Abstract
Introduction
Elevated pulse pressure (ePP) is an independent marker of cardiovascular risk (CVR) in people older than 60, and a functional marker of subclinical target organ damage (sTOD) which can predict cardiovascular events in patients with hypertension (HTN), regardless of sTOD.
Objective
To evaluate the prevalence of ePP in adult population seen in primary care and its association with other vascular risk factors, sTOD and with cardiovascular disease (CVD).
Materials and methods
Observational multicentre study conducted in Spain (8,066 patients, 54.5% women) from the prospective cohort study IBERICAN recruited in Primary Care. Pulse pressure (PP) was defined as the difference between the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) ≥60 mmHg. Adjusted (for age and sex) ePP prevalence were determined. Bivariate and multivariate analyses of the possible variables associated with ePP were carried out.
Results
The mean of PP was 52.35 mmHg, and was significantly higher (p < 0.001) in patients with HTN (56.58 vs. 48.45 mmHg) The prevalence of ePP adjusted for age and sex was 23.54% (25.40% men vs. 21.75% women; p < 0.0001). The ePP prevalence rates increased linearly with age (R2 = 0.979) and were significantly more frequent in population aged ≥65 than in population aged <65 (45.47% vs. 20.98%; p < 0.001). HTN, left ventricular hypertrophy, low estimated glomerular filtration rate, alcohol consumption, abdominal obesity, and CVD were independently associated with ePP. 66.27% of patients with ePP had a high or very high CVR, as compared with 36.57% of patients without ePP (OR: 3.41 [95% CI 3.08–3.77]).
Conclusions
The ePP was present in a quarter of our sample, and it was increased with the age. Also, the ePP was more frequent in men, patients with HTN, other TOD (as left ventricular hypertrophy or low estimated glomerular filtration rate) and CVD; because of this, the ePP was associated a higher cardiovascular risk. In our opinion, the ePP is an importer risk marker and its early identification lets to improve better diagnostic and therapeutic management.
Keywords: hypertension, pulse pressure, cardiovascular risk factors, subclinical target organ damage, hypertensive cardiovascular disease, cardiovascular disease
Introduction
Hypertension (HTN) is an important cardiovascular risk factor (CVRF), both at individual and population levels (1, 2). Its control is important because, after nutritional alterations, HTN ranks second in terms of factors responsible for both worldwide mortality and years of life lost and disability-adjusted life years (3). Its association with other factors multiplies the cardiovascular risk (CVR) (4), which justifies the multifactorial approach to these patients.
The pulse pressure (PP) is an index of the distensibility of the great arteries, and therefore it is a functional marker of subclinical target organ damage (sTOD), it predicts cardiovascular events in patients with HTN (5, 6), and it is an independent marker of CVR in population aged >60 (7).
From a pathophysiological point of view, the early phases of HTN are characterised by changes in the blood circulation of the small blood vessels caused by the systemic vascular resistance. The stiffness of the great vessels increases and they lose elasticity as they age, so a greater pressure is needed which causes left ventricular hypertrophy (LVH). In adults aged <55, the increased vascular resistance results in elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP), and both are predictors of cardiovascular disease (CVD). On the other hand, in people aged >55, the DBP tends to increase until it reaches its peak at the age of 55–60, and then it decreases, in such a way that whereas the DBP decreases, the SBP continues to increase. This would explain the fact that an elevated DBP on its own is less useful as a CVR predictor in older patients, while the prediction of the SBP for CVD is maintained (8).
Kodama et al.'s meta-analysis (9) showed that, in patients with DM, for each 10 mmHg increase, the PP had a higher relative risk of CVD than the SBP, DBP and mean BP. The 33-year follow-up study of the Chicago Heart Association Detection Project (10) showed the predictive usefulness of the PP when it is associated with cerebrovascular disease, coronary heart disease (CHD) and heart failure (HF). The elevation of the PP, caused progressively by ageing, was associated with LVH, albuminuria, carotid intima-media thickness (11) and CVD (12). All this caused that, with age, the elevated pulse pressure (ePP) was more closely correlated with SBP (5, 7, 13).
Like other biological variables, PP is a continuous variable that can increase the absolute risk of cardiovascular events in older subjects (≥50) despite the observed decrease in the relative risk (14). It can also be an independent predictor of mortality from any cause and of coronary origin, especially when the PP reaches values ≥65 mmHg (15), being more remarkable in patients with HTN with high levels of PP (13).
It should be noted that the population with HTN and very high CVR [with diabetes mellitus (DM) and/or previous CVD] has higher values of PP than the rest of patients without DM or CVD (16, 17). Moreover, the hypertensive patients with a PP ≥65 mmHg present LVH or echocardiographic diastolic dysfunction more frequently than those with PP <65 mmHg (18). Finally, a significant proportion of treated hypertensive patients have increased arterial stiffness, a finding that can partly explain the remarkable residual risk of CVD associated even with a well-controlled HTN (19).
It is very important to consider a comprehensive approach to CVR in all patients in primary prevention, before the development of CVD, and which includes the determination of the PP together with the rest of main CVRF. In order to increase knowledge in this regard, the objective of this study is to evaluate, in the context of the IBERICAN study, the presence of ePP in population seen in Primary Care, and its association with other CVRF, sTOD and CVD.
Methods
An observational, cross-sectional analysis was carried out from the inclusion visit of the IBERICAN cohort, which is a multicentre study conducted in Primary Care centres of the Spanish National Health System and whose methodology has been previously published (20). Using consecutive non-probability sampling, 8,066 subjects aged 18–85 were recruited in Primary Care, who consulted their family physician for whatever reason. Blood Pressure was measured with calibrated devices commonly available in clinical practice. The ePP was defined as the difference between SBP and DBP ≥60 mmHg. The rest of variables considered in this study can be found in the additional material.
Statistical analysis
The statistical analysis was performed with the program SPSS® (IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.). The qualitative variables were analysed with frequency distribution, percentages, chi squared test, and odds ratios (OR). The continuous variables were evaluated with the determination of the arithmetic means with standard deviation (±SD), median and interquartile range (IQR) of the variables age and PP, t-Student test or analysis of variance. The association between variables was estimated with a 95% confidence interval (95% CI) and level of significance p < 0.05. The crude prevalences and prevalences adjusted for age and sex were determined through direct method, using standardized 10-year age groups according to the information on the Spanish population aged 18–85 provided by the National Institute of Statistics on July 1st 2021 (21).
To assess the individual effect of comorbidities and CVRF on the dependent variable ePP, a binary unconditional multivariate logistic regression analysis was performed using the backward stepwise method, initially introducing into the model all the variables which showed association in the univariate analysis up to a value of p < 0.10, except the variables age, sex and CVR categories which were analyzed individually. The distribution of the specific rates of ePP prevalence by 10-year age groups was analysed using linear regression. Collinearity was previously examined through Spearman's rank correlation coefficient. The model included the variables that showed correlation coefficients higher than 0.5. Then, the variable that contributed least to the adjustment of the analysis was eliminated in each step. All the tests were considered to be statistically significant if the two-tailed p value was lower than 0.05. A literature search was carried out on PubMed, Medline, Embase, Google Scholar and Web of Science to compare this study with other similar studies published since 1997.
Results
The IBERICAN cohort included 8,066 subjects aged between 18 and 85 (54.5% women), with a mean (±SD) age of 58.41 (±14.83) and a median (IQR) of 59.77 (48.97–69.91) years. The mean (±SD) and the median (IQR) of the PP of the study population were 52.35 (±12.95) mmHg and 50 (43–60) mmHg respectively, where the mean PP was significantly higher (p < 0.001) in men [53.65 (±12.50) mmHg] than in women [51.26 (13.21) mmHg]. In patients with HTN, the mean (±SD) and the median (IQR) of the PP were 56.58 (±13.22) mmHg and 55.0 (49.0–64.0) mmHg respectively, where the mean PPs were practically the same (p = 0.981) in men [56.58 (±13.17) mmHg] and in women [56.57 (±13.29) mmHg]. In patients without HTN, the mean (±SD) and median (IQR) of the PP were 48.45 (±11.37) mmHg and 50.0 (40.0–55.0) mmHg respectively, where the mean PP in men [50.31 (±10.77) mmHg] was significantly higher (p < 0.001) than in women [47.16 (±11.60) mmHg].
The crude prevalence of ePP was 30.03% (95% CI 29.03–31.04), being significantly different (p < 0.001) in men [32.55% (95% CI 31.04–34.10)] and in women (27.92% [95% CI 26.60–29.27]). The prevalence of ePP adjusted for age and sex was 23.54% (25.40% in men; 21.75% in women).
The distribution of specific rates of ePP prevalence by 10-year age groups increased with age in a clear way (R2 = 0.979) according to the function y = 0.095x–0.0194, being significantly higher in men up to the age group 50–59, and without significant differences in the oldest age groups (Figure 1). The OR of the prevalence of ePP between the populations aged ≥65 and <65 was 2.57 (95% CI 2.23–2.96). The prevalence of ePP in patients aged ≥65 was 45.47% (95% CI 43.67–47.26), which was similar (p = 0.983) in men (45.49% [95% CI 42.88–48.09]) and women (45.45% [95% CI 42.99–47.92]). The prevalence of ePP in population aged <65 was 20.98% (95% CI 19.86–22.12), which was significantly different (p < 0.001) in men (24.50% [95% CI 22.73–26.28]) and in women (18.16% [95% CI 16.74–19.58]).
Figure 1.
Linear correlation between prevalence of elevated pulse pressure (ePP ≥60 mmHg) and age of the IBERICAN cohort.
The clinical characteristics of the patients with and without ePP are shown in Table 1. All the variables were significantly higher in the population with ePP, except height, total cholesterol and non-HDL cholesterol (with non-significant differences), and the estimated glomerular filtration rate (eGFR) and HDL cholesterol (significantly higher in patients without ePP).
Table 1.
Clinical characteristics of populations with and without elevated pulse pressure.
| With PP ≥60 mmHg | With PP <60 mmHg | Difference of means | p c | |||
|---|---|---|---|---|---|---|
| N a | Mean (±SD)b | N a | Mean (±SD)b | |||
| Age (years) | 2,422 | 65.00 (12.82) | 5,644 | 55.58 (14.74) | 9.42 | <0.001 |
| Weight (kg) | 2,422 | 77.91 (15.24) | 5,644 | 76.16 (15.94) | 1.75 | <0.001 |
| Height (m) | 2,422 | 1.63 (0.09) | 5,644 | 1.64 (0.09) | −0.01 | 0.360 |
| BMI (kg/m2) | 2,422 | 29.25 (5.04) | 5,644 | 28.10 (5.15) | 1.15 | <0.001 |
| Abdominal girth (cm) | 2,394 | 99.36 (14.86) | 5,563 | 95.21 (14.88) | 4.15 | <0.001 |
| SBP (mmHg) | 2,422 | 142.93 (13.89) | 5,644 | 123.04 (12.78) | 19.89 | <0.001 |
| DBP (mmHg) | 2,422 | 75.41 (10.76) | 5,644 | 77.21 (9.81) | −1.80 | <0.001 |
| PP (mmHg) | 2,422 | 67.52 (8.92) | 5,644 | 45.84 (8.00) | 21.69 | <0.001 |
| HR (bpm) | 2,422 | 72.86 (10.94) | 5,644 | 73.50 (10.84) | −0.64 | 0.013 |
| Fasting blood glucose (mg/dl)d | 2,422 | 109.91 (33.36) | 5,644 | 99.04 (25.77) | 10.88 | <0.001 |
| HbA1c (%) | 708 | 7.14 (1.23) | 898 | 6.95 (1.18) | 0.18 | 0.003 |
| Total cholesterol (mg/dl)e | 2,422 | 194.13 (41.35) | 5,644 | 195.60 (55.44) | −1.47 | 0.127 |
| HDL-C (mg/dl)e | 2,277 | 53.73 (15.10) | 5,212 | 55.44 (15.44) | −1.71 | <0.001 |
| Non-HDL-C (mg/dl)e | 2,277 | 140.74 (40.27) | 5,212 | 141.07 (38.15) | −0.33 | 0.734 |
| LDL-C (mg/dl)e | 2,277 | 116.05 (36.89) | 5,212 | 118.13 (34.81) | −2.08 | 0.020 |
| Triglycerides (mg/dl)f | 2,422 | 131.53 (74.81) | 5,644 | 122.16 (84.19) | 9.37 | <0.001 |
| Uric acid (mg/dl) | 2,099 | 5.46 (1.48) | 4,828 | 5.16 (1.45) | 0.30 | <0.001 |
| Creatinine (mg/dl) | 2,397 | 0.90 (0.45) | 5,562 | 0.86 (0.47) | 0.04 | 0.001 |
| eGFR (ml/min/1.73m2) | 2,397 | 82.05 (19.51) | 5,562 | 90.38 (19.76) | −8.33 | <0.001 |
| ACR (mg/g) | 1,759 | 28.39 (95.86) | 3,882 | 18.61 (65.58) | 9.78 | <0.001 |
PP, pulse pressure; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR (bpm), heart rate (beats per minute); HbA1c, glycated haemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; Non-HDL-C, non-high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate according to CKD-EPI; ACR, albumin-to-creatinine ratio in urine.
N: sample size.
SD: standard deviation.
p: p-value of the difference of means.
To convert from mg/dl to mmol/L, multiply by 0.05556.
To convert from mg/dl to mmol/L, multiply by 0.02586.
To convert from mg/dl to mmol/L, multiply by 0.01129.
All the CVRF and the comorbidities assessed were significantly associated with ePP, except the variable first-degree family history of early atherosclerotic CVD (ACVD) and smoking (Table 2). The ePP was significantly (p < 0.001) more frequent in patients with HTN (41.65% [95% CI 40.09–43.20]) than in patients without HTN (19.28% [95% CI 18.09–20.48]) (OR: 2.99 [2.70–3.30]), and mainly in patients with SBP/DBP ≥140/90 mmHg (64.66% [95% CI 62.34–66.98]) as compared with those who had SBP/DBP <140/90 mmHg (24.99% [95% CI 23.20–26.78]) (OR: 5.49 [4.78–6.31]). Among the population with HTN, the proportion of patients who had ePP was similar (p = 0.678) in men (41.32% [95% CI 39.12–43.52]) and in women (41.98% [95% CI 39.75–44.20]). The other CVRF and comorbidities which showed greater degree of association were LVH, HF, low eGFR (<60 ml/min/1.73m2) and DM (Figure 2). In the multivariate analysis, the CVRF and comorbidities which were independently associated with ePP were HTN, LVH, DM, low eGFR, alcohol consumption, abdominal obesity and cardiovascular diseases (Table 3).
Table 2.
Factors and comorbidities in populations with and without elevated pulse pressure.
| PP ≥60 mmHg | PP <60 mmHg | p C | |||
|---|---|---|---|---|---|
| N a | %(95% CI)b | N a | %(95% CI)b | ||
| Current smoking | 364 | 15.03 (13.61–16.45) | 1047 | 18.55 (17.54–19.56) | <0.001 |
| Sedentary lifestyle | 791 | 32.66 (30.79–34.53) | 1580 | 27.99 (26.82–29.11) | <0.001 |
| Alcohol consumption | 365 | 15.11 (13.69–16.54) | 669 | 11.93 (11.08–12.78) | <0.001 |
| Overweight | 1288 | 53.29 (51.28–55.29) | 2563 | 45.50 (44.20–46.80) | <0.001 |
| Obesity | 975 | 40.26 (38.29–42.22) | 1746 | 30.94 (29.73–32.15) | <0.001 |
| Abdominal obesity | 1501 | 62.70 (60.76–64.64) | 2926 | 52.60 (51.29–53.91) | <0.001 |
| Diabetes | 718 | 29.64 (27–83–31–46) | 906 | 16.05 (15.09–17.01) | <0.001 |
| Hypertension | 1608 | 66.56 (64.67–68.44) | 2253 | 39.98 (38.70–41.26) | <0.001 |
| Dyslipidemia | 1401 | 58.04 (56.07–60.01) | 2650 | 47.04 (45.74–48.35) | <0.001 |
| TG/HDL-c > 2 | 1298 | 57.00 (54.94–59.02) | 2570 | 49.31 (47.94–50.66) | <0.001 |
| Premature CVD FH | 375 | 16.86 (15.31–18.42) | 792 | 15.27 (14.30–16.25) | 0.086 |
| LVH | 162 | 6.69 (5.69–7.68) | 155 | 2.75 (2.32–3.17) | <0.001 |
| ABI ≤0,9 | 60 | 2.48 (1.86–3.10) | 89 | 1.58 (1.25–1.90) | 0.006 |
| Low eGFR | 316 | 13.18 (11.83–14.54) | 358 | 6.44 (5.79–7.08) | <0.001 |
| Albuminuria | 252 | 10.40 (9.19–11.62) | 363 | 6.43 (5.79–7.07) | <0.001 |
| CKD | 406 | 23.08 (21.11–25.05) | 555 | 14.30 (13.20–15.40) | <0.001 |
| sTOD | 626 | 26.12 (24.36–27.87) | 831 | 14.94 (14.00–15.88) | <0.001 |
| Coronary heart disease | 233 | 9.62 (8.45–10.79) | 350 | 6.20 (5.57–6.83) | <0.001 |
| Stroke | 134 | 5.53 (4.62–6.44) | 189 | 3.35 (2.88–3.82) | <0.001 |
| PAD | 121 | 5.00 (4.13–5.86) | 144 | 2.55 (2.14–2.96) | <0.001 |
| Heart failure | 120 | 4.95 (4.09–5.82) | 129 | 2.29 (1.90–2.68) | <0.001 |
| Atrial fibrillation | 137 | 5.66 (4.74–6.58) | 201 | 3.56 (3.08–4.04) | <0.001 |
| ACVD | 429 | 17.71 (16.19–19.23) | 619 | 10.97 (10.15–11.78) | <0.001 |
| CVD | 599 | 24.73 (23.01–26.45) | 868 | 15.38 (14.44–16.32) | <0.001 |
| Low CVR | 268 | 11.11 (9.85–12.36) | 2125 | 37.81 (36.54–39.08) | <0.001 |
| Moderate CVR | 546 | 22.63 (20.96–24.30) | 1440 | 25.62 (24.48–26.76) | 0.004 |
| High CVR | 475 | 19.69 (18.10–21.27) | 979 | 17.42 (16.43–18.41) | 0.015 |
| Very high CVR | 1124 | 46.58 (44.59–48.57) | 1076 | 19.15 (18.12–20.17) | <0.001 |
N: sample size.
95% CI: 95% confidence interval.
p: p-value.
PP, pulse pressure; TG/c-HDL, triglycerides/HDL-cholesterol; CVD FH, first-degree family history of premature cardiovascular disease (<55 years [men]; <65 years [women]); LVH, left ventricular hypertrophy; ABI, ankle-brachial index; albuminuria, albumin-creatinine ratio (ACR)≥30 mg/g (including proteinuria, ACR >300 mg/g); low eGFR, glomerular filtration rate <60 mL/min/1.73m2 estimated according to CKD-EPI; CKD, chronic kidney disease (low eGFR and/or albuminuria); sTOD, subclinical target organ damage (LVH, albuminuria, low eGFR, ABI ≤0.9); PAD, peripheral artery disease, ABI ≤0.9; ACVD, atherosclerotic cardiovascular disease (coronary heart disease, stroke, PAD); CVD (cardiovascular disease), ACVD, heart failure, atrial fibrillation; CVR, cardiovascular risk according to SCORE. (Consult additional material for reference-checking).
Figure 2.
Forest Plot representation of associations between various factors and ePP in the IBERICAN cohort ePP, elevated pulse pressure; PP pulse pressure; TG/c-HDL, triglycerides/HDL-cholesterol; CVD FH, first-degree family history of premature cardiovascular disease [<55 years (men); <65 years(women)]; LVH, left ventricular hypertrophy; ABI, ankle-brachial index; albuminuria, low eGFR: glomerular filtration rate <60 ml/min/1.73 m2 estimated according to CKD-EPI; albumin-creatinine ratio (ACR) 30 mg/g (including proteinuria: ACR > 300 mg/g); CKD, chronic kidney disease (low eGFR and/or albuminuria); sTOD, subclinical target organ damage (LVH, albuminuria, low e GER, ABI a0.9); PAD, peripheral artery disease, ABI ≤0.9; ACVD, atherosclerotic cardiovascular disease (coronary heart disease, stroke, heart failure, atrial fibrillation, PAD); CVD cardiovascular disease; CVR, cardiovascular risk according to SCORE. 95% CI: 95% confidence interval; p, p-value.
Table 3.
Multivariate analysis of risk factors and comorbidities associated with elevated pulse pressure (≥60 mmHg).
| ACVD model | β a | OR Exp (β)b | p c | CVD model | β a | OR Exp (β)b | p c |
|---|---|---|---|---|---|---|---|
| Hypertension | 0.88 (0.06) | 2.41 (2.16–2.68) | <0.001 | Hypertension | 0.87 (0.06) | 2.93 (2.14–2.67) | <0.001 |
| LVH | 0.48 (0.12) | 1.62 (1.27–2.05) | <0.001 | LVH | 0.46 (0.12) | 1.58 (1.25–2.01) | <0.001 |
| Diabetes | 0.43 (0.06) | 1.53 (1.36–1.73) | <0.001 | Diabetes | 0.42 (0.06) | 1.53 (1.35–1.72) | <0.001 |
| Low eGFR | 0.39 (0.09) | 1.48 (1.25–1.75) | <0.001 | Low eGFR | 0.38 (0.09) | 1.46 (1.23–1.73) | <0.001 |
| Alcohol consumption | 0.22 (0.07) | 1.25 (1.08–1.45) | 0.002 | Alcohol consumption | 0.22 (0.07) | 1.25 (1.08–1.45) | 0.002 |
| ACVD | 0.20 (0.07) | 1.23 (1.06–1.41) | 0.006 | CVD | 0.20 (0.06) | 1.22 (1.07–1.38) | 0.002 |
| Central obesity | 0.12 (0.05) | 1.13 (1.02–1.26) | 0.023 | Central obesity | 0.12 (0.05) | 1.13 (1.01–1.25) | 0.029 |
LVH, left ventricular hypertrophy; low eGFR, glomerular filtration rate <60 ml/min/1.73m2 estimated according to CKD-EPI; ACVD, atherosclerotic cardiovascular disease (coronary heart disease, stroke, peripheral artery disease); CVD (cardiovascular disease), ACVD, heart failure, atrial fibrillation.
β coefficient (± deviation).
Odds-ratio Exp (β) (95% confidence interval).
p: p-value of Wald test with one degree of freedom.
66.27% (95% CI 64.38–68.15) of patients with ePP had a high or very high CVR, as against the patients without ePP, of whom 36.57% (95% CI 35.31–37.83) had a high or very high CVR (OR: 3.41 [95% CI 3.08–3.77]) (Table 2, Figure 2).
Discussion
This subanalysis of the cohort of the IBERICAN study describes the characteristics of the population according to the presence of ePP, with a prevalence adjusted for age and sex of 23.5%. This prevalence increases with age, is higher in men, and is more frequently associated with HTN, DM, low eGFR, LVH and HF, which increases the CVR of patients with ePP.
After a detailed revision of bibliography, our results represents the first time that are described the prevalence of ePP and its associations with other cardiovascular risk factors, TOD and CVD simultaneously in the same cohort, using a clínica population, recruited in primary care.
The prevalence of ePP observed in our study (23.5%) are similar to observed in other studies as NHANES survey (26.91%) using PP > 55 mmHg in a sample with 5,771 subjects (22) or 12.1% of patients aged <55 and 27.8% of those aged ≥55 in a French study about a sample with 19,083 men (15). The main variable associated with ePP prevalence was the age, with a quasi-perfect linear correlation, variable also associated with the cardiovascular mortality (25), and in older 60 years the ePP has an important predictive value of the cardiovascular risk (26).
The relationship between ePP and other variables as HTN o LVH was described by Vasan et al. that described the association of these TOD with central PP (12). In the same line, other studies analysed the role of ePP in the develop of chronic kidney disease (CKD) (23) or other organ targeting as HF (24). These associations of the ePP can explain that we observed two-thirds of the patients with ePP had higher cardiovascular risk, in the same line observed in the MRFIT study that described the association between PP and cardiovascular mortality in hypertensive patients (27).
These relationships with other cardiovascular risk factor, TOD and CVD describes the ePP as a early risk marker and the importance of and early identification to introduce changes in the treatment of the patients and improve their prognosis. In really, maybe we need more studies, and clinical trials, that confirm that this reduction of PP would reduce the cardiovascular events and mortality.
Strengths and limitations
This subanalysis of the IBERICAN study has certain limitations derived from its very design and from the interpretation of some of the variables. The study sample has the bias of being a clinical cohort between the age of 18 and 85 seen in Primary Care with a possible accumulation of risk factors and comorbidities as compared with the rest of the population. Thus, the results obtained could be only extrapolated to the clinical population, despite the validity of the associations found. This study does not differentiate whether the ePP was detected during the day or at night, even though the ePP is associated with LVH regardless of the moment of detection whereas the greatest increase of ventricular mass has been associated with ePP during night time. Like SBP and DBP, PP is a continuous variable, so the decision to establish the ePP at an easy-to-remember threshold of 60 mmHg is an arbitrary one, though justified by the available literature (28, 29). The analysis of the variable ACVD (CHD, stroke and PAD) does not differentiate between type-1 (atherothrombotic) and type-2 (non-atherothrombotic) coronary ischemic heart disease, or between ischemic strokes and hemorrhagic strokes. From a strictly clinical point of view, our results can be considered to show the relationship between the set of processes included in the variable ACVD and ePP, because the existence of such association has been previously demonstrated not only with atherothrombotic disease but also with hemorrhagic strokes (30) and with non-obstructive coronary ischemia in stressful situations (31).
Among the strengths of this study are the large sample of the IBERICAN cohort, the adjustment for age and sex of the prevalence rates (which makes it easier to compare the results with other populations), the assessment of the association of ePP with numerous cardiovascular, cardiometabolic and renal variables, and the presentation of relevant results on ePP which did not exist in Spain before.
Clinical implications
There are no well-designed intervention studies which assess the potential cardiovascular benefits of specific therapeutic strategies for ePP. This may justify the fact that no PP objectives or appropriate treatment has been established. It has been found that the levels of PP reached with antihypertensive treatment form a curved (J-shaped) association for most cardiovascular events, and a linear one when it was associated with myocardial infarction, setting the optimum level of PP at 50 mmHg (32). A strict control of BP lowers the PP levels in varying degrees according to the drug treatment used (Supplementary Figure S3 in the additional material). Emphasis should be placed on individualising HTN treatments, especially in patients with CHD (even in its silent forms), DM or fragile elderly patients, since an excessive reduction of both the SBP and DBP may lead to new cardiovascular events (33–38).
Conclusions
The observational multicentre IBERICAN study, recruited in primary care in Spain, showed that near a quarter of the patients had ePP, and this prevalence increases with the age of the patients.
The prevalence of ePP showed an independent association with other cardiovascular risk factors, as HTN, diabetes, abdominal obesity and alcohol consumption; other TOD, as LVH and low eGFR; and CVD.
This association with other cardiovascular determinants and the higher cardiovascular risk associated become the ePP in the interesting risk marker to identify in the clinical practice to introduce more intensive treatments to improve the cardiovascular prognosis. However, this affirmation needs to be confirmed in a prospective observational studies and clinical trials.
Acknowledgments
To the SEMERGEN Foundation for funding the study, to the researchers who have actively participated in the recruitment of patients, and to the patients for their participation.
Funding Statement
The researchers, members of the Scientific Committee or the Steering Committee, general coordinator and principal investigator have not received any remuneration for participating in the IBERICAN study. The IBERICAN study is financed by the SEMERGEN Foundation with its own funds and has received aid to defray occasional expenses for statistical analysis and dissemination of results (AstraZeneca, Menarini).
Contributor Information
the researchers of the IBERICAN study:
Alfonso Barquilla García, Ángel Díaz Rodríguez, Carlos Escobar Cervantes, Francisco Javier Alonso Moreno, Jesús Vergara Martín, Juan José Badimón, José Polo García, Luis Rodríguez Padial, Miguel Ángel Prieto, Rafael Vidal Pérez, Sergio Cinza Sanjurjo, Sònia Miravet Jiménez, Sonsoles Velilla Zancada, José Ramón Banegas, Vicente Martín Sánchez, Vicente Pallares Carratalá, Antonio Segura Fragoso y Rafael Manuel Micó Pérez, Antonio López Téllez, Jesús Vergara Martin, María De Los Ángeles Ortega Osuna, Cristóbal Prieto Cid, Mª José Hidalgo Fajardo, José Lorente Serna, Ángel Domínguez Requena, Ricardo Alberola Cañizares, Manuel Ruiz Peña, Filomena Herrero Collado, Marcela Montes Vázquez, Rafael Ángel Carrascal Garrido, María Reyes Herrera Lozano, Beatriz Ortiz Oliva, Francisco José Anguita, Carmen Pérez Ibáñez, Carlos Alberto Cabrera Rodríguez, María José Cruz Rodríguez, Sandra Bonilla Ruiz, Rocio Reina González, Salome Abad Sánchez, Inmaculada Santana Martínez, Rafael Sánchez Jordán, Juan Mª Ramos Navas-Parejo, José Manuel Ramírez Torres, José María Beltrán Poveda, María Adoración De Cruz Benayas, Carmen Fernández Gil, Jon Iñaki Esturo Alcaine, Antonio Mora Quintero, Fernando Leiva Cepas, José Luis Carrasco Martín, Emilio García Criado, Mercedes Vázquez Blanco, Isabel Mora Ortiz, Leovigildo Ginel Mendoza, Juan Carlos Aguirre Rodríguez, Esperanza María Romero Rodríguez, José Acevedo Vázquez, Juan Gabriel García Ballesteros, María De La Paz Fernández Lara, Patricia Agüera Moreno, Eduardo Paños Maturana, Juan Manuel Ignacio Expósito, Noelia Carrillo Peñas, Carmen María Abad Faya, Ana Marina Almagro Duque, Rubén Torrescusa Camisón, Paloma Menéndez Polo, Marina Peña García, Cristina López Fernández, Ascensión Estepa Torres, Miguel Gutiérrez Jansen, Esperanza Loizaga González, Lisardo García Matarín, Enrique José Gamero De Luna, Javier Benítez Rivero, María José Gómez González, Carmen Gómez Montes, Juan Carlos Rodríguez Rodríguez, Juana María González Barranco, Josefa Ramírez Vizcaíno, María Ángeles Miranda Sánchez, Eva Trillo Calvo, Concepción Bayod Calvo, Susana Larripa De La Natividad, German Grasa Lambea, Emilio Jiménez Marín, Ana Cristina Navarro Gonzalvo, Antonio Pablo Martínez Barseló, Irene Peña León, Ángel González Pérez, Liliana Mahulea, María José Pérez Martínez, Ana Piera Carbonell, Margarita Alonso Fernández, María Montserrat Rueda Cuadrado, Rodrigo Abad Rodríguez, José Miguel Álvarez Cabo, Rubén Sánchez Rodríguez, Eva María Cano Cabo, Anny Romero Secin, Miguel Ángel Prieto Díaz, Juan Jesús García Fernández, Saúl Suárez García, Fernando García Romanos, Antonia Moreno González, María Lara Amengual Sastre, Susana Martínez Palli, José Alfonso Ramón Bauza, Jose Ortiz Bolinches, Carmen Fernández Fernández, María Isabel Orlandis Vázquez, Ana Sanchís Mezquita, Fernando Unceta Aramburu, Juan Fernando Peiró Morant, Ana Moyá Amengual, Matéu Seguí-Díaz, José Félix Zuazagoitia Nubla, Ana Echevarría Ituiño, Gregorio Mediavilla Tris, María Carmen Noriega Bosch, Esther González, María Luisa Ruiz Macho, Ruth Sendino Del Olmo, Asunción Olagorta De Prado, Ana López De Viñaspre Muguerza, Jesús Iturralde Iriso, Mª Rosario Virtus Iñurrieta, Lucas Ulloa Bahamonde, Isidro Godoy García, Fernando Rubio Sevillano, María Isabel González González, Marta Pérez Souto, Raquel De León Contreras, Sara Isabel Almeida González, Irene Almería Diez, Virginia Maria Mirabal Sánchez, Francisco José Escobar Lavado, Yoel Anta Pérez, Nayra Sánchez Hernández, Juan Luis Alonso Jerez, Ricardo Koch, Nayra Ramírez Mendoza, Héctor Suárez Hernández, Francisco Jesús Morales Escobar, E Lidia Gutiérrez Fernández, Fernando Andrés Mantecón, Ana Belén García Garrido, Asunción Vélez Escalante, Luisa Alonso Rentería, Jesús Sainz Jiménez, Guillermo Pombo Alles, Esperanza Rueda Alonso, Juan Antonio Divisón Garrote, Pedro Martínez Sotodosos, Juan Antonio Vivancos Fuster, María García Palencia, José Ambrosio Torres Moraleda, Sara González Ballesteros, Ana Carmen Gil Adrados, Antonio González Cabrera, Miguel Ángel Babiano Fernández, Guillermo Rico García, Juan José Criado-Álvarez, Pilar Torres Moreno, Francisco Javier Arribas Aguirregaviria, Alicia Sahuquillo Martínez, Lourdes Maria Santos Bejar, Miguel Laborda Peralta, Raúl Piedra Castro, Carlos Santos Altozano, Lucia González-Tarrio Polo, Pedro Valiente Maresca, Reinilda Mota Santana, Noemi Elizabeth Terrero Ledesma, Noelia Garrido Espada, Francisco Javier Alonso Moreno, Gabriela Delia Rosa Zambrana Calvi, Cristina de Castro Mesa, Blanca Cordero García, Pilar Sorrius Sitges, Ana María de Santiago Nocito, César Lozano Suárez, Juan Lorenzo Gutiérrez Montero, Juan Ignacio López Gil, María Dolores Fernández Ortega, Miren Elizari Roncal, María Ascensión López Serrano, Nuria Esther Adrián De La Fuente, Belén Angulo Fdez. De Larrea, Naiara Cubelos Fernández, Guiomar Luz Ferreiro Gómez, Diana Gómez Rodríguez, Sonia María Andrés Tuñón, María Ajenjo González, Serafín De Abajo Olea, Juan José León Regueras, César Manuel Gallego Nieto, Delio Vázquez Mallada, Maria De La O Gutiérrez García, Pablo Baz Rodríguez, José Ignacio Ferradal García, Blanca Delia De Román Martínez, Ana Arconada Pérez, Omar Mahmoud Atoui, Álvaro Morán Bayón, María Teresa Armenteros Del Olmo, Francisco Javier García-Norro Herreros, Enrique Méndez Rodríguez, Diana María Narganes Pineda, Ángel Díaz Rodríguez, Verónica Ortiz Ainaga, Milagros Sonlei Sánchez Guevara, Laura Villota Ferreiro, M Teresa Grande Grande, Francisco Vicente Martínez Gracia, Jesús Palomo del Arco, María Dolores Moriano García, Beatriz Jiménez Muñoz, Gemma Rovira Marcelino, Diana Elizabeth Fernández Valverde, Roser Rodó Bernadó, Maria Teresa Ortiz Lupiañez, Najlaa Najih, José María Diéguez Parra, Mª Rosa Benedicto Acebo, Mari Luz Bravo Vicien, Alberto Ramón León Estella, Juan Antonio Muñoz Gómez, Alicia Mostazo Muntané, Isabel Ortega Abarca, Anna Gasol Fargas, Brenda Elizabeth Riesgo Escudero, Susana Elizabeth Riesgo, Edgar Zaballos Castellvi, Celia Cols Sagarra, Marta Herranz Fernández, Josep Alins Presas, Idaira Damas Pérez, Rosa M Alcolea Garcia, Ines Monte Collado, Roberto Genique Martínez, María José Guasch Villanueva, Sònia Miravet Jiménez, Teresa Rama Martínez, Lucio Pinto Pena, Josefa María Panisello Royo, Inés Gil Gil, Carlos Gómez Ruiz, Rita Sahun Font, Anna Fuentes Lloveras, Alberto Calderón Montero, María Del Mar Zamora Gómez, Elena Alarcón Cebrián, Mª José Piñero Acin, Celia Pecharroman Sacristán, M Soledad Mayayo Vicente, Mª Paz Pérez Unanua, Nuria Marañón Henrich, Saray Gómez Monreal, Sonia Redondo De Pedro, Blanca Sanz Pozo, Irene Moreno Martínez, Beatriz Lopez Uriarte, Carmelina Sanz Velasco, Amaya Gárriz Aguirre, Montserrat Rivera Teijido, German Reviriego Jaén, Jose Ignacio Aza Pascual-Salcedo, Josefa Vázquez Gallego, Julia Caballer Rodilla, Aida Herrera, Ezequiel Arranz Martínez, Ana María Gómez Calvo, Paula Morán Oliva, Mª Milagros González Béjar, Julio Antonio Heras Hitos, Olga García Vallejo, Manuel De Jesús Frías Vargas, María Jesús Castillejo Boguerin, Aurora García Lerín, Miguel Ángel María Tablado, Elena Concepción García García, Leticia De Miguel Acero, Carmen Zárate Oñate, Aránzazu Barranco Apoita, María Ester Montes Belloso, Ana María Huertas Velasco, Rafael Sáez Jiménez, Julia Natividad García Pascual, María Clemencia Zuluaga Zuluaga, Mª Cruz Díez Pérez, Antonio Ruiz García, Cristina Murillo Jelsbak, Virginia Lasso Oria, Amelia González Gamarra, Elena Rodilla Rodilla, Alberto Galgo Nafría, María Mestre de Juan, Mª Carmen García Albiñana, Mª del Pilar Moreno Cano, Paula Hernanz López, Paloma Casado Pérez, Jacinto Espinosa García, José Ignacio Prieto Romo, Leandro Fernández Fernández, Javier Sierratapia, Nieves Moreno Regidor, Francisco Javier Zaballos Sánchez, Ana Moreno Moreno, Francisco Carramiñana Barrera, Juan Jose Torres Vázquez, María José Gamero Samino, Miguel Ángel De Santiago Rodríguez, Pablo Rafael Gómez Martínez, Antonio Carlos Elías Becerra, Javier Soto Olivera, Víctor Cambero, Julián Domínguez Ávila, Andrés Simón Fuentes, Jorge Manuel De Nicolás Jiménez, Dimas Igual Fraile, Guadalupe Nieto Barco, Ignacio Araujo Ramos, Mª Luz Serrano Berrocal, Francisco Buitrago Ramírez, Minerva Gallego Marcos, Félix Suarez González, Victoriano Chavero Carrasco, José Polo García, Francisco Guerra Peguero, Francisco Javier Sánchez Vega, Manuel Tejero Mas, Alba Palmerín Donoso, Miguel Turégano Yedro, María Beatriz Esteban Rojas, Fátima Cabezudo Moreno, Nawson Elver Quevedo Saldaña, María Del Mar García Fenés, Alfonso Barquilla García, Timotea Garrote Florencio, José María Fernández Toro, Vicente Caballero Pajares, María José Gómez Barquero, Alejandra Rey Rañal, Elena García Del Río, Enrique Nieto Pol, Julio Álvarez Fernández, Pilar Alonso Álvarez, Mª Luisa Jorge Gómez, Antonio Calvo Guerrero, Isabel Celemín Colomina, Lucia Barreiro Casal, Juana Fernández Moreno, Mª Angelines Carballal Martínez, Nabor Díaz Rodríguez, Carlos Moral Paredes, Dolores Recarey García, Francisco Javier Iglesias Mato, Antonio Fouz Ulloa, Amparo Fidalgo González, Noelia Dios Parada, Patricia Conde Sabarís, Ana Isabel Rodríguez Pérez, Ana Inés García Palacio, Víctor Julio Quesada Varela, Lidia Romero Iglesias, Ángel Lado Llerena, Carmen Lires Rodríguez, María Luisa Carretero Díaz, José Carreira Arias, José Luís Vázquez Camino, María Del Carmen Torreiro Penas, Sandra Yáñez Freire, Sergio Cinza Sanjurjo, Daniel Rey Aldana, Carlos Piñeiro Díaz, Portal González Lorenzo, José Rodríguez Campos, Rubén Blanco Rodríguez, Manuel Portela Romero, Lucía Vilela de Castro, Sonsoles María Velilla Zancada, Rafael Crespo Sabarís, Oscar Fernando Isaula Jiménez, Jesús Manuel González Puga, Jorge Antonio Benaín Ávila, Óscar Del Toro González, Vicente Llorca Bueno, Ana María Ballesteros Pérez, Domingo J Rubira López, Mª Dolores Esteve Franco, Elena Sánchez Pablo, María Teresa Palacios López, Juan Castillo Meroño, José María Lobo Martínez, Isabel María Peral Martínez, J Eduardo Carrasco Carrasco, Armando Santo González, Juan Gomáriz García, Beatriz Ríos Morata, Laura Sánchez Iñigo, Inés Sanz Pérez, Vicente Pascual Fuster, Mª Dolores Aicart Bort, Natividad Vázquez Gómez, Carlos Lluna Gasco, Teresa Amorós Barber, Pedro Antonio Medina Cano, Miguel Monteagudo Moncho, María Jesús Larré Muñoz, Raquel Navarro Hernández, Francisco José Martínez Egea, Antonio Tramontano, Marta Ferrer Royo, Belén Persiva Saura, Juan A Contreras Torres, José Mª Tirado Moliner, Alejandro Salanova Penalba, Ariadna Cucó Alberola, Fernando María Navarro I Ros, Enrique Beltrán Llicer, Ana Seoane Novás, Inmaculada Martín Valls, Gracia Verdú Mahiques, Enrique Peña Forcada, Nieves Aguilar Gómez, Francisco Javier Sanz García, María Dolores Paradís Bueso, María Eugenia Alegre Romero, Antonio Francés Camus, María Amparo Antón Peinado, Rosa Latorre Santos, Mª Asunción Palomar Marín, María Carmen Botella García, Eva Sánchez Fresquet, Pedro Sala Paños, Tomás Sánchez Ruiz, Rosa Ana Valero Valero, María Seoane Vicente, Magdalena Martin Llinares, Antonio Masiá Alegre, José Luis Llisterri Caro, Irene Lluch Verdu, Vicente Pallarés Carratalá, Francisco Valls Roca, Rafael Manuel Micó Pérez, Carmen Barceló Dupuy, Elena Benages Vicente, María José Gimeno Tortajada, Mercedes Calleja del Ser, Martín Menéndez Rodríguez, and Rosalía Victoria Carbonell Castelló
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.
Ethics statement
This study was conducted according to the guidelines of the Declaration of Helsinki and approved by the ECCR of Hospital Clínico San Carlos in Madrid on February 21, 2013 (C.P. IBERICAN-C.I. 13/047-E) and is registered in https://clinicaltrials.gov with the number NCT02261441. The information obtained was treated with absolute confidentiality, respecting the principles of the Declaration of Helsinki. Participants’ EHR data was anonymized upon extraction. All patients, when invited to be included in the health system through their personalized identification system (PIS), give their authorization to the Regional Ministry of Health (RMoH) so that the information contained in their EHR can also be used for research purposes, in compliance with data protection regulations.
Author contributions
Conceptualization, methodology, writing—review and editing: AM-A, AR-G, VP-C, AS-C, MP-D, AS-F and SC-S; writing—original draft preparation: AM-A, AR-G, VP-C, and AS-C; supervision: AM-A, AR-G, VP-C, AS-C, MP-D, AS-F and SC-S; project administration: SC-S; funding acquisition: AM-A, AR-G, VP-C, AS-C, MP-D, AS-F and SC-S. All authors contributed to the article and approved the submitted version.
Group members of the IBERICAN study
The full list of members can be found in the Supplementary material.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcvm.2023.1090458/full#supplementary-material.
References
- 1.Multiple Risk Factor Intervention Trial Research Group. Multiple risk factor intervention trial: risk factor changes and mortality results. J Am Med Assoc. (1982) 248:1465–77. 10.1001/jama.1982.03330120023025 [DOI] [PubMed] [Google Scholar]
- 2.Yusuf S, Hawken S, Ôunpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. (2004) 364:937–52. 10.1016/S0140-6736(04)17018-9 [DOI] [PubMed] [Google Scholar]
- 3.GBD 2013 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the global burden of disease study 2013. Lancet. (2015) 386:2287–323. 10.1016/S0140-6736(15)00128-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Kannel WB. Office assessment of coronary candidates and risk factor insights from the framingham study. J Hypertens Suppl. (1991) 9:S13–9. 10.1097/00004872-199112007-00005 [DOI] [PubMed] [Google Scholar]
- 5.SHEP Cooperative Research Group. Prevention of stroke by anthipertensive drug treatment in older persons with isolated systolic hypertension: final results systolic hypertension in the elderly program (SHEP). J Am Med Assoc. (1991) 265:3255–64. 10.1001/jama.1991.03460240051027 [DOI] [PubMed] [Google Scholar]
- 6.Mancusi C, Losi MA, Izzo R, Canciello G, Carlino MV, Albano G, et al. Higher pulse pressure and risk for cardiovascular events in patients with essential hypertension: the campania salute network. Eur J Prev Cardiol. (2018) 25:235–43. 10.1177/2047487317747498 [DOI] [PubMed] [Google Scholar]
- 7.Villa ER, Tranche IS, Marín IR, Prieto DM, Hevia RE, Grupo Oviedo de Hipertensión. Pulse pressure as a marker of cardiovascular risk among the elderly. Aten Primaria. (2002) 30:374–80. 10.1016/s0212-6567(02)79050-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jr, et al. Joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. National heart, lung, and blood institute; national high blood pressure education program coordinating committee. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. (2003) 42:1206–52. 10.1161/01.HYP.0000107251.49515.c2 [DOI] [PubMed] [Google Scholar]
- 9.Kodama S, Horikawa C, Fujihara K, Yoshizawa S, Yachi Y, Tanaka S, et al. Meta-analysis of the quantitative relation between pulse pressure and mean arterial pressure and cardiovascular risk in patients with diabetes mellitus. Am J Cardiol. (2014) 113:1058–65. 10.1016/j.amjcard.2013.12.005 [DOI] [PubMed] [Google Scholar]
- 10.Mosley WJ, Greenland P, Garside DB, Lloyd-Jones DM. Predictive utility of pulse pressure and other blood pressure measures for cardiovascular outcomes. Hypertension. (2007) 49:1256–64. 10.1161/HYPERTENSIONAHA.106.083592 [DOI] [PubMed] [Google Scholar]
- 11.Viazzi F, Leoncini G, Parodi D, Ravera M, Ratto E, Vettoretti S, et al. Pulse pressure and subclinical cardiovascular damage in primary hypertension. Nephrol Dial Transplant. (2002) 17:1779–85. 10.1093/ndt/17.10.1779 [DOI] [PubMed] [Google Scholar]
- 12.Vasan RS, Short MI, Niiranen TJ, Xanthakis V, DeCarli C, Cheng S, et al. Interrelations between arterial stiffness, target organ damage, and cardiovascular disease outcomes. J Am Heart Assoc. (2019) 8:e012141. 10.1161/JAHA.119.012141 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice: developed by the task force for cardiovascular disease prevention in clinical practice with representatives of the European society of cardiology and 12 medical societies with the special contribution of the European association of preventive cardiology (EAPC). Eur Heart J. (2021) 42:3227–337. 10.1093/eurheartj/ehab484 [DOI] [PubMed] [Google Scholar]
- 14.Melgarejo JD, Thijs L, Wei DM, Bursztyn M, Yang WY, Li Y, et al. The international database on ambulatory blood pressure in relation to cardiovascular outcome investigators. Relative and absolute risk to guide the management of pulse pressure, an age-related cardiovascular risk factor. Am J Hypertens. (2021) 34:929–38. 10.1093/ajh/hpab048 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Benetos A, Safar M, Rudnichi A, Smulyan H, Richard J-L, Ducimetière P, et al. Pulse pressure: a predictor of long-term cardiovascular mortality in a French male population. Hypertension. (1997) 30:1410–5. 10.1161/01.HYP.30.6.1410 [DOI] [PubMed] [Google Scholar]
- 16.Rodríguez RG, Alonso MF, García JA, Llisterri CJ. Factores condicionantes de la presión de pulso en los diabéticos tipo 2 de una población hipertensa de atención primaria. Aten Primaria. (2003) 31:486–92. 10.1016/s0212-6567(03)70721-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Buda VA, Ciobanu DM, Roman G. Pulse pressure is more relevant than systolic and diastolic blood pressure in patients with type 2 diabetes and cardiovascular disease. Clujul Med. (2018) 91:408–13. 10.15386/cjmed-972 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhäger WH, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The systolic hypertension in Europe (syst-eur) trial investigators. Lancet. (1997) 350:757–64. 10.1016/s0140-6736(97)05381-6 [DOI] [PubMed] [Google Scholar]
- 19.Niiranen TJ, Kalesan B, Hamburg NM, Benjamin EJ, Mitchell GF, Vasan RS. Relative contributions of arterial stiffness and hypertension to cardiovascular disease: the framingham heart study. J Am Heart Assoc. (2016) 5:e004271. 10.1161/JAHA.116.004271 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Cinza SS, Llisterri CJ, Barquilla GA, Polo GJ, Velilla ZS, Rodríguez RG, et al. , investigadores del estudio IBERICAN. Descripción de la muestra, diseño y métodos del estudio para la identificación de la población española de riesgo cardiovascular y renal (IBERICAN). Semergen. (2020) 46:4–15. http://dx.doi.org/10.1016/j.semerg.2019.10.006 [DOI] [PubMed] [Google Scholar]
- 21.Instituto Nacional de Estadística. INEbase. Demografía y población. Cifras de población y Censos demográficos. Cifras de población. Series detalladas desde (2002). Available at: https://www.ine.es/jaxiT3/Tabla.htm?t=9673&L=0 (Accessed September 13, 2022).
- 22.Domanski M, Norman J, Wolz M, Mitchell G, Pfeffer M. Cardiovascular risk assessment using pulse pressure in the first national health and nutrition examination survey (NHANES I). Hypertension. (2001) 38:793–7. 10.1161/hy1001.092966 [DOI] [PubMed] [Google Scholar]
- 23.Pérez-Castañeda AI, Vázquez-de Anda GF, Cerecero-Aguirre P, Rivas-Ruíz R, Delaye-Aguilar MG, Talavera JO. Sensitivity and specificity of increased pulse pressure as a diagnostic test for K/DOQI stage III-b CKD. Gac Med Mex. (2020) 156:424–9. 10.24875/GMM.M20000431 [DOI] [PubMed] [Google Scholar]
- 24.Chae C, Pfeffer M, Glynn R, Mitchell G, Taylor J, Hennekens C. Increased pulse pressure and risk of heart failure in the elderly. J Am Med Assoc. (1999) 281:634–9. 10.1001/jama.281.7.634 [DOI] [PubMed] [Google Scholar]
- 25.Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. (2002) 360:1903–13. 10.1016/S0140-6736(02)11911-8 [DOI] [PubMed] [Google Scholar]
- 26.Franklin SS, Lopez VA, Wong ND, Mitchell GF, Larson MG, Vasan RS, et al. Single versus combined blood pressure components and risk for cardiovascular disease: the framingham heart study. Circulation. (2009) 119:243–50. 10.1161/circulationaha.108.797936 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Miura K, Dyer A, Greenland P, Daviglus M, Hill M, Liu K, et al. Pulse pressure compared with other blood pressure indexes in the prediction of 25-year cardiovascular and all-cause mortality rates the Chicago heart association detection project in industry study. Hypertension. (2001) 38:232–7. 10.1161/01.HYP.38.2.232 [DOI] [PubMed] [Google Scholar]
- 28.Sedaghat S, Mattace-Raso F, Hoom E, Uitterlinden A, Hofman A, Ikram M, et al. Arterial stiffness and decline in kidney function. Clin J Am Soc Nephrol. (2015) 10:2190–7. 10.2215/CJN.03000315 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Asmar R, Vol S, Brisac AM, Tichet J, Topouchian J. Reference values for clinic pulse pressure in a nonselected population. Am J Hypertens. (2001) 14:415–8. 10.1016/s0895-7061(01)01284-5 [DOI] [PubMed] [Google Scholar]
- 30.Williams B, Mancia G, Spiering W, Rosei EA, Azizi M, Burnier M, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European society of cardiology (ESC) and the European society of hypertension (ESH). Eur Heart J. (2018) 39:3021–104. 10.1093/eurheartj/ehy339 [DOI] [PubMed] [Google Scholar]
- 31.Park J, Lee J, Kwon S, Kwon H, Lee M, Kang D. Elevated pulse pressure and recurrent hemorrhagic stroke risk in stroke with cerebral microbleeds or intracerebral hemorrhage. J Am Heart Assoc. (2021) 10:e022317. 10.1161/JAHA.121.022317 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Lønnebakken M, Eskerud I, Larsen T, Midtbø H, Kokorina M, Gerdts E. Impact of aortic stiffness on myocardial ischaemia in non-obstructive coronary artery disease. Open Heart. (2019) 6:e000981. 10.1136/openhrt-2018-000981 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Böhm M, Schumacher H, Teo KK, Lonn E, Mahfoud F, Mann JFE, et al. Achieved diastolic blood pressure and pulse pressure at target systolic blood pressure (120–140 mmHg) and cardiovascular outcomes in high-risk patients: results from ONTARGET and TRANSCEND trials. Eur Heart J. (2018) 39:3105–14. 10.1093/eurheartj/ehy287 [DOI] [PubMed] [Google Scholar]
- 34.Vidal-Petiot E, Ford I, Greenlaw N, Ferrari R, Fox K, Tardif J, et al. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study. Lancet. (2016) 388:2142–52. 10.1016/S0140-6736(16)31326-5 [DOI] [PubMed] [Google Scholar]
- 35.Hernández C, Candell-Riera J, Ciudin A, Francisco G, Aguadé-Bruix S, Simó R. Prevalence and risk factors accounting for true silent myocardial ischemia: a pilot case-control study comparing type 2 diabetic with non-diabetic control subjects. Cardiovasc Diabetol. (2011) 10:9. 10.1186/1475-2840-10-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Inoue T, Matsuoka M, Shinjo T, Tamashiro M, Oba K, Kakazu M, et al. Blood pressure, frailty status, and all-cause mortality in elderly hypertensives; the nambu cohort study. Hypertens Res. (2022) 45:146–54. 10.1038/s41440-021-00769-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.O’Donoghue P, O’Halloran A, Kenny R, Romero-Ortuno R. Do the frail experience more adverse events from intensive blood pressure control? A 2-year prospective study in the Irish longitudinal study on ageing (TILDA). EClinicalMedicine. (2022) 45:101304. 10.1016/j.eclinm.2022.101304 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Benetos A, Petrovic M, Strandberg T. Hypertension management in older and frail older patients. Circ Res. (2019) 124:1045–60. 10.1161/CIRCRESAHA.118.313236 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.