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Therapy of hypertensives with dyslipidaemia Unlearning towards better learning

Hypertensive Dyslipidaemics

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Page 1: Hypertensive Dyslipidaemics

Therapy of hypertensives with dyslipidaemia

Unlearning towards better learning

Page 2: Hypertensive Dyslipidaemics

The agenda for today

• Hypertension – the background

• Current status of dyslipidaemia

• The case studies

• The clinical trials & the observations

• The learnings

• The summary

Page 3: Hypertensive Dyslipidaemics

Hypertension

The background

Page 4: Hypertensive Dyslipidaemics

Hypertension

• What we record as B.P.– It is only a marker of the bigger problem

• The Truth is–Hypertension is a multi-organ systemic disease

• The Problem is–Hypertension is asymptomatic in 85% of cases

Page 5: Hypertensive Dyslipidaemics

Hypertension – Be wise

• It is wrong– To consider Hypertension as an isolated disease

• The Truth is–Hypertension, DM, Dyslipidemia, Obesity coexist–They are the 4 pallbearers to the grave of CHD/CVD

• For all of them–Primary & secondary prevention by TLC = answer–Afflicted with one, must be screened for all other thieves

Page 6: Hypertensive Dyslipidaemics

Hypertension – Therapy goal

• Goal BP– To Keep B.P. < 140/90 mm Hg in each patient– This may be revised to 120/80 may be ? 110/70 – MRFIT’s cut off values are 115/75 mm Hg

• The Truth is–It is essential to keep the B.P at or below the goal–But, It also matters how the goal B.P. is achieved !

Page 7: Hypertensive Dyslipidaemics

Current status

Hypertension and dyslipidaemia

Page 8: Hypertensive Dyslipidaemics

Rule of halves in hypertension

• What is this rule of halves in HT ?

JNC 7. May 2003; Third National Health and Nutrition Examination Survey, 1988-1994, NHANES III.

• For every 800 adults in the community–400 are HT (either ↑ SBP or ↑ DBP or both)–Of them only 200 are diagnosed HT–Of them only 100 are started on treatment–Of them only 50 are on correct drug–Of them in only 25 the goal B.P. is attained–Means 25 ÷ 400 = 6% only have goal BP–And we have yet to look at HT with other conditions

Page 9: Hypertensive Dyslipidaemics

90 million with dyslipidemia

People with concomitant hypertension & dyslipidemia

JNC 7. May 2003; Third National Health and Nutrition Examination Survey, 1988-1994, NHANES III.

27 million with concomitant hypertension, dyslipidemia

50 millionwith

hypertension

Page 10: Hypertensive Dyslipidaemics

People with concomitant hypertension & dyslipidemia

9 million diagnosed

(33%) 18 million undiagnosed

(67%)

Third National Health and Nutrition Examination Survey, 1988-1994, NHANES III.

Page 11: Hypertensive Dyslipidaemics

Source: Unpublished data from the Third National Health and Nutrition Examination Survey (NHANES-III), CDC 1994; data from 1999.

People with concomitant hypertension & dyslipidemia

Treated for neither43%

Treated for 1

47%

Treated for both10%

Treated for neither Treated for 1 Treated for both

Page 12: Hypertensive Dyslipidaemics

People with concomitant hypertension & dyslipidemia

10% Treated 10% Treated For Hypertension For Hypertension & Dyslipidemia& Dyslipidemia

3% at Goal

Source: Unpublished data from the Third National Health and Nutrition Examination Survey (NHANES-III), CDC 1994; data from 1999.

Page 13: Hypertensive Dyslipidaemics

The prevalence of coexistence of dyslipidemia

andhypertension

in patients surveyed at

Apollo Hospitals (n=501)

Indian Heart Journal 1996: 48(4): 371-374

0 10 20 30 40 50Percent

60 70 80 90 1000

TC>200 mg/dl(n=501)

LDL>130 mg/dl(n=486)

HDL<35 mg/dl(n=501)

TG>200 mg/dl(n=496)

TC/HDL ratio>4.5(n=500)

Co-prevalence of dyslipidemia & hypertension in India

Page 14: Hypertensive Dyslipidaemics

MRFIT - Hypertension and Dyslipidemia and CAD Risk

Adapted from Neaton JD, et al. Arch Intern Med. 1992;152:56-64.

Age-adjusted CAD death rates

Page 15: Hypertensive Dyslipidaemics

The approach

• Global risks assessment and reduction is the best way to reduce CV events.

• Hypertension and Hyperlipidemia are 2 most common risks found in our population.

• New antihypertensive drugs are beneficial in BP control and prevention of CV events.

• Multi-drug combinations should be used to modify risk factors and/or metabolic disturbances but is usually associated with poor compliance.

Page 16: Hypertensive Dyslipidaemics

Whom to Screen for Dyslipidemia?Influenced by cardiac risk factors:• By age alone:

–Men over age 40–Women over age 50 (or post-menopausal)

• Other risk factors (at any age):–DM, HTN, Smoking, Abdominal Obesity–Family history of early cardiovascular disease

• Physical signs of hyperlipidemia (at any age):–Xanthomata, xanthelasmas, arcus corneae, etc

• Evidence of existing atherosclerosis (any age)

Page 17: Hypertensive Dyslipidaemics

Factors Influencing Risk Assessment

• Metabolic Syndrome• Abdominal Obesity• Apolipoprotein B (apoB)• Lipoprotein(a)• Homocysteine• C-Reactive Protein (CRP)• Genetic Risk• Hormone Replacement Therapy (HRT)

Page 18: Hypertensive Dyslipidaemics

Factors Influencing Risk Assessment

• Presence of the Metabolic Syndrome–A clustering of cardiovascular risk factors,

including abdominal obesity, insulin resistance, and hypertension, as well as lipid abnormalities (↑TGs and ↓HDL)

• Presence of Abdominal Obesity– with waist circumference

as a useful estimate

Page 19: Hypertensive Dyslipidaemics

Factors Influencing Risk Assessment

• Apolipoprotein B (apoB)–There is 1 molecule of apoB in each atherogenic

lipid particle (VLDL, IDL, LDL, lp(a))’–↑apoB (for the same lipid levels) = smaller,

denser, more atherogenic LDL particles–Better estimate than LDL of cardiovascular risk–ApoB levels correlate better than LDL levels to

clinical outcomes in statin trials–For ‘high risk’ patients, target apoB <0.9g/L–Sample does not need to be fasting

Page 20: Hypertensive Dyslipidaemics

Factors Influencing Risk Assessment

• Lipoprotein(a) (lp(a))–Appears to be an independent risk factor for

premature atherosclerosis and CAD–Its atherogenicity seems to depend on the presence

of other factors, and its utility as a risk factor seems to disappear if the LDL is markedly lowered

–Monogenic and not responsive to diet–Lp(a) >30mg/dL in patients with TC/HDL ratio >5.5

or other major risk factors may indicate need for earlier and more intensive LDL-lowering therapy

Page 21: Hypertensive Dyslipidaemics

Factors Influencing Risk Assessment

• Homocysteine–↑homocysteine levels predict adverse outcomes

in patients with CAD–Fixed-dose folate & B12 trials looking at

cardiovascular endpoints are ongoing–No ‘treat-to-target’ trial (to homocysteine

<9μmol/L)–No evidence yet to screen for homocysteine

Page 22: Hypertensive Dyslipidaemics

Factors Influencing Risk Assessment

• C-Reactive Protein (CRP)–↑CRP may add prognostic information to Framingham

Study data–↑CRP associated with abdominal obesity and the

metabolic syndrome–May be clinically useful in identifying people who are at

higher risk than their Global Risk Assessment would indicate (especially for people with a calculated 10-year risk of 11-19%, so calculated to be at ‘moderate risk’)

Page 23: Hypertensive Dyslipidaemics

Factors Influencing Risk Assessment

• C-Reactive Protein (CRP)–Do not measure during an acute illness or in

patients with chronic inflammatory disease–Measure 2x, two weeks apart, and use the lower

value–Low risk <1 mg/ml & high risk 3-10mg/ml–If >10mg/ml, look for infection/inflammation

Page 24: Hypertensive Dyslipidaemics

Hypertensive patient with Dyslipidaemia

Case study

Page 25: Hypertensive Dyslipidaemics

Patient # 1• A 57-year old man, who staying in a small town,

comes to see his son in the big city and the son gets him to you for opinion. – Approximately a year back, he suffered a myocardial

infarction, but has since been asymptomatic. He does not have any other significant past medical history.

– His current medications include aspirin 81 mg daily and a beta-blocker. • His sitting blood pressure is 155/95 mmHg, heart rate 58 beats/min. • Pertinent laboratory values: glucose 86 mg/dl; total cholesterol 228

mg/dl; HDL-C 37 mg/dl; LDL-C 128 mg/dl. • An echocardiogram shows concentric LVH and preserved left

ventricular systolic function (ejection fraction 56%).

Page 26: Hypertensive Dyslipidaemics

Question # 1

1. A statin (to reduce LDL-C to ≤ 100 mg/dl), a calcium channel blocker, and a diuretic.

2. An angiotensin-receptor blocker and a statin (to reduce LDL-C to ≤ 70 mg/dl).

3. An ACE inhibitor and a statin (to reduce LDL-C to ≤ 120 mg/dl).

4. Oral nitrates, hydralazyne, and a statin (to reduce LDL-C to ≤ 70 mg/dl).

5. Niacin, a calcium channel blocker, and a diuretic.

Which of the following should be done?

• An ACE inhibitor and a statin (to reduce LDL-C to ≤ 120 mg/dl).

Page 27: Hypertensive Dyslipidaemics

*Men aged 35-57 years followed for a mean of 12 years.*Men aged 35-57 years followed for a mean of 12 years.

<120<120120-139120-139

140-159140-159160+160+

CHD Death Rate per 10,000 Person-Years

100+100+

80-8980-89

70-7470-74<70<70

75-7975-79

90-9990-99

MRFIT - Effect of Systolic & Diastolic BP on CHD Mortality

48.348.3

37.437.434.734.7 43.843.8

38.138.1

80.680.631.031.0

25.525.524.624.6

25.325.325.225.2

24.924.9

23.823.8

16.916.913.913.9

12.812.812.612.6

11.811.8

20.620.6

10.310.311.811.8

8.88.88.58.5

9.29.2

Systolic BPSystolic BP(mm Hg)(mm Hg)

Diastolic BPDiastolic BP(mm Hg)(mm Hg)

Patient in Question # 1

Neaton et al. Arch Intern Med. 1992;152:56-64. 

Page 28: Hypertensive Dyslipidaemics

Treatment of hypertensive patients with Dyslipidaemia

The learning from different studies

Page 29: Hypertensive Dyslipidaemics

Selected major trials

• PROVE IT – TIMI 22

• MRC/BHF Heart Protection Study

• ASCOT- LLA

• ALLHAT

Page 30: Hypertensive Dyslipidaemics

Lower is better• statin therapy provides benefits even with

lower LDL-C

Adapted from Kastelein JJP. Atherosclerosis. 1999;143(suppl 1):S17-S21., Sever PS, et al. Lancet. 2003;361:1149-1158., Heart Protection Study Collaborative Group. Lancet. 2003;361:2005-2016

0

210

Pat

ient

s w

ith C

HD

Eve

nt (%

)

Mean LDL-C Level at Follow-up (mg/dL)

Secondary prevention

Primary prevention

Atorvastatin

90 110 130 150 170 190

5

10

15

20

25

AFCAPS-S

WOSCOPS-S

WOSCOPS-PCARE-S

LIPID-P

4S-P

LIPID-S

CARE-P

4S-S

AFCAPS-PASCOT-SASCOT-P

Simvastatin

Pravastatin

Lovastatin

HPS-S

HPS-S

HPS-P

HPS-P

S=statin treatedP=placebo treated

Page 31: Hypertensive Dyslipidaemics

PROVE IT – TIMI 22: moderate vs intensive statin therapy in pts. with ACS

Cannon CP, et al. N Engl J Med. 2004;350:1-10.

106 10695

62

0

20

40

60

80

100

120

Pravastatin 40 mg/day(n=2063)

Atorvastatin 80 mg/day(n=2099)

Med

ian

LDL-

C (m

g/dL

)BaselineFinal (Mean, 24 mo) P <0.001

No. at Risk

PravastatinAtorvastatin

20632099

16881736

15361591

14231485

810842

138133

Page 32: Hypertensive Dyslipidaemics

PROVE IT: Intensive Statin Therapy ↓ All-Cause Mortality and Risk of MACE

No. at Risk

PravastatinAtorvastatin

20632099

16881736

15361591

14231485

810842

138133

Cannon CP, et al. N Engl J Med. 2004;350:1-10.

Months of Follow-up

Page 33: Hypertensive Dyslipidaemics

MRC/BHF Heart Protection Study

• HPS: Lancet 360(9326):7-22, 6 July 2002– 20,556 men & women aged 40-80 with TC >3.5– All at ‘high risk’ of CAD

• Known CAD/MI/PVD/CVS• DM, HTN, or both

– RCT: Simvastatin 40mg vs. placebo• Decreased death rate by 13%• Decreased combined cardiovascular end points by 24%

– Benefits in all subgroups, including baseline LDL <2.6– Very compelling, well done trial– Ultimate LDL target still unclear, other studies now

looking at LDL targets of <1.8

Page 34: Hypertensive Dyslipidaemics

ASCOT – LLA - Rationale

• Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm

• Premise– High prevalence of dyslipidemia in

hypertensive patients– Most CV disease events occur in patients with

BP and lipid concentrations deemed normal

• Hypothesis– Lipid lowering will benefit hypertensive

patients, not conventionally deemed dyslipidemic

Page 35: Hypertensive Dyslipidaemics

ASCOT – LLA - Findings

• In patients with hypertension and additional CV risk factors, addition of atorvastatin

– Had significant effects on nonfatal CVD and fatal MI– Benefits even in absence of traditional dyslipidaemia

• Identification of the at-risk patient with hypertension and other CV risk factors enables appropriate treatment for CV event prevention

• Study was stopped after 3 years because of significant benefit in the treatment group

Page 36: Hypertensive Dyslipidaemics

Diet control & dyslipidaemia reduction

Page 37: Hypertensive Dyslipidaemics

Time course of Statin effects

* Time course establishedDaysDays YearsYears

LDL-C LDL-C lowered*lowered*

InflammationInflammationreducedreduced

VulnerableplaquesVulnerableplaquesstabilizedstabilized

EndothelialEndothelialfunctionfunctionrestoredrestored

IschemicIschemicepisodesepisodesreducedreduced

Cardiac eventsCardiac eventsreduced*reduced*

Page 38: Hypertensive Dyslipidaemics

Therapy

• In ‘high risk’ patients:– Start drug treatment immediately, concurrently

with diet and lifestyle modification– Priority is to get LDL <2.5 and TC/HDL <4– Given HPS data, treat with Simvastatin 40mg

or equivalent statin for LDL target.– If can’t reach LDL target:

• Bile acid sequestrants (cholestyramine, colestipol), or

• Ezetimibe - better tolerated• Either can decrease LDL by another 10-20%

compared with statin alone

Page 39: Hypertensive Dyslipidaemics

Treatment of hypertensive patients with Dyslipidaemia

Different antihypertensive perspectives

Page 40: Hypertensive Dyslipidaemics

Stamler J et al. Diabetes Care. 1993;16:434-444.

Elevated SBP increases risk of CV death almost twofold in diabetic vs nondiabetic patients

Car

diov

ascu

lar M

orta

lity

Rat

e pe

r 10,

000

Patie

nt-Y

ears

SBP (mm Hg)

Nondiabetic patientsDiabetic patients

250

200

150

100

50

0<120 120–139 140–159 160–179 180–199 200

MRFIT20

Elevated SBP in Type 2 Diabetes Increases Cardiovascular Risk

Page 41: Hypertensive Dyslipidaemics

Hypertension Optimal Treatment (HOT) Study

Lancet 1998; 351: 1755–62

p=0.005 (DM)

0

5

10

15

20

25

Even

ts/1

000

pt-y

ears

<90 <85 <80Target diastolic BP

DMnon-DM

Reduction in CV events

Page 42: Hypertensive Dyslipidaemics

Questions on antihypertensives

• Antihypertensives are very effective in reducing clinical outcomes. But the adverse metabolic effects of these agents significantly reduce their benefit, in comorbid hypertension especially in hypertension with dyslipidaemia and in Syndrome-X cases.

• Is the “how to” of hypertension control as important as the “how well” of hypertension control in patients requiring more than one anti-hypertensive agent?

Page 43: Hypertensive Dyslipidaemics

Questions on antihypertensives

• Is there synergy between certain anti-hypertensive medication combinations that outweigh benefits of the individual medications?

• The adverse effects of thiazide-type diuretics on blood cholesterol, glucose, potassium, uric acid have been known for more than 40 years

Page 44: Hypertensive Dyslipidaemics

Approaches to hypertension therapy

Page 45: Hypertensive Dyslipidaemics

Lifestyle Modification approach in hypertension therapy

Modification Approximate BP reduction [range]

Weight reduction 5–20 mm/10 kg wt lossAdopt DASH [Dietary Approaches to Stop Hypertension] eating plan

8–14 mmHg

Dietary sodium reduction 2–8 mmHgPhysical activity 4–9 mmHgAbstinence from alcohol 2–4 mmHg

All put together reduce BP by 20 to 55 mmHg

Page 46: Hypertensive Dyslipidaemics

ALLHAT

• ALLHAT is the first study to report on the effect of antihypertensive regimens on clinical outcomes in hypertensives with the MetS.

• ALLHAT was designed to evaluate the effect of diuretics on clinical outcomes compared to agents without these adverse metabolic effects

ALLHATALLHAT

Page 47: Hypertensive Dyslipidaemics

ALLHAT - Definition of MetS (DS) participants

• Any 3 or more of the following:–Hypertension (present in all as a condition of

enrollment into ALLHAT)–Fasting glucose >100 mg/dl or 100-125 mg/dl in

non-diabetics with MetS –BMI ≥ 30 kg/m2–Fasting triglycerides ≥ 150 mg/dL–HDL cholesterol <40 mg/dl in men, <50 mg/dl in

women

ALLHATALLHAT

Page 48: Hypertensive Dyslipidaemics

ALLHAT

• How large is the difference in metabolic effects, esp the effect on glucose?

• Does the effect associate with an increase in adverse clinical outcomes compared to drugs with a more favorable metabolic profile?

• Are patients at higher risk (e.g. patients with diabetes or the metabolic syndrome) more vulnerable to the adverse effects of available antihypertensive agents?

ALLHATALLHAT

Page 49: Hypertensive Dyslipidaemics

42,418 high-riskhypertensive patients

90% previously treated, 10% untreated

STEP 1 AGENTSSTEP 1 AGENTS

Chlorthalidone12.5-25 mg

Amlodipine2.5-10 mg

Lisinopril10-40 mg

Doxazosin1-8 mg

N=15,255 N=9,048 N=9,054 N=9,061

STEP 2 AND 3 AGENTS (5 years)*STEP 2 AND 3 AGENTS (5 years)*

Atenolol28.0%

Clonidine10.6%

Reserpine4.3%

Hydralazine10.9%

* Of participants with data available for determination.

Hypertension Trial ALLHATALLHAT

Page 50: Hypertensive Dyslipidaemics

Outcomes in ALLHAT participants with the metabolic syndrome

• Patients with metabolic syndrome (MetS) are at very high risk for complications of hypertension

• Use of agents with favorable metabolic effects esp recommended in hypertensives with MetS

• Alpha-blockers and RAS inhibitors demonstrate the most favorable effect on blood glucose and lipids,

• CCBs are intermediate, followed by THZ-diuretics.

ALLHAT

Page 51: Hypertensive Dyslipidaemics

Summary & conclusions

• Despite a more favorable metabolic profile, antihypertensive therapy initiated with an - blocker, an ACEI, or a CCB was NOT superior to one initiated with a thiazide-type diuretic, including in those with MetS.

• ALLHAT fails to support an increase in CVD risk associated with diuretic-induced glucose elevation or incident diabetes in hypertensive patients.

ALLHATALLHAT

Page 52: Hypertensive Dyslipidaemics

Summary & conclusions

• ALLHAT provides further evidence against the consideration of intermediate outcomes in the selection of antihypertensive agents.

• Findings apply equally to Black and non-Black populations

ALLHATALLHAT

Page 53: Hypertensive Dyslipidaemics

Effect of various antihypertensives on coexisting disorders

Page 54: Hypertensive Dyslipidaemics

Effect of various antihypertensives on coexisting disorders

Parameter Diuretic ACEi, ARB βblocker Ca+ Blocker

Ischemia No effect Improves Improves Negative

LVH, LVF Improves Improves Improves* Negative

CV Mortality Improves Improves Improves Increases

Heart rate No effect No effect Bradycardia Tachycardia

Use in DM Negative Excellent Negative Negative

Lipid effects Negative Excellent Negative Neutral

Fluid & Na Enhances No effect Vasoconstr. Vasodilatory

K ex / bronchi Enhances No effect Bronchospa No effect

UA / Conduct. ↑ Uric acid No effect ↓conduction No effect

Page 55: Hypertensive Dyslipidaemics

Treatment of hypertensive patients with Dyslipidaemia

Learning on alpha blockade

Page 56: Hypertensive Dyslipidaemics

Effect of various drugs on CHD riskDrug Effect on CHD risk

Doxazosin 15-45%

Enalapril 18%

Captopril 19%

Atenolol 14% – 25%

Drugs 1995

Page 57: Hypertensive Dyslipidaemics

Change in Lipid Levels with Doxazosin Treatment: HALT Study

-8.3

-6.9

-8.9

0.4

-10

-8

-6

-4

-2

0

2Total-C LDL-C Triglycerides

HDL-C

Cha

nge

in L

ipid

Lev

els

(mg/

dl)

Am Heart J 1996;131: 966-973

Page 58: Hypertensive Dyslipidaemics

Changes in Lipid Parameters after 24 weeks

-25-20-15-10-505

1015202530

DoxazosinHydrochlorothiazide

Total Chol.HDL Chol.

HDLTotal Chol.

Triglyc

Am J Card 1987;59:103G

Ave

rage

(+S

.E.)

Page 59: Hypertensive Dyslipidaemics

How does doxazosin reduce lipids

• Upregulation of LDL receptors

• Decreased cholesterol synthesis

• Decreased absorption of cholesterol from GIT

• Decrease in lipoprotein lipase activity

• Inhibition of VLDL synthesis

Page 60: Hypertensive Dyslipidaemics

Doxazosin and CHD risk reduction

1. Beneficial effect on lipids

2. Beneficial effect on insulin resistance

3. Improved fibrinolytic activity

4. Reduces left ventricular hypertrophy– All these should effectively reduce the risk of CHD

Page 61: Hypertensive Dyslipidaemics

Summary for all studies

• Lower pill burden was associated with better Adherence to AHT [antihypertensive treatment] and LLT [lipid lowering treatment]–Patients who initiated AHT and LLT concurrently

were significantly more likely to be adherent to both regimens

• Single-pill regimens were associated with significantly better persistence to ACE inhibitors, diuretics, and antidiabetic agents

Page 62: Hypertensive Dyslipidaemics

Concomitant Hypertension/Dyslipidemia: Key Management Principles

• Individualize but avoid unduly prioritizing treatment of 1 condition over the other

• Educate patients about CVD risk reduction– Simultaneous blood pressure control and lipid-lowering

through TLC

• Employ treatment approaches that facilitate long-term adherence by considering real-world issues– Drug cost– Dosing schedules / Number of pills taken per day– Adverse effects

Page 63: Hypertensive Dyslipidaemics

Concomitant Hypertension/Dyslipidemia: Key Management Principles

• Regularly update patients on current numbers and goals for both blood pressure and lipids–Explain significance of numbers–Record goal in chart to prompt follow-up at each

visit

Page 64: Hypertensive Dyslipidaemics

Recording Chart

Page 65: Hypertensive Dyslipidaemics

Treatment of hypertensive patients with Syndrome X

The approach

Page 66: Hypertensive Dyslipidaemics

Remember

• The deadly trio to manage, whenever you see any one-

1. Hypertension2. Dyslipdeamia3. Insulin resistance

• Why is this so?1. FFAs

Page 67: Hypertensive Dyslipidaemics

Elevated FFAP: contribute to hypertension, dyslipidemia, and insulin resistance

Eckel RH et al. Lancet. 2005;365:1415-28.VLDL = very low density lipoproteins

Hypertension

Triglyceride (intramuscular droplet)

Sympathetic nervous system

Glycogen

Insulin

FFAFFA

GlucoseVLDL

HDL-CSmall dense LDL

FFA InsulinTriglyceride

C-IIC-IIIB-100 and

CO2

Page 68: Hypertensive Dyslipidaemics

Am. J. Med., 1998; 105(1A): 1S-3S

HypertensionObesityHyperinsulinaemiaDiabetesHypertriglyceridaemiaSmall, dense LDLLow HDLHypercoagulability

Insulinresistance

Atherosclerosis

Endothelialdysfunction

The cardiovascular dysmetabolic syndrome

Page 69: Hypertensive Dyslipidaemics

Participants with Diabetes in ANTI-HYPERTENSIVE drug trials

•ALLHAT 15,297•ASCOT 5,145•VALUE 4,891•HOPE 3,577 (43.6% hypertensive)•CONVINCE 3,266•HOT 1,501•LIFE 1,195•UKPDS 1,148•SHEP 583•Syst-Eur 492•ABCD 470•ANBP-2 426

Page 70: Hypertensive Dyslipidaemics

Treatment of hypertensive patients with Dyslipidaemia

Summary of Learning

Page 71: Hypertensive Dyslipidaemics

Key Challenges Overview: Summary

• Obesity is significant risk factor for several interrelated conditions– Hypertension– Dyslipidemia– Diabetes– Atherosclerosis

• Even relatively low levels of elevated blood pressure and lipids impart significant increased CVD risk

• Hypertension and dyslipidemia often occur concomitantly

• Concomitant hypertension and dyslipidemia increase CVD risk exponentially

Page 72: Hypertensive Dyslipidaemics

72

Paradigm shift in anti-hypertensive therapy

• It is not just ↓B.P., but today we must strive to1. Alter the modifiable risk factors

2. Keep the SBP < 140 and DBP < 90

3. Prevent or halt or reduce Target Organ Damage – • LVH, CHD, CHF, CVA, CRF, PVD & Retina.

4. Prevent or control DM (as HT + DM is hazardous)

5. Prevent or control Dyslipidemia (Endothelial Dysf.)

6. Reduce morbidity and mortality

7. Improve QUALY – Quality Adjusted Life Years

Page 73: Hypertensive Dyslipidaemics

73

What is the essential approach in hypertension treatment?

Page 74: Hypertensive Dyslipidaemics

74

What is MOST essential in hypertension treatment?

• Not that ‘my drug is superior to yours’

• Not that ‘this trial is better than that’

• Nor ‘this combination is better than that’

• But to get AS MANY PEOPLE as we can to goal SBP < 140 & DBP < 90

• And prevent or halt TOD.

• Of course, tailor the treatment as per individual patient’s co-morbidities.

Page 75: Hypertensive Dyslipidaemics

What is new in hypertension treatment?

• HT is a multi-organ disease, and so not to consider in isolation but to look for ‘Co-Thieves’

• Today’s goal BP is 140/90 – It will sure be less tomorrow

• It matters to attain goal; matters more how it is attained. Monotherapy is gone; Combined Rx replaces

• In DM, CKD, IHD the cut off values are 10 mm less

Page 76: Hypertensive Dyslipidaemics

76

What is new in hypertension treatment?

• ↑ SBP is more important than ↑ DBP; Often ignored!

• Wide pulse pressure (SBP-DBP) signifies arterial damage

• Target organ damage (TOD) must be investigated and treated.

• LVH = single imp. predictor of mortality and morbidity

• ABI, MAU, ABPM, PWV etc., identify high risk cases early