Sahrai Saeed

Impact of stroke volume on cardiovascular risk during progression of aortic valve stenosis

Objective In severe aortic valve stenosis (AS), low left ventricular (LV) stroke volume has been associated with increased cardiovascular (CV) mortality, but this association has not been explored during progression of AS in a large prospective study. Methods In 1671 patients from the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study, the association of stroke volume indexed for body surface area (SVI) with major CV events during a median of 4.3-year follow-up was assessed in Cox and time-varying Cox regression analyses. Low SVI was defined as <35 mL/m2. Results Peak aortic jet velocity in the total study population was 3.1 ±0.7 m/s. Low SVI was found in 23% at baseline and associated with higher age, body mass index (BMI), heart rate and global LV load, and with lower mean aortic gradient, aortic valve area index, energy loss index, LV mass and ejection fraction and more often inconsistent AS grading (all p<0.05). A 5 mL/m2 lower SVI at baseline was associated with higher HRs of major CV events (n=544) (HR 1.09, 95% CI 1.05 to 1.13, p<0.001) and higher total mortality (n=147) (HR 1.08, 95% CI 1.01 to 1.16, p=0.038), independent of age, sex, atrial fibrillation, mean aortic gradient, LV ejection fraction, LV mass, BMI and study treatment. Adjusting for the same covariates, low SVI at baseline and in-study low SVI were also associated with increased rate of major CV events. Conclusion In patients with AS in the SEAS study, lower baseline SVI was associated with higher HR of major CV events and total mortality independent of major confounders. Trial registration number NCT00092677: Results

Covariates of non-dipping and elevated night-time blood pressure in ischemic stroke patients: the Norwegian Stroke in the Young Study*

Abstract Abnormal night-time blood pressure (BP) reduction is associated with increased cardiovascular risk in hypertension. Little is known about the prevalence and covariates of night-time BP reduction in ischemic stroke patients. Clinic and ambulatory BP measurements were recorded in 268 stroke survivors aged 15–60 years. The degree of night-time dipping was calculated from the difference between day-time and night-time mean BP, and defined as non-dipping if < 10%. Aortic stiffness was derived from carotid–femoral pulse-wave velocity (PWV) by applanation tonometry and carotid intima–media thickness (cIMT) by ultrasound. A non-dipping pattern was found in 38%. Non-dippers had higher PWV, mean cIMT and night-time BP, and included more patients with history of hypertension, diabetes and high for age PWV compared to dippers (all p < 0.05). In multivariate logistic regression analyses, non-dipping was associated with high for age PWV [odds ratio (OR) = 2.28; 95% confidence interval (CI) 1.06–4.92, p < 0.05] independent of history of hypertension and other confounders, while elevated night-time BP was associated with increased cIMT (OR = 3.83; 95% CI 1.01–14.50, p < 0.05) independent of non-dipping status, male gender, obesity, antihypertensive treatment and high for age PWV. In conclusion, in the Norwegian Stroke in the Young Study, non-dipping BP pattern was common and associated with increased aortic stiffness.

Early Vascular Aging in Young and Middle-Aged Ischemic Stroke Patients: The Norwegian Stroke in the Young Study

Background Ischemic stroke survivors have high risk of cardiovascular morbidity and mortality even at young age, suggesting that early arterial aging is common among such patients. Methods We measured aortic stiffness by carotid-femoral pulse wave velocity (PWV) in 205 patients (69% men) aged 15–60 years with acute ischemic stroke in the prospective Norwegian Stroke in the Young Study. High for age carotid-femoral PWV was identified in the reference normogram. Results Patients were on average 49±10 years old, 34% had a history of hypertension and 37% had metabolic syndrome (MetS). In the total study population, higher PWV was associated with history of hypertension (β = 0.18), higher age (β = 0.34), systolic blood pressure (BP) (β = 0.28) and serum creatinine (β = 0.18) and lower high-density lipoprotein (HDL) cholesterol (β = –0.10, all p<0.01) in multivariate linear regression analysis (multiple R2 = 0.42, p<0.001). High for age PWV was found in 18% of patients. In univariate analyses, known hypertension was associated with a 6-fold, MetS with a 4-fold and presence of carotid plaque with a 3.7-fold higher risk for high for age PWV (all p<0.01). In multiple logistic regression analysis higher systolic BP (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.02–1.06; p<0.01), history of hypertension (OR 3.59; 95% CI 1.52–8.51; p<0.01), low HDL cholesterol (OR 3.03; 95% CI 1.00–9.09; p = 0.05) and higher serum creatinine (OR 1.04; 95% CI 1.01–1.06; p<0.01) were associated with high for age PWV. Conclusions Higher PWV is common in younger and middle-aged ischemic stroke patients and associated with a clustering of classical cardiovascular risk factors. ClinicalTrials.gov NCT01597453

Masked hypertension in obesity: potential predictors and arterial damage.

Background Masked hypertension (MHT), defined as normal office blood pressure (BP) but high ambulatory BP, has been associated with increased cardiovascular risk. Although MHT has been associated with obesity, there is limited knowledge on the prevalence and covariates of MHT in obese cohorts. Methods Office and ambulatory BP recordings and other cardiovascular risk factors were assessed in 323 obese participants included in the fat-associated cardiovascular dysfunction study (mean age 48.9±9.0 years, 55% women, mean BMI 32.3±4.4 kg/m2). Office BP 130–139/85–89 mmHg was considered high-normal. Subclinical arterial damage was identified as carotid–femoral pulse wave velocity more than 10 m/s by applanation tonometry or carotid plaque by ultrasound (maximal intima–media thickness ≥1.5 mm). Results MHT was present in 17.1% of the population. Patients with MHT had a higher prevalence of metabolic syndrome, high-normal office BP, and were more often male compared with the normotensive (NT) individuals (all P<0.05), but were younger and had lower prevalence of diabetes and subclinical arterial damage than the sustained hypertensive group (all P<0.05). In multinomial logistic regression analysis, MHT was associated with the presence of metabolic syndrome and high-normal office BP compared with NT individuals, and lower pulse wave velocity and fewer carotid plaques than sustained hypertension (all P<0.05). Conclusion In obese patients, MHT was associated with the presence of metabolic syndrome and high-normal office BP compared with NT individuals, but less subclinical arterial damage than sustained hypertensive patients.

Obesity-associated metabolic changes influence resting and peak heart rate in women and men

Abstract> Objectives: To study the relationship between obesity and heart rate (HR) in women and men. Design: We studied 241 overweight and obese subjects without known heart disease. All subjects underwent ergospirometry during maximal exercise testing on treadmill and recording of body composition, electrocardiogram and clinic and ambulatory blood pressure. Results: Women (n = 132) were slightly older and had higher fat mass, but lower weight, blood pressure and prevalence of metabolic syndrome (MetS) than men (n = 109) (all p < 0.05), while prevalences of obesity and hypertension did not differ. A significant interaction between sex and HR was demonstrated (p < 0.05). In multivariate analysis, female sex (β = 0.99, p < 0.01) predicted higher resting HR independent of confounders. Higher resting HR was particularly associated with presence of MetS, hypertension, higher insulin resistance and lower relative muscle mass in men (all p < 0.05). Female sex also predicted higher peak exercise HR (β = 0.48, p < 0.01) independent of confounders. Higher peak exercise HR was particularly associated with higher exercise capacity and lower age and self-reported physical activity in men, while lower HbA1c and absence of obesity were the main covariates in women in multivariate analyses (all p < 0.05). Conclusions: In our study population, obesity and obesity-associated metabolic changes influenced both resting and peak exercise HR.

Exercise testing in patients with asymptomatic moderate or severe aortic stenosis

Objective To assess the safety and tolerability of treadmill exercise testing and the association of revealed symptoms with outcome in apparently asymptomatic patients with moderate to severe aortic stenosis (AS). Methods A retrospective cohort study of 316 patients (age 65±12 years, 67% men) with moderate and severe AS who underwent echocardiography and modified Bruce exercise treadmill tests (ETTs) at a specialist valve clinic. The outcome measures were aortic valve replacement (AVR), all-cause mortality or a composite of AVR and all-cause mortality. Results At baseline, there were 210 (66%) patients with moderate and 106 (34%) with severe AS. There were 264 (83%) events. 234 (74%) patients reached an indication for AVR, 145 (69%) with moderate and 88 (83%) with severe AS (p<0.05). Of the 30 (9%) deaths recoded during follow-up, 20 (67%) were cardiovascular related. In total, 797 exercise tests (mean 2.5±2.1 per patient) were performed. No serious adverse events were observed. The prevalence of revealed symptoms at baseline ETT was 29% (n=91) and was significantly higher in severe AS compared with moderate AS (38%vs23%, p=0.008). Symptoms were revealed in 18%–59% of patients during serial ETT conducted over a follow-up period of 34.9 (SD 35.1) months. The event-free survival at 24 months with revealed symptoms was 46%±4% and without revealed symptoms was 70%±4%. Conclusions ETT in patients with moderate or severe AS is safe and tolerable. Serial exercise testing is useful to reveal symptoms not volunteered on the history and adds incremental prognostic information to baseline testing.

Prevalence and covariates of masked hypertension in ischemic stroke survivors: the Norwegian Stroke in the Young Study.

BackgroundMasked hypertension (MHT) is characterized by normal clinic blood pressure (BP), but elevated ambulatory BP has been associated with a higher prevalence of cardiovascular organ damage. MethodsWe assessed the prevalence and characteristics of MHT in 298 ischemic stroke patients aged 15–60 years. High-normal office BP was considered present if systolic BP was 130–139 mmHg and/or diastolic BP was 85–89 mmHg. Arterial damage was defined as increased pulse wave velocity measured by applanation tonometry and/or mean common carotid intima-media thickness more than 0.9 mm measured by ultrasound. ResultsMHT was found in 12% of patients. In multivariable logistic regression analysis, MHT patients were characterized by higher BMI [odds ratio (OR) 1.09; 95% confidence interval (CI) 1.03–1.16], high-normal office BP (OR 2.30; 95% CI 1.26–4.21), and higher serum triglycerides (OR 1.32; 95% CI 1.01–1.47, all P<0.05) in the total study population. Compared with normotensive patients, MHT was characterized by a higher prevalence of high-normal office BP (OR 2.05; 95% CI 1.08–3.90), obesity (OR 2.67; 95% CI 1.31–5.47), and arterial damage (OR 2.87; 95% CI 1.46–5.66, all P<0.05). Compared with patients with sustained hypertension, MHT was associated with a lower prevalence of arterial damage (OR 0.48; 95% CI 0.23–0.99, P=0.05) despite a higher prevalence of high-normal office BP and comparable ambulatory BP values. ConclusionAmong young and middle-aged ischemic stroke patients, MHT was found in 12% and associated with high-normal office BP, obesity, and more prevalent arterial damage compared with normotensive patients, underscoring the importance of identification of MHT in these patients.

THE IMPACT OF EXAGGERATED BLOOD PRESSURE RESPONSE DURING TREADMILL EXERCISE TEST ON OUTCOME IN MODERATE TO SEVERE ASYMPTOMATIC AORTIC STENOSIS PATIENTS

Objective: Exaggerated blood pressure (BP) response (EBPR) during exercise predicts future hypertension and cardiovascular events in different patients groups and general population. However, the clinical and prognostic implications of EBPR during exercise treadmill test (ETT) in patients with aortic stenosis (AS) have not been tested before. Design and method: We retrospectively assessed 316 patients with moderate (66%) or severe (34%) asymptomatic AS (age 65 ± 12 years) who underwent echocardiography and modified Bruce ETT at a specialist valve clinic. EBPR was defined as peak systolic BP 190mmHg or above. Results: The prevalence of EBPR was 22%. There was no difference in exercise duration, metabolic equivalents or severity of AS between patients with normal BP response and EBPR (all p = NS). Patients with EBPR were more likely to have hypertension, higher pre-test systolic BP, left ventricular (LV) ejection fraction and increased LV mass (all p < 0.05) (Table). A total of 264 events occurred during a mean follow up period of 34.9 ± 35.1 months. 234 patients reached an indication for aortic valve replacement (AVR), 75% in patients with normal BP response vs. 73% in patients with EBPR, p = NS). Among 30 (9%) deaths, 9.4% occurred in patients with normal BP response vs. 8.1% in EBPR group, p = NS). In univariate Cox regression analysis, the presence of EBPR was neither associated with all-cause mortality {HR 0.89, 95%CI 0.33–2.36, p = 0.814} nor AVR {HR 0.96, 95%CI 0.69–1.33, p = 0.785}. Conclusions: EBPR during treadmill exercise test in moderate to severe asymptomatic AS patients was strongly associated with hypertension and increased LV mass, but could not predict adverse outcomes.

3D.04: BLUNTED NIGHTLY BLOOD PRESSURE REDUCTION IS ASSOCIATED WITH INCREASED ARTERIAL STIFFNESS IN ISCHEMIC STROKE PATIENTS: A NORWEGIAN STROKE IN THE YOUNG STUDY.

Objective: Lack of nightly blood pressure (BP) reduction is associated with increased cardiovascular risk. The aim of this study was to assess the association of nightly BP reduction with arterial stiffness in young and middle-aged ischemic stroke patients. Figure. No caption available. Design and method: Clinic and ambulatory BP measurements were performed 3 ± 1 month after the acute stroke in 261 patients (aged 15–60 years) included in the prospective Norwegian Stroke in the Young Study. The percent reduction in nocturnal BP was calculated from mean BP and defined as dipping if > =10%. Arterial stiffness was derived from carotid-femoral pulse wave velocity (PWV) using applanation tonometry with a Sphygmocor device. Results: Non-dipping pattern was found in 38%. Non-dipping patients had higher PWV (8.2 ± 2.2 vs. 7.5 ± 1.7 m/s) and lower renal function, and included more patients with hypertension (51 vs. 26%) or diabetes (16 vs. 8%, all p < 0.05). Furthermore, 26% of the non-dippers had high for age PWV, reflecting early arterial stiffening. Age, anthropometric variables and the level of serum lipids did not differ significantly between the groups. In multivariate logistic regression analysis, non-dipping BP pattern was associated with high for age PWV (OR 2.22 [95% CI 1.05–4.70], p < 0.05) independent of higher creatinine, known hypertension, mean day BP or diabetes (Table 1). In multivariate linear regression analysis, non-dipping pattern was also associated with higher PWV (Beta = 0.18, p = 0.01). Conclusions: In the Norwegian Stroke in the Young Study, blunted nightly BP reduction was common and associated with premature arterial stiffness.

Managing complications of hypertension in aortic valve stenosis patients

ABSTRACT Introduction: Hypertension is highly prevalent in aortic valve stenosis (AS) patients as the prevalence of both disorders increases with age. Hypertension and associated stiffening of the large arteries increase afterload and thereby influence both the transvalvular flow and the remodeling of the aortic root and the left ventricle during AS progression. Area covered: The present review gives an overview on complications of hypertension in AS, how these can be diagnosed, and potentially may be managed. Expert commentary: Hypertension-mediated cardiovascular (CV) damage in AS is associated with increased morbidity and a twofold higher mortality even in asymptomatic patients, and also limits the symptomatic and survival benefit from valve replacement. Data from registries and post hoc analyses from outcome studies in AS suggest that treatment with angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and β-blockers, respectively, is safe and associated with improved survival and reduced CV events in these patients. However, optimal blood pressure (BP) target in AS patients is not documented, and strict BP control in the early postoperative phase in AS patients treated with transcatheter aortic valve replacement (TAVR) may be associated with adverse events. Thus, randomized studies on BP management in asymptomatic AS and post-TAVR patients are highly needed.