Systemic hemodynamic atherothrombotic syndrome (SHATS): Diagnosis and severity assessment score

1. INTRODUCTION

A novel disease entity, call the systemic hemodynamic atherothrombotic syndrome (SHATS), has been proposed.1, 2, 3 It is considered imperative that clinicians recognize the synergistic relationship between exaggerated blood pressure (BP) variability (BPV) and vascular damage, ultimately triggering cardiovascular disease (CVD) events (Figure 1).2 Even when average BP values are controlled, underlying BPV may mean that some patients with hypertension are at risk for target organ damage and cardiovascular events. This is particularly relevant in high‐risk patients with advanced vascular disease. We have recently also focused on the pathogenic mechanism of arterial stiffness as HATS (hemodynamic arteriosclerotic syndrome), separately from atherosclerosis.4 Aging, sympathetic activation, and cardiovascular risk factors accelerate HATS.

Figure 1.

Systemic hemodynamic atherothrombotic syndrome (SHATS). AI, augmentation index; BP, blood pressure; CAVI, cardio‐ankle vascular index; ECG, electrocardiography; Echo, echocardiography; FMD, flow‐medicated dilatation; MRI, magnetic resonance imaging; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide; PWV, pulse wave velocity; UACR, urinary albumin/creatinine ratio

Until now, there has not been any consensus on how to diagnose SHATS or define its severity. This is important in the assessment of SHATS and development of an individualized, integrated strategy for CVD protection that targets BPV and vascular damage. Therefore, we have developed a SHATS score, based on the concept that both BP and vascular disease form part of a vicious cycle to accelerate organ damage and trigger CVD events in SHATS (Table 1).

Table 1.

Systemic hemodynamic atherothrombotic syndrome (SHATS) score

Component	Score
A. BP score	Total 10 points
1. Office BP	Maximum 2 points
Office SBP ≥ 140 mm Hg	1 point
Office SBPV↑a	1 point
2. Home BP	Maximum 3 points
Home SBP↑(morning or evening ≥ 135 mm Hg, or nighttime* ≥120 mmHg	2 points
Home SBPV↑b	1 point
3. ABPM**	Maximum 3 point
Ambulatory SBP↑ (daytime/morning ≥ 135 mm Hg, nighttime* ≥120 mm Hg, or 24‐h ≥ 130 mm Hg)	2 points
Ambulatory SBPV↑c	1 point
4. Diurnal variation***	Maximum 2 points
Riser pattern	2 points
Extreme‐dipper pattern, or morning surge↑	1 point
5. Atrial fibrillation	5 points #
B. Vascular score	Total 10 points
1. CVDd	Maximum 5 points
One CVD	2 points
Two CVD	4 points
Three or more CVD	5 points
2. Asymptomatic CVDe	Maximum 3 points
One abnormal finding	1 point
Two abnormal findings	2 points
Three or more abnormal findings	3 points
3. Microvascular disease	Maximum 2 points
Diabetes‐related CKD (albuminuria, eGFR < 60 mL/min/1.73 m2)	1 point
Small artery retinopathy	1 point

Abbreviations: ABPM, ambulatory blood pressure monitoring; BP, blood pressure; CKD, chronic kidney disease; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure; SBPV, systolic blood pressure variability.

^aDefined as maximum SBP ≥ 180 mm Hg, visit‐to‐visit standard deviation [SD] ≥ 20 mm Hg, orthostatic change (increase or decrease) of ≥20 mm Hg (calculated as the change in BP from the resting sitting position [baseline] to the active standing position], or seasonal variation (SBP in winter minus SBP in summer) <0 mm Hg or ≥ 20 mm Hg.

^bDefined as maximum morning/evening SBP ≥ 180 mm Hg, maximum nighttime SBP ≥ 160 mm Hg, morning‐evening difference ≥ 20 mm Hg, or day‐by‐day coefficient of variation ≥ 6.1%, or seasonal variation (SBP in winter minus SBP in summer) <0 mm Hg or ≥9.1 mm Hg.

^cDefined as maximum daytime SBP ≥ 180 mm Hg, maximum nighttime SBP ≥ 160 mm Hg, or weighted SD ≥ 20 mm Hg.

^dCVD = stroke, coronary artery disease, heart failure, aortic stenosis, cognitive dysfunction, or peripheral arterial disease/aortic dissection.

^eDefined as: 1) pulse pressure ≥ 70 mmHg; 2) ankle‐brachial index ≤ 0.9 or ≥1.3 (or inter‐arm difference in SBP of ≥15 mm Hg); 3) cardio‐ankle vascular index (CAVI) ≥ 9 [or brachial‐ankle pulse wave velocity ≥ 18 m/s, or carotid‐femoral pulse wave velocity ≥ 10 m/s; 4) abnormal cardiac findings (left ventricular hypertrophy defined by ECG or echocardiography; or N‐terminal pro‐brain natriuretic peptide [NT‐proBNP] level ≥ 125 pg/mL); 5) other specific abnormalities, such as flow‐mediated dilatation (FMD) of the brachial artery < 4%; maximum intima‐media thickness of the carotid artery ≥  1.1 mm; peak systolic velocity of the renal artery ≥ 220 cm/s; white matter lesion, silent cerebral infarct, or microbleeds assessed by brain magnetic resonance imaging.

^*Nighttime SBP can be measured using ABPM or home BP monitoring.

^**When ABPM is not performed, the total score for ABPM and diurnal variation is 1.

^***Diurnal variation is assessed by ABPM.

^#When atrial fibrillation is present (score = 5), then SBPV scores and the diurnal variation score are 0.

The two components of the SHATS score are the BP score and the vascular score. The novelty of this concept is the synergistic, rather than additive, effects of BP and vascular disease in contributing to organ damage and CVD events. To reflect this, the BP and vascular scores are multiplied (rather than added) to calculate the SHATS score (an indication of SHATS severity). Another new feature is the inclusion of BPV measures in the BP score. The weight assigned to each component of the two scores is based on relative risks defined using existing literature as a reference. A Core Score is used to facilitate the diagnosis of SHATS.

2. BP SCORE

This includes systolic BP (SBP), systolic BPV and/or the presence of atrial fibrillation (AF) (Table 1). Both BP and BPV can be determined using office BP measurement or out‐of‐office measurement techniques (home BP monitoring [HBPM] and/or ambulatory blood pressure monitoring [ABPM]). The presence of AF is considered an extreme pattern of BPV; therefore, when AF is detected, all other BPV measures are assigned a score of 0.

2.1. Office BP

The pathological threshold of average office SBP is ≥140 mm Hg. We used maximum SBP, standard deviation (SD) of visit‐to‐visit systolic BPV across ≥5 readings, and orthostatic SBP change as measures of office BPV, all of which have been associated with cardiovascular risk independent of average office BP.1, 5, 6, 7 There is also significant seasonal variation in BP. Both BP and BPV are increased in the winter,8, 9, 10 and inverse and exaggerated seasonal BP variation increased the risk of CVD.11 Pathological thresholds are ≥180 mm Hg for maximum SBP, ≥20 mm Hg for SD of visit‐to‐visit systolic BPV, ≥20 mm Hg for orthostatic SBP change (increase or decrease by ≥20 mm Hg), and <0 mm Hg or ≥20 mm Hg for winter increase in SBP (SBP in winter minus SBP in summer; seasonal variation). Orthostatic BP change is calculated as the BP change when the patient moves from the resting sitting position (baseline) to the active standing position.

2.2. Home BP

The averaged home SBP level pathological threshold is ≥135 mm Hg. We used maximum SBP, morning‐evening (ME) difference, and coefficient of variation (CV) of day‐by‐day systolic BPV based on ≥5 readings as measures of home BPV. These have all been associated with organ damage and CVD event risk, independent of average home BP.12, 13, 14, 15, 16 Pathological thresholds are ≥180 mm Hg for maximum morning home SBP and maximum evening home SBP, ≥160 mm Hg for maximum nighttime home SBP, ≥20 mm Hg for ME difference, and 6.1% for CV of day‐by‐day home systolic BP,12 and <0 mm Hg or ≥9.1 mm Hg for winter increase in home SBP (SBP in winter minus SBP in summer; seasonal variation).11

2.3. ABPM

The pathological threshold of averaged ambulatory BP is ≥135 mm Hg for 24‐hour SBP. Ambulatory BPV measures used are maximum SBP and weighted SD of 24‐hour SBP readings. Short‐term ambulatory BPV has been associated with organ damage and CVD event risk independent of average ambulatory BP.17, 18, 19, 20 Pathological thresholds are ≥180 mm Hg for maximum daytime/morning ambulatory SBP, ≥160 mm Hg for maximum nighttime ambulatory SBP, and ≥20 mm Hg for the weighted SD of 24‐hour SBP.

Blood pressure parameters used to diagnose morning, daytime, and nocturnal hypertension are average morning, daytime, nighttime BP, respectively, regardless of office BP. Average home BP could be used instead of average daytime ambulatory BP, while nocturnal home BP could be used as alternative to nighttime BP evaluated by ABPM.21, 22 The patient is classified as having masked (uncontrolled) hypertension when office BP is <140/90 mm Hg.

2.4. Diurnal variation

The riser pattern (higher nighttime versus daytime SBP) is reported to be associated with the highest risk of CVD, independent of 24‐hour BP.23, 24, 25, 26 Other patterns that have been shown to increase cardiovascular risk include extreme‐dipper (excessive [≥20%] dipping of nocturnal BP) and exaggerated morning BP surge (morning SBP minus the lowest three SBP readings) of ≥35 mm Hg.26, 27, 28 Disrupted diurnal BP variation patterns, including those mentioned above, can be assessed using ABPM.

3. VASCULAR SCORE

The vascular score is based on the presence of clinically overt CVD, asymptomatic CVD, and/or microvessel disease. The number of overt CVD conditions (listed in the Table 1 footnote) is used to determine the CVD score, and the number of abnormal vascular test findings (listed in the Table 1 footnote) is used to calculate the asymptomatic CVD score. These abnormal findings have been associated with organ damage, future development of hypertension and CVD event risk.29, 30, 31, 32, 33, 34, 35 The microvessel disease score includes the presence of diabetes‐related chronic kidney disease and/or small artery retinopathy.

4. SCORE CALCULATION

Blood pressure and vascular scores each have a possible score of 0‐10 points and are calculated separately. Total BP score and total vascular score are then multiplied the calculate the overall SHATS score (with possible scores of 0‐100, and higher scores indicating greater SHATS severity).

5. SHATS DIAGNOSIS

A wide range of BP and vascular measures are included to define SHATS severity. For diagnosis, the approach is simplified. This is based on the Core Score, which is calculated by multiplying scores for office BP and one of the 2 out‐of‐office BP measurements (HBPM and ABPM) with the score for either clinical CVD or asymptomatic (subclinical) vascular disease. SHATS is diagnosed when the SHATS Core Score is ≥5 points.

6. IN PRACTICE

As an example, when a patient has hypertension based on office BP (BP Score = 1) and morning home BP (BP Score = 2), with increased office and home BPV (BP Score = 2) plus a cardio‐ankle vascular index (CAVI) of ≥9.0 (vascular Score = 1), the SHATS Core Score would be 5 (2 + 2 + 1 [BP score] × 1 [vascular score]) and SHATS is diagnosed. If the patient had a vascular score of 0, then the SHATS Core Score would be 0 (2 + 2 + 1 [BP Score] × 0 [vascular score]) and the patient would not have SHATS. The severity of SHATS in this patient would be relatively low (total SHATS score 5 on a scale from 5 to 100).

7. CONCLUSIONS

This newly proposed SHATS score required validation in future studies. It is hoped that it will facilitate the diagnosis, risk stratification, and management of this important entity, with the goal of improving BP control and outcomes, achieving precision medicine and personalized prevention of CVD, and, ultimately, contributing to the goal of zero cardiovascular events in patients with hypertension.

DISCLOSURES

None

AUTHOR CONTRIBUTIONS

K.Kario drafted the manuscript and approved the final submitted manuscript.

Kario K. Systemic hemodynamic atherothrombotic syndrome (SHATS): Diagnosis and severity assessment score. J Clin Hypertens. 2019;21:1011–1015. 10.1111/jch.13542