Lezione Magistrale del Prof. Cerasola al congresso di Nefrocardiologia su ipertensione e rischio cardio renale
Trani Nov 2013
Prof. Giovanni Cerasola
Professore di Medicina Interna
Head of the European Society of Hypertension Excellence Centre e Presidente della Società Italiana di NefroCardiologia
Delegato del Rettore per l'attività edilizia ed il potenziamento infrastrutturale del Policlinico Universitario.
Dipartimento di Medicina Interna e Specialistica - Università degli Studi di Palermo
2. Percentuale di eventi
cerebrovascolari fatali nel mondo
attribuibili all’ipertensione
51%
Casi di ESRD attribuibili
all’ipertensione
negli Stati Uniti
Altre cause
Diabete (45%)
Percentuale di eventi coronarici
fatali nel mondo attribuibili
all’ipertensione
Ipertensione 29%
45%
http ://www.who.int/healthinfo/global_burden_disease/
USRDS 2012 annual data report
G.Cerasola 2013
3. Fattori di rischio, danno d’organo subclinico
ed eventi cardiovascolari maggiori
Ipertensione
Dislipidemia
Diabete
Obesità
Fumo
,
FATTORI DI
RISCHIO
Ipertrofia del VS
⇑ IMT e placche
carotidee
⇑ PWV aortica
⇓ I.W.
Lieve ⇑ Creats
o ⇓ GFR o
Microalbuminuria
DANNO D’ORGANO
SUBCLINICO
IMA/Angina
Insufficienza
cardiaca
Morte
improvvisa
Ictus/TIA
Vasculopatia
periferica
Insufficienza
renale
terminale
EVENTI
G.Cerasola 2013
4. PREVALENZA PERCENTUALE DEI FATTORI DI RISCHIO
ASSOCIATI ALL’IPERTENSIONE ARTERIOSA NEI 2.258
PAZIENTI IPERTESI DELLO STUDIO REDHY
Fumo
Ipertrigliceridemia^
Basso HDLc^^
Ipercolesterolemia*
IGT**
Diabete
^ TG >150 mg/dl; ^^ HDLc < 40 mg/dl; U/< 46 D mg/dl; * Colesterol. totale > 190 mg/dl;
** Alterata glicemia a digiuno: 100-125 mg/dl
G.Cerasola et al. ;Am.J.Hypert.2013 (submitted)
5. 5-Year CVD Risk per 100 People
Multiple CV Risk Factors in Addition to Hypertension
Result in a High CVD Risk
50
45
40
35
30
25
20
15
10
5
0
BP (mm Hg)
110
44%
120
130
33%
140
150
24%
160
18%
170
12%
180
3%
Reference
6%
+ TC+
+ Male
+ HDL7 mmol/L Smoker 1 mmol/L
+
Diabetes
+ 60
years
Increasing No. of Additional Risk Factors
*Reference=nondiabetic, nonsmoker woman, aged 50 years with total cholesterol (TC)=4.0
mmol/L and HDL-C=1.6 mmol/L.
G.Cerasola 2013
Jackson R et al. Lancet. 2005;365:434-441.
6. Prevalence of patterns of l eft
ventricular hypertrophy (LVH) in
patients with essential hypertension
and normal renal function
Essential hypertensives
LVH prevalence: 32.8%
LVH
Normal LVM
Nardi E, Cerasola G, et al. J Hypertens 2009,27,663
Cerasola G, Nardi E, et al. J Nephrol 2010,121,3422
7. Adjusted hazard ratio and 95% confidence interval for the
incidence of total CV events between patients with LVH
regression/persistent normal LVM and those with LVH
persistence/LVH development.
Hazard ratio
Limits
p
Verdecchia 1998
0.180
0.049-0.664
0.010
Devereux 2004
0.580
0.386-0.873
0.009
Muiesan 2007
0.550
0.322-0.938
0.028
Pierdomenico 2008 0.360
0.190-0.681
0.002
Yasuno 2009
1.210
0.620-2.361
0.576
0.542
0.348-0.844
Hazard ratio and 95% CI
0.007
OVERALL
0.1
0.2
0.5
Favors LVH regression/
persistent normal LVM
1
2
Favors LVH
persistence/LV
H development
modificata da: Pierdomenico SD and Cuccurullo F, Am J Hypertens 2010; 23:876-81
G.Cerasola 2013
8. Analisi di Kaplan-Meier di probabilità cumulativa di un primo evento CV
in 2.232 partecipanti al Framigham Heart Study (età media 63 aa) distinti in
quartili di velocità dell’onda sfigmica (PWV) carotido-femorale (aortica)
Probabilità cumulativa
di eventi CV maggiori
PWV aortica (m/sec)
> 11.8
9.3 - 11.7
7.8 - 9.2
0.20 –
0.15 –
≤ 7.7
0.10 –
HR = 3.4**
(p = 0.008)
0.05 –
0.00 –
I
I
I
I
0
2
4
6
* Rapporto di rischio IV vs I quartile corretto
per età, sesso ed i classici fattori di rischio CV
° Follow-up mediano 7.8 anni
I
8
Anni°
Mitchell GF et al, Circulation 2010;121:505-511
G.Cerasola 2013
9. Il danno renale nell’ipertensione arteriosa
Meccanismi Funzionali
e Strutturali
• Ipertensione
glomerulare,iperfiltrazione, stretch
delle cellule endoteliali e mesangiali
• Disfunzione endoteliale ed
alterazione della permselettività della
membrana basale glomerulare
• Micro-macroalbuminuria
•Stress ossidativo e flogosi intrarenale
• Iperplasia cellulare mesangiale e
proliferazione delle cellule muscolari
lisce vascolari
Glomerulosclerosi e Fibrosi tubulointerstiziale - Riduzione del GFR
G.Cerasola 2013
Pressione Arteriosa
Rene normale
10. REDHY(REnal Dysfunction in HYpertension)
Renal parameters in the 1.856, non diabetics,
essential hypertensive patients
Microalbum
inuria
22.7%
Macroalbuminuria
0.7%
1
Overall albuminuria prevalence: 23.4%
G.Cerasola et al. J.Nephrol. 2008 and J. Human Hypert. 2009
11. REDHY(REnal Dysfunction in HYpertension)Study
Prevalenza della albuminuria ( > 20 µg/min) in 1.856 soggetti
ipertesi
Soggetti normotesi
(n = 155)
7%
20.3 %
Ipertensione grado 2
(n = 533)
21.9 %
Ipertensione grado 3
(n = 328)
p < 0.001
Ipertensione grado 1
(n = 995)
35.2 %
0%
G.Cerasola, et Al, J. Nephrol 2008;21:368
10 %
20 %
30 %
40 %
50 %
12. Left ventricular
hypertrophy (%)
LVMH
(g/m)
155 –
150 –
145 –
140 –
135 –
130 –
Hypertensive
retinopathy (%)
100
80
60
40
20
0
100
80
60
40
20
0
AER ≤ 11 µg/min
AER 11-20
µg/min
AER > 20 µg/min
137
n=217
38
62
Microalbuminuria, renal dysfunction
and cardiovascular complication in
essential hypertension
*
147
142
n=67
45
55
n=99
*
55
45
*
48
57
52
43
G. Cerasola et al,
Journal of Hypertension 1989,7,S332
Journal of Hypertension 1996,14: 915
69
31
* Group A vs Group C: p<0.001
With
LVH
Without
LVH
AER
r
24-h MBP (mmHg) 0.21
p<
0.001
LVMH* (g/m)
0.001
With
* Adjusted for 24-h MBP
retinopathy
Without
retinopathy
0.19
13. Left ventricular mass index (g/m2)
310
260
r = 0.20
p < 0.001
210
160
Relationship between
albumin excretion rate
(logarithmically
transformed for its
skewed distribution) and
LVM indexed for BSA in
455 essential
hypertensives without
diabetes enrolled in the
REDHY study.
This association
remained statistically
significant
110
60
(β = 0.13; p < 0.05), even
after adjustment for age,
sex, 24-h systolic and
10
diastolic BPs, duration of
-1.5 0.0 1.5 3.0 4.5 6.0 7.5 hypertension, BMI,
smoking habit, and GFR.
(Log) Albumin Excretion Rate
Adapted from G.Cerasola et al. Nephrology 2010
14. Velocità dell’onda sfigmica
carotido-femorale (m/sec)
Relazione univariata tra velocità dell’onda sfigmica
carotido-femorale (PWV) ed escrezione urinaria di
albumina (Log AER) in 140 pazienti ipertesi
22
Predittori indipendenti della PWV
r = 0.41
p < 0.0001
20
β
18
p
16
Età
0.55
< 0.001
14
PAM clinica
0.29
< 0.001
MAU (Log)
0.2
4
<0.001
hs-CPR
0.15
<0.03
12
10
8
6
4
0.0
0.5
1.0
1.5
2.0
2.5
3.0
(Log) Escrezione urinaria
di albumina (µg/min)
Mulè G, Cerasola G et al. Am J Hypertens. 2009
15. Meta-analisi di dati ottenuti da 45
coorti (25 di popolazione generale,
7 ad alto rischio e 13 di soggetti
con CKD) con 1.127.656
partecipanti, 364.344 dei quali con
ipertensione arteriosa.
Rischio (hazard ratio), corretto per vari
fattori confondenti, di mortalità totale
(A) e cardiovascolare (C) .in relazione
ai livelli di rapporto
albuminuria/creatininuria (ACR) in
soggetti con e senza ipertensione.
Il valore di riferimento per l’ ACR è 5
mg/g (rombo). I cerchi rossi e blu
indicano p < 0.05 vs il valore di
riferimento, in tutti i grafici.
Mahmoodi BK et al for the Chronic Kidney Disease
Prognosis Consortium, The Lancet, Available
online 23 September 2012
G.Cerasola 2013
16. Populationbased sample
of 1.968
subjects
that was
followed
for a median
of 12.8 years.
The cumulative probability (%) and hazard ratios of CV death adjusted for
(mean or ratio) age and gender (A) and SCORE (</ ≥ 5%) (B), according to
the total number of different types of subclinical organ damage. The
different types were: left ventricular hypertrophy, atherosclerotic plaques,
PWV > 12 m/s, and UACR ≥ 90th percentile.
G.Cerasola 2013
Sehestedt T et al, Eur Heart J (2010) 31 (7): 883
17. Incidenza di ESRD corretta per età
per 100.000 persone per anno
120
10/
>2
120
10/
<2
110
80/
<1
100
60/
<1
90
40/
<1
84
30/
<1
80
20/
<1
Valori di pressione arteriosa (mmHg)
Incidenza di insufficienza renale cronica terminale (ESRD), in relazione
ai valori pressori ed al sesso, in 316.675 soggetti adulti californiani, senza
patologie renali alla valutazione basale, partecipanti tra il 1964 ed il 1985,
al “Multiphasic Health Checkups” del Kaiser Permanente.
G.Cerasola 2013
Hsu CY et al. Arch Intern Med 2005;165:923-928
18. Prevalence of CKD in General Population (CARHES Study) (left side)
and in 1.856 Hypertensive Patients (REDHY Study) (right side)
CARHES Study
REDHY Study
General population (8 %)
Stage 1
Essential Hypertension (28.4%)
*
5%
Stage 2
Stage 3
9.6 %
7.5 %
**
18.4%
**
10%
2.3 %
3%
Stage 4
*
8.8 %
0.2 %
Stage 5
0
2
4
6
8
10
De Nicola et al. G. Ital. Nefrol. 2011
* Mild renal dysfunction
0
2
4
6
8
10
12 %
Cerasola G et al, J.Nephrol.2008 and
J. Hum Hypertens 2009
* * Overt renal insufficiency
19. Pooled relative risks for CV mortality and
ESRD according to eGFR and albuminuria
≥300 mg/g
30-299 mg/g
< 30 mg/g
ACR (Albumin to creatinine ratio)
Cardiovascular mortality
ESRD
1024
Hazard Ratio
16
256
8
64
4
16
2
4
1
1
0.5
0.5
15
30
45
60
75
90
105
eGFR(mL/min/1.73m )
2
G.Cerasola 2013
120
15
30
45
60
75
90
105
120
eGFR(mL/min/1.73m2)
Levey et al, Kidney Int (e-pub Dec 08 2010)
20. Richard Bright
Richard Bright
1789-1858
“La nefropatia interessa così tanto l a
circolazione minuta e capillare del
rene, da i mporre al c uore una più
intensa attività per f orzare il sangue
nelle più lontane s uddivisioni del
sistema vasale”
G.Cerasola 201
21. Prevalence of patterns of l eft ventricular
hypertrophy (LVH) in patients with
essential hypertension and normal renal
function, and in hypertensives with
chronic kidney disease (CKD) stage 2-5.
Hypertensives
with CKD;stage 2-5
Essential
hypertensives
p<0.0001
LVH prevalence: 32.8%
LVH
LVH prevalence: 47.1%
Normal LVM
Nardi E, Cerasola G, et al. J Hypertens 2009,27,6
Cerasola G, Nardi E, et al. J Nephrol 2010,15.203
22. Correlations between GFR and left ventricular mass in
455 hypertensive patients free of diabetes and of CHD
150
300
270
r = - 0.26;
p < 0.0001
LVMH2.7 (g/m2.7)
LVMI (g/m2)
240
135
210
180
150
120
r = - 0.28;
p < 0.0001
120
105
90
75
60
90
45
60
30
30
25 50 75 100 125 150 175 200
15
25 50 75 100 125 150 175 200
GFR (ml/min/1.73 m2)
GFR (ml/min/1.73 m2)
Cerasola G, et al. Nephrology 2010;15:203
23. Prevalence
of
inappropriate
left
ventricular mass (LVM) in 289 patients
with essential hypertension and normal
renal function (EH) and
in
293
hypertensives with CKD.
CKD
CKD
EH
30,5%
P < 0.0001
52,6%
Inappropriate LVM
Nardi E, Cerasola G, et al.J. Hypertens 2009,27,633
G.Cerasola et al. J.Nephrol 2010 ,15,203
24. Sopravvivenza libera
da eventi (%)
100 –
Persistenza di LVM appropriata
90 –
80 –
Regressione di
LVM inappropriata
70 –
60 –
Sviluppo di LVM inappropriata * $
Persistenza di LVM
inappropriata**$$
50 –
40 –
I
I
I
I
I
I
0
50
100
150
200
250
(Follow-up, mesi)
Sopravvivenza libera da eventi cardiovascolari (metodo di Kaplan-Meier) in
436 ipertesi in relazione alle variazioni della “appropriatezza” della massa
ventricolare sx (LVM), rispetto al carico emodinamico, nel corso del follow-up
(mediana della durata: 108 mesi)
**P<0.0001 vs regressione della LVM inappropriata; $$ <0.001 vs persistenza di LVM appropriata
•P = 0.03 vs regressione della LVM inappropriata; $ = 0.0451 vs persistenza di LVM appropriata
G.Cerasola 2013
Muiesan ML et al Hypertension 2007
25. MAIN PATTERNS OF LEFT VENTRICULAR
HYPERTROPHY
Concentric
LVH
LVM
RWT >0.45
LV-EDD<
3.1cm/m2
LVM
RWT >0.45
LV-EDD >
3.1 cm/m2
Normal LV
LVM
RWT <0.44
LV-EDD >
3.1 cm/m2
Mixed LVH
Eccentric-Dilatated
G.Cerasola
2013
26. o
Prevalenza dei diversi pattern di ipertrofia ventricolare sinistra (IVS) nei
pazienti con ipertensione essenziale e normale funzione renale (EH) e nei
pazienti con chronic kidney disease (CKD) ,stratificati secondo il grado di
disfunzione renale.
IVS concentrica
IVS eccentrica
IVS mista
Prevalenza di IVS
P = 0.0001
21.4%
P = 0.027
9.1%
35.%
12.3%
3.3%
41.3%
33.33%
36.7%
46.4%
60%
EH
10.2%
Overall
CKD
38.5%
66.67%
51.3%
52.3%
Stage 2
CKD
Stage 3
CKD
38.6%
Stage 4
CKD
42.9%
Stage 5
CKD
Nardi E, Cerasola G et al., J Hypertens 2009
27. NO LVH
LVH
Eccentric
Indeterminate
LVM
ConcenNA
centricity0.67
LVEDV/BSA NA
+
-
% Low EF
3%
NT Pro-BNP(pg/ml) 26.9
2%
30.2
Dilated
Concentric
+
-
Both Tick
and Dilated
Tick
+
+
+
38%***
119.1***
+
+
-
7%
39.0
Modified by Khouri MG et al, Circulation Cardiovasc Imaging 2010 and
Casper N.Bang et al. J.Hypertens. October 2013
+
62%***
247.3***
G.Cerasola 2013
28. LVH and LV Dysfunction in
CKD
Hypertension
CKD
Pressure overload
Increased
systolic stress
Oxidative stress
Endothelial disfunction
Inflammation and Fibrosis
Activation .
Parallel addition of
new myofibrills
and wall
thickening
Concentric
hypertrophy and
diastolic dysfunction
Anemia
Hyperparathiroidism
and CaxP
Arterial stiffness
Endocrine factors
Other factors
Heart
Failure
Volume overload
Increased
diastolic stress
Series addition of
new sarcomeres
and chamber
enlargement
Eccentric
hypertrophy and
systolic dysfunction
G.Cerasola 2013
29. Left ventricular hypertrophy vs. chronic
kidney disease
as
predictors
of
cardiovascular events in hypertension
Relative hazards for cardiovascular morbidity and mortality using
the group LVH (-) CKD (-) as a reference for each other.
Follow-up: 6 years
LVH (-)
CKD RF (-)
n = 888
LVH (+)
CKD RF (-)
n = 443
LVH (-)
CKD RF (+)
n = 97
Tsioufis C et al, J Hypertens 2009
LVH (+)
CKD RF (+)
n = 102
G.Cerasola
30. ertensione ,Insufficienza Renale Cronica
Rischio CardioRenale
Ipertensione
Arteriosa
Sovraccarico Emodinamico
Angiotensina II - Aldosterone
Iperattività Simpatica
Insufficienza
renale
cronica
Aldosterone
NAPDH Ossidasi
↑ ROS ↓NO
STRESS OSSIDATIVO
TGFβ
PIP →CT1
↑CRP ↑TNFα ↑IL6
Ipertrofia e fibrosi cardiaca
e perivascolare coronarica
Disfunzione
diastolica
Endotelina 1
ICAM 1 VCAM 1
Cellule endoteliali
↓Fetuina A
Calcificazioni valvolari
e coronariche
Ridotta performance sistolica
EVENTI CARDIACI e RENALI
G.Cerasola et al.J.Neprol 2011,mod.
Malattia micro e
macrovascolare
31. Meta-analysis: Effects of ACEI, ARB and combined therapy
with ACEI + ARBs on cardiovascular outcomes in people
with albuminuria and one or more CV risk factors.
Randomized therapy
Relative Risk (95 % CI)
Non fatal CV events
ACEI vs placebo/no therapy
(9 trials; n =8231)
0.88 (0.82–0.94)
ARBs vs placebo/no therapy
(4 trials; n =3888)
0.77 (0.61–0.98)
0
0.5
1
1.5
favors active therapy
Maione A et al., Nephrol Dial Transplant (2011)
G.Cerasola 2013
32. All cause
mortality
CV death
Composite
CV endpoint
Combined
Renal
endpoint
Decrease > 50%
vs minor change
<0.026
Increase > 100%
vs minor change
< 0.0001
Decrease > 50%
vs minor change
<0.140
Increase > 100%
vs minor change
< 0.0001
Decrease > 50%
vs minor change
<0.032
Increase > 100%
vs minor change
< 0.0001
Decrease > 50%
vs minor change
<0.019
Increase > 100%
vs minor change
< 0.005
0.0
0.2
0.4
0.6
Decrease > 50%
0.8
1.0
1.2
Hazard Ratio
1.4
1.6
1.8
2.0
Inccrease > 100%
Adjusted HR (95 CI %) of changes in UACR from baseline to 2-year visit in
the whole study group (N = 23.480). Minor change of albuminuria was taken as
reference group (HR = 1.0) and P values are given in the figure next to the circles.
Schmieder RE on behalf of the ONTARGET Investigators J Am Soc Nephrol 22: 1353–1364, 2011
33. Meta-analysis: Effect of Monotherapy
Combination Therapy with Inhibitors of the RAS
on Proteinuria in Renal Disease
Randomized therapy
Over 5-12 months
Ratio of means (95%
CI)* for change in
proteinuria
ARB+ACE-I vs ARBs
(n = 181/181)
ARB+ACE-I vs ACE-I
(n = 638/634)
0.75 (0.61–0.92)
0.82 (0.67–1.01)
ACE-I=angiotensin-converting-enzyme inhibitor
ARB=angiotensin-receptor blocker
0
0.5
1
1.5
*Ratio of means=ratio of the average treatment effect in
the intervention group relative to the control group,
with 95% Confidence Interval
Kunz R et al., Ann Intern Med 2008; 148:3048
G.Cerasola 2013
34. Meta-analysis: Effect of Monotherapy and
Combination Therapy with Inhibitors of the
RAS on Proteinuria in Renal Disease
Risk for Medication Discontinuation
Randomized therapy
Rate of discontinuation
ARBs vs placebo
0.86 (0.78–0.96)
ARBs vs ACE-I
0.78 (0.45–1.11)
ARBs vs CCBs
0.71 (0.43–1.15)
ARB+ACE-I vs ARBs
3.98 (0.47–33.85)
ARB+ACE-I vs ACE-I
5.59 (0.29–103.38)
ACE-I=angiotensin-converting-enzyme inhibitor
ARB=angiotensin-receptor blocker
CCB=calcium-channel blocker
Kunz R et al., Ann Intern Med 2008; 148:30-48.
35. Meta-analysis: Effects of ACEI, ARB and combined
therapy with ACEI + ARBs on cardiovascular
outcomes in people with albuminuria and one or
more CV risk factors.
There was no significant reduction in the risk of fatal
Cardiovascular Events
with ACEI vs ARBs
or with combined therapy based on ACEI + ARBs
when compared to each monotherapy
Maione A et al., Nephrol Dial Transplant (2011)
G.Cerasola 2013
36. Associations between systolic blood pressure reduction and risk
reduction for major vascular events according to kidney function
status.
Blood Pressure Lowering Treatment Trialists’
Collaboration BMJ 2013;347:bmj.f5680
G.Cerasola 2013
40. CONCLUSIONI
Nei pazienti ipertesi ,con danno cardio-renale , diabetici e non
diabetici, il trattamento protettivo deve mirare alla riduzione della
pressione arteriosa,dell’ipertrofia ventricolare sinistra e della
proteinuria ; una riduzione degli eventi CV ed una lenta progressione
dell’insufficienza renale caratterizza i pazienti con regressione
dell’ipertrofia ventricolare e con bassa proteinuria residua.
L’obiettivo di ridurre i valori pressori al di sotto di 130/85
mmHg e la proteinuria al di sotto di 1 g/die nei pazienti nefropatici
può essere raggiunto nella maggior parte dei casi solo aggiungendo
ad un regime terapeutico, che comprende gli ACEI o gli AT1bloccanti, uno o più farmaci antiipertensivi.
L’associazione ACEI e AT1 bloccanti ha mostrato effetti favorevoli
sulla proteinuria,specie nei pazienti diabetici e nei pazienti con
glomerulonefrite. Tuttavia, i risultati dello studio ONTARGET e delle
meta-analisi di Kunz e di Maione, le linee guida ESH 2013 fanno
ritenere che l’associazione ACEI+ARB sia da ritenere eccezionale
nella pratica clinica e da riservare soltanto a pazienti particolari.
G.Cerasola 2013
41. Grazie per l’attenzione
Un ringraziamento particolare ai miei
Allievi
Giuseppe Andronico
Santina Cottone
Giuseppe Mulè
Emilio Nardi
Luisa Arsena
Marco Guarneri
Alessandro Palermo
ed a tutti gli altri
che con capacità, entusiasmo ed affettuosa
collaborazione hanno consentito in questi
anni lo svolgimento delle ricerche di Scuola
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Editor's Notes
This slide demonstrates the effect on absolute cardiac risk of adding risk factors in patients with different SBP levels. Many factors interact to determine absolute risk, including increasing BP, lipids, smoking, male sex, and renal impairment. Single risk factors have a minor effect on a patient’s absolute risk in the absence of other risk factors; however, they can have a major effect in the presence of several risk factors, as demonstrated above.
The authors outline the rationale for targeting BP and cholesterol-lowering therapy to patients at high CV risk, irrespective of their BP or cholesterol levels. The theory behind this is that specific levels of BP and cholesterol are of little clinical relevance when considered independently of other risk factors. The authors propose that separate management guidelines for elevated BP and blood cholesterol be replaced by integrated CV risk management guidelines.
Consequences of Renal Damage in HTN
This slide graphically illustrates the deleterious consequences of glomerular hypertension and proteinuria on a single nephron. Function changes that result from hypertension include a decline in glomerular filtration rate (GFR) and abnormalities in tubular function, including new onset or worsening of proteinuria. These functional changes lead to structural changes in the glomerular basement, expansion of the mesangial and interstitial matrix, ultimately resulting in sclerosis of both glomerular and tubular elements. More detail about the mechanisms by which this process is thought to occur can be found in the description of the previous slide.
Figure 2. Relationship between albumin excretion rate (logarithmically transformed for its skewed distribution) and left ventricular mass indexed for body surface area in 455 essential hypertensive patients without diabetes enrolled in the REDHY study. This association remained statistically significant (beta = 0.13; p < 0.05), even after adjustment for age, sex, 24-h systolic and diastolic blood pressures, duration of hypertension, body mass index, smoking habit, and glomerular filtration rate.
Fig 1 Effects of angiotensin converting enzyme inhibitor or calcium antagonist based regimens v placebo for risk of major cardiovascular events according to kidney function status. P value for homogeneity indicates consistency of effect of treatment regimen among subgroup. Overall mean difference in systolic and diastolic blood pressure during follow-up in actively treated/first listed regimens v control/second listed regimens, calculated by weighting difference observed in each contributing trial by number of patients in trial. Negative values indicate lower mean systolic and diastolic blood pressure during follow-up in actively treated/first listed groups than in control/second listed groups