Proteomic-biostatistic integrated approach for finding the underlying molecular determinants of hypertension in human plasma

Despite advancements in lowering blood pressure, the best approach to lower it remains controversial because of the lack of information on the molecular basis of hypertension. We, therefore, performed plasma proteomics of plasma from patients with hypertension to identify molecular determinants detectable in these subjects but not in controls and vice versa. Plasma samples from hypertensive subjects (cases; n=118) and controls (n=85) from the InGenious HyperCare cohort were used for this study and performed mass spectrometric analysis. Using biostatistical methods, plasma peptides specific for hypertension were identified, and a model was developed using least absolute shrinkage and selection operator logistic regression. The underlying peptides were identified and sequenced off-line using matrix-assisted laser desorption ionization orbitrap mass spectrometry. By comparison of the molecular composition of the plasma samples, 27 molecular determinants were identified differently expressed in cases from controls. Seventy percent of the molecular determinants selected were found to occur less likely in hypertensive patients. In cross-validation, the overall R(2) was 0.434, and the area under the curve was 0.891 with 95% confidence interval 0.8482 to 0.9349, P<0.0001. The mean values of the cross-validated proteomic score of normotensive and hypertensive patients were found to be -2.007±0.3568 and 3.383±0.2643, respectively, P<0.0001. The molecular determinants were successfully identified, and the proteomic model developed shows an excellent discriminatory ability between hypertensives and normotensives. The identified molecular determinants may be the starting point for further studies to clarify the molecular causes of hypertension

Blood pressure control in Italy: analysis of clinical data from 2005-2011 surveys on hypertension

Introduction: Blood pressure (BP) control is poorly achieved in hypertensive patients, worldwide. Aim: We evaluated clinic BP levels and the rate of BP control in hypertensive patients included in observational studies and clinical surveys published between 2005 and 2011 in Italy. Methods: We reviewed the medical literature to identify observational studies and clinical surveys on hypertension between January 2005 and June 2011, which clearly reported information on clinic BP levels, rates of BP control, proportions of treated and untreated patients, who were followed in different clinical settings (mostly in general practice, and also in outpatient clinics and hypertension centres). Results: The overall sample included 158 876 hypertensive patients (94 907 women, mean age 56.6 +/- 9.6 years, BMI 27.2 +/- 4.2 kg/m(2), known duration of hypertension 90.2 +/- 12.4 months). In the selected studies, average SBP and DBP levels were 145.7 +/- 15.9 and 87.5 +/- 9.7 mmHg, respectively; BP levels were higher in patients followed in hypertension centres (n = 10 724, 6.7%; 146.5 +/- 17.3/88.5 +/- 10.3 mmHg) than in those followed by general practitioners (n = 148 152, 93.3%; 143.5 +/- 13.9/84.8 +/- 8.9 mmHg; P < 0.01). More than half of the patients were treated (n = 91 318, 57.5%); among treated hypertensive patients, only 31 727 (37.0%) had controlled BP levels. Conclusion: The present analysis confirmed inadequate control of BP in Italy, independently of the clinical setting. Although some improvement was noted compared with a similar analysis performed between 1995 and 2005, these findings highlight the need for a more effective clinical management of hypertension

Influence of high cardiovascular risk in asymptomatic people on the duration and cost of sick leave: results of the ICARIA study

Aims We investigated the potential influence of a moderate-to-high cardiovascular (CV) risk (CVR) (defined as a Systematic COronary Risk Evaluation model, or SCORE ≥ 4%), in the absence of an established CV disease, on the duration and cost of CV and non-CV sick leave (SL) resulting from common and occupational accidents or diseases. Methods and results We conducted a prospective cohort study on 690 135 workers with a 1-year follow-up and examined CV- and non-CV-related SL episodes. To obtain baseline values, CVR factors were initially assessed at the beginning of the year during routine medical examination. The CVR was calculated with the SCORE charts for all subjects. Moderate-to-high CVR was defined as SCORE ≥ 4%. A baseline SCORE ≥ 4% was associated with a higher risk for long-term CV and non-CV SL, as revealed by follow-up assessment. This translated into an increased cost, estimated at €5 801 464.18 per year. Furthermore, pharmacological treatment for hypertension or hyperlipidaemia was significantly associated with longer SL duration. Conclusion Moderate-to-high CVR in asymptomatic subjects was significantly associated with the duration and cost of CV and non-CV SL. These results constitute the first body of evidence that the SCORE charts can be used to identify people with a non-established CV disease, which might ultimately translate into more lost workdays and therefore increased cost for societ

Comparison of hypertension healthcare outcomes among older people in the USA and England

Funding: Economic and Social Research Council. G1001375/1. Medical Research Council. G1001375/1. US Department of Health and Human Services. National Institutes of Health. National Institute on Aging. 2R01 AG030153.Background The US and England have very different health systems. Comparing hypertension care outcomes in each country enables an evaluation of the effectiveness of each system. Method The English Longitudinal Study of Ageing and the Health and Retirement Survey are used to compare the prevalence of controlled, uncontrolled and undiagnosed hypertension in the population aged over 50 in the US and in England. Results Controlled hypertension is more prevalent in the US (age 50 to 64: 0.53 (0.50-0.57) and age 65+: 0.51 (0.49-0.53)) than in England (age 50 to 64: 0.45 (0.42-0.48) and age 65+: 0.42 (0.40-0.45)). This difference is driven by lower undiagnosed hypertension in the US (age 50 to 64: 0.18 (0.15-0.21) and age 65+: 0.13 (0.12-0.14)) relative to England (age 50 to 64: 0.26 (0.24-0.29) and age 65+: 0.22 (0.20-0.24)). The prevalence of uncontrolled hypertension is very similar in the US (age 50 to 64: 0.29 (0.26-0.32) and age 65+: 0.36 (0.34-0.38)) and England (age 50 to 64: 0.29 (0.26-0.32) and age 65+: 0.36 (0.34-0.39)). Hypertension care outcomes are comparable across US insurance categories. In both countries undiagnosed hypertension is positively correlated with wealth (ages 50-64). Uncontrolled hypertension declines with rising wealth in the US. Conclusions Different diagnostic practices are likely to drive the cross-country differences in undiagnosed hypertension. US government health systems perform at least as well as private health care and are more equitable in the distribution of care outcomes. Higher undiagnosed hypertension among the affluent may reflect less frequent medical contact.Publisher PDFPeer reviewe

VALUE trial: Long-term blood pressure trends in 13,449 patients with hypertension and high cardiovascular risk

Background: The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study compares cardiovascular outcomes in 15,314 eligible patients from 31 countries randomized to valsartan or amlodipine-based treatment. Methods: The blood pressure (BP) trends are analyzed in 13,449 of VALUE study patients who had baseline BP and 24 months BP and treatment data. Results: In a cohort of 12,570 patients, baseline 24 and 30 months BP, but not 30 months treatment data, were available. Of 13,449 patients, 92% (N = 12,398) received antihypertensive therapy at baseline. The baseline BP was 153.5/86.9 mm Hg in treated compared to 168.1.8/95.3 mm Hg in 1051 untreated patients. After 6 months both groups had indistinguishable BP values. At 12 months the BP decreased to 141.2/82.9 mm Hg (P < .0001 for systolic BP and diastolic BP versus baseline), at 24 months to 139.1/80 mm Hg (P < .0001 v 12 months), and to 138/79 mm Hg at 30 months (P < .0001 v 24 months). The systolic BP control (<140 mm Hg) at 30 months increased from 21.9% at baseline to 62.2%, the diastolic BP (< 90 mm Hg) from 54.2% to 90.2% and the combined control (<140 and <90 mm Hg) from 18.9% to 60.5%. At 24 months 85.8% of patients were on protocol drugs: monotherapy = 39.7%, added hydrochlorothiazide = 26.6%, add-on drugs = 15.1%, and protocol drugs in nonstandard doses = 4.3%. Conclusions: The achieved BP control exceeds values reported in most published large-scale trials. The VALUE study is executed in regular clinical settings and 92% of the patients received antihypertensive drugs at baseline. When an explicit BP goal is set, and a treatment algorithm is provided, the physicians can achieve better control rates than in their regular practice. Am J Hypertens 2003;16: 544-548 @ 2003 American Journal of Hypertension, Lt

Blood pressure control in Italy: analysis of clinical data from 2005-2011 surveys on hypertension

INTRODUCTION: Blood pressure (BP) control is poorly achieved in hypertensive patients, worldwide. AIM: We evaluated clinic BP levels and the rate of BP control in hypertensive patients included in observational studies and clinical surveys published between 2005 and 2011 in Italy. METHODS: We reviewed the medical literature to identify observational studies and clinical surveys on hypertension between January 2005 and June 2011, which clearly reported information on clinic BP levels, rates of BP control, proportions of treated and untreated patients, who were followed in different clinical settings (mostly in general practice, and also in outpatient clinics and hypertension centres). RESULTS: The overall sample included 158 876 hypertensive patients (94 907 women, mean age 56.6 ± 9.6 years, BMI 27.2 ± 4.2 kg/m(2), known duration of hypertension 90.2 ± 12.4 months). In the selected studies, average SBP and DBP levels were 145.7 ± 15.9 and 87.5 ± 9.7 mmHg, respectively; BP levels were higher in patients followed in hypertension centres (n = 10 724, 6.7%; 146.5 ± 17.3/88.5 ± 10.3 mmHg) than in those followed by general practitioners (n = 148 152, 93.3%; 143.5 ± 13.9/84.8 ± 8.9 mmHg; P < 0.01). More than half of the patients were treated (n = 91 318, 57.5%); among treated hypertensive patients, only 31 727 (37.0%) had controlled BP levels. CONCLUSION: The present analysis confirmed inadequate control of BP in Italy, independently of the clinical setting. Although some improvement was noted compared with a similar analysis performed between 1995 and 2005, these findings highlight the need for a more effective clinical management of hypertension

Angiotensin II receptor blockers and cardiovascular protection: Focus on left ventricular hypertrophy regression and atrial fibrillation prevention

Left ventricular hypertrophy (LVH) and atrial fibrillation (AF) are strong predictors of cardiovascular (CV) morbidity and mortality, independently of blood pressure levels and other modifiable and nonmodifiable risk factors. The actions of circulating and tissue angiotensin II, mediated by AT1 receptors, play an important role in the development of a wide spectrum of cardiovascular alterations, including LVH, atrial enlargement and AF. Growing experimental and clinical evidence suggests that antihypertensive drugs may exert different effects on LVH regression and new onset AF in the setting of arterial hypertension. Since a number of large and adequately designed studies have found angiotensin II receptor blockers (ARBs) to be more effective in reducing LVH than beta-blockers and data are also available showing their effectiveness in preventing new or recurrent AF, it is reasonable to consider this class of drugs among first line therapies in patients with hypertension and LVH (a very high risk phenotype predisposing to AF) and as adjunctive therapy to antiarrhythmic agents in patients undergoing pharmacological or electrical cardioversion of AF