D. Armstrong

Gestational hypertension in atrial natriuretic peptide knockout mice and the developmental origins of salt-sensitivity and cardiac hypertrophy

OBJECTIVE To determine the effect of gestational hypertension on the developmental origins of blood pressure (BP), altered kidney gene expression, salt-sensitivity and cardiac hypertrophy (CH) in adult offspring. METHODS Female mice lacking atrial natriuretic peptide (ANP-/-) were used as a model of gestational hypertension. Heterozygous ANP+/- offspring was bred from crossing either ANP+/+ females with ANP-/- males yielding ANP+/-(WT) offspring, or from ANP-/- females with ANP+/+ males yielding ANP+/-(KO) offspring. Maternal BP during pregnancy was measured using radiotelemetry. At 14weeks of age, offspring BP, gene and protein expression were measured in the kidney with real-time quantitative PCR, receptor binding assay and ELISA. RESULTS ANP+/-(KO) offspring exhibited normal BP at 14weeks of age, but displayed significant CH (P<0.001) as compared to ANP+/-(WT) offspring. ANP+/-(KO) offspring exhibited significantly increased gene expression of natriuretic peptide receptor A (NPR-A) (P<0.001) and radioligand binding studies demonstrated significantly reduced NPR-C binding (P=0.01) in the kidney. Treatment with high salt diet increased BP (P<0.01) and caused LV hypertrophy (P<0.001) and interstitial myocardial fibrosis only in ANP+/-(WT) and not ANP+/-(KO) offspring, suggesting gestational hypertension programs the offspring to show resistance to salt-induced hypertension and LV remodeling. Our data demonstrate that altered maternal environments can determine the salt-sensitive phenotype of offspring.

Factors influencing the echocardiographic estimate of right ventricular systolic pressure in normal patients and clinically relevant ranges according to age

BACKGROUND Previous studies have shown that in the absence of underlying cardiac pathology, the echocardiographic estimate of right ventricular systolic pressure (RVSP) increases progressively and normally with age. There are limited data in patients older than 60 years of age. OBJECTIVE To define the ranges of RVSP according to age and to include more elderly patients than have previously been reported. METHODS All patients undergoing echocardiography since May 26, 1999, at the Kingston Heart Clinic (Kingston, Ontario) have had their data entered into a locally designed cardiology database (CARDIOfile; Registered trademark, Kingston Heart Clinic). RVSP was calculated from the peak tricuspid regurgitant jet velocity (V) using the modified Bernoulli equation (RVSP = 4V2 + RAP), with the mean right atrial pressure (RAP) estimated to be 10 mmHg. Of the 22,628 patients who had undergone echocardiography, 10,905 had RVSP measured. All abnormal echocardiograms were excluded, leaving 1559 echocardiograms for analysis. RESULTS Patient age ranged from 15 to 93 years. The mean age was 49 years. RVSP increased significantly only after the age of 50 years. The mean (+/- SD) RVSP for those younger than 50 years, 50 to 75 years, and older than 75 years of age was 27.3+/-5.7 mmHg, 30.2+/-7.6 mmHg and 34.8+/-8.7 mmHg, respectively (P<0.0001 among all age groups). The normal range (95% CI) of RVSP in those younger than 50 years, 50 to 75 years, and older than 75 years of age was 16 mmHg to 39 mmHg, 15 mmHg to 45 mmHg, and 17 mmHg to 52 mmHg, respectively. Multivariate analysis indicated that age, mitral diastolic early-to-late filling velocity ratio, ejection fraction, aortic size and early mitral filling velocity/ early diastolic mitral annular velocity were the only significant independent variables. There were significant changes in diastolic function with increasing age, which may have been responsible for the changes in RVSP. CONCLUSIONS RVSP remains stable in both men and women until the age of 50 years. Thereafter, RVSP increases progressively in a linear manner with age and is significantly higher in patients older than 75 years of age. The changes may relate to changes in diastolic function. These ranges should be taken into account when using echocardiogram-derived RVSP for the diagnosis of pulmonary hypertension in the absence of cardiovascular disease.

Sex-specific differences in natriuretic peptide and nitric oxide synthase expression in ANP gene-disrupted mice

Sex-specific differences in hormone-mediated gene regulation may influence susceptibility to cardiac hypertrophy, a primary risk factor for cardiovascular disease. Under hormonal influence, natriuretic peptide (NP) and nitric oxide synthase (NOS) systems modulate cardio-protective gene programs through common downstream production of cyclic guanosine 3′–5′ monophosphate (cGMP). Ablation of either system can adversely affect cardiac adaptation to stresses and insults. This study elucidates sex-specific differences in cardiac NP and NOS system gene expression and assesses the impact of the estrous cycle on these systems using the atrial natriuretic peptide gene-disrupted (ANP−/−) mouse model. Left ventricular expression of the NP and NOS systems was analyzed using real-time quantitative polymerase chain reaction in 13- to 16-week-old male, proestrous and estrous female ANP+/+ and ANP−/− mice. Left ventricular and plasma cGMP levels were measured to assess the convergent downstream effects of the NP and NOS systems. Regardless of genotype, males had higher expression of the NP system while females had higher expression of the NOS system. In females, transition from proestrus to estrus lowered NOS system expression in ANP+/+ mice while the opposite was observed in ANP−/− mice. No significant changes in left ventricular cGMP levels across gender and genotype were observed. Significantly lower plasma cGMP levels were observed in ANP−/− mice compared to ANP+/+ mice. Regardless of genotype, sex-specific differences in cardiac NP and NOS system expression exist, each sex enlisting a predominant system to conserve downstream cGMP. Estrous cycle-mediated alterations in NOS system expression suggests additional hormone-mediated gene regulation in females.

The Effect of the Change in the Framingham Risk Score Calculator Between the 2006 and 2009 Canadian Lipid Guidelines

BACKGROUND Recent Canadian lipid guidelines changed the methodology used for calculating the Framingham Risk Score (FRS). We assessed the impact this would have on management when related to baseline lipid profiles and the possible need for statin drug therapy. METHODS Patients with their FRS calculated between November 2006 and March 2010 were considered. There were 247 patients categorized as either low or intermediate risk. RESULTS The study population consisted of 91 men and 156 women with a mean (SD) age of 52.7 ± 15.0 years. The average FRS was 5.6 ± 4.8 vs 11.5 ± 8.3 (2006 vs 2009) (P < .00010). The number of FRS patients categorized as low and intermediate risk requiring some form of lipid-lowering treatment increased from 35 (14.2%) to 81 (32.8%), a 2.3-fold increase. Of 41 high-risk patients, 40 had a baseline low-density lipoprotein cholesterol of ≥ 2.0 mmol/L and would qualify for not only health behaviour interventions but also statin drug treatment. CONCLUSIONS The new FRS increases the number of 2006 patients with low and intermediate scores who move from low to high risk (n = 11, 5.9%), from low to intermediate risk (n = 50, 26.9%), and from intermediate to high risk (n = 30, 49.2%), leading to a 2.3-fold increase in the need for lipid-lowering treatment. Therapies intended to improve lipid profiles and potentially patient outcomes include both health behaviour interventions alone or in combination with lipid-lowering drug therapy. Given the relationship between low-density lipoprotein cholesterol and cardiovascular events is linear, treating more patients is likely to lead to a further reduction in cardiovascular events.

ICEBERG: Intimal Carotid Evaluation Before Echocardiography Reveals Global Vascular Risk

BACKGROUND There is growing evidence that carotid ultrasonography provides important prognostic information about cardiovascular risk assessment. Our objective was to determine whether abbreviated rapid carotid ultrasonographic screening would reveal important global vascular risk information in statin-naive patients referred for routine transthoracic echocardiography (TTE). METHODS Abbreviated carotid ultrasonographic imaging was performed in 560 consecutive patients undergoing TTE. The common carotid artery (CCA), the carotid bulb, and the internal carotid artery (ICA) were scanned. Maximal CCA intima-media thickness (IMT) was measured in the far wall. Carotid plaque was defined using the Atherosclerosis Risk in Communities (ARIC) study criteria. RESULTS Of the 2283 patients who underwent TTE during a 1-year period, a total of 560 patients met inclusion criteria. There were 241 men, with a mean age of 63.2 ± 12.8 years and a mean CCA IMT of 1.11 ± 0.48 mm; 61% (147) had carotid plaque. The 319 women had a mean age of 66.3 ± 10.8 years and a mean CCA IMT of 1.03 ± 0.36 mm; 62.4% (199) had carotid plaque. All patients with plaque were considered to be at high risk. CONCLUSIONS Of the 560 consecutive statin-naive patients referred for TTE with no history of vascular disease, a large proportion of both men (61%) and women (62.4%) had carotid plaque, indicating a high risk for vascular events according to the Canadian lipid guidelines. Although such patients are seen in the echocardiography laboratory, the addition of an abbreviated carotid ultrasonographic screening provides important information regarding risk stratification and the implementation of preventive therapy.

The Global Tobacco Epidemic Requires Further Canadian Action at Home

To the Editor: In 1965 approximately 50% of adult Canadians smoked tobacco. Recent data from 2013 reported that figure at 14.6%. This extraordinary accomplishment was the result of aggressive public awareness campaigns and a legal and taxation framework that reduces tobacco consumption. The resulting social inertia has also fostered universal political support and flexibility required to implement an evolving tobacco use reduction strategy. Nonetheless, there is room for improvement. Health Canada reports tobacco use remains the single most preventable cause of premature death in Canada. The World Health Organization reported that 6 million people die annually from tobacco use. International trends mute any extension of confidence from the Canadian experience: global tobacco consumption has doubled compared to four decades ago, and 80% of smokers live in lowand middle-income countries. The contemporary vigor of Big Tobacco is also evident in stock prices, which are a testament to the industries’ ability to adapt and metastasize to emerging and susceptible markets. Continued advocacy and leadership are required to confront this formidable global health challenge of the 21st century. All Canadian provinces currently prohibit the display of tobacco for sale. For example, the Smoke-Free Ontario Act states, “No person shall display or permit the display of tobacco. or offer for sale in any manner that permits the purchaser to handle the tobacco product before purchasing it.” However, the Act later states that duty-free retailers are exempt. Similarly, Canadian airplanes on international flights are exempt and covered under The Customs Act. This asymmetric legislation thus permits these enterprises to function as islands that are legally immune to otherwise effective antitobacco legislation. These practices also illustrate

CARDIOVASCULAR INVESTIGATION OF WOMEN A COMPARISON OF 1999-2007 WITH 2007-2014

consecutive patients were considered for analysis, 68% were between 40 and 70 years old, and only 17% were females. Reported risk factors included hypertension (42%), dyslipidemia (43%), diabetes (16%), family history of coronary artery disease (22%) and smoking (59%). Reported comorbidities included coronary artery disease (27%), previous coronary revascularization (15%; PCI 9% and CABG 6%), known heart failure (18%), chronic renal failure (13%), valvular disease (11%), non-ischemic cardiomyopathy (7%) and primary electrophysiological abnormalities (1%). The vast majority of cardiac arrests occurred at rest (82%), between 12 PM and 12 AM (61%), and were witnessed (81%). CPR was initiated within the first 5 minutes in 65% of cases, and lasted less than 10 minutes in 35% of patients. Ventricular fibrillation was identified as the first cardiac rhythm in 37 % of patients and pulseless ventricular tachycardia was present in 30%. Acute coronary syndrome (ACS) was diagnosed in 44% of patients, and 81 % were STEMI. Coronary catheterization was performed in 82% of patients, of which 69% underwent subsequent coronary revascularization (80% PCI and 20% CABG). During the hospitalization, hypothermia was used in 72% of patients and 32% received an implantable cardiac device, which consisted of an implantable cardioverter defibrillator in 85% of cases. The in-hospital mortality was 32%. The other reported in-hospital complications included renal insufficiency (46%), respiratory insufficiency (55%), and anoxic encephalopathy (40%). Fourteen percent of patients were discharged to a recovery centre and 54% were discharged home. CONCLUSION: Despite a relatively low incidence of ACS in patients following out-of-hospital cardiac arrest, a high number of patients were treated with hypothermia and underwent coronary catheterization allowing subsequent revascularization. This cohort of patients surviving out-ofhospital cardiac arrest had a relatively low mortality rate, highlighting the fact that this condition is becoming a treatable condition with a reasonable potential for neurological recovery.

THERE IS NO CLINICAL JUSTIFICATION FOR CAROTID SCREENING IN MALES OVER 70 YEARS OR FEMALES OVER 75 YEARS

BACKGROUND: Acute pulmonary thromboembolism (APTE) is common and potentially life-threatening cardiovascular emergency. The fatality rate in acute cases ranges from 7-11%. There are many predisposing risk factors for APTE. Depressed, inactive patients would appear to be at significant risk for pulmonary embolism, given their lack of activity and putative platelet pathology. METHODS AND RESULTS: We report a clinical case of a 41 years old patient flowed for depression 4 months ago who reported that he spent almost all of his time in bed, sleeping with limited physical activity, that presenting at the emergency for acute onset of fatigue, shortness of breath and dyspnoea a few hours before admission, the anamnesis revealed no classical factors of veinous thromboembolism, the clinical examination fount a tachycardia, tachypnea, without clinical evidence of heart failure, the D-Dimer level was elevated, and the thoracic CT angiogram revealed intraluminal thrombi in lobar and segmental branches of the pulmonary arteries causing incomplete luminal obstruction. Diagnosis of APTE was confirmed, further etiological investigations ruled out other etiology of the venous thromboembolism. the patient was treated by anticoagulant, and antidepressant therapy with good clinical improvement. CONCLUSION: Severe major depression associated with psychomotor retardation and immobility can be a risk factor for pulmonary embolism. We must remember to search a depression in patients with pulmonary embolism and may be use a prophylaxis for this kind of patients.

027 The prevalence of resistant hypertension in a large outpatient 24 hour ABPM population

were recruited between July 2010 and August 2010. METHODS: Data were collected by both evaluators during a 2-hour period. Peripheral BP was measured by the auscultation method accordingtotheguidelinesof theCanadianHypertensionSociety.Central BP and AIx@HR75 were measured using the Sphygmocor system (AtCor Medical, Sydney, Australia) and PWV with two techniques, AT (Millar Instruments, Houston, Texas, USA) and PPG (ADInstruments Corporation, Sydney, Australia). AIx@HR75 was measured bilaterally at the radial artery and PWV between the carotid and radial sites bilaterally. A two-way repeated measures ANOVA and two-way random model ICC were conducted. RESULTS: Results are summarized (means SE) in Table 1.

151 The decrease in diastolic blood pressure occurs at a much earlier age than indicated by Framingham

BACKGROUND: The Framingham data regarding hypertension and age shows a progressive increase in systolic blood pressure with age. However diastolic blood pressure gradually increases until age 55 years and then progressively falls. METHODS: CARDIOfile was searched for all 24hr ABPMs. A scattergram of age versus the 18,987 ABPMs for both systolic an diastolic blood pressure was produced. Linear regression was performed for systolic BP data points and 2nd to 4th order polynomial regression for the diastolic BP data points. The inflection point for diastolic BP was calculated using differential calculus. This is the point on the diastolic curve where the curvature sign changes. This corresponds to the age at which diastolic BP begins to decrease. RESULTS: See Figure 1. The inflection point as described above was calculated as 42 years. CONCLUSION: Our data indicates that the age of onset of the fall in diastolic BP occurs much earlier than is generally accepted. In fact 13 years earlier than indicated by the Framingham data. The reasons for this change are unknown at this time but could be related to the fact that Framingham is a population based study and our population is a hypertensive population. It is possible that changes in arterial stiffness may occur ealier in the hypertensive population than in the general population. 152 E-COUNSELING IS ASSOCIATED WITH THERAPEUTIC CHANGE IN LIFESTYLE AND BLOOD PRESSURE IN HYPERTENSION INDEPENDENT OF SYMPTOMS OF DEPRESSION