Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

BACKGROUND: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort. METHODS AND RESULTS: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P<0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P=0.004) and 1.150 (95% CI, 1.021-1.295, P=0.02), respectively. CONCLUSIONS: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

Regional and temporal differences in the associations between cardiovascular disease and its classic risk factors: an analysis of 49 cohorts from 11 European countries.

AIMS: The regional and temporal differences in the associations between cardiovascular disease (CVD) and its classic risk factors are unknown. The current study examined these associations in different European regions over a 30-year period. METHODS AND RESULTS: The study sample comprised 553 818 individuals from 49 cohorts in 11 European countries (baseline: 1982-2012) who were followed up for a maximum of 10 years. Risk factors [sex, smoking, diabetes, non-HDL cholesterol, systolic blood pressure (BP), and body mass index (BMI)] and CVD events (coronary heart disease or stroke) were harmonized across cohorts. Risk factor-outcome associations were analysed using multivariable-adjusted Cox regression models, and differences in associations were assessed using meta-regression. The differences in the risk factor-CVD associations between central Europe, northern Europe, southern Europe, and the UK were generally small. Men had a slightly higher hazard ratio (HR) in southern Europe (P = 0.043 for overall difference), and those with diabetes had a slightly lower HR in central Europe (P = 0.022 for overall difference) compared with the other regions. Of the six CVD risk factors, minor HR decreases per decade were observed for non-HDL cholesterol [7% per mmol/L; 95% confidence interval (CI), 3-10%] and systolic BP (4% per 20 mmHg; 95% CI, 1-8%), while a minor HR increase per decade was observed for BMI (7% per 10 kg/m2; 95% CI, 1-13%). CONCLUSION: The results demonstrate that all classic CVD risk factors are still relevant in Europe, irrespective of regional area. Preventive strategies should focus on risk factors with the greatest population attributable risk.

All classic cardiovascular disease (CVD) risk factors are still relevant in Europe, irrespective of regional area. The differences in the associations of CVD risk factors with overt CVD between regions of Europe are generally small. Minor temporal hazard decreases were observed for non-HDL cholesterol and systolic blood pressure, while a minor hazard increase was observed for body mass index.

Anthropometric Measures of Adiposity as Markers of Kidney Dysfunction: A Cross-Sectional Study.

The present study was designed to provide information on the ability of several different anthropometric markers to reflect the renal impairment associated with body weight increase and to predict the development of renal alterations linked to overweight and obesity. In 574 subjects representative of the general population of the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study, with an age range between 57 and 73 years, we investigated the association between different anthropometric markers of body fat, as alternative to body mass index, and renal failure, to obtain information useful for determining their potential predictive value. Renal dysfunction was significantly associated with almost all anthropometric markers of adiposity related to body weight and body shape. After adjustment for confounders, such as age, sex, office blood pressure, serum glucose, antihypertensive drugs and smoking habit, association remained significant only for waist-to-hip ratio (WHR), lipid accumulation product (LAP) and visceral adiposity index (VAI). These 3 markers also displayed at the receiver operating curves (ROC) analysis the best ability to detect subjects with or without kidney dysfunction. The results of the present study provide evidence that WHR, LAP and VAI represent the best markers of renal dysfunction associated with visceral body fat accumulation.

Coffee consumption, clinic, 24-hour and home blood pressure. Findings from the PAMELA study.

BACKGROUND AND AIMS: Chronic coffee consuption has been reported to be associated with a modest but significant increase in blood pressure (BP), although some recent studies have shown the opposite. These data, however, largely refer to clinic BP and virtually no study evaluated cross-sectionally the association between chronic coffee consuption, out-of-office BP and BP variability. METHODS AND RESULTS: In 2045 subjects belonging to the population of the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, we analyzed cross-sectionally the association between clinic, 24-hour, home BP and BP variability and level of chronic coffee consumption. Results show that when adjusted for confounders (age, gender, body mass index, cigarette smoking, physical activity and alcohol drinking) chronic coffee consumption does not appear to have any major lowering effect on BP values, particulary when they are assessed via 24-hour ambulatory (0 Cup/day: 118.5 ± 0.7/72.8 ± 0.4 mmHg vs 3 cups/day: 120.2 ± 0.4/74.8 ± 0.3 mmHg, PNS) or home BP monitoring (0 cup/day: 124.1 ± 1.2/75.4 ± 0.7 mmHg vs 3 cups/day: 123.3 ± 0.6/76.4 ± 0.36 mmHg, PNS). However, daytime BP was significantly higher in coffee consumers (about 2 mmHg), suggesting some pressor effects of coffee which vanish during nighttime. Both BP and HR 24-hour HR variability were unaffected. CONCLUSION: Thus chronic coffee consumption does not appear to have any major lowering effect either on absolute BP values, particulary when they are assessed via 24-hour ambulatory or home BP monitoring, or on 24-hour BP variability.

Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study.

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.

Left ventricular mass reduction and hypertrophy regression following renal artery revascularization: a meta-analysis.

AIM: Few echocardiographic studies have focused on regression of left ventricular hypertrophy (LVH) in patients with renal artery stenosis after revascularization, with inconsistent results. We performed a systematic meta-analysis of these studies in order to offer a comprehensive information on this topic. METHODS: The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English-language articles published from 1 January 1990 up to 31 March 2020. Studies were identified by crossing the following terms: 'renal artery stenosis', 'renovascular hypertension', 'fibromuscular dysplasia', 'renal artery stenting', 'renal artery surgery' with 'cardiac damage', 'hypertensive heart disease' 'left ventricular mass', 'left ventricular hypertrophy', 'echocardiography'. RESULTS: A total of 726 hypertensive patients with renal artery stenosis (mean age 61 years, 64% men, 98% treated, 10% with fibromuscular dysplasia) were included in 13 studies. Baseline and postintervention pooled mean LVM values were 220 ±â€Š15 and 203 ±â€Š19 g, respectively (SMD -0.24 ±â€Š0.06, CI -0.37 to -0.21, P<0.0001); corresponding values for LV mass index were 129.0 ±â€Š6 and 115 ±â€Š7 g/m, respectively (SMD -0.28 ±â€Š0.04, CI -0.36 to 0.21, P < 0.0001). Renal revascularization was associated with a 40% lower risk of LVH. This trend was accompanied by a reduction in the number of antihypertensive drugs (SMD -0.27 ±â€Š0.04, CI -0.37 to 0.17, P < 0.0001). CONCLUSION: The present meta-analysis suggests that renal artery revascularization added to antihypertensive therapy promotes a favourable effect on LV structure, as reflected by a significant decrease in absolute and indexed LV mass index as well by a lower risk of LVH. Limitations include: high prevalence of modest renal artery stenosis (≥50%); small sample of fibromuscular dysplasia; lack of randomized design of most studies.

Sympathetic Overactivation in Patients With Essential Hypertension and Hepatic Iron Overload.

Iron overload has been recently shown to be associated with a hyperadrenergic state in genetic hemochromatosis. Whether this is also the case in essential hypertension, characterized by sympathetic activation and frequently by body iron overload, is unknown. In 17 healthy normotensive controls (age 52.3±3.2 years, mean±SE), in 21 age-matched patients with hypertension with iron overload (HT+), defined by serum ferritin levels, and in 28 hypertensives without this condition, we measured efferent postganglionic muscle sympathetic nerve traffic (microneurography), heart rate and blood pressure variability (power spectral analysis), serum ferritin, and metabolic variables. Muscle sympathetic nerve traffic was significantly (P<0.02 at least) greater in HT+ than in patients with hypertension without iron overload and normotensive subjects both when expressed as bursts incidence over time (41.8±1.4 versus 31.5±1.4 and 23.6±0.9 bursts/min) and as bursts corrected for heart rate (55.3±1.8 versus 42.3±1.2 and 31.7±1.2 bursts/100 heartbeats). In HT+, low-frequency systolic blood pressure variability was significantly reduced. In HT+, but not in the other 2 groups, muscle sympathetic nerve traffic was significantly related to serum ferritin (r=0.51, P<0.03), transferrin saturation (r=0.47, P<0.03), and hepatic iron load (r=0.76, P<0.0001, magnetic resonance imaging), as well as to homeostatic model assessment index values (r=0.46, P<0.05). These data provide the first evidence that in HT+ elevated serum ferritin is associated with a hyperadrenergic state of greater magnitude than the one seen in patients with hypertension without iron overload. They also show that the potentiation of the sympathetic activation detected in HT+ is related to elevated serum ferritin and to the associated metabolic alterations, possibly participating in the increased cardiovascular risk characterizing iron overload.

Serum uric acid and fatal myocardial infarction: detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study.

OBJECTIVE: The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men. METHODS: The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ±â€Š66.9 months. RESULTS: A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P < 0.01), but not in men. CONCLUSION: The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.

HYT-hypertension in Turkey: a cross-sectional survey on blood pressure control with calcium channel blockers alone or combined with other antihypertensive drugs.

INTRODUCTION: Although improved during the past few years, high blood pressure control still remains an unmet goal of antihypertensive drug treatment. Among different antihypertensive agents, calcium channel blockers (CCBs), either as monotherapy or in combination with other drugs are recommended by several guidelines for initiation and maintenance of antihypertensive treatment. AIM: The HYT-HYperTension survey, carried out in Turkey was aimed to assess (a) blood pressure control in hypertensive patients under treatment with dihydropyridine CCBs, either as monotherapy or in combination with other drugs and (b) the prevalence of blood pressure control in subgroups of patients with cardiovascular risk factors (previous cardiovascular disease, diabetes, renal disease, isolated systolic hypertension, visceral obesity, overweight, current smoking habit). METHODS: More than 7000 hypertensive patients (60.0 % men, mean age 61.2 ± 11.5 years), routinely visited by either a specialist or a non-specialist physician in the Primary Care Units of 26 cities across Turkey, were enrolled in the survey. Only patients treated with dihydropyridine-type CCBs, as mono- or combination therapy were included in the study, whereas individuals treated with non-dihydropyridine-type CCBs or with other drug classes (as monotherapy or combination therapy), were excluded. Demographic data (age, gender, height, weight, waist circumference, current smoker habit), clinical data and drug treatments were collected at each visit. Blood pressure was measured with a semiautomatic device (Omron-M6) with the patient in sitting position and after at least 5 min of rest. Measurements were repeated three times, at intervals of 5 min each other. RESULTS: In the overall survey population blood pressure control (blood pressure <140/90 mmHg) was achieved in 31.7 % of patients and the average systolic and diastolic blood pressure was 145.3/88.2 mmHg. Prevalence of patients treated with dihydropyridine-type CCBs, either as monotherapy or combined with other drugs, was superimposable (51.6 vs 48.4 %, P = NS). Dihydropyridine-type CCBs were more frequently combined with drugs acting on the renin-angiotensin-aldosterone system (86.4 %), particularly with ACE-inhibitors (34.1 %) and angiotensin II receptor antagonists (52.3 %), while in 13.6 % of patients CCBs were combined with diuretics and/or beta-blockers. Diabetes mellitus was detected in 22.7 % of patients, obesity in 41.5 % and history of cardiovascular disease in 23.0 % (coronary artery disease in 19.2 % and stroke in 3.8 %). Blood pressure control was more difficult to be achieved in complicated hypertension, particularly when cigarette smoking, obesity, overweight, visceral obesity and renal disease were associated with hypertension. CONCLUSIONS: Taken together these findings provide evidence that dihydropyridine-type CCBs, particularly when combined with ACE-inhibitors or angiotensin II receptors blockers, allow to achieve a blood pressure control better than the one reported in the same geographic area by other treatment strategies based on different combinations of diuretics, beta-blockers, ACE-inhibitors, angiotensin II receptors blockers and calcium channel blockers.

Endocan, a novel marker of endothelial dysfunction in patients with essential hypertension: comparative effects of amlodipine and valsartan.

Vascular inflammation plays an important role in the pathophysiology of hypertension and high levels of endocan may reflect ongoing vascular inflammation in hypertensive patients. In the present hypothesis-generating study, we aimed at investigating the comparative effects of amlodipine and valsartan on endocan levels in newly diagnosed hypertensive patients. The study population consisted of 37 untreated hypertensive patients who were randomized to the two treatment arms. After baseline assessment, each patient was randomly allocated to either 10 mg daily of amlodipine (n = 18, 7 males) or 160 mg daily of valsartan (n = 19, 3 males) and treated for a 3-month period. Sphygmomanometric blood pressure (BP) and serum endocan were measured before and every 2 weeks during drug treatment. There was no statistically significant difference between the two treatment arms as far as baseline socio-demographic and clinical characteristics are concerned. After a 3-month treatment period, systolic and diastolic BP values significantly reduced by antihypertensive treatment (p < 0.001). Furthermore, endocan levels were significantly decreased in both treatment arms (p < 0.05). However, amlodipine caused a greater percent decrease in circulating endocan levels compared with valsartan at the end of the treatment period. Both drugs reduced high sensitivity C-reactive protein values. However, the statistical significant difference vs baseline was achieved only in the group treated with amlodipine. No correlation was found between endocan plasma levels and BP reduction. The results of this hypothesis-generating study suggest that amlodipine and valsartan decrease endocan levels in newly diagnosed hypertensive patients. The effects, which are more evident with amlodipine, may contribute to the anti-inflammatory effects exerted by the two drugs on the vascular target.