Association of Fatal and Nonfatal Cardiovascular Outcomes With 24-Hour Mean Arterial Pressure

Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R2 statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of \u3c90 (normotension, n=6183), 90 to \u3c92 (elevated MAP, n=909), 92 to \u3c96 (stage-1 hypertension, n=1544), and ≥96 (stage-2 hypertension, n=2960) mm Hg yielded equivalent 10-year major adverse cardiovascular events risks as office MAP categorized using 2017 American thresholds for office SBP and DBP. Compared with 24-hour MAP normotension, hazard ratios were 0.96 (95% CI, 0.80–1.16), 1.32 (1.15–1.51), and 1.77 (1.59–1.97), for elevated and stage-1 and stage-2 hypertensive MAP. On top of 24-hour MAP, higher 24-hour SBP increased, whereas higher 24-hour DBP attenuated risk (P\u3c0.001). Considering the 24-hour measurements, R2 statistics were similar for SBP (1.34) and MAP (1.28), lower for DBP than for MAP (0.47), and reduced to null, if the base model included SBP and DBP; if the ambulatory BP indexes were dichotomized according to the 2017 American guideline and the proposed 92 mm Hg for MAP, the R2 values were 0.71, 0.89, 0.32, and 0.10, respectively. In conclusion, the clinical application of 24-hour MAP thresholds in conjunction with SBP and DBP refines risk estimates

Cost-effectiveness of secondary screening modalities for hypertension

Background: Clinic-based blood pressure (CBP) has been the default approach for the diagnosis of hypertension, but patients may be misclassified because of masked hypertension (false negative) or ‘white coat’ hypertension (false positive). The incorporation of other diagnostic modalities, such as home blood pressure monitoring (HBPM) and ambulatory blood pressure monitoring (ABPM), holds promise to improve diagnostic accuracy and subsequent treatment decisions. Materials and methods: We reviewed the literature on the costs and cost-effectiveness of adding HBPM and ABPM to routine blood pressure screening in adults. We excluded letters, editorials, and studies of pregnant and/or pre-eclamptic patients, children, and patients with specific conditions (e.g. diabetes). Results: We identified 14 original, English language studies that included cost outcomes and compared two or more modalities. ABPM was found to be cost saving for diagnostic confirmation following an elevated CBP in six studies. Three of four studies found that adding HBPM to an elevated CBP was also cost-effective. Conclusion: Existing evidence supports the cost-effectiveness of incorporating HBPM or ABPM after an initial CBP-based diagnosis of hypertension. Future research should focus on their implementation in clinical practice, long-term economic values, and potential roles in identifying masked hypertension

Opposing Age-Related Trends in Absolute and Relative Risk of Adverse Health Outcomes Associated With Out-of-Office Blood Pressure

Participant-level meta-analyses assessed the age-specific relevance of office blood pressure to cardiovascular complications, but this information is lacking for out-of-office blood pressure. At baseline, daytime ambulatory (n=12 624) or home (n=5297) blood pressure were measured in 17 921 participants (51.3% women; mean age, 54.2 years) from 17 population cohorts. Subsequently, mortality and cardiovascular events were recorded. Using multivariable Cox regression, floating absolute risk was computed across 4 age bands (80 years). Over 236 491 person-years, 3855 people died and 2942 cardiovascular events occurred. From levels as low as 110/65 mm Hg, risk log-linearly increased with higher out-of-office systolic/diastolic blood pressure. From the youngest to the oldest age group, rates expressed per 1000 person-years increased (P<0.001) from 4.4 (95% CI, 4.0-4.7) to 86.3 (76.1-96.5) for all-cause mortality and from 4.1 (3.9-4.6) to 59.8 (51.0-68.7) for cardiovascular events, whereas hazard ratios per 20-mm Hg increment in systolic out-of-office blood pressure decreased (P <= 0.0033) from 1.42 (1.19-1.69) to 1.09 (1.05-1.12) and from 1.70 (1.51-1.92) to 1.12 (1.07-1.17), respectively. These age-related trends were similar for out-of-office diastolic pressure and were generally consistent in both sexes and across ethnicities. In conclusion, adverse outcomes were directly associated with out-of-office blood pressure in adults. At young age, the absolute risk associated with out-of-office blood pressure was low, but relative risk high, whereas with advancing age relative risk decreased and absolute risk increased. These observations highlight the need of a lifecourse approach for the management of hypertension

Accelerated aging after hematopoietic stem cell transplantation in childhood : Early menopause, premature cardiovascular aging and frailty

Long-term ovarian function was retrospectively evaluated after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence. Cardiovascular risk factors, arterial morphology and stiffness, left ventricular (LV) mass and function, physical fitness and frailty were investigated in adult and adolescent survivors of high-risk neuroblastoma (HR NBL) after autologous HSCT in childhood. The first study population included a cohort of 92 female long-term survivors who were less than 20 years of age when treated at the Children s Hospital, Helsinki University Hospital, or Karolinska University Hospital, Huddinge, between 1978 and 2000. The follow-up data included signs of spontaneous puberty, age at menarche, the use of hormone replacement therapy, pregnancies, and information about pubertal or postpubertal serum FSH levels. The second study population included the Finnish national cohort of 19 long-term HR NBL survivors treated between 1980 and 2000, and 20 age- and sex-matched controls. Clinical examinations included 24h ambulatory blood pressure (BP), very-high-resolution vascular ultrasound, 3D echocardiography and Tissue Doppler Imaging ultrasounds, body composition, physical performance tests and interview. Older age at HSCT and total body irradiation and busulfan-based conditionings were risk factors for early ovarian aging. Leukemia survivors with previous cranial radiotherapy or transplanted after disease relapse were at high risk of premature ovarian failure. The HR NBL survivors showed increased carotid intima-media thickness, plaque formation and stiffness, increased radial artery intima thickness, and increased cardiovascular risk profile when compared to the controls. They had increased LV mass, decreased systolic and diastolic LV function when compared to the controls. Poor LV function associated with cardiac biomarkers, poor physical performance and increased BP. The survivors showed shorter telomere length and increased frequency of frailty phenotype when compared to the controls. The frailty phenotype associated with cardiovascular health and chronic inflammation. In conclusion, our study shows that the adult survivors after HSCT in young age are at risk of early reproductive and vascular aging and frailty. The survivors of pediatric HSCT require regular follow-up in adulthood and interventions for declining ovarian function, cardiovascular risk factors, high BP, subclinical signs of atherosclerosis and decreased cardiac function. Since lifestyle choices can influence cardiovascular health and frailty status, a healthy non-smoking lifestyle and physical activity should be advocated among all survivors who have received HSCT in childhood.Altistuminen lapsena DNA:ta vaurioittavalle säde- tai solunsalpaajahoidolle altistaa ennenaikaiselle vanhenemiselle. Tutkimuksen tavoitteena oli selvittää, todetaanko lapsena kantasolusiirtohoidon saaneilla ikäverrokkeja useammin raihnaisuutta tai suonten tai sukurauhasten vanhenemista. Pyrimme lisäksi arvioimaan raihnaisuuden yhteyttä sydän- ja verisuoniterveyteen, tulehdukseen ja telomeerien pituuteen. Ensimmäinen tutkimuskohortti käsitti 92 parantunutta naispotilasta, jotka olivat alle 20-vuotiaita saadessaan kantasolusiirron Lastenklinikalla Helsingin yliopistollisessa sairaalassa tai Karoliinisessa yliopistosairaalassa Tukholmassa vuosina 1978-2000. Toinen potilasryhmä oli vuosina 1980-2000 Suomessa hoidettu kansallinen kohortti, joka koostui 19:stä korkean riskin neuroblastoomasta parantuneesta potilaasta. Korkeampi ikä kantasolusiirron hetkellä ja koko kehon sädetys tai busulfan-pohjainen esihoito ennustivat munasarjatoiminnan ennenaikaista loppumista ja munasarjojen vanhenemista. Leukemiasta parantuneilla pään sädehoito ennen kantasolusiirtoa tai kantasolusiirto taudin uusimisen jälkeen lisäsivät riskiä munasarjojen toiminnan hiipumiseen. Korkean riskin neuroblastoomapotilaiden valtimoissa todettiin useammin plakkeja, verisuonen sisäkerroksen paksuuntumista, valtimoiden joustavuuden alentumista sekä enemmän sydän- ja verisuoniriskitekijöitä kuin ikävakioiduilla verrokeilla. Potilailla sydämen vasemman kammion massa oli lisääntynyt, systolinen ja diastolinen toiminta huonontunut, merkkiaineet veressä olivat koholla ja fyysinen suorituskyky oli alentunut verrokkeihin verrattuna. Lisäksi todettiin yhteys kohonneen verenpaineen ja lisääntyneen vasemman kammion massan välillä. Potilailla oli lyhyemmät telomeerit kuin verrokeilla, minkä lisäksi heillä todettiin useammin raihnaisuuteen liittyviä löydöksiä, kuten vähentynyttä lihasmassaa, hitautta, heikkoutta ja vähäistä fyysistä aktiivisuutta. Raihnaisuus liittyi huonoon sydän- ja verisuoniterveyteen sekä krooniseen tulehdukseen. Johtopäätöksenä todetaan, että lapsuuden kantasolusiirtohoitoon liittyy riski verisuonten ja sukurauhasten ennenaikaiseen vanhenemiseen ja raihnaisuuteen. Lapsena kantasolusiirtohoidon saaneita tulee seurata säännöllisesti aikuisiässä mahdollisesti heikkenevän sydän- ja munasarjatoiminnan, kohonneen verenpaineen ja kehittyvän ateroskleroosin vuoksi. Koska elämäntapavalinnoilla voidaan vaikuttaa sydän- ja verisuoniterveyteen ja raihnaisuuteen, tulee kaikkia lapsuudessa kantasolusiirron saaneita aktiivisesti ohjata terveellisiin elämäntapoihin, tupakoinnin välttämiseen ja kuntoiluun

Carotid sinus baroreceptor reflexes and their interactions with trigeminal and respiratory stimuli in man, and their modification by sex, age, hypertension, antihypertensive therapy, alcohol and endogenous opioids

The work in this thesis follows the use of the established neck suction technique for the assessment of carotid sinus baroreceptors in man and the development of a computer-based system for the analysis of responses to baroreceptor, trigeminal and respiratory stimuli. These methods have been used to study the carotid sinus baroreceptor reflexes, their interactions with trigeminal and respiratory stimuli, and their modification by gender, alcohol consumption, increasing age, essential hypertension and antihypertensive therapy. The role of endogenous opioids as putative neurotransmitters in these reflex pathways has been examined. The results obtained indicate that; 1) Endogenous opioids do not modulate carotid sinus baroreceptor reflexes and their interactions in normal man. 2) There was a difference in the extent of the linear portion of the carotid sinus baroreceptor heart rate reflex between closely age matched groups of young men and women. 3) The acute administration of alcohol reduced the sensitivity of the carotid sinus baroreceptor heart-rate reflex, but did not alter the response to cold facial stimuli, or the nature of the interaction of these (a simple linear summation of the effects of each applied separately). The effectiveness of respiratory stimuli in reducing vagal tone may have been reduced by alcohol. 4) The sensitivity of the carotid sinus baroreceptor reflex declined with increasing age, and with hypertension. This decline was significantly correlated with age, systolic, diastolic and arterial pulse pressure. 5) The response to trigeminal (cold facial) stimuli declined with age, but did not decline further in hypertension. Because the trigeminal and baroreceptor reflexes share a common efferent pathway, the vagus nerve, this is strong evidence for the preservation of the efferent pathway of the baroreceptor reflex in essential hypertension. The qualitative nature of the interaction between inspiration and the carotid sinus baroreceptor reflex was unchanged by hypertension. 6) The administration of two different antihypertensive agents, atenolol and lisinopril, whilst effective in reducing blood pressure, did not alter the sensitivity of the carotid sinus baroreceptor reflex, but the reflex was reset in each case to operate around a lower blood pressure, and with atenolol was also reset towards bradycardia. The response to cold facial stimuli, and the interaction with the carotid sinus baroreceptor heart- rate reflex were unchanged by therapy with either agent

Assessment and risk stratification of ageing-related target organ damage and adverse health outcomes in the general population

The objectives of this doctoral thesis are to address the contribution of blood pressure to the presence of subclinical target-organ damage and the development of adverse health complications that associate with a poor life course of aging. This thesis focuses on ambulatory blood pressure monitoring to provide the most accurate information about the blood pressure level and variability over a 24-hour period. Moreover, by investigating the role of novel markers, including imaging markers and biomarkers, this thesis also provides possible pathophysiological and biological mechanisms that might explain the association between vascular risk factors and adverse health complications. We envisage that the results of our study will contribute to the refinement of risk stratification of major micro- (ophthalmological, neurological) and macro‑vascular (neurological, cardiovascular) complications associated with poor aging