Short-Term and Long-Term Blood Pressure Changes and the Risk of All-Cause and Cardiovascular Mortality.

BACKGROUND: Few studies compared the effects of BP changes in short- and long-terms on all-cause mortality and CVD mortality. METHODS: We performed a 12.5-year follow-up study to examine the association between short- (2008 to 2010) and long-term [baseline (2004-2006) to 2010] BP changes and the risk of mortality (2010 to 2017) in the Fuxin prospective cohort study. The Cox proportional hazards model was used for this study, and the average BP was stratified according to the Seven Joint National Committee (JNC7). RESULTS: We identified 1496 (805 CVD deaths) and 2138 deaths (1222 CVD deaths) in short- and long-term study. Compared with BP maintainer, in short-term BP changes, for participants from normotension or prehypertension to hypertension, the hazards ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality were 1.948 (1.118-3.392) and 1.439 (1.218-1.700), respectively, while for participants from hypertension to prehypertension, the HRs (95% CIs) were 0.766 (0.638-0.899) for all-cause mortality and 0.729 (0.585-0.908) for CVD mortality, respectively. In long-term BP changes, for participants from normotension or prehypertension to hypertension, the HRs (95% CIs) of all-cause mortality were 1.738 (1.099-2.749) and 1.203 (1.023-1.414), and they were 2.351 (1.049-5.269) and 1.323 (1.047-1.672) for CVD mortality, respectively. In addition, the effects of short-term BP changes on all-cause and CVD mortality, measured as regression coefficients (ß), were significantly greater than those in long-term change (all P<0.05). CONCLUSIONS: Our study emphasizes that short-term changes in BP have a greater impact on all-cause and CVD mortality than long-term changes and assess the cut-off value of the changes in blood pressure elevation.

Association of blood pressure components with mortality and cardiovascular events in prehypertensive individuals: a nationwide population-based cohort study.

BACKGROUND: The effects of each blood pressure index [systolic and diastolic blood pressure (SBP, DBP), pulse pressure (PP), mean arterial pressure (MAP)] on the occurrence of mortality and cardiovascular (CV) events have not yet been investigated in prehypertensive populations. METHODS: A total of 30,258 prehypertensive Korean participants underwent periodic health examination between 2003 and 2004 were enrolled, and the associations of BP components with mortality and CV events were investigated. Moreover, based on the DBP [80 ≤ DBP <90 mmHg (N = 21,323) and DBP <80 mmHg (N = 8,935)], the effects of BP components were also evaluated. RESULTS: Multivariate Cox analyses in prehypertensive group revealed that the hazard ratios (HRs) were 1.121 and 1.130 per 10 mmHg increase in SBP and PP for mortality, respectively. Additionally, 10 mmHg increase of SBP (HR:1.090) was still significantly, but increase of PP (HR:1.060) was marginally associated with higher incidence of CV events. However, there were no significant associations with increase in DBP or MAP on adverse clinical outcomes in prehypertensive group. In the prehypertensive subjects with DBP <80 mmHg, CV events more frequently occurred by 38.8% and 28.5% per 10 mmHg increase in SBP and PP, respectively. CONCLUSIONS: Prehypertensive subjects might need to be cautioned when they have high SBP or PP with low DBP even in healthy populations. Key message Prehypertensive subjects should be cautioned when they have high-systolic blood pressure or pulse pressure with low-diastolic blood pressure, even without previous hypertension, diabetes mellitus or chronic kidney disease.

Cardiovascular Risk in Patients with Prehypertension and the Metabolic Syndrome.

Prehypertension (pHTN) and metabolic syndrome (MetS) are both lifestyle diseases that are potentiated by increased adiposity, as both disease processes are closely related to weight. In the case of pHTN, increased adiposity causes dysregulation of the renin-angiotensin-aldosterone-system (RAAS) as well as adipokine- and leptin-associated increases in adrenergic tone. In MetS, excess weight potentiates hyperglycemia and insulin resistance which causes positive feedback into the RAAS system, activates an inflammatory cascade that potentiates atherosclerosis, and causes lipid dysregulation which together contribute to cardiovascular disease, especially coronary heart disease (CHD) and heart failure (HF). The relationship with all-cause mortality is not as clear-cut in part because of some protective effects associated with the obesity paradox in chronic diseases such as CHD and HF. However, in healthy populations, the absence of excess weight and its associated effects on prehypertension and MetS are associated with a longer absolute and disease-free lifespan.

Potential health impact and cost-effectiveness of drug therapy for prehypertension.

BACKGROUND: Studies have reported that pharmacologic interventions with candesartan or ramipril could reduce the risk of hypertension among prehypertensive subjects free of clinical cardiovascular disease (CVD), however, the cost-effectiveness and long-term cardiovascular risk of drug treatment among these population is unclear. METHOD: A Markov state-transition model was developed to simulate a hypothetical cohort of Chinese adults with high-range prehypertension (130-139/85-89mmHg) but without CVD. Data on the incidence of CVD and hypertension was obtained from corresponding risk equations. Utility and disease-related costs were obtained from published literatures. Robustness and uncertainty was evaluated using deterministic and probabilistic sensitivity analyses. RESULTS: Compared with placebo, drug treatment resulted in delaying the development of hypertension by nearly 12years and reducing the absolute incidence of hypertension by 32.01% over lifetime. The cumulative incidence of coronary heart disease, stroke and heart failure were reduced and survival was improved from 28.46 to 28.80years. The average incremental cost effectiveness ratio for drug treatment was $12,994 per quality-adjusted life-year and the value was mostly sensitive to the effect size of treatment and age starting treatment. At a willingness-to-pay threshold of >3×China gross domestic product per capita in 2014, there was a 30.48% chance that drug treatment would remain cost-effective and a low chance of being cost-effective if relative risk of treatment on hypertension was larger than 0.64. CONCLUSION: Drug treatment for prehypertension may help stem the current epidemic of hypertension among Chinese adults free of CVD, which may in turn reduce CVD complications and potentially be cost effective.

Pre-hypertension, pre-diabetes or both: which is best at predicting cardiovascular events in the long term?

The present study aimed to assess the value of pre-diabetes and pre-hypertension in predicting cardiovascular events. A population-based, cross-sectional survey was conducted, representing a large sample of the general Iranian population aged 35 years and older from the Isfahan Province and determined using a random, multistage cluster-sampling 10-year cohort. The five end points considered as study outcome were unstable angina (UA), acute occurrence of myocardial infarction (MI), sudden cardiac death (SCD), brain stroke and cardiovascular disease (CVD). Of the 6323 subjects scheduled for assessment of diabetes state 617 were diabetics and 712 were pre-diabetic. In addition, of these subjects, 1754 had hypertension and 2500 had pre-hypertension. Analysing only pre-hypertension, pre-diabetes and its combination and adjusted for gender and age variables, pre-hypertension and pre-diabetes status together, could only effectively predict occurrence of MI (hazard ratio (HR)=3.21, 95% confidence interval (CI): 1.06-9.76, P=0.04). In the same COX regression models, pre-hypertension status could predict UA and CVD occurrence (HR=2.94, 95% CI: 1.68-5.14, P<0.001 and HR=1.74, 95% CI: 1.23-2.47, P=0.002, respectively). However, pre-diabetes status could not predict any of these events after adjustment for gender and age. Our data provide valuable evidence of the triggering role of pre-hypertension and pre-diabetes together, on appearance and progression of MI even in healthy individuals and the significant predicting value of pre-hypertension on the occurrence of UA and CVD. In this regard, the value of pre-hypertension and pre-diabetes together, and the pre-hypertension state alone, are clearly superior to pre-diabetes state alone in predicting cardiovascular events.

Effects of aliskiren in diabetic and non-diabetic patients with coronary artery disease: Insights from AQUARIUS.

BACKGROUND: Aliskiren previously was found to have potentially harmful effects in diabetic individuals prescribed concomitant angiotensin converting enzyme inhibitors (ACEI) or angiotenisn receptor antagonists (ARB). We explored potential effects of aliskiren on coronary atheroma progression and major adverse cardiovascular events (MACE: death/non-fatal MI/non-fatal stroke/hospitalization for heart failure/hospitalization for ACS/arterial revascularization) in patients with and without diabetes mellitus (DM). METHODS: AQUARIUS employed serial intravascular ultrasound measures of coronary atheroma volume in coronary artery disease patients randomized to receive daily aliskiren 300 mg or placebo for 104 weeks. This post hoc analysis compared changes in plaque volume [percent atheroma volume (PAV) and total atheroma volume (TAV)] and MACE in patients with (n = 115) and without (n = 343) DM stratified by treatment allocation. RESULTS: In multivariable propensity-weighted analyses, which included controlling for baseline and concomitant ACEI/ARB therapy and duration of aliskiren therapy, aliskiren-treated non-DM patients demonstrated the greatest PAV and TAV regression, whereas aliskiren-treated DM patients demonstrated the greatest TAV progression and greater PAV. Aliskiren-treated non-DM patients appeared at significantly lower risk of MACE compared with their aliskiren-treated DM counterparts [HR 95% CI 0.28 (0.10, 0.80)]. Statistical interactions were noted between DM status and treatment allocation for both changes in PAV (p < 0.001), TAV (p = 0.010) and MACE (p = 0.057). CONCLUSIONS: Aliskiren appears to be relatively anti-atherosclerotic in non-diabetic patients. Due to the limited number MACE and low numbers of diabetic patients in AQUARIUS, the pro-atherosclerotic effects of aliskiren in this population are inconclusive, and these results should be thus considered hypothesis generating. Further outcome studies are required in non-diabetic patients to confirm the possible favorable effects of aliskiren.

Low midlife blood pressure, survival, comorbidity, and health-related quality of life in old age: the Helsinki Businessmen Study.

OBJECTIVE: The aim of the present study was to examine the long-term impact of midlife blood pressure (BP) on mortality, comorbidity, and health-related quality of life (HRQoL) in old age. METHODS: These are longitudinal analyses of the Helsinki Businessmen Study, a cohort of business executives, born in 1919-1934, whose BP was measured between 1964 and 1973 (n = 3267). Comorbidity and HRQoL with RAND-36 [Short Form (SF)-36] were assessed from questionnaires in 2000; mortality up to 31 July 2012 was ascertained from national registers. Baseline BP was categorized as normal, less than 120  mmHg systolic and less than 80  mmHg diastolic (n = 121); prehypertension, 120-139  mmHg systolic or 80-89  mmHg diastolic (n = 2131); stage 1 hypertension, 140-159 mmHg systolic or 90-99  mmHg diastolic (n = 757); and stage 2 hypertension, more than 160  mmHg systolic or more than 100  mmHg diastolic (n = 258). Main outcome measures were long-term mortality, comorbidity, and HRQoL in old age. RESULTS: During the 48-year follow-up, 2013 men (61.6%) died. There was a graded relationship between BP and total mortality (P < 0.001). The men with normal BP had the lowest mortality; the age-adjusted difference in mean survival was 7.5 years between the normal and stage 2 baseline BP groups, and 11.2 months between normal and prehypertension groups. Lower BP in midlife was associated with better scores in the physical functioning (P-linear trend <0.001) and general health (P = 0.01) scales of RAND-36 in old age. RAND-36 scales associated with mental health were not affected by midlife BP. CONCLUSION: Lower BP in midlife is associated with longer life and better physical HRQoL in old age.

Association of all-cause and cardiovascular mortality with prehypertension: a meta-analysis.

BACKGROUND: Studies of prehypertension and mortality are controversial after adjusting for other cardiovascular risk factors. This meta-analysis sought to evaluate the association of prehypertension with all-cause and cardiovascular disease (CVD) mortality. METHODS: The PubMed, EMBASE, Cochrane Library databases, and conference proceedings were searched for studies with data on prehypertension and mortality. The relative risks (RRs) of all-cause, CVD, coronary heart disease (CHD), and stroke mortality were calculated and presented with 95% CIs. Subgroup analyses were conducted according to blood pressure, age, gender, ethnicity, follow-up duration, participant number, and study characteristics. RESULTS: Data from 1,129,098 participants were derived from 20 prospective cohort studies. Prehypertension significantly increased the risk of CVD, CHD, and stroke mortality (RR 1.28, 95% CI 1.16-1.40; RR 1.12, 95% CI 1.02-1.23; and RR 1.41, 95% CI 1.28-1.56, respectively), but did not increase the risk of all-cause mortality after multivariate adjustment (RR 1.03, 95% CI 0.97-1.10). The difference between CHD mortality and stroke mortality was significant (P < .001). Subgroup analyses showed that CVD mortality was significantly increased in high-range prehypertension (RR 1.28, 95% CI 1.16-1.41) but not in low-range prehypertension (RR 1.08, 95% CI 0.98-1.18). CONCLUSION: Prehypertension is associated with CVD mortality, especially with stroke mortality, but not with all-cause mortality. The risk for CVD mortality is largely driven by high-range prehypertension.

Prehypertension is not associated with all-cause mortality: a systematic review and meta-analysis of prospective studies.

OBJECTIVES: Quantitative associations between prehypertension or its two separate blood pressure (BP) ranges and cardiovascular disease (CVD) or all-cause mortality have not been reliably documented. In this study, we performed a comprehensive systematic review and meta-analysis to assess these relationships from prospective cohort studies. METHODS: We conducted a comprehensive search of PubMed (1966-June 2012) and the Cochrane Library (1988-June 2012) without language restrictions. This was supplemented by review of the references in the included studies and relevant reviews identified in the search. Prospective studies were included if they reported multivariate-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CIs) of CVD or all-cause mortality with respect to prehypertension or its two BP ranges (low range: 120-129/80-84 mmHg; high range: 130-139/85-89 mmHg) at baseline. Pooled RRs were estimated using a random-effects model or a fixed-effects model depending on the between-study heterogeneity. RESULTS: Thirteen studies met our inclusion criteria, with 870,678 participants. Prehypertension was not associated with an increased risk of all-cause mortality either in the whole prehypertension group (RR: 1.03; 95% CI: 0.91 to 1.15, P = 0.667) or in its two separate BP ranges (low-range: RR: 0.91; 95% CI: 0.81 to 1.02, P = 0.107; high range: RR: 1.00; 95% CI: 0.95 to 1.06, P = 0.951). Prehypertension was significantly associated with a greater risk of CVD mortality (RR: 1.32; 95% CI: 1.16 to 1.50, P<0.001). When analyzed separately by two BP ranges, only high range prehypertension was related to an increased risk of CVD mortality (low-range: RR: 1.10; 95% CI: 0.92 to 1.30, P = 0.287; high range: RR: 1.26; 95% CI: 1.13 to 1.41, P<0.001). CONCLUSIONS: From the best available prospective data, prehypertension was not associated with all-cause mortality. More high quality cohort studies stratified by BP range are needed.

White coat hypertension is more risky than prehypertension: important role of arterial wave reflections.

Arterial aging may link cardiovascular risk to white coat hypertension (WCH). The aims of the present study were to investigate the role of arterial aging in the white coat effect, defined as the difference between office and 24-hour ambulatory systolic blood pressures, and to compare WCH with prehypertension (PH) with respect to target organ damage and long-term cardiovascular mortality. A total of 1257 never-been-treated volunteer subjects from a community-based survey were studied. WCH and PH were defined by office and 24-hour ambulatory blood pressures. Left ventricular mass index, carotid intima-media thickness, estimated glomerular filtration rate, carotid-femoral pulse wave velocity, carotid augmentation index, amplitude of the reflection pressure wave, and 15-year cardiovascular mortality were determined. Subjects with WCH were significantly older and had greater body mass index, blood pressure values, intima-media thickness, carotid-femoral pulse wave velocity, augmentation index, amplitude of the backward pressure wave, and a lower estimated glomerular filtration rate than PH. Amplitude of the backward pressure wave was the most important independent correlate of the white coat effect in multivariate analysis (model r(2)=0.451; partial r(2)/model r(2)=90.5%). WCH had significantly greater cardiovascular mortality than PH (hazard ratio, 2.94; 95% confidence interval, 1.09-7.91), after accounting for age, sex, body mass index, smoking, fasting plasma glucose, and total cholesterol/high-density lipoprotein-cholesterol ratio. Further adjustment of the model for amplitude of the backward pressure wave eliminated the statistical significance of the WCH effect. In conclusion, the white coat effect is mainly caused by arterial aging. WCH carries higher risk for cardiovascular mortality than PH, probably via enhanced wave reflections that accompany arterial aging.

Combined effect of high-normal blood pressure and low HDL cholesterol on mortality in an elderly Korean population: the South-West Seoul (SWS) study.

BACKGROUND: It is unclear whether prehypertension by the seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) criteria (systolic blood pressure (SBP) 120-139 or diastolic blood pressure (DBP) 80-89 mm Hg) or high-normal blood pressure (HNBP) by the European Society of Hypertension and European Society of Cardiology (ESH/ESC) criteria (SBP 130-139 or DBP 85-89 mm Hg) predicts mortality in elderly Koreans. We compared the mortality risk between those with prehypertension and HNBP and evaluated whether the presence of components of metabolic syndrome (MetS) can improve the prediction of mortality in subjects with HNBP. METHODS: We analyzed all-cause and cardiovascular disease (CVD) mortality according to the JNC-7 and ESH/ESC categories using follow-up data of the South-West Seoul (SWS) Study, a prospective cohort study of 2,376 elderly Koreans, aged >60 years. RESULTS: During the median follow-up of 7.6 years, 353 deaths occurred from all causes, and 113 of these were attributed to CVD. Prehypertension was nonsignificantly associated with an increased risk of mortality (hazard ratio (HR): 1.06, 95% confidence interval (CI): 0.68-1.64). Subjects with HNBP exhibited a nonsignificantly higher risk of mortality compared with those with optimal blood pressure by the ESH/ESC guideline (HR: 1.35, 95% CI: 0.84-2.18). However, the combination of low high-density lipoprotein (HDL) cholesterol and HNBP showed a twofold higher risk of all-cause mortality (HR: 2.01, 95% CI: 1.11-3.64) independent of other risk factors. CONCLUSIONS: Although prehypertension was not associated with increased risk of mortality, individuals in the elderly Korean population with HNBP, especially when combined with low HDL cholesterol, showed a significantly increased risk of all-cause mortality.

The role of diets, food, and nutrients in the prevention and control of hypertension and prehypertension.

Hypertension is the leading risk factor for death worldwide, even surpassing tobacco use, high blood glucose, high blood cholesterol, and obesity. Globally, the estimated prevalence of hypertension is nearly 1 billion persons with an annual mortality of almost 7.5 million deaths. In the United States, hypertension affects an estimated 65 million Americans, and is the leading risk-factor cause of death in women and only second to tobacco use as a contributory cause of death in men. Multiple sources of data from prospective observational, cohort, and randomized controlled clinical trials show that hypertension and its complications are highly preventable when the raised blood pressure is prevented, or treated and controlled. To promote positive behavior change and create a broader impact on public health, it has become necessary to leverage multilevel stakeholders such as all health care providers, researchers, policy makers, schools, the food industry, and the general public to drive policy changes and future innovation from research and development endeavors, and to emphasize the importance of diet-related lifestyle modifications to effectively prevent and control hypertension and prehypertension.