Sex-specific relationships of inflammatory biomarkers with blood pressure in older adults.

Emerging evidence indicates an association between blood pressure and inflammation, yet this relationship remains unclear in older adults, despite the elevated prevalence of hypertension. We investigated the association between blood pressure, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and white blood cell (WBC) count in a cohort of 3571 older adults aged 65 and above, and 587 middle-aged participants (55-59 years old). In women aged 65 and above, the relationship between inflammatory markers and blood pressure was consistent, with hs-CRP and WBC emerging as predictors of high blood pressure. For hs-CRP, the adjusted odds ratio (OR) was 1.5 (95% CI, 1.07 to 2.10, P = 0.02), and for WBC, the adjusted OR was 1.41 (95% CI, 1.02 to 1.94, P = 0.04), comparing the highest to the lowest quartiles. In men, only the WBC count was significantly associated with an increased OR for high BP (adjusted OR 1.49, 95% CI, 1.09 to 2.02, P = 0.01) across quartiles. Across the entire study population, in a fully adjusted model, all inflammatory markers were modestly associated with blood pressure levels, while the effect of being over 65 years was the most significant predictor of high blood pressure (OR 1.84, 95% CI, 1.50 to 2.25, P < 0.001). The link between key inflammation markers and blood pressure in older adults varies by sex and biomarker type and may differ from the relationship observed in younger individuals. These relationships are likely to be affected by factors linked to age.

Malignant Hypertension:A Systemic Cardiovascular Disease: JACC Review Topic of the Week.

Malignant hypertension (MHT) is a hypertensive emergency with excessive blood pressure (BP) elevation and accelerated disease progression. MHT is characterized by acute microvascular damage and autoregulation failure affecting the retina, brain, heart, kidney, and vascular tree. BP must be lowered within hours to mitigate patient risk. Both absolute BP levels and the pace of BP rise determine risk of target-organ damage. Nonadherence to the antihypertensive regimen remains the most common cause for MHT, although antiangiogenic and immunosuppressant therapy can also trigger hypertensive emergencies. Depending on the clinical presentation, parenteral or oral therapy can be used to initiate BP lowering. Evidence-based outcome data are spotty or lacking in MHT. With effective treatment, the prognosis for MHT has improved; however, patients remain at high risk of adverse cardiovascular and kidney outcomes. In this review, we summarize current viewpoints on the epidemiology, pathogenesis, and management of MHT; highlight research gaps; and propose strategies to improve outcomes.

Soluble fms-like tyrosine kinase 1 (sFlt-1): A novel biochemical marker for acute fatty liver of pregnancy.

INTRODUCTION: Acute fatty liver of pregnancy (AFLP) substantially contributes to maternal and neonatal morbidity and mortality. Other liver-associated pregnancy complications such as preeclampsia-associated HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome may be difficult to differentiate from AFLP as these diseases overlap with regard to multiple clinical and laboratory features. The aim of this study was to investigate angiogenic profiles by measuring soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in pregnancies compromised by AFLP and to compare them with those complicated by HELLP syndrome. MATERIAL AND METHODS: Pregnant women affected by AFLP or HELLP syndrome were enrolled. The study population of women with HELLP syndrome was part of a larger data collection obtained in our clinic that has been used for previous work. Patients' angiogenic profiles were assessed by measuring sFlt-1 and PlGF serum levels. To assess the diagnostic potential of these angiogenic markers in AFLP, as well as discriminating it from HELLP syndrome, non-parametric tests were used and receiver operating curves were calculated. RESULTS: Six women with AFLP and 48 women with HELLP syndrome were included in the study. Patients with AFLP showed significantly higher sFlt-1 levels (median: 57 570 pg/mL; range 31 609-147 170 pg/mL) than patients with HELLP syndrome (9713 pg/mL; 1348-30 781 pg/mL; p < 0.001). PlGF serum levels were higher in patients with AFLP compared with those with HELLP syndrome (197 pg/mL; 127-487 pg/mL vs. 40 pg/mL; 9-644 pg/mL, respectively; p < 0.01). sFlt-1/PlGF ratios were not significantly different between AFLP and HELLP syndrome patients (192; 157-1159 vs. 232; 3-948, respectively; NS). In our study population, an sFlt-1 cut-off value of 31 100 pg/mL allowed differentiation between these two diseases with a sensitivity and specificity of 100%. A linear correlation was found between the cumulative numbers of Swansea criteria and sFlt-1 serum levels (r = 0.97; p < 0.01). CONCLUSIONS: AFLP is associated with very high sFlt-1 serum levels in particular in women fulfilling eight or more Swansea criteria. Besides the suggested Swansea criteria to diagnose AFLP, an sFlt-1 value above 31 100 pg/mL may be an additional biochemical feature improving discrimination between AFLP and HELLP syndrome. However, because of the small number of pregnancies affected by AFLP included in this work further studies are needed to corroborate our findings.

Ultra-high sensitive C-reactive protein during normal pregnancy and in preeclampsia: a pilot study.

INTRODUCTION: Angiogenic and inflammatory factors have been shown to play an important role in the pathogenesis of preeclampsia. However, there is little information on their interaction. The aims of this study were to investigate the longitudinal pattern of inflammatory markers, such as interleukin-6 (IL-6) and C-reactive protein (CRP) using a novel ultra-high sensitive assay method (uhsCRP), and to explore their relationship with angiogenic factors such as placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and vascular endothelial growth factor (VEGF) in normal pregnancies and pregnancies complicated by preeclampsia. MATERIALS AND METHODS: Serum levels of uhsCRP, IL-6, PLGF, VEGF and s-Flt-1 were longitudinally determined in 16 women with normal, singleton healthy pregnancies at 7-13, 17-22, 27-31 and 37-41 weeks of gestation by ELISA. uhsCRP was measured using a ultra-high sensitivity ELISA test. Serum of women with preeclampsia (n = 15) was available only once, usually in the third trimester of pregnancy. Women with premature rupture of membranes (PROM) or infection such as chorioamnionitis were excluded. Spearman rank correlation, logistic regression, ROC analysis, ANOVA and Mann-Whitney U-test were used for statistical purposes. RESULTS: In normal pregnancies, serum uhsCRP showed a gestational age-dependent increase (r = 0.40; P < 0.001). In women suffering from preeclampsia, uhsCRP levels were higher than in gestational age-matched controls (18010 ±â€Š4763 versus 3026 ±â€Š587 ng/ml; P < 0.001). Similarly, serum IL-6 levels increased throughout pregnancy and correlated with uhsCRP in normal pregnancies and in preeclampsia (n = 64, r = 0.37; P < 0.01 and n = 15, r = 1.00, P < 0.0001). uhsCRP levels were positively correlated with sFlt-1 levels (n = 64, r = 0.34; P < 0.01). CONCLUSION: The increases in uhsCRP (and IL-6) serum levels with advancing gestation indicate a shift towards an inflammatory state during normal pregnancy. The excessive rise in uhsCRP and sFlt-1 in preeclampsia indicate that both may be involved in its pathogenesis. uhsCRP may be useful as an early marker for preeclampsia and studies defining the pattern of its rise throughout pregnancies at risk are urgently needed.

Gaisböck syndrome (polycythemia and hypertension) revisited: results from the national inpatient sample database.

BACKGROUND: Polycythemia is characterized by increased blood viscosity and a chronic inflammatory state possibly giving rise to excessive thromboembolic events and hypertensive cardiovascular disease. We aimed to study the relationship between polycythemia and cardiac risk factors using a large national registry. METHODS: Patients more than 18 years with a diagnosis of polycythemia were identified from the National Inpatient Sample 2009-2010 database using International Classification of Diseases; Ninth Edition (ICD-9) code 238.4. Demographics, cardiac risk factors, and cardiovascular events were identified. RESULTS: Polycythemia was present in 0.1% (n = 37 922) of hospital-discharged patients. Patients with polycythemia had a significantly increased prevalence of all cardiac risk factors and events, except for diabetes mellitus and chronic kidney disease. Hypertension was more prevalent in polycythemia compared to controls (61 vs. 46%; P < 0.0001). After adjusting for age, sex, race, diabetes mellitus, hyperlipidemia, tobacco use, obesity, coronary artery disease, heart failure, and chronic kidney disease, polycythemia was still a determinant of hypertension [1.37 (1.28-1.45); P < 0.001]. CONCLUSION: Polycythemia had high prevalence of all cardiac risk factors and was independently associated with increased prevalence of hypertension even after adjusting. Our findings from the National Inpatient Sample provide an epidemiological correlate of Gaisböck's original observation of the association of polycythemia and hypertension more than a century ago.

Misconceptions and Facts About Mitral Regurgitation.

Mitral regurgitation is a common heart valve disease. It is defined to be primary when it results from the pathology of the mitral valve apparatus itself and secondary when it is caused by distortion of the architecture or function of the left ventricle. Although the diagnosis and management of mitral regurgitation rely heavily on echocardiography, one should bear in mind the caveats and shortcomings of such an approach. Clinical decision making commonly focuses on the indications for surgery, but it is complex and mandates precise assessment of the mitral pathology, symptom status of the patient, and ventricular performance (right and left) among other descriptors. It is important for healthcare providers at all levels to be familiar with the clinical picture, diagnosis, disease course, and management of mitral regurgitation.

No evidence for a J-shaped curve in treated hypertensive patients with increased cardiovascular risk: The VALUE trial.

Previous studies have debated the notion that low blood pressure (BP) during treatment, particularly diastolic (DBP), is associated with increased risk of cardiovascular disease. We evaluated the impact of low BP on cardiovascular outcomes in a high-risk population of 15,244 hypertensive patients, almost half of whom had a history of coronary artery disease (CAD). In the prospective Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, patients were randomized to valsartan or amlodipine regimens and followed for 4.2 years (mean) with no difference in the primary cardiovascular endpoint. A Cox proportional hazards model was used to evaluate the relationship between average on-treatment BP and clinical outcomes. The relationship between BP and cardiovascular events was adjusted for age, gender and body mass index, and baseline qualifying risk factors and diseases (smoking, high total cholesterol, diabetes mellitus, proteinuria, CAD, previous stroke and left ventricular hypertrophy). DBP ≥ 90 mmHg, compared with < 90 mmHg, was associated with increased incidence of the primary cardiovascular endpoint (all cardiac events); however, DBP < 70 mmHg, compared with ≥ 70 mmHg, was not associated with increased incidence after covariate adjustment (no J-shaped curve). Similar results were observed for death, myocardial infarction (MI), heart failure and stroke, considered separately. Nadir for MI was at DBP of 76 mmHg and for stroke 60 mmHg. The ratio of MI to stroke increased with lower DBP. In CAD patients the MI to stroke ratio was more pronounced than in patients without CAD but there was no significant J-curve in either group. Systolic BP ≥ 150 but not < 130 mmHg, compared with 130-149 mmHg, similarly was associated with increased risk for primary outcome. In conclusion, patients in BP strata ≥ 150/90 mmHg, but not patients in BP strata < 130/70 mmHg, were at increased risk for adverse outcomes in this hypertensive, high-risk population. Although benefit in preventing MI in relation to preventing stroke levels off for the lowest BPs, these data provide no support for a J-curve in the treatment of high-risk hypertensive patients . The increase in the ratio of MI to stroke with lower DBP indicates target organ heterogeneity in that the optimal on-treatment DBP for cerebroprotection is below that for cardioprotection.

Atrioesophageal fistula following ablation procedures for atrial fibrillation: systematic review of case reports.

BACKGROUND: Atrioesophageal fistula (AEF) is a rare but serious adverse event of atrial fibrillation (AF) ablation. OBJECTIVE: To identify the clinical characteristics of AEF following ablation procedures for AF and determine the associated mortality. METHODS: A systematic review of observational cases of AEF following ablation procedures for AF was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. RESULTS: 53 cases were identified. Mean age was 54±13 years; 73% (39/53) of cases occurred in males. Mean interval between procedure and presentation was 20±12 days, ranging from 2 to 60 days. AEF was observed in 12 patients who underwent surgical radiofrequency ablation (RFA) and in 41 patients with percutaneous RFA. Fever was the most common presenting symptom (n=44) followed by neurological deficits (n=27) and haematemesis (n=19). CT of the chest (n=27) was the preferred diagnostic test. Patients who did not receive a primary esophageal repair were more likely to have a deadly outcome (34% vs 83%; p<0.05). No difference in mortality rate was found between patients who underwent surgical RFA when compared with percutaneous RFA (58% vs 56%; p=0.579). No association was found between onset of symptoms and mortality (19±10 vs 23±14 days; p=0.355). CONCLUSIONS: AEF following ablation procedures for AF is a serious complication with high mortality rates. Presenting symptoms most often include a triad of fever, neurological deficit and/or haematemesis within 60 days of procedure. The preferred diagnostic test is CT of the chest. The treatments of choice is surgical repair.

Drug induced hypertension--An unappreciated cause of secondary hypertension.

Most patients with hypertension have essential hypertension or well-known forms of secondary hypertension, such as renal disease, renal artery stenosis, or common endocrine diseases (hyperaldosteronism or pheochromocytoma). Physicians are less aware of drug induced hypertension. A variety of therapeutic agents or chemical substances may increase blood pressure. When a patient with well controlled hypertension is presented with acute blood pressure elevation, use of drug or chemical substance which increases blood pressure should be suspected. Drug-induced blood pressure increases are usually minor and short-lived, although rare hypertensive emergencies associated with use of certain drugs have been reported. Careful evaluation of prescription and non-prescription medications is crucial in the evaluation of the hypertensive individual and may obviate the need for expensive and unnecessary evaluations. Discontinuation of the offending agent will usually achieve adequate blood pressure control. When use of a chemical agent which increases blood pressure is mandatory, anti-hypertensive therapy may facilitate continued use of this agent. We summarize the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action.

Meta-Analysis of Comparison of the Newer Oral P2Y12 Inhibitors (Prasugrel or Ticagrelor) to Clopidogrel in Patients With Non-ST-Elevation Acute Coronary Syndrome.

Newer oral P2Y12 inhibitors are more potent and have faster onset of action than clopidogrel. However, the efficacy and safety in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are not well studied. A systemic search of MEDLINE and EMBASE databases was performed to identify randomized clinical trials comparing newer oral P2Y12 inhibitors (prasugrel or ticagrelor) to clopidogrel in patients with NSTE-ACS. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and stroke (major cardiovascular events [MACE]). Secondary outcomes were individual components of the primary outcome, all-cause mortality, and Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding. A total of 31,470 patients with NSTE-ACS from 4 randomized clinical trials were included (newer oral P2Y12 inhibitors: 15,951; clopidogrel: 15,519). Newer oral P2Y12 inhibitors significantly decreased MACE (relative risk [RR] 0.87, 95% confidence interval [CI] 0.80 to 0.95) and MI (RR 0.85, 95% CI 0.75 to 0.96) and showed a trend toward reduction of cardiovascular death (RR 0.89, 95% CI 0.71 to 1.01). There was a significant increase in TIMI major bleeding (RR 1.27, 95% CI 1.07 to 1.50) and TIMI major or minor bleeding (RR 1.20, 95% CI 1.02 to 1.42). Results were largely similar when stratified by ticagrelor versus prasugrel (pinteraction >0.05) except for increased TIMI major/minor bleeding with prasugrel than ticagrelor (pinteraction = 0.01). In conclusion, in patients with NSTE-ACS, newer oral P2Y12 inhibitors decrease MACE and MI at the expense of a significant increase in the risk of bleeding. Treatment of 1,000 patients with newer oral P2Y12 inhibitors will prevent 16 MACE and 13 MIs at the expense of increase in 6 major bleeding events.

Role of neprilysin inhibitor combinations in hypertension: insights from hypertension and heart failure trials.

Neprilysin is a neutral endopeptidase and its inhibition increases bioavailability of natriuretic peptides, bradykinin, and substance P, resulting in natriuretic, vasodilatatory, and anti-proliferative effects. In concert, these effects are prone to produce a powerful ventricular unloading and antihypertensive response. LCZ696 (Valsartan/sacubitril) is a first-in-class angiotensin II-receptor neprilysin inhibitor. LCZ696 is a novel drug not only for the treatment of heart failure but it is also likely to be a useful antihypertensive drug and may have a preferential effect on systolic pressure. This review discusses (i) the mechanism of action, pharmacokinetics, and pharmacodynamics of this novel drug, (ii) the efficacy, safety, and tolerability of LCZ696 in treatment of hypertension from the available trials, (iii) evidence from other contemporary trials on combined Neprilysin inhibitors, (iv) future trials and areas of research to identify hypertensive patient populations that would most benefit from LCZ696.

Secondary arterial hypertension: when, who, and how to screen?

Secondary hypertension refers to arterial hypertension due to an identifiable cause and affects ∼5-10% of the general hypertensive population. Because secondary forms are rare and work up is time-consuming and expensive, only patients with clinical suspicion should be screened. In recent years, some new aspects gained importance regarding this screening. In particular, increasing evidence suggests that 24 h ambulatory blood pressure (BP) monitoring plays a central role in the work up of patients with suspected secondary hypertension. Moreover, obstructive sleep apnoea has been identified as one of the most frequent causes. Finally, the introduction of catheter-based renal denervation for the treatment of patients with resistant hypertension has dramatically increased the interest and the number of patients evaluated for renal artery stenosis. We review the clinical clues of the most common causes of secondary hypertension. Specific recommendations are given as to evaluation and treatment of various forms of secondary hypertension. Despite appropriate therapy or even removal of the secondary cause, BP rarely ever returns to normal with long-term follow-up. Such residue hypertension indicates either that some patients with secondary hypertension also have concomitant essential hypertension or that irreversible vascular remodelling has taken place. Thus, in patients with potentially reversible causes of hypertension, early detection and treatment are important to minimize/prevent irreversible changes in the vasculature and target organs.