in the early stages of hypertension. Caution should be used in subjects with more severe hypertension and every hypertensive athlete should be thoroughly investigated to exclude target organ damage and coronary artery disease.

European Society of Hypertension practice guidelines for home blood pressure monitoring.

Self-monitoring of blood pressure by patients at home (home blood pressure monitoring (HBPM)) is being increasingly used in many countries and is well accepted by hypertensive patients. Current hypertension guidelines have endorsed the use of HBPM in clinical practice as a useful adjunct to conventional office measurements. Recently, a detailed consensus document on HBPM was published by the European Society of Hypertension Working Group on Blood Pressure Monitoring. However, in daily practice, briefer documents summarizing the essential recommendations are needed. It is also accepted that the successful implementation of clinical guidelines in routine patient care is dependent on their acceptance by involvement of practising physicians. The present document, which provides concise and updated guidelines on the use of HBPM for practising physicians, was therefore prepared by including the comments and feedback of general practitioners.

Maintenance of blood-pressure-lowering effect following a missed dose of aliskiren, irbesartan or ramipril: results of a randomized, double-blind study.

Most patients inadvertently miss an occasional dose of antihypertensive therapy, and hence drugs that provide sustained blood-pressure (BP) reduction beyond the 24-h dosing interval are desirable. The primary objective of this study was to compare the 24-h mean ambulatory BP reductions from baseline after a simulated missed dose of the direct renin inhibitor aliskiren, irbesartan or ramipril. In this double-blind study, 654 hypertensive patients (24-h mean ambulatory diastolic BP (MADBP) >or=85 mm Hg) were randomized 1:1:1 to once-daily aliskiren 150 mg, irbesartan 150 mg or ramipril 5 mg. Doses were doubled after 2 weeks. At day 42, patients were again randomized equally within each group to receive 1 day of placebo ('missed dose') on either day 42 or day 49. Patients with a successful 24-h ambulatory BP measurement at baseline and on day 42/49 were included in the analyses. The 24-h mean ambulatory systolic BP (MASBP)/MADBP reductions from baseline after a missed dose of aliskiren 300 mg (9.3/7.0 mm Hg) were similar to irbesartan 300 mg (9.5/7.3 mm Hg) and significantly larger than ramipril 10 mg (7.1/5.0 mm Hg, P

High angiotensin II state without cardiac remodeling (Bartter's and Gitelman's syndromes): are angiotensin II type 2 receptors involved?

BACKGROUND/AIMS: While Angiotensin II (Ang II) is a major factor in the development of cardiomyocyte hypertrophy and a pivotal role for Ang II signals via ERK1/2 has been identified, mechanism(s) responsible are still unclear. As Bartter's and Gitelman's syndrome patients (BS/GS) have increased Ang II, and yet normo/hypotension, hyporesponsiveness to pressors and blunted Ang II signaling via type 1 receptors (AT1R), this study assesses BS/GS's left ventricular (LV) mass and structure as well as Ang II induced ERK1/2 phosphorylation compared with essential hypertensive patients (EH) and normotensive healthy subjects (C) to gain insight into Ang II mediated processes. METHODS: Indices of cardiac hypertrophy were determined by M-mode, two-dimensional echo Doppler and ERK phosphorylation by Western blot. RESULTS: None of BS/GS exhibited LV remodelling; LV mass, LV end-diastolic volume and mass/volume ratio were unchanged vs C (60+/-14 g/m2 vs 64+/-12, 64+/-12 ml/m2 vs 60+/-8 and 0.95+/-0.2 vs 1.0+/-0.2, respectively) and reduced vs EH (119+/-15, p<0.001, 78+/-9, p<0.05 and 1.52+/-0.15, p<0.01). Despite BS/GS's higher plasma renin activity and aldosterone and unchanged level of AT1R, Ang II induced ERK1/2 phosphorylation was reduced vs both C and EH: 0.64 d.u.+/-0.08 vs 0.90+/-0.06 in C, p<0.006, and vs 1.45+/-0.07 in EH, p<0.001. CONCLUSION: The data point to a direct cardioremodeling role for Ang II and support a role of Ang II type 2 receptor (AT2R) signaling as involved in the lack of cardiovascular remodeling in BS/GS. However, further studies using more direct approaches to demonstrate the effects of AT2R signaling must be pursued.

Atrial fibrillation during acute myocardial infarction: association with all-cause mortality and sudden death after 7-year of follow-up.

AIMS: Atrial fibrillation/flutter (AF/FL) is a common complication of acute myocardial infarction (AMI). Indeed, the determinants of AF/FL in AMI-patients and the association of AF/FL with mortality are not well-known. The purpose of the present study was to investigate the relationship between presence of AF/FL and mortality in patients with AMI and to report on predictors of AF/FL. METHODS: We studied 505 patients enrolled in three intensive care units with definite AMI and followed up for 7 years. No patient was lost to follow-up. Patients with AF/FL during the 1st week of hospitalisation were compared with those with steady sinus rhythm. End-points were all-cause mortality and modes of death. RESULTS: At multivariable logistic regression analysis, elderly, body mass index, congestive heart failure (CHF), history of hypertension and plasma cholesterol (in a negative fashion) were independently associated with the presence of AF/FL. At survival analysis, after full adjustment, AF/FL was not associated with in-hospital mortality. After 7 years of follow-up, AF/FL was found to be associated with all-cause mortality [adjusted odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.2-2.3], together with age, diabetes mellitus, creatine kinase-MB isoenzyme (CK-MB) peak, CHF, estimated glomerular filtration rate and thrombolysis. At adjusted logistic polynomial regression analysis, AF/FL was found to be associated with an excess of mortality for reasons of sudden death (SD) (adjusted OR = 2.7; 95% CI = 1.2-6.4). No interaction was observed between AF/FL and medications on in-hospital mortality. For 7-year mortality, angiotensin-converting enzyme (ACE)-inhibitors and digitalis showed an independent negative (protective) interaction chiefly on SD (adjusted OR = 0.06; 95% CI = 0.01-0.74, and RR = 0.10; 95% CI = 0.02-0.58, respectively). CONCLUSIONS: Patients with AMI and AF/FL portend a poor prognosis in the long-term chiefly because of an excess of SD. Treatment with ACE-inhibitors and digitalis may have long-term beneficial effects on SD.

Irreversible CYP3A inhibition accompanied by plasma protein-binding displacement: a comparative analysis in subjects with normal and impaired liver function.

In this study, quinine was used as a probe substrate and erythromycin as a prototypical irreversible inhibitor of CYP3A to ascertain whether, like reversible CYP inhibition, the magnitude of irreversible inhibition is also strictly dependent on the status of liver function. The effect of erythromycin on oral quinine disposition was studied in 10 healthy subjects and in 20 patients with cirrhosis of the liver who had varying degrees of liver dysfunction. This effect was shown to be the result of two types of interaction: (i) irreversible inhibition of CYP3A-mediated quinine metabolism, the extent of which proved to be independent of liver function, and (ii) displacement of quinine from plasma protein-binding sites, the magnitude of the displacement increasing dramatically as liver function worsened. Such an interaction causes limited increases in the total concentration of the displaced drug but disproportionate increases in its free concentration; the latter increases are magnified by liver dysfunction, thereby requiring that the monitoring of free drug concentrations be made mandatory.

Glomerular hyperfiltration predicts the development of microalbuminuria in stage 1 hypertension: the HARVEST.

Factors related to the development of microalbuminuria in hypertension are not well known. We did a prospective study to investigate whether glomerular hyperfiltration precedes the development of microalbuminuria in hypertension. We assessed 502 never-treated subjects screened for stage 1 hypertension without microalbuminuria at baseline and followed up for 7.8 years. Creatinine clearance was measured at entry. Urinary albumin and ambulatory blood pressure were measured at entry and during the follow-up until subjects developed sustained hypertension needing antihypertensive treatment. Subjects with hyperfiltration (creatinine clearance >150 ml/min/1.73 m2, top quintile of the distribution) were younger and heavier than the rest of the group and had a greater follow-up increase in urinary albumin than subjects with normal filtration (P<0.001). In multivariable linear regression, creatinine clearance adjusted for confounders was a strong independent predictor of final urinary albumin (P<0.001). In multivariable Cox regression, patients with hyperfiltration had an adjusted hazard ratio for the development of microalbuminuria based on at least one positive measurement of 4.0 (95% confidence interval (CI), 2.1-7.4, P<0.001) and an adjusted hazard ratio for the development of microalbuminuria based on two consecutive positive measurements of 4.4 (95% CI, 2.1-9.2, P<0.001), as compared with patients with normal filtration. Age, female gender, and 24 h systolic blood pressure were other significant predictors of microalbuminuria. In conclusion, stage 1 hypertensive subjects with glomerular hyperfiltration are at increased risk of developing microalbuminuria. Early intervention with medical therapy may be beneficial in these subjects even if their blood pressure falls below normal limits during follow-up.

Albumin excretion in diabetic patients in the setting of acute myocardial infarction: association with 3-year mortality.

AIMS/HYPOTHESIS: Diabetes mellitus is associated with increased mortality in subjects with acute myocardial infarction (AMI). We aimed to estimate the risk of mortality in AMI patients with and without diabetes using the urinary albumin : creatinine ratio (ACR). METHODS: This is a prospective study of 121 consecutive, non-selected diabetic AMI patients, 121 age- and sex-matched non-diabetic AMI patients and 61 diabetic non-AMI outpatients as control subjects. All data were obtained during the first 7 days of hospitalisation and each AMI patient was followed for a period of exactly 3 years. Baseline ACR RIA measurements were made on the 1st, 3rd and 7th days of admission. RESULTS: Adjusted ACR values were significantly higher in the diabetic AMI patients than in the diabetic control outpatients ( p<0.0001), and a significant difference was observed between the weekly ACR slopes for these two groups ( p<0.0001). Microalbuminuria was more prevalent in the diabetic AMI patients than in the non-diabetic AMI patients on the 1st day (62% vs 46%, p=0.01) and 3rd day (41% vs 29%, p=0.04). Among the AMI patients with normoalbuminuria (ACR <30 microg/mg), the mortality rate was 11.6% for the patients without diabetes and 33.8% for those with diabetes ( p=0.001). The mortality rate was much higher among the AMI patients with microalbuminuria (ACR >/=30 microg/mg) and similar for the diabetic (68.0%) and non-diabetic patients (74.3%). In a multivariable Cox model, ACR ( p<0.0001) and diabetes status ( p=0.01) were associated with adverse outcome even when several other clinical variables were included in the model. Furthermore, a negative interaction was found between diabetes and ACR ( p=0.01). CONCLUSIONS/INTERPRETATION: Microalbuminuria frequently occurs in diabetic and non-diabetic AMI patients during the first 3 days of admission to hospital and can be used to identify subjects at high risk of mortality.

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 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. 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.

Heritability of left atrial size in the Tecumseh population.

BACKGROUND: Little is known about the determinants of atrial size, and no study has analyzed whether genetic factors are involved in the pathogenesis of LA enlargement. MATERIALS AND METHODS: We studied the heritability of echocardiographic left atrial size in 290 parents from the Tecumseh Blood Pressure Study and 251 children from the Tecumseh Offspring Study. All data from the parents and children were obtained at the same field office in Tecumseh, USA. Left atrial dimension was determined echocardiographically in accordance with American Society of Echocardiography guidelines with the use of leading-edge-to-leading-edge measurements of the maximal distance between the posterior aortic root wall and the posterior left atrial wall at end systole. RESULTS: For correlation between the left atrial dimensions of the parents and their offspring, several models were generated to adjust the atrial dimensions in both groups for an increasing number of clinical variables. After removing the effect of age, gender, height, weight, skinfold thickness, and systolic blood pressure, parent-child correlation for left atrial size was 0.19 (P = 0.007). Further adjustment for left ventricular mass and for measuring left ventricular diastolic function increased the correlation to 0.25 (P = 0.001). CONCLUSIONS: The present data indicate that heredity can explain a small but definite proportion of the variance in left atrial dimension.

Comparison of benazepril-amlodipine and captopril-thiazide combinations in the management of mild-to-moderate hypertension.

OBJECTIVE: To compare the efficacy and tolerability of benazepril 10 mg + amlodipine 5 mg combination (BZ+AM) versus captopril 50 mg + hydrochlorothiazide 25 mg (CP+HT) combination. MATERIAL: 405 outpatients with mild-to-moderate arterial hypertension not adequately controlled by a monotherapy with ACE inhibitors or calcium channel blockers or diuretics entered this multicenter, double-blind, randomized, parallel-group study. METHOD: After a 2-week placebo run-in, 397 patients with sitting diastolic (D) blood pressure (BP) > 95 mmHg and/or sitting systolic (S) BP > 160 mmHg were randomized to receive either BZ+AM (201 patients) or CP+HT (196 patients) once daily for 12 weeks. Main outcome measure was sitting DBP and SBP values at the end of active treatment. The response rate was defined as the proportion of patients with either a final sitting DBP < 90 mmHg or decreased by at least 10 mmHg or a sitting SBP < 150 mmHg or decreased by at least 20 mmHg from baseline. RESULTS: The DBP and SBP values obtained with BZ+AM were, respectively, 2.7 and 3.7 mmHg lower than those obtained with CP+HT (both p < 0.001 vs. CP+HT). The response rate in the BZ+AM group (94.8%) was better than that observed in the CP+HT group (86.0%, p = 0.004). The incidence of adverse events was similar with the 2 treatment regimens (17.9% for both). CONCLUSIONS: These data suggest a higher antihypertensive efficacy of the fixed combination BZ 10 mg+AM 5 mg as compared with CP 50 mg+HT 25 mg.

Effects of physical exercise on clinic and 24-hour ambulatory blood pressure in young subjects with mild hypertension.

BACKGROUND: The aim of the study was to assess the effect of physical activity on 24-hr ambulatory blood pressure (ABPM) and office blood pressure (BP) in 572 male subjects with borderline to mild hypertension from the HARVEST study. METHODS: Subjects were 18 to 45 years old with diastolic BP of 90-99 mmHg and/or systolic BP of 140-159 mmHg. They never took any anti-hypertensive therapy. All subjects underwent physical examination, office BP measurement and two 24-hr ambulatory BP monitorings performed three months apart. Subjects were classified as non exercisers, group 1 (n=331), mild exercisers, group 2 (n=192) and heavy exercisers, group 3 (n=49). During the three months of follow-up subjects maintained the same physical activity habits. There was no difference in smoking and alcohol consumption between the 3 groups. As the groups differed significantly in age and body mass index data were adjusted for these confounders. RESULTS: At baseline office and ambulatory systolic BP were similar in the 3 groups, while diastolic BP was proportional to the level of physical activity although the difference was significant only between the group of non-exercisers and mild exercisers. Heart rate (HR) was always inversely related to the intensity of exercise. After three months follow-up office systolic BP was similar among the three groups and diastolic BP slightly decreased in the exercisers (group 1 vs group 3 p=0.02, group 2 vs group 3 p=0.04). At ABPM the group of heavy exercisers showed a significant decrease in daytime systolic BP (135.4plus minus0.6 vs 134plus minus0.8 vs 132.2plus minus1.6 mmHg; group 1 vs group 3 p<0.05) and the difference between systolic ambulatory BP at the 3rd month and at baseline, showed an additional significant decrease according to exercise intensity (24-hr systolic BP group 1 vs group 3 p=0.001, group 2 vs group 3 p=0.004; daytime systolic BP group 1 vs group 3 p=0.0009, group 2 vs group 3 p=0.004; night-time systolic BP group 1 vs group 3 p=0.02, group 2 vs group 3 p=0.02). No changes in ambulatory diastolic BP were observed. CONCLUSIONS: In conclusion, physical activity has a positive effect in lowering BP attenuating the risk of hypertension in young subjects with borderline hypertension. The anti-hypertensive effect of physical activity persisted after three months and the group of exercisers had an additional reduction in systolic BP detected by ABPM. To obtain accurate information on chronic levels of arterial pressure over time 24-hr ambulatory BP should be preferred to traditional casual readings.

Early signs of cardiac involvement in hypertension.

BACKGROUND: Whether abnormalities of diastolic function are the earliest cardiac change in hypertension is still a matter for dispute. The aim of this study was to assess whether left ventricular diastolic dysfunction is an early sign of cardiac involvement in hypertension. METHODS: In 578 young patients with stage I hypertension from the Hypertension and Ambulatory Recording Venetia Study (HARVEST) and 101 normotensive control patients echocardiographic Doppler examination and ambulatory blood pressure monitoring were performed. RESULTS: Left ventricular mass, wall thickness, and relative wall thickness, adjusted for confounders, were greater in the hypertensive than in the normotensive patients (all P <.0001). After adjustment for confounders, the A-wave peak velocity was higher in the hypertensive patients (51.5 +/- 11.5 vs 43.4 +/- 8 cm/s, P <.001) as were A-wave velocity time integral (5.6 +/- 1.7 vs 4.6 +/- 1.3 cm, P =.01), total area (16.9 +/- 4.4 vs 15.6 +/- 3.1 cm, P =.04), and E-wave peak velocity (69.9 +/- 15.2 vs 67.5 +/- 13.3 cm/s, P =.03). All indexes of diastolic function were similar in the hypertensive subjects subdivided according to whether they had "white-coat" or sustained hypertension. Among the hypertensive subjects, age and heart rate were the strongest predictors of diastolic indexes, whereas ambulatory blood pressure explained only a marginal part of the E/A ratio, A-wave peak velocity, and the first one third total area ratio (P =.04, P =.02, and P =.05, respectively). Left ventricular mass and wall thickness were not associated with any Doppler index. When a clustering of diastolic indexes (E/A wave ratio, deceleration time, first one third of diastole, and peak E-wave-velocity) was used to identify subjects with diastolic dysfunction, no significant differences in either clinic or ambulatory blood pressure were observed between the group with diastolic dysfunction and the group with normal function. CONCLUSIONS: We conclude that the earliest signs of cardiac involvement in hypertension are left ventricular structural abnormalities. Left ventricular diastolic function is only marginally affected, even when multiple parameters of left ventricular filling are taken into account.

Clinical features associated with pre-hospital time delay in acute myocardial infarction.

BACKGROUND: The pre-hospital time delay in acute myocardial infarction (AMI) is still a challenging problem since for many patients there are long intervals between the onset of symptoms and the initiation of therapy. The aim of this study was to verify which, among several clinical variables, are associated with a prolonged pre-hospital time delay. METHODS: Five hundred and twenty-six unselected patients with AMI and consecutively admitted to three coronary care units were enrolled. The pre-hospital time delay was defined as the time interval from the onset of symptoms to admission to the coronary care unit. Clinical variables included: age, gender, body mass index, level of education, alcohol consumption, smoking habits, regular physical activity, history of hypertension, diabetes mellitus, history of coronary artery disease (documented history of angina and/or previous myocardial infarction), chronic atrial fibrillation, Q-wave AMI and off hours onset of symptoms. After univariate analysis, multivariable regression analysis was used. RESULTS: The mean age of the patients was 66.6 +/- 12.1 years and 28.7% were female. The median pre-hospital time interval was 200 min (95% confidence interval 60-1140). For 342 patients the pre-hospital time interval was < or = 6 hours and for 184 patients it was > 6 hours. Those variables which, at univariate analysis, were found to significantly influence the pre-hospital delay were analyzed using a multivariable regression model where the dependent variable was the pre-hospital time interval. Chronic atrial fibrillation (p = 0.010), a history of coronary artery disease (p = 0.017), diabetes (p = 0.016) and age > or = 70 years (p = 0.009) were found to be independently associated with a prolonged prehospital time interval. Similar results were obtained when considering only Q-wave AMI. As expected, the thrombolytic therapy rate was much lower in patients with a longer pre-hospital time delay. CONCLUSIONS: The present study shows that, in case of AMI, the time interval between the onset of symptoms and a patient's arrival to hospital is still far from being optimal. This is especially true for older patients with diabetes, a history of coronary artery disease or chronic atrial fibrillation. Cardiologists should be aware of this problem and should implement adequate educational strategies addressed to those patients at highest risk.

Antihypertensive treatment of patients with diabetes and hypertension.

Whereas individual research papers about antihypertensive treatment in diabetics might be somewhat confusing, the weight of the evidence strongly suggests that: 1) In patients with type 1 diabetes, it is advantageous to use angiotensin-converting enzyme (ACE) inhibitors as primary treatment. 2) In type 2 diabetics, aggressive blood pressure (BP) lowering is warranted and, the calcium antagonist controversy notwithstanding, all drugs appear to be similarly useful in reducing cardiovascular mortality. Specifically, in the Systolic Hypertension in Europe study, compared with placebo, a calcium antagonist dramatically reduced cardiovascular (CV) events in elderly diabetics. The Hypertension Optimal Treatment study showed that, using a calcium antagonist-based regimen, the degree of BP lowering determines the degree of CV event reduction. Furthermore, the United Kingdom Prospective Diabetes Study (UKPDS) did not find a difference in CV events reduction in patients treated with beta-blockers or with ACE inhibitors. In the UKPDS, the effect of BP lowering on reduction in CV events was more substantial than the degree of CV reduction by blood sugar lowering. 3) Both the CAPtopril Prevention Project (CAPPP) and the Heart Outcomes Prevention Evaluation (HOPE) studies found that treatment with an ACE inhibitor may be useful in reducing the incidence of new-onset type 2 diabetes mellitus. 4) Finally, insulin resistance, a precursor of diabetes mellitus and a strong predictor of future CV disease, is differentially affected by antihypertensive treatment. beta-Blockers and diuretics worsen insulin resistance, whereas alpha-adrenergic blockers and central imidazoline binding agents increase insulin sensitivity. The effect of ACE inhibitors and angiotensin blockers may also positively affect insulin resistance, but the results are not uniformly positive. It stands to reason that the differential effect of various drugs on insulin resistance and primary CV events may be clinically relevant particularly in the course of the long-term prevention of mild hypertension. All current trials investigate the effect of the treatment on secondary prevention of CV events among patients with advanced complicated diabetes and hypertension.