Table 1 Included papers

Eeftinck Schattenkerk et al. (2018) [19]

Prospective cohort Study

3744 Participants

Assessed prevalence of ISHY and compared differences in cSBP and arterial stiffness between ISHY and other hypertensive phenotypes.

Large multi-ethnic HELIUS study was used. The cohort age was under 40 years, with the average 29 ± 6 years. 83% were male.

The study assessed the prevalence and haemodynamic parameters (cBP and atrial stiffness) of ISH. These findings were compared with normotensive, SDH, and IDH. Those with diabetes with identified in the HELIUS study.

ISH represented 2.7% of the population (greatest prevalence in African ethnicity), ISH individuals had lower cSBP and PWV compared to IDH or SDH. ISH individuals were taller had lower AIx and larger SV in comparison to other subgroups. Having increased SBP amplitude was associated with being male, Dutch, younger, taller, a lower AIx and an increased SV. Overall, the study indicated that the haemodynamic profile of ISH was similar to that of ‘high-normal’ BP.

Palatini et al. (2018) [20]

Long-term prospective cohort study

1206 Participants

Investigate the risk of hypertension requiring pharmacological treatment in ISH.

209 Individuals between 18 and 45 years. 89.9% were male.

Data was collected from the Hypertension and Ambulatory Recording Ventia Study. Using a 24 h BP monitor, 209 individuals were found to have ISH. Cox survival analyses were used to evaluate the role of ISH in predicting hypertension development.

ISH individuals were more frequently young males active in sport, had a low heart rate and low cholesterol. In a 6.9-year follow-up, 61.1% had developed SDH. ISH had non-significant increase in hypertension compared to the normotensive group; SDH and IDH groups had a significant increase. The study suggested mean BP identified with 24-h ABPM, is required for identification and predictive risk. ISHY identified with 24 ABPM does not imply an increased CVD risk.

Gaddum et al. (2017) [21]

Experimental study

Bovine and silicon models

Characterize individual parameters contributing to arterial pressure and its amplification.

Bovine V silicon model.

Silicon arterial tree was compared to a bovine aorta to study variable SV profiles. Inotropy was altered in the ventricles and arterial parameters were altered to replicate wall thickness, taper, diameter and bifurcation to compare bovine to silicone.

Amplification increased with bifurcation, and CO, decreased with wall thickness and vessel taper. PP increased with wall thickness (stiffness) and taper angle and decreasing diameter. According to the study conclusions, PP amplification is primarily due to ventricles and not arterial stiffness.

Radchenko et al. (2016) [13]

Cohort study

44 Participants

To identify simple clinical predictors for increased cBP in ISHY.

All participants were males, average age of 32.2 ± 1.3 years. Individuals significant comorbidities were excluded.

Measurements including weight, height, office BP, HR, ambulatory BP, PWV, cBP, biochemical blood test, ECG, echo, carotid u/s were included. These measurements were used to identify links to cBP. Organ damage and pathology were also assessed.

Independent predictors of increased cBP included height < 178 cm, weight > 91 kg, DBP > 80 mmHg. The presence of two or more increased the risk of elevated cBP more than ×10. PWV and SVR were significantly higher in ISH individuals with elevated cBP, were as CO and SV were higher with normal cBP. Increased cBP occurred most frequently in those who were older, shorter and had a higher BMI. The study recommended lifestyle modification for ISHY, and not BP medication.

Johnson et al. (2015) [22]

Multi-disciplinary observational study

3003 Participants

Compare the rates of receiving a hypertension diagnosis and antihypertensives among young adults with ISH, IDH, and SDH.

The included participants (61% males) ranged from 18 to 39, each with hypertension. 45% were identified to have ISH.

Participants with a pre-existing diagnosis of hypertension were excluded. Participants were all require to be currently being managed: receiving regular primary care contact (2 office encounters in 3 years, 1 being in the last 2 years).

The study found that 56% with ISH received a diagnosis compared to 63% with SDH. 32% with ISH were given antihypertensives compared with 52% in the SDH cohort. ISH was found to have a 50% poorer diagnosis and 31% treatment rates.

Musinguzi, Van Geertruyden, & Bastianens (2015) [23]

Comparative cross-sectional study

4432 Participants

Identify the prevalence of uncontrolled hypertension.

Participants in two Ugandan districts. Cohorts were divided on age groupings: 15–34, 35–49, 50+. 36.3% were male.

BP measurements were taken three times, at 1 min apart, after the participant had been seated for 5 min. The assessment was conducted in one visit only. All participants that had already achieved hypertension control were excluded.

The study identified the prevalence of uncontrolled hypertension to be a total of 20.2%. ISH represented 7.2% of those who had uncontrolled hypertension. The results were not found to differ between the genders.

Yano et al. (2015) [24]

Retrospective study

39,441 Participants

Assess CVD risk of ISH in young and middle-aged adults.

The study included 15, 868 males and 11,213 females (58.5% male) between the ages of 18–49 from Chicago, USA between 1967 and 1973

Chicago Heart Association Detection Project in Industry study. Participants were classified into the following: (1) SBP < 130 mmHg & DBP < 85 mmHg; (2) SBP 130–139 mmHg and DBP 85–89 mmHg; (3) ISH; (4) IDH; (5) SDH.

Over long-term follow-up, younger and middle-aged adults with ISH had higher relative risk for CVD mortality than those with optimal-normal BP. The study did not recommend antihypertensive medication to reduce risk.

Saladini et al. (2011) [14]

Long-term prospective cohort study

388 Participants

Investigated prognosis of ISH in young-to-middle-aged individuals differs according to cBP.

Participants included 18–45 years from the Hypertension and Ambulatory Recording Ventia Study.

354 Participants with stage 1 hypertension and 34 with normotension to identify which individuals would progress to require antihypertensives. Baseline BP was the mean of six, over two visits that were two weeks apart. ISH-high (high cSBP) and ISH-low (low cSBP) were separated and assessed.

ISH predominately affected younger males. ISH-low was represented by 93.9% males, and ISH-high was composed of 88.2% males. ISH-high was identified to have decreased larger arteries and higher peripheral resistance. ISH-low had similar variables to normotensive. They were identified to have a low-risk of HTN requiring treatment. ISH-low were younger, had a lower BMI, smoked less, had a lower total cholesterol and lower triglycerides than all other groups including normotensive individuals.

Sundstrom et al. (2011) [25]

Nationwide cohort study

1,207,141 Participants

Investigate the nature and magnitude of relations of systolic and diastolic blood pressures in late adolescence to mortality.

All participants were males, Swedish males conscripted to military. The average age was 18.4, with a follow-up age of 24.

Data from Swedish Military Conscription Registry. Individuals were born between 1949 and 1979. 2–3% were exempt due to disability or chronic disease, 17% lost data. The remaining 1,207,141 males had SBP 80–184 and DBP 30–120. The Cox proportional hazards models were used to investigate relations of BP to risk of death.

The study identified 28, 934 males (2.4%) had died. DBP below 90 mmHg was unrelated to mortality, and above which significantly increased risk. The lowest risk identified was found to be associated with a SBP around 130 mmHg. The optimal SBP is unclear however, may correlate with age. The association between SBP and mortality was unclear.

Grebla et al. (2010) [11]

Prospective cohort study

5685 Participants

The study examined the prevalence and determinants of ISH in 18 to 39-year-olds.

Data was collected from three consecutive NHANES reports from 1999 to 2004 (49.6% male).

Participants had prevalence and risk estimated by age and gender, those who were already prescribed antihypertensive medications were removed.

The total prevalence of ISH was 1.57% ± 0.23%, with the greatest prevalence in 18–29 years. ISH was associated with being male, smoker, obese and of a low socioeconomic status. ISH individuals were younger, have a higher PP than all groups and taller than the normotensive group. The study also identified that the prevalence of IDH and SDH increased with age where as ISH decreased.

Hulsen et al. (2006) [26]

Prospective cohort study

750 Participants

Investigated prevalence and determinants of SSH in young adults and their 20-year risk of CHD.

352 Males and 398 Females (46.9% male) aged 26–31. 57 Males has ISH.

Data from the Atherosclerosis Risk in Young Adults study. Measurements included brachial BP and aortic pressures. Central haemodynamic measured with SphygmoCor.

SSH males had a higher BMI, had a significantly higher brachial and cBP, PP and MAP. AIx was significantly lower compared to normotensive individuals. SSH males smoked less, and were taller than all other groups, other characteristics were not significantly different. In conclusion, SSH individuals did not have a statistically significant increased risk of CVD.

McEniery et al. (2005) [27]

Long-term prospective cohort study

1008 Participants

Test the hypothesis that ISHY and essential hypertension (SDH) have different haemodynamic mechanisms.

Participants from the ENIGMA study (49.2% male) who were aged 17–27 (91.4% male).

Participants were randomly selected from 2 UK universities. They had their haemodynamic measurements recorded, those with pre-existing conditions were excluded. Brachial BP was taken 5 min after rest. The SphygomoCor was used to obtain central haemodynamic readings. Subjects were required to complete a lifestyle and medical history questionnaire. The study examined peripheral and cBP, aortic PWV, CO, SV, PVR. Comparisons were then made between the hypertensive subtypes and normotensive group.

The study identified individuals with ISHY to have significantly higher brachial BP, cBP, MAP, aortic PWV, CO, and SV compared to other hypertensive subtype groups. ISH were taller, weighed more, smoked significantly less, exercised more than all groups. There was no difference in PVR, HR, or PP amplification in comparison to normotensive individuals. Compared to SDH, MAP, HR, and PVR were all significantly lower; whereas PP amp, aortic PWV, CO, SV were significantly higher. The study concluded that ISH and SDH have different haemodynamic mechanisms. ISH appears to come from increased SV and/or aortic stiffness where as SDH appears to result from increased PVR.

Mahmud and Feely (2003) [12]

Cohort study

174 Participants

Examine the role of high PP in SSH.

174 Healthy medical students (50% male); average age was 23 ± 0.5 years.

Measurements including brachial BP, aortic BP, arterial wave reflection, PP amplification, height and weight were recorded. BP was assessed after 15 min in supine position. Participants completed questionnaire about smoking, physical activity, alcohol.

ISHY with normal cBP were commonly associated with being tall, active, non-smoking males. These individuals also had normal aortic pressure waveform, slower HR, reduced arterial wave reflection and increased PP amplification. Whereas SDH had reduced amplification and enhanced arterial wave reflection. Findings are thought to be the result of exaggerated first systolic peak in brachial artery waveform. PP amplification is an indication of elasticity and reduces with age. AIx is an indication of atrial stiffness. All ISH participants were physically active and regularly participated in sport.