[Hydrochlorothiazide and skin cancer]. / Hydrochloorthiazide en huidkanker.

Hydrochlorothiazide and skin cancer Hydrochlorothiazide is a frequently prescribed diuretic with known photosensitizing properties. Recently, a large case-control study in a Danish population found an association between the use of hydrochlorothiazide and an increased risk of developing non-melanoma skin cancer. These data suggest that it may be wise to limit the use of hydrochlorothiazide for the treatment of hypertension. We reviewed the current literature to examine whether a causal relationship between hydrochlorothiazide and non-melanoma skin cancer exists. We consider that the evidence for a causal relationship is limited and contradicting. Moreover, we found that other antihypertensive agents such as calcium blockers and angiotensin receptor blockers are also associated with basal cell carcinoma. Based on the current literature, there seems to be insufficient evidence to advice against the use of hydrochlorothiazide.

A six question screen to facilitate primary cardiovascular disease prevention.

BACKGROUND: European guidelines on primary prevention of cardiovascular disease (CVD) recommend the SCORE risk charts for determining CVD risk, which include blood pressure and serum cholesterol as risk parameters. To facilitate cost-effective large-scale screening, we aimed to construct a risk score with 'non-invasive' parameters as a first screening step to identify persons at increased CVD risk requiring further risk assessment. METHODS: We used data of Dutch employees from 25 organisations participating in a health risk assessment between August 2007 and January 2013. Backward multivariate logistic regression analysis was employed to select non-invasive, independent predictors of high CVD risk, defined as the 10-year risk of fatal CVD of ≥5 % based on the SCORE formula. The total CVD risk score was calculated as the summed coefficients of the retained variables. RESULTS: Data of 6189 male participants was used for the development and validation of the risk score. Age, tobacco use, history of hypertension, alcohol consumption, BMI, and waist circumference were independent predictors of high CVD risk. Ten-fold cross-validation resulted in an area under the curve of 0.95 (SE 0.01, 95 % confidence interval 0.94-0.96). A cut-off score ≥45 on the CVD risk score yielded a sensitivity of 0.93, and a specificity of 0.85. CONCLUSIONS: We developed a simple, non-invasive risk score that accurately identifies persons at increased CVD risk according to the SCORE formula in a population of working men. The risk score enables a stepwise approach in large screening programmes, strongly reducing the number of persons that require full risk estimation including blood pressure and cholesterol measures.

Mortality and cardiovascular risk in patients with a history of malignant hypertension: a case-control study.

The survival of patients with malignant hypertension (MHT) has considerably improved over the past decades. Data regarding the excess risk of mortality and the contribution of conventional cardiovascular risk factors are lacking. The authors retrospectively assessed cardiovascular risk factors and all-cause mortality in 120 patients with a history of MHT and compared them with 120 normotensive and 120 hypertensive age-, sex-, and ethnicity-matched controls. Total cholesterol, low-density lipoprotein cholesterol, and body mass index were lower in MHT patients compared with hypertensive controls, whereas blood pressure, high-density lipoprotein cholesterol, and smoking habit were similar. Median estimated glomerular filtration rate was lower in MHT patients compared with normotensive and hypertensive controls (both P<.01). The annual incidence of all-cause mortality per 100 patient-years was higher in MHT patients (2.6) compared with normotensive (0.2) and hypertensive (0.5) controls (both P<.01). Mortality of patients with a history of MHT remains high compared with normotensive and hypertensive controls. Patients with MHT had a more favorable cardiovascular risk profile compared with hypertensive controls but a higher prevalence of renal insufficiency.

Home blood pressure measurement as a screening tool for hypertension in a web-based worksite health promotion programme.

BACKGROUND: Guidelines on home blood pressure measurement (HBPM) recommend taking at least 12 measurements. For screening purposes, however, it is preferred to reduce this number. We therefore derived and validated cut-off values to determine hypertension status after the first duplicate reading of a HBPM series in a web-based worksite health promotion programme. METHOD: Nine hundred forty-five employees were included in the derivation and 528 in the validation cohort, which was divided into a normal (n = 297) and increased cardiometabolic risk subgroup (n = 231), and a subgroup with a history of hypertension (n = 98). Six duplicate home measurements were collected during three consecutive days. Systolic and diastolic readings at the first duplicate measurement were used as predictors for hypertension in a multivariate logistic model. Cut-off values were determined using receiver operating characteristics analysis. RESULTS: Upper (≥ 150 or ≥ 95 mmHg) and lower limit (<135 and <80 mmHg) cut-off values were derived to confirm or reject presence of hypertension after one duplicate reading. The area under the curve was 0.94 (standard error 0.01, 95% confidence interval 0.93-0.95). In 62.5% of participants, hypertension status was determined, with 1.1% false positive and 4.7% false negatives. Performance was similar in participants with high and low cardiometabolic risk, but worse in participants with a history of hypertension (10.4% false negatives). CONCLUSION: One duplicate home reading is sufficient to accurately assess hypertension status in 62.5% of participants, leaving 37.5% in which the whole HBPM series needs to be completed. HBPM can thus be reliably used as screening tool for hypertension in a working population.

Simultaneous compared with sequential blood pressure measurement results in smaller inter-arm blood pressure differences.

There are currently few recommendations on how to assess inter-arm blood pressure (BP) differences. The authors compared simultaneous with sequential measurement on mean BP, inter-arm BP differences, and within-visit reproducibility in 240 patients stratified according to age (<50 or ≥60 years) and BP (<140/90 mm Hg or ≥140/90 mm Hg). Three simultaneous and three sequential BP measurements were taken in each patient. Starting measurement type and starting arm for sequential measurements were randomized. Mean BP and inter-arm BP differences of the first pair and reproducibility of inter-arm BP differences of the first and second pair were compared between both methods. Mean systolic BP was 1.3±7.5 mm Hg lower during sequential compared with simultaneous measurement (P<.01). However, the first sequential measurement was on average higher than the second, suggesting an order effect. Absolute systolic inter-arm BP differences were smaller on simultaneous (6.2±6.7/3.3±3.5 mm Hg) compared with sequential BP measurement (7.8±7.3/4.6±5.6 mm Hg, P<.01 for both). Within-visit reproducibility was identical (both r=0.60). Simultaneous measurement of BP at both arms reduces order effects and results in smaller inter-arm BP differences, thereby potentially reducing unnecessary referral and diagnostic procedures.

'Diagnostic mode' improves adherence to the home blood pressure measurement schedule.

BACKGROUND: The accuracy of home blood pressure measurement (HBPM) depends on adherence to the measurement schedule. We investigated the number of deviations from the requested schedule using an HBPM device equipped with a diagnostic mode that only allows patients to take a fixed number of BP readings at preset times. METHODS: We randomized patients to measure their BP as recommended by the European Society of Hypertension guideline in either the usual mode or the diagnostic mode. RESULTS: A total of 135 patients were included, mean age 54.4 ± 13.6 years, 57 (42.2%) men, with a mean systolic BP of 147.0 ± 18.4 mmHg and a mean diastolic BP of 88.0 ± 10.3 mmHg. In 66 patients, BP was measured in the diagnostic mode, whereas in 69 patients BP was measured in the usual mode. In the diagnostic mode, 40% of patients showed full adherence to the measurement schedule, compared with 23% of patients in the usual mode (P = 0.02). Unscheduled measurements were performed by 55% of patients measuring BP in the usual mode and none in the diagnostic mode. The number of patients who omitted readings was similar in the diagnostic and the usual mode (P = 0.9). Compared with scheduled readings only, 12% of patients measuring BP in the usual mode fell into a different BP category, whereas reclassification did not occur in patients using the diagnostic mode (P = 0.03). CONCLUSION: HBPM in the diagnostic mode almost doubled the number of patients with full adherence to the measurement schedule and eliminated the number of patients who were reclassified in a different BP category.

Endothelial dysfunction, platelet activation, thrombogenesis and fibrinolysis in patients with hypertensive crisis.

BACKGROUND: Hypertensive crisis is an extreme phenotype of hypertension and hypertension-related thrombotic complications. This is most evident in patients with hypertensive crisis having advanced retinopathy and thrombotic microangiopathy (TMA). We examined whether hypertensive crisis complicated by advanced retinopathy is associated with endothelial dysfunction, platelet activation, thrombin generation and decreased fibrinolytic activity. In addition, we tested the association between these procoagulant changes and the development of TMA and end-organ dysfunction. METHODS: Several key mediators of coagulation were assessed in 40 patients with hypertensive crisis with and without retinopathy and compared with 20 age, sex and ethnicity-matched normotensive controls. In patients with hypertensive crisis, associations with markers of TMA and renal dysfunction were assessed by regression analysis. RESULTS: Soluble P-selectin levels were higher in patients with hypertensive crisis compared with controls regardless of the presence or absence of retinopathy (P<0.01). Levels of von Willebrand factor (VWF), VWF propeptide, prothrombin fragment 1+2 (F1+2) and plasmin-antiplasmin (PAP) complexes were significantly higher in hypertensive crisis with retinopathy compared with normotensive controls (P-values<0.01), whereas in patients without retinopathy only VWF propeptide was higher (P=0.04). VWF, VWF propeptide, soluble tissue factor, F1+2 and PAP were positively associated with markers of TMA and renal dysfunction (P≤0.05). CONCLUSION: Hypertensive crisis with retinopathy confers a prothrombotic state characterized by endothelial dysfunction, platelet activation and increased thrombin generation, whereas fibrinolytic activity is enhanced. The observed changes in prothrombotic and antithrombotic pathways may contribute to the increased risk of ischaemic and haemorrhagic complications in this extreme hypertension phenotype.

Reliability of palpation of the radial artery compared with auscultation of the brachial artery in measuring SBP.

BACKGROUND: Systolic blood pressure contributes more to cardiovascular disease than DBP, especially in elderly persons. Palpation of the radial artery to assess SBP - Riva-Rocci's technique - may be an attractive alternative for auscultatory SBP in these patients. Therefore, we investigated the difference between SBP determined by palpation of the radial artery (pSBP) and SBP assessed by auscultation of the brachial artery (aSBP). METHODS: Patients were included from the waiting room of a hypertension outpatient clinic. In each patient eight simultaneous pSBP and aSBP measurements were assessed by two observers in the same arm. After every two readings the observers switched between pSBP and aSBP. RESULTS: Forty patients were included, 25 men (62.5%), mean age 55.3 years (range 24-78). From a total of 320 measurements, mean difference between pSBP and aSBP was -5.2 mmHg (range -12-26 mmHg) (P < 0.01). This difference correlated significantly with BMI (r = 0.51, P < 0.01), but not with age (r = 0.15, P = 0.35), pulse rate (r = 0.29, P = 0.09) or mean SBP (r = 0.03, P = 0.85). After averaging the first three comparisons, reproducibility did not improve when increasing the number of comparisons. When correcting for the underestimation of 6 mmHg over the first three comparisons, Riva-Rocci's technique estimates SBP with an acceptable accuracy. CONCLUSION: In clinical practice, Riva-Rocci's palpatory technique offers an acceptable alternative for auscultatory SBP measurement. It is recommended to take three measurements and then correct for the average underestimation of 6 mmHg.

Poor adherence to home blood pressure measurement schedule.

BACKGROUND: Consensus dictates that devices used for home blood pressure (BP) measurement should be equipped with a memory to store readings, rather than trusting patients' logbooks. However, data entered in the memory rely on patients' adherence to measurement schedules. We investigated the number and relevance of deviations from the requested measurement schedule. METHODS: We instructed 106 patients to perform 28 BP readings in a 2-week period with a memory-equipped electronic device. Patients were requested to note their scheduled BP values in their logbook and were not informed of the presence of a memory function. RESULTS: The concordance between all BP recordings in both memory and logbook was 90.1% of possible total scheduled readings. The difference in mean BP of all readings from memory compared with all readings from the logbook was -0.06 mmHg (95% confidence interval -0.79 to 0.68) systolic and -0.28 mmHg (95% confidence interval -0.97 to 0.40) diastolic. Unscheduled measurements were performed by 57.5% of patients. Missing scheduled readings in both logbook and memory were found in 34.0% of patients. Fictional data were present for 16.0% of patients. When comparing all individual BP readings from the memory and the logbook, 10.4% of patients were classified in another hypertension stratum according to the European Society of Hypertension criteria. In 23.6% of patients, we did not find any bias. CONCLUSION: In spite of the use of memory-equipped devices, to ensure patients' adherence to measurement schedules, patients still need proper instruction and a close watch.

Association between thrombotic microangiopathy and reduced ADAMTS13 activity in malignant hypertension.

The thrombotic microangiopathy observed in malignant hypertension is similar to that of thrombotic thrombocytopenic purpura, which is associated with a deficiency of ADAMTS13, a von Willebrand factor (VWF)-cleaving protease that cleaves large prothrombogenic multimers. We hypothesized that ADAMTS13 is deficient in malignant hypertension and that the severity of thrombotic microangiopathy is associated with decreased ADAMTS13 activity. We included 20 patients with malignant and 20 patients with severe hypertension, and 20 matched normotensive individuals served as control subjects. VWF, active VWF, and free hemoglobin were assessed to explore predictors of ADAMTS13 activity. Patients with malignant hypertension had lower ADAMTS13 activity (80%; interquartile range: 53% to 130%) compared with control subjects (99% interquartile range: 82% to 129%; P<0.01) but not compared with patients with severe hypertension (P=0.14). ADAMTS13 activity negatively correlated with lactic dehydrogenase levels after logarithmic transformation (r=-0.65; P<0.001) and was associated with platelet count (r=0.34; P=0.04) and the presence of schistocytes (r=-0.37; P=0.02). Apart from the association with thrombotic microangiopathy, ADAMTS13 was inversely associated with creatinine (r=-0.42; P=0.008). Increasing levels of VWF were associated with a decrease in ADAMTS13 activity (r=-0.34; P=0.03). There was no significant association between ADAMTS13 activity and other parameters, including blood pressure. In conclusion, ADAMTS13 is decreased in malignant hypertension and associated with the severity of thrombotic microangiopathy, likely because of the release of VWF after endothelium stimulation. A severe deficiency could not be demonstrated. More studies are needed to identify the role of ADAMTS13 in the thrombotic microangiopathy and ischemic complications of malignant hypertension.