Joint Modeling of Blood Pressure Measurements and Survival Time to Cardiovascular Disease Complication among Hypertension Patients Follow-up at DebreTabor Hospital, Ethiopia

Figures & data

Table 1 Distribution of Important Socio-Demographic and Clinical Characteristics of Hypertensive Patients Follow-up at DebreTabor Hospital

Variables	Categories	Status (n=178)
		Censored: n (%)	Event: n (%)
Sex	Female	72 (69.2)	32 (30.8)
	Male	54 (73)	20 (27)
Residence	Rural	63 (75)	21 (25)
	Urban	31 (51.7)	29 (48.3)
FHHTN	No	105 (82)	23 (18)
	Yes	31 (51.7)	29 (48.3)
Diabetic disease	No	82 (79.6)	21 (20.4)
	Yes	44 (85.7)	31 (41.3)
SHTN	Pre stage	53 (84.1)	10 (15.9)
	Stage I	49 (72.1)	19 (27.9)
	Stage II	34 (59.6)	23 (40.4)
FHCVD	No	116 (82.9)	24 (17.1)
	Yes	10 (26.3)	28 (73.7)
Adherence status	Poor	32 (57.1)	24 (42.9)
	Fair	35 (63.6)	20 (36.4)
	Good	59 (88.1)	8 (11.9)

Note: n, sample outpatients.

Abbreviations: FHHTN, family history of hypertension; FHCVD, family history of cardiovascular disease; SHTN, WHO clinical stage of hypertension.

Figure 1 Kaplan–Meier survival estimates of different groups of hypertensive patients at DebreTabor Hospital, Ethiopia.

Table 2 Results of the Log Rank Test for the Significant Categorical Variables of HTN Patients Follow-up at DebreTabor Hospital

Predictors	Categories	DF	Chi-square Statistic	P-value
Sex	Female	1	26.37	0.0001
	Male
Residence	Rural	1	13.27	0.0003
	Urban
FHHTN	No	1	36.64	0.0001
	Yes
Diabetic disease	No	1	76.74	0.0001
	Yes
SHTN	Pre stage	2	102.74	0.0001
	Stage I
	Stage II
FHCVD	No	1	34.42	0.0001
	Yes
Adherence status	Poor	2	56.86	0.084
	Fair
	Good

Abbreviations: FHHTN, family history of hypertension; FHCVD, family history of cardiovascular disease; SHTN, WHO clinical stage of hypertension.

Table 3 Results of Proportionality Assumption for the Significant Categorical Variables of HTN Patients Follow-up at DebreTabor Hospital

Variables	Categories	rho	Chi-Square Statistic	p-value
Age		−0.17029	2.06291	0.151
Sex (ref= Female)	Male	−0.03453	0.06737	0.795
FHHTN (ref=No)	Yes	−0.06311	0.16370	0.686
Diabetic disease (ref=No)	Yes	−0.09774	0.58520	0.444
SHTN (ref= Pre stage)	Stage I	−0.11181	0.60931	0.435
	Stage II	−0.1548	1.16853	0.280
FHCVD (ref=No)	Yes	−0.00465	0.00143	0.907
Adherence status (ref= Poor)	Fair	−0.0216	0.03082	0.861
	Good	−0.11851	1.04430	0.307
Global			5.01631	0.890

Figure 2 Schonfildes residual plot for significant categorical variables of HTN patients follow-up at DebreTabor Hospital.

Table 4 Cox Proportional Hazards Regression Analysis of Time to CVDC of Hypertensive Patients Follow-up at DebreTabor Hospital

Predictors	Categories	Estimates	Std error	HR	95% CI (L-U)	P-value
Age		0.00465	0.3200	1.0046	0.985–1.024	0.03711
Sex (ref=female)	Male	0.1665	0.3404	1.1812	0.606–2.302	0.62463
Residence (ref=Urban)	Rural	−0.7718	0.3200	0.4621	0.246–0.865	0.0158
Diabetes (ref=No)	Yes	1.394	0.1419	4.033	2.212–9.466	0.0002
FHTN (ref=No)	Yes	1.2932	0.4641	3.644	1.467–9.0521	0.00534
SHTN (ref=pre-stage)	Stage I	1.5449	0.1425	0.6659	1.286–2.242	0.01734
	Stage II	−0.4064	0.1708	1.2089	0.5049–1.573	0.1831
FHCVD (ref=No)	Yes	1.8791	0.1443	6.5480	2.823–10.602	0.0001
Adherence (ref=Good)	Fair	0.2723	0.3779	1.3129	0.626–2.754	0.4712
	Poor	−0.5305	0.4156	0.5882	0.260–1.328	0.20185

Note: ref, reference category of the categorical variable.

Abbreviations: HR, hazard ratio; CI, confidence interval.

Figure 3 Individual and mean profile plots of the SBP and DBP of HTN patients.

Figure 4 Average trend line of SBP, and DBP over time with cardiovascular disease complication status at DebreTabor Hospital, Ethiopia.

Table 5 Bivariate Random Mixed-Effects Model for SBP and DBP of HTN Outpatients Follow-up at Debre Tabor Hospital, Ethiopia

Predictors	Categories	SBP		DBP
		Estimates (se)	p-value	Estimates (se)	p-value
Intercept		120.83(9.98)	0.0001	80.17(6.70)	0.0001
Age		0.129(0.073)	0.0388	0.022(0.039)	0.544
BSBP		0.194(0.072)	0.0007	0.017(0.039)	0.116
BDBP		−0.109(0.089)	0.2202	0.181(0.049)	0.0002
Sex (ref=Female)	Male	−2.966(2.483)	0.2324	−0.844(1.977)	0.67
Diabetes (ref=No)	Yes	8.085(2.661)	0.0001	4.356(1.842)	0.0004
Residence (ref=Urban)	Rural	4.478(2.118)	0.0345	1.059(1.234)	0.391
FHHTN (ref=No)	Yes	7.625(2.837)	0.0072	2.39(1.648)	0.147
SHTN (ref=pre-stage)	Stage I	27.03(14.22)	0.1054	1.361(1.861)	0.464
	Stage II	41.39(12.81)	0.0021	5.843(1.88)	0.002
Adherence (ref=good)	Fair	0.409(1.963)	0.8348	−5.249(1.505)	0.001
	Poor	0.813(1.984)	0.6819	−6.24 (1.441)	0.0001
Time		−0.581(0.131)	0.0001	−0.187(0.066)	0.001
Variance covariance estimates		Intercept for SBP	Time for SBP	Intercept for DBP	Time for DBP
SBP	Intercept for SBP	178.46	−6.618	41.929	−1.962
	Time for SBP		0.868	0.298	0.453
DBP	Intercept for DBP			86.45	−3.797
	Time for DBP				0.524
Standard deviation		13.88	0.8683	9.29	0.524
Residual standard error
Sigma2 for SBP	15.30
Sigma2 for DBP	10.32

Abbreviations: BSBP, baseline systolic blood pressure; BDBP, baseline diastolic blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; FHHTN, family history of hypertension; FHCVD, family history of cardiovascular disease; SHTN, clinical stage of hypertension.

Table 6 Joint Model of Longitudinal SBP & DBP with Survival Time to Cardiovascular Disease Complication

Predictors	Categories	Longitudinal Sub Model					Survival Sub Model
		SBP			DBP		Estimate (se)	HR	P-value
		Estimate (se)		P-value	Estimate (se)	P-value
Intercept		120.123(11.849)		0.0001	78.37(5.311)	0.0001
Age		0.143(0.068)		0.035			0.003 (0.018)	1.39	0.022
BDBP		0.129(0.083)		0.123	0.189(0.045)	0.0001
BSBP		0.359(0.13)		0.006	0.048(0.033)	0.143
Sex (ref=Female)	Male	−2.243(2.286)		0.327			0.086 (0.607)	1.090	0.887
Residence (ref=Urban)	Rural	3.747(2.275)		0.0996			−1.207 (0.606)	0.299	0.046
Diabetes (ref=No)	Yes	7.037(2.314)		0.002			1.686 (0.716)	5.400	0.0002
FHHTN (ref=No)	Yes	7.929(2.488)		0.001	2.863(1.358)	0.035	1.252 (0.732)	3.496	0.017
SHTN (ref=pre-stage)	Stage I	27.95(14.487)		0.054	1.71(1.862)	0.359	−0.901(1.038)	0.403	0.185
	Stage II	41.03(14.083)		0.004	5.134(1.883)	0.014	0.657 (0.884)	1.93	0.037
FHCVD (ref=No)	Yes						2.253 (0.617)	9.511	0.0003
Adherence (ref=good)	Fair				−5.877(1.307)	0.0001	−1.066(0.778)	0.344	0.642
	Poor				−6.346(1.408)	0.0001	0.286 (0.615)	1.33	0.17
Time		−0.601(0.114)		0.0001	−0.154(0.078)	0.04
Random effects variance covariance matrix
	Intercept (SBP)		Time (SBP)	Intercept (DBP)	Time (DBP)
Intercept (SBP)	180.64		−6.025	46.226	−2.66
Time (SBP)			0.431	0.298	0.006
Intercept (DBP)				92.213	−3.647
Time (DBP)					0.274
Standard deviation	13.44		0.656	9.603	0.523
Residuals standard errors
SBP –σ1	15.25
DBP –σ2	10.33
Association
SBP –γ1							0.65 (0.028)		0.027
DBP –γ2							0.963 (0.044)		0.039

Abbreviations: BSBP, baseline systolic blood pressure; BDBP, baseline diastolic blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; FHHTN, family history of hypertension; FHCVD, family history of cardiovascular disease; SHTN, clinical stage of hypertension.