Chagai Grossman

Prevalence and Factors Associated With Resistant Hypertension in a Large Health Maintenance Organization in Israel

Previous assessments of the prevalence of resistant hypertension (RH) in uncontrolled blood pressure (BP) have ranged from 3% to 30%. Using real-world data, our aim was to estimate the prevalence of RH in patients belonging to the Maccabi Healthcare Services, a 2-million-member health organization in Israel. From 2010 to 2011, all hypertensive patients with ≥2 recorded BP measurements during a minimum period of 6 months were identified. Patients were considered uncontrolled if their most recent BP during the study period and their mean systolic BP or diastolic BP during a preceding period of ≥6months were systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, or systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg in chronic kidney disease or diabetes mellitus. Uncontrolled patients taking diuretics and ≥2 antihypertensive therapy classes at their maximal recommended dose were regarded as resistant hypertensives. A total of 172 432 patients were eligible for the study. Uncontrolled BP was found in 35.9% (n=65 710). Overall, 2.2% of the uncontrolled patients (n=1487) were resistant hypertensives. Patients with RH were characterized by a significantly (P<0.01) older age, higher body mass index, and multicomorbidity (including dyslipidemia, diabetes mellitus, and impaired renal function) compared with patients with controlled hypertension receiving equivalent treatment. The results of this large population-based study indicate a substantially lower prevalence of RH than previously reported. Most patients with uncontrolled BP took less than the maximal recommended antihypertensive treatment.

Anakinra for Colchicine‐Resistant Familial Mediterranean Fever: A Randomized, Double‐Blind, Placebo‐Controlled Trial

Familial Mediterranean fever (FMF) is refractory to colchicine prophylaxis in 10–20% of patients. In a number of patient series, treatment with anakinra, an interleukin‐1–blocking agent, prevented FMF attacks in those with colchicine‐resistant FMF. This study was undertaken to evaluate the efficacy and safety of anakinra in the treatment of colchicine‐resistant FMF, using a randomized controlled trial.

Orthostatic Hypotension Is Associated With Nocturnal Change in Systolic Blood Pressure

BACKGROUND The circadian pattern of blood pressure (BP) has yet to be defined among individuals with orthostatic hypotension (OH). The objective of this study was to evaluate whether OH is associated with nocturnal change in systolic BP. METHODS In a prospective study, we evaluated patients who were referred for 24-h ambulatory blood pressure monitoring (ABPM). All subjects underwent orthostatic BP testing before recording their respective 24-h ABPM. RESULTS The study includes 185 subjects, 114 males, mean age 58 ± 18 years (range 19-89). Participants were classified, based on pattern of systolic BP changes at night, as dippers (greater than 10% decrease; n = 74), nondippers (0-10% decrease; n = 77), and reverse-dippers (increase; n = 34). Nineteen patients (10.3%) had OH. Almost all participants with OH (95%) had an abnormal diurnal BP pattern, and most of them (58%) were reverse-dippers, whereas only 56% of the participants without OH had an abnormal diurnal BP variation, and only 14% were reverse-dippers (P < 0.001). Systolic BP decreased with upright posture by 12 and 2 mm Hg in the reverse-dippers and the nondippers, respectively, and increased by 2 mm Hg in the dippers (P < 0.001). Postural changes in systolic BP were inversely related to the changes between day and night BP readings(r = -0.43; P < 0.01). In a multivariate linear regression analysis, orthostatic BP change, use of ≥2 antihypertensive drugs and female sex were related to nocturnal BP changes. CONCLUSIONS The decrease in BP during upright posture may be a marker of nondipping or reverse-dipping pattern of diurnal BP.

Familial Mediterranean fever without MEFV mutations: a case–control study

BackgroundAlthough familial Mediterranean fever (FMF) was originally defined as an autosomal recessive disorder, approximately 10–20% of FMF patients do not carry any FMF gene (MEFV) mutations. Fine phenotype characterization may facilitate the elucidation of the genetic background of the so called “FMF without MEFV mutations”. In this study we clinically and demographically characterize this subset.MethodsMEFV mutation-negative FMF and control patients were recruited randomly from a cohort followed in a dedicated FMF clinic. The control subjects comprised 2 groups: 1. typical population of FMF, consisting of genetically heterogeneous patients manifesting the classical spectrum of FMF phenotype and 2. a severe phenotype of FMF, consisting of FMF patients homozygous for the p.M694V mutation.ResultsForty-seven genetic-negative, 60 genetically heterogeneous and 57 p.M694V homozygous FMF patients were enrolled to the study. MEFV-mutation negative FMF patients showed a phenotype closely resembling that of the other 2 populations. It differed however from the p.M694V homozygous subset by its milder severity (using Mor et al. scoring method), as determined by the lower proportion of patients with chest and erysipelas like attacks, lower frequency of some of the chronic manifestations, lower colchicine dose and older age of disease onset.ConclusionsMEFV mutation-negative FMF by virtue of its classical FMF phenotype is probably associated with a genetic defect upstream or downstream to MEFV related metabolic pathway.

Interventricular Septum Thickness Predicts Future Systolic Hypertension in Young Healthy Pilots

Left ventricular hypertrophy (LVH) has been associated with hypertension, although debate exists as to whether LVH is caused by elevated blood pressure (BP) or is a risk factor for its development. The present study evaluates the association between left ventricular structure and the development of hypertension in a young healthy population. We followed young healthy Israeli Air Force aviators from initial echocardiography at the start of their military service to a mean of 7.5±3.0 years. Data collection included annual BP measurements, height, weight, smoking habits, and lipid profile. We monitored 500 Air Force men with a mean age of 20.5±3.3 (range, 17−40) years and baseline BP of 125±13/74±8 mmHg. Systolic BP during follow-up was associated with baseline systolic BP, interventricular septum (IVS) thickness, and ejection fraction, whereas diastolic BP was associated only with baseline diastolic BP and body mass index. The probability that the systolic BP during follow-up would be higher than the median was twice that in those with an IVS thickness greater than the median. In conclusion, IVS thickening was associated with long-term elevation of systolic BP. Therefore, it seems that IVS thickening is not merely a result of long-term BP elevation, but may predict the development of systolic hypertension. (Hypertens Res 2008; 31: 15−20)

Diabetes mellitus with normal renal function is associated with anaemia.

Anaemia is a common complication of diabetes mellitus (DM), usually related to renal failure. There is scarce information as to the levels of haemoglobin (Hb) and the rate of anaemia in diabetic patients with normal renal function. We, therefore, evaluated haemoglobin levels and the rate of anaemia in diabetic subjects with normal renal functions [estimated glomerular filtration rate (eGFR) > 60 mL/min].

Baseline clinical predictors of an ultimate giant cell arteritis diagnosis in patients referred to temporal artery biopsy.

The diagnosis of giant cell arteritis (GCA) is based on clinical grounds and confirmed by characteristic histological findings on temporal artery biopsy (TAB). Patients may be diagnosed with GCA based on clinical grounds only, despite negative histological findings. We aimed to investigate which baseline clinical and laboratory features best predict an ultimate diagnosis of giant cell arteritis among patients referred to TAB. We retrospectively analyzed 224 patients who underwent TAB in our hospital between 2000 and 2014. Patients were diagnosed with GCA if TAB was positive for GCA, or by clinical grounds only despite a negative biopsy, provided they fulfilled the American College of Rheumatology 1990 criteria. Baseline clinical and laboratory features were obtained from medical records. Predictors of an ultimate GCA diagnosis were investigated. Overall, 82 patients were diagnosed with GCA—57 had histological evidence of GCA and 25 were diagnosed with GCA despite a negative biopsy. One hundred and forty-two patients were not diagnosed with GCA. Predictors of an eventual diagnosis of GCA in a multivariate logistic regression analysis were headache (OR = 6; p < 0.001), jaw claudication (OR 4.5; p = 0.007), erythrocyte sedimentation rate (ESR) (OR = 1.5; p = 0.032) and platelet count (OR = 1.74; p = 0.004). Among patients referred to TAB, headache, jaw claudication, ESR, and thrombocyte levels are predictors for an ultimate diagnosis of GCA. These clinical and laboratory features should be considered when contemplating the diagnosis and treatment of GCA.

Serum Uric Acid Is Associated With Coronary Artery Calcification

Uric acid (UA) is associated with atherosclerosis, and coronary artery calcium (CAC) is a marker of atherosclerosis. The authors studied the association between UA and CAC. A total of 663 asymptomatic patients (564 men; mean age, 55±7 years) were evaluated for the presence of CAC. The study population was divided into three tertiles according to their UA levels, and the prevalence of CAC was compared between the tertiles. CAC was detected in 349 (53%) patients. Levels of UA were significantly higher in those with CAC than in those without CAC (5.6+1.2 vs 5.3+1.3; P=.003). The odds ratio for the presence of CAC in the highest vs lowest UA tertile was 1.72 (95% confidence interval, 1.17–2.51). The highest UA tertile remained associated with the presence of CAC after adjustment for known cardiovascular risk factors. The results show that high serum UA levels are associated with the presence of CAC.

Coronary Artery Calcification Is Associated With the Development of Hypertension

BACKGROUND Hypertension (HTN) is associated with coronary artery calcification (CAC). We hypothesized that preexisting CAC is associated with the development of HTN. METHODS This study included 483 normotensive subjects (mean age 54 years, 83% males) who underwent a baseline evaluation of their CAC score with ungated dual-section computed tomography during 2001-2002 and returned for at least the first annual follow-up. All subjects underwent an annual examination and were followed for a mean period of 6.6 ± 3.2 years to identify newly developed HTN. Data on the patients medical history, physical examination and laboratory evaluations were collected. RESULTS During the follow-up, 104 subjects developed HTN. The rate of newly developed HTN was significantly higher among those with CAC (60 of 223 subjects; 27%) than among those without CAC (44 of 260; 17%) (P < 0.01). The presence of CAC predicted the development of HTN with a hazard ratio of 1.73 (95% confidence interval, 1.17-2.56; P < 0.01). After adjustment for age, sex, body mass index, smoking, baseline systolic blood pressure, and levels of glucose, triglycerides, and low-density lipoprotein cholesterol, the presence of CAC still predicted the development of HTN with a hazard ratio of 1.63 (95% confidence interval, 1.02-2.60; P = 0.04). CONCLUSIONS Preexisting CAC is associated with the development of HTN.

Progression of coronary artery calcification is associated with long-term cardiovascular events in hypertensive adults.

Objectives: Coronary artery calcification (CAC) is an independent predictor of cardiovascular (CV) events in hypertensive adults. However, the additive value of serial CAC measurements for risk stratification is unclear. The aim of the present study was to find whether CAC progression predicts long-term CV events in hypertensive patients. Methods: The study group included 210 patients (mean age 64 ± 5.6 years, 54% men), a subgroup of 544 participants in the calcification side arm of the INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy). All were free of symptoms or known CV disease, had at least two CT scans 1 year apart, and had available long-term follow-up. Progression of CAC was defined as the absolute change in CAC score between maximal score during follow-up and baseline score. The endpoint was the first CV event after the last CT scan. Three categories of CAC progression were defined. Zero progression was defined as ‘nonprogressors’, and progression below and above the median of maximal progression were defined as ‘slow progressors’ and ‘rapid progressors’, respectively. Results: During 15 years of follow-up (mean 11.4 ± 4.4), 83 patients experienced a first CV event. The rate of events was higher in rapid (29/59, 49%), and slow (36/78 46%) than in nonprogressors (18/73 25%); (P = 0.005). Compared with nonprogressors, the adjusted hazard ratio for CV events was 1.91 [95% confidence interval (95% CI); 1.05–3.47] in the slow, and 2.13 (95% CI; 1.12–4.03) in the rapid progressors. Conclusion: In hypertensive patients, progression of CAC is associated with long-term CV events.