Place · Level 3 · Condition
Hypertension
RAAS + 内皮 + 钠钾平衡 · 中国 2.5 亿患者 · DASH RCT · SPRINT 130/80 标准 · ACEi/ARB 一线
Story path
Chapter 1
HTN · what + China
HTN · what + China
The plain version first: the scary thing about high blood pressure isn't any single number — it's that over decades it silently wears down your vessels, heart, kidneys, and eyes, and most people feel nothing the whole time, which is why it's called "the silent killer". Below: the definition, the real numbers in China, and how blood pressure actually climbs.
Hypertension = sustained elevation of blood pressure that, over time → damage to cardiac, cerebral, and renal vasculature → MI / stroke / heart failure / kidney failure.
Diagnostic thresholds (2017 ACC/AHA update):
Normal: < 120 / 80 mmHgElevated: 120-129 / < 80Stage 1 hypertension: 130-139 / 80-89Stage 2 hypertension: ≥ 140 / 90Hypertensive emergency: ≥ 180 / 120 + organ damage
The SPRINT trial (2015 NEJM) moved the target from < 140/90 to < 130/80 (and < 120/80 in high-risk patients) — a clinical-guideline paradigm shift noted across the atlas.
Chinese epidemiology (Wang 2018 Circulation, national survey):
Prevalence 27.9% (~ 250 million patients)Awareness 51% / treatment 46% / control 16.8%"The silent killer": most patients are asymptomatic until complications appearSalt intake ~ 11 g/day (WHO recommends < 5 g) — China has one of the highest salt intakes worldwide
Why these numbers matter:
Cardiovascular deaths account for 40%+ of all-cause mortality in China (GBD 2019)The number-one modifiable risk factor for cardiovascular disease = hypertensionRaising the control rate from 17% to 50% (US / Japan level) → about 700,000-1,000,000 fewer deaths per year
Home BP monitoring:
Home measurement is preferred over office measurement (avoids "white-coat" + "masked" hypertension)Twice in the morning (1 h after waking) and twice before bed; take the averageUpper-arm electronic monitors are accurate; wrist and finger monitors are unreliableDiagnosis requires multiple measurements, not a single reading
How blood pressure rises (brief mechanism — next scene goes deeper):
1. Cardiac output ↑ (heart rate × stroke volume) — anxiety + hypervolemia + high sympathetic tone
2. Peripheral resistance ↑ — vasoconstriction + endothelial dysfunction + vascular stiffening
3. Blood volume ↑ — sodium retention + renin–angiotensin–aldosterone system: A hormone chain that controls blood pressure and fluid — when tense it narrows vessels and holds water and sodium. activation
Atlas connections: atherosclerosis (cardiovascular L4) + sleep-apnea (upper-airway collapse + HTN) + endocrine/metabolic-syndrome (second MetSyn criterion) + magnesium/relax (Mg and BP) + potassium-sodium/gradient (Na/K balance basics).
Hypertension = sustained elevation of blood pressure that, over time → damage to cardiac, cerebral, and renal vasculature → MI / stroke / heart failure / kidney failure.
Diagnostic thresholds (2017 ACC/AHA update):
Normal: < 120 / 80 mmHgElevated: 120-129 / < 80Stage 1 hypertension: 130-139 / 80-89Stage 2 hypertension: ≥ 140 / 90Hypertensive emergency: ≥ 180 / 120 + organ damage
The SPRINT trial (2015 NEJM) moved the target from < 140/90 to < 130/80 (and < 120/80 in high-risk patients) — a clinical-guideline paradigm shift noted across the atlas.
Chinese epidemiology (Wang 2018 Circulation, national survey):
Prevalence 27.9% (~ 250 million patients)Awareness 51% / treatment 46% / control 16.8%"The silent killer": most patients are asymptomatic until complications appearSalt intake ~ 11 g/day (WHO recommends < 5 g) — China has one of the highest salt intakes worldwide
Why these numbers matter:
Cardiovascular deaths account for 40%+ of all-cause mortality in China (GBD 2019)The number-one modifiable risk factor for cardiovascular disease = hypertensionRaising the control rate from 17% to 50% (US / Japan level) → about 700,000-1,000,000 fewer deaths per year
Home BP monitoring:
Home measurement is preferred over office measurement (avoids "white-coat" + "masked" hypertension)Twice in the morning (1 h after waking) and twice before bed; take the averageUpper-arm electronic monitors are accurate; wrist and finger monitors are unreliableDiagnosis requires multiple measurements, not a single reading
How blood pressure rises (brief mechanism — next scene goes deeper):
1. Cardiac output ↑ (heart rate × stroke volume) — anxiety + hypervolemia + high sympathetic tone
2. Peripheral resistance ↑ — vasoconstriction + endothelial dysfunction + vascular stiffening
3. Blood volume ↑ — sodium retention + renin–angiotensin–aldosterone system: A hormone chain that controls blood pressure and fluid — when tense it narrows vessels and holds water and sodium. activation
Atlas connections: atherosclerosis (cardiovascular L4) + sleep-apnea (upper-airway collapse + HTN) + endocrine/metabolic-syndrome (second MetSyn criterion) + magnesium/relax (Mg and BP) + potassium-sodium/gradient (Na/K balance basics).
Chapter 2
RAAS + endothelium
RAAS + endothelium
Two core axes of blood-pressure regulation:
① renin–angiotensin–aldosterone system: A hormone chain that controls blood pressure and fluid — when tense it narrows vessels and holds water and sodium. system (renin-angiotensin-aldosterone):
The liver makes angiotensinogen; renin released by the kidney cleaves it into angiotensin I; lung ACE then converts that into angiotensin II — a potent vasoconstrictor. Angiotensin II does four things at once: it constricts vessels directly (peripheral resistance ↑); it drives adrenal aldosterone, which retains sodium and excretes potassium to build blood volume; it triggers hypothalamic vasopressin to hold water; and it raises sympathetic activity.
This is why ACEi (enalapril) + ARB (losartan) are first-line HTN drugs — they block this axis at multiple points.
② Vascular endothelium + nitric oxide: A small signal molecule from the vessel lining that relaxes the vessel-wall muscle so the vessel widens. pathway:
Endothelial cells produce nitric oxide (NO) → vascular smooth muscle cGMP ↑ → vasodilationHealthy: normal NO production → compliant vesselsEndothelial dysfunction: ROS ↑ (smoking / hyperglycemia / dyslipidemia / aging) → NO oxidised → vessels fail to dilateDietary nitrate (leafy greens + beetroot) → oral bacteria → nitrite → systemic NO pool (see atlas citrulline L4)This is the mechanistic basis for DASH and beetroot lowering BP
③ Sodium-potassium balance (covered in detail in atlas potassium-sodium/gradient L4):
High sodium + low potassium = HTN driverDaily sodium < 2300 mg + potassium ≥ 3500 mg → BP -5-10 mmHg (Aburto 2013 BMJ meta-analysis)Typical Chinese intake: sodium 4500 mg+ / potassium 1500 mg — completely inverted
Secondary vs primary hypertension:
Primary (~ 90-95%): multifactorial / genetic + lifestyleSecondary (~ 5-10%):Renovascular stenosis (abnormal RAAS activation)GlomerulonephritisPheochromocytoma (catecholamine-secreting adrenal tumor)Cushing's syndrome (cortisol)Primary aldosteronism (Conn's syndrome) — unilateral adrenal adenoma, severely under-diagnosed, accounting for ~ 10-20% of resistant hypertensionObstructive sleep apnea (OSA) — covered in atlas sleep-apnea L4Oral contraceptives / steroids / chronic NSAIDs / decongestantsResistant hypertension (still > 140/90 on 3 drugs) mandates secondary work-up
Practice:
HTN + young (< 40) + severe → must screen for secondary causesHTN + hypokalemia → screen for primary aldosteronism (often missed)HTN + snoring / daytime sleepiness → screen for OSA
① renin–angiotensin–aldosterone system: A hormone chain that controls blood pressure and fluid — when tense it narrows vessels and holds water and sodium. system (renin-angiotensin-aldosterone):
The liver makes angiotensinogen; renin released by the kidney cleaves it into angiotensin I; lung ACE then converts that into angiotensin II — a potent vasoconstrictor. Angiotensin II does four things at once: it constricts vessels directly (peripheral resistance ↑); it drives adrenal aldosterone, which retains sodium and excretes potassium to build blood volume; it triggers hypothalamic vasopressin to hold water; and it raises sympathetic activity.
This is why ACEi (enalapril) + ARB (losartan) are first-line HTN drugs — they block this axis at multiple points.
② Vascular endothelium + nitric oxide: A small signal molecule from the vessel lining that relaxes the vessel-wall muscle so the vessel widens. pathway:
Endothelial cells produce nitric oxide (NO) → vascular smooth muscle cGMP ↑ → vasodilationHealthy: normal NO production → compliant vesselsEndothelial dysfunction: ROS ↑ (smoking / hyperglycemia / dyslipidemia / aging) → NO oxidised → vessels fail to dilateDietary nitrate (leafy greens + beetroot) → oral bacteria → nitrite → systemic NO pool (see atlas citrulline L4)This is the mechanistic basis for DASH and beetroot lowering BP
③ Sodium-potassium balance (covered in detail in atlas potassium-sodium/gradient L4):
High sodium + low potassium = HTN driverDaily sodium < 2300 mg + potassium ≥ 3500 mg → BP -5-10 mmHg (Aburto 2013 BMJ meta-analysis)Typical Chinese intake: sodium 4500 mg+ / potassium 1500 mg — completely inverted
Secondary vs primary hypertension:
Primary (~ 90-95%): multifactorial / genetic + lifestyleSecondary (~ 5-10%):Renovascular stenosis (abnormal RAAS activation)GlomerulonephritisPheochromocytoma (catecholamine-secreting adrenal tumor)Cushing's syndrome (cortisol)Primary aldosteronism (Conn's syndrome) — unilateral adrenal adenoma, severely under-diagnosed, accounting for ~ 10-20% of resistant hypertensionObstructive sleep apnea (OSA) — covered in atlas sleep-apnea L4Oral contraceptives / steroids / chronic NSAIDs / decongestantsResistant hypertension (still > 140/90 on 3 drugs) mandates secondary work-up
Practice:
HTN + young (< 40) + severe → must screen for secondary causesHTN + hypokalemia → screen for primary aldosteronism (often missed)HTN + snoring / daytime sleepiness → screen for OSA
Conn syndrome · the missed diagnosis
Primary aldosteronism (PA, formerly Conn's syndrome) is the most severely under-diagnosed treatable cause of hypertension.Real epidemiology:
Historical underestimate: PA was thought to account for only 1-2% of HTNModern studies (Funder 2016 Endocr Soc + Brown 2020 Ann Intern Med): 5-10% of general HTN, ≥ 20% of resistant HTN, ≥ 50% of HTN + hypokalemiaIn other words, of China's 250 million HTN patients, an estimated 10-20 million have PA, yet < 1% are diagnosed
Mechanism:
Unregulated aldosterone secretion from the adrenal zona glomerulosa (unilateral adenoma / bilateral hyperplasia / rare carcinoma)renin–angiotensin–aldosterone system: A hormone chain that controls blood pressure and fluid — when tense it narrows vessels and holds water and sodium.-independent — uncoupled from normal aldosterone regulationAldosterone ↑ → sodium retention + potassium excretion + blood volume ↑ + vascular injury (BP-independent fibrotic effect)
Clinical clues (any one warrants screening):
1. Resistant hypertension: ≥ 140/90 despite 3 drugs (one a diuretic)
2. HTN + spontaneous or drug-induced hypokalemia (K < 3.5)
3. HTN + adrenal incidentaloma
4. Early-onset HTN (< 40 y/o) or severe HTN (> 160/100)
5. HTN + first-degree relative with PA
6. HTN + OSA
7. Any HTN where low-sodium / diuretic treatment is appropriate but works poorly
Screening (first-line):
Plasma aldosterone / renin activity ratio (ARR)Threshold: ARR > 30 ng/dL ÷ ng/mL/h (lab-dependent)Prerequisite: patient off or switched antihypertensives for 4-6 weeks (ACEi/ARB/diuretics/β-blockers distort ARR); maintain on CCB / α-blockerIf unable to stop drugs: maintaining ACEi/ARB suppresses ARR → a negative result cannot be trusted; a high ARR still suggests PA
Confirmation (via endocrinology):
One of four confirmatory tests: oral salt load / fludrocortisone suppression / captopril / IV salineImaging: 4-phase contrast adrenal CTLateralisation: adrenal venous sampling (AVS) — distinguishes unilateral adenoma vs bilateral hyperplasia (entirely different treatments)
Treatment (by type):
Unilateral adenoma: laparoscopic adrenalectomy → 30-60% of patients are fully cured of HTN (no drugs needed), the rest substantially improvedBilateral hyperplasia: lifelong spironolactone / eplerenone + sodium restriction
Why this story matters:
A curable cause of hypertension — early diagnosis = substantially lower long-term cardiovascular riskA 30-year-overlooked clinical reality — Brown 2020 rang the bell again with NHANES + multi-center dataAlcohol / OSA / psychological stress are widely discussed, while PA remains "a specialist's topic" with little patient-facing education
Practice:
Any resistant HTN / HTN + hypokalemia: request an ARR5-10% of general HTN still has PA, but routine screening is not recommended (limited negative predictive value + many false positives)See endocrinology / hypertension specialist, not just a generalist
Atlas closure: endocrine/metabolic-syndrome + cardiovascular/atherosclerosis + sleep-apnea (OSA + PA comorbidity is high).
Chapter 3
DASH diet · A-tier
DASH diet · A-tier
DASH (Dietary Approaches to Stop Hypertension) is one of the most classic dietary RCTs on the atlas:
DASH RCT (Appel 1997 NEJM, NHLBI-funded):
N = 459 hypertensive + prehypertensive patients3 arms over 8 weeks:Control: typical American dietFruits-and-vegetables arm: more produceDASH arm: more fruit / vegetables / whole grains / low-fat dairy / lean meat / nuts + less processed meat / soft drinks / red meat
Results (8 weeks):
DASH arm SBP ↓ 11.4 / vitamin D-binding protein: The blood transport protein that carries vitamin D to organs. ↓ 5.5 (in hypertensive patients)Stronger than many BP monotherapiesThe produce-only arm was intermediate; the control was unchanged
DASH-Sodium follow-up (Sacks 2001 NEJM):
DASH × three sodium levels (high / medium / low)Low-sodium DASH vs high-sodium typical diet: SBP ↓ 12 mmHg
DASH composition (at 2000 kcal/day):
Vegetables 4-5 servings (1 serving = 1 cup raw / 0.5 cup cooked)Fruit 4-5 servingsWhole grains 6-8 servingsLow-fat dairy / yoghurt 2-3 servingsLean meat / fish / egg ≤ 6 servings/dayNuts / legumes / seeds 4-5 servings/weekLimit: added sugar / processed meat / soft drinks / sodium < 2300 mg
DASH vs Mediterranean:
Mediterranean emphasises olive oil + fish + red wine + whole grainsDASH emphasises low-fat dairy + K/Mg loadingSimilar BP-lowering effect, both long-term sustainableChinese implementation: "whole grains + lots of vegetables + less salt + more fish, less red meat" = culturally-adapted DASH
The truth about "less salt":
Chinese dietary sodium sources are mostly cooking salt + soy sauce + condiments (~ 70%), unlike Western diets where ~ 70% comes from packaged foodIn practice: halve soy sauce + separate dipping sauces + add salt at the end + choose sodium-free or low-sodium saltLow-sodium salt (LightSALT): NaCl + KCl mix (China Salt Substitute Trial 2021 NEJM: mortality ↓ 12% + stroke ↓ 14%) — Chinese-domestic 21K RCT with global guideline-level significance
Practical "more potassium":
Dark leafy greens / banana / avocado / sweet potato / legumes / dried fruitCaution in CKD patients — impaired potassium metabolism
Exercise:
150 min/week moderate aerobic → SBP ↓ 5-7 mmHgStrength training → synergisticHIIT may be even more effective but requires safety assessment
Quitting smoking:
Smoking → short-term SBP ↑ 5-10, long-term endothelial damageBenefit of quitting: substantially lower CV risk at 1 year, near non-smoker risk at 5 years
Moderate alcohol:
Alcohol > 20-30 g/day → SBP ↑Stopping alcohol → SBP ↓ 3-5 mmHg within weeksSee atlas alcohol-metabolism (the J-curve has been overturned)
DASH RCT (Appel 1997 NEJM, NHLBI-funded):
N = 459 hypertensive + prehypertensive patients3 arms over 8 weeks:Control: typical American dietFruits-and-vegetables arm: more produceDASH arm: more fruit / vegetables / whole grains / low-fat dairy / lean meat / nuts + less processed meat / soft drinks / red meat
Results (8 weeks):
DASH arm SBP ↓ 11.4 / vitamin D-binding protein: The blood transport protein that carries vitamin D to organs. ↓ 5.5 (in hypertensive patients)Stronger than many BP monotherapiesThe produce-only arm was intermediate; the control was unchanged
DASH-Sodium follow-up (Sacks 2001 NEJM):
DASH × three sodium levels (high / medium / low)Low-sodium DASH vs high-sodium typical diet: SBP ↓ 12 mmHg
DASH composition (at 2000 kcal/day):
Vegetables 4-5 servings (1 serving = 1 cup raw / 0.5 cup cooked)Fruit 4-5 servingsWhole grains 6-8 servingsLow-fat dairy / yoghurt 2-3 servingsLean meat / fish / egg ≤ 6 servings/dayNuts / legumes / seeds 4-5 servings/weekLimit: added sugar / processed meat / soft drinks / sodium < 2300 mg
DASH vs Mediterranean:
Mediterranean emphasises olive oil + fish + red wine + whole grainsDASH emphasises low-fat dairy + K/Mg loadingSimilar BP-lowering effect, both long-term sustainableChinese implementation: "whole grains + lots of vegetables + less salt + more fish, less red meat" = culturally-adapted DASH
The truth about "less salt":
Chinese dietary sodium sources are mostly cooking salt + soy sauce + condiments (~ 70%), unlike Western diets where ~ 70% comes from packaged foodIn practice: halve soy sauce + separate dipping sauces + add salt at the end + choose sodium-free or low-sodium saltLow-sodium salt (LightSALT): NaCl + KCl mix (China Salt Substitute Trial 2021 NEJM: mortality ↓ 12% + stroke ↓ 14%) — Chinese-domestic 21K RCT with global guideline-level significance
Practical "more potassium":
Dark leafy greens / banana / avocado / sweet potato / legumes / dried fruitCaution in CKD patients — impaired potassium metabolism
Exercise:
150 min/week moderate aerobic → SBP ↓ 5-7 mmHgStrength training → synergisticHIIT may be even more effective but requires safety assessment
Quitting smoking:
Smoking → short-term SBP ↑ 5-10, long-term endothelial damageBenefit of quitting: substantially lower CV risk at 1 year, near non-smoker risk at 5 years
Moderate alcohol:
Alcohol > 20-30 g/day → SBP ↑Stopping alcohol → SBP ↓ 3-5 mmHg within weeksSee atlas alcohol-metabolism (the J-curve has been overturned)
Salt substitute deep dive
The China Salt Substitute Study (SSaSS, Neal 2021 NEJM) is the most important domestic Chinese cardiovascular RCT on the atlas, with global guideline-level significance.Why this trial is especially important for China:
Chinese per-capita salt intake ~ 11 g/day — one of the highest worldwide (WHO recommends < 5 g)70% comes from cooking salt + soy sauce + condiments (vs ~ 70% from packaged food in the West) → intervention is possible at the individual / household levelCardiovascular deaths account for 40%+ of all-cause mortality in China; HTN is the leading modifiable risk factorOverall salt reduction is hard (taste habits) → salt substitution becomes a smart intermediate path
Trial design:
N = 20,995 (across 600 rural communities in 5 northern Chinese provinces)Eligibility: prior stroke + 60+ y/o + hypertension (88% of those enrolled had HTN)Intervention arm: low-sodium salt (LightSALT) = 75% NaCl + 25% KCl, replacing household cooking saltControl arm: regular salt (100% NaCl)Follow-up ~ 5 years
Results (primary endpoints):
Stroke ↓ 14% (HR 0.86, 95% CI 0.77-0.96, p = 0.006)MACE (MI + stroke + CV death) ↓ 13%All-cause death ↓ 12%Safety: no increase in clinically-significant hyperkalemia (the major concern was dispelled)
Why this is a "trial of the century":
N = 21,000 Chinese locals — ordinary populations, not elite hospitalsSimple intervention: change the salt, no drugs / devices requiredHuge public-health implication: scaled nationally → about 450,000 fewer cardiovascular deaths per year (Marklund 2020 modelling)Together with SPRINT (2015 NEJM intensive BP control), it is one of the two landmark trials in BP-lowering
Practice:
Where to buy "low-sodium / potassium salt": common in Chinese supermarkets, labelled "light salt" or "low-sodium salt"; major brands include Zhong Yan (China Salt)Price: slightly more than regular salt (¥3-5 per pack vs ¥2-3), but much cheaper than antihypertensive drugsSame 1 g of salt, but 25% less sodium + 25% more potassium — a bidirectional interventionUsed like regular salt, with similar taste (a slight metallic bitterness that most people don't notice)
Contraindicated populations (important):
Chronic kidney disease (CKD stage 3-5, eGFR < 30) — impaired potassium excretion, hyperkalemia riskOn ACEi / ARB / spironolactone / eplerenone without renal monitoring — hyperkalemia riskCKD + ACEi/ARB combination: strict contraindicationNormal renal function + not on K-sparing drugs: safe
Real salt reduction (the ultimate goal):
Target: WHO < 5 g/day (about one teaspoon)Practice:Halve soy sauce + try concentrated low-sodium soySeparate dipping sauces (dip before eating, do not mix in)Salt at the end of cooking + do not pre-salt meatReduce / cut pickled vegetablesRead food labels for sodium: < 1.5 g Na/100 g qualifies as low-sodiumProcess: taste buds adapt within 3-4 weeks; afterwards, regular-salt food tastes too salty
Potassium-rich foods (synergistic with substitute salt):
1 banana (~ 400 mg)1 large mango (~ 320 mg)1/2 avocado (~ 480 mg)1 medium cooked sweet potato (~ 540 mg)1 cup cooked spinach (~ 840 mg)1 cup cooked legumes (~ 700 mg)Target: 3500 mg/day (Chinese NHANES average is only 1500 mg)
Atlas position:
The China Salt Substitute Trial is China's biggest single contribution to global nutrition medicine featured on the atlasSalt substitution = the highest-ROI ¥5/month intervention for Chinese householdsIt is not "perfect" — it is a "realistic path to substantial improvement"
Chapter 4
BP meds · 5 classes
BP meds · 5 classes
5 classes of first-line antihypertensives (international consensus):
① ACEi / ARB (renin–angiotensin–aldosterone system: A hormone chain that controls blood pressure and fluid — when tense it narrows vessels and holds water and sodium. inhibition):
ACEi: captopril / enalapril / perindopril / ramiprilARB: valsartan / irbesartan / losartan / telmisartanMechanism: blocks angiotensin II formation (ACEi) or receptor (ARB)Indications: HTN + HF + CKD + diabetic nephropathy protectionSide effects: ACEi → dry cough (10-20%) (bradykinin accumulation) — switch to ARB; hyperkalemia + acute kidney injury (contraindicated in bilateral renal-artery stenosis)Pregnancy contraindicated (teratogenic)
② Calcium channel blockers (CCB):
Dihydropyridines: amlodipine / nifedipine / lacidipine — primarily vasodilatorsNon-dihydropyridines: verapamil / diltiazem — also reduce heart rateIndications: HTN + the elderly + anginaSide effects: ankle edema (amlodipine 5-15%) + tachycardia + gingival hyperplasiaStrengths: especially effective in older patients + Black populations (relatively weak RAAS suppression in these groups)
③ Diuretics:
Thiazides: hydrochlorothiazide / indapamide — reduce blood volume + moderate BP-loweringLoop diuretics: furosemide — HF / emergencyK-sparing diuretics: spironolactone / eplerenone — aldosterone antagonists (resistant HTN + HF)Side effects: hypokalemia + hyponatremia + gout (thiazides) + hyperglycemiaStrengths: cheap + long safety record + synergistic when combined
④ β-blockers:
Bisoprolol / metoprolol / atenololMechanism: ↓ heart rate + ↓ cardiac output + ↓ reninIndications: HTN + angina + arrhythmia + post-MISide effects: fatigue + cold extremities + asthma worsening + sexual dysfunctionNo longer first choice for uncomplicated HTN (unless a comorbid indication exists)
⑤ Others:
α-blockers (prazosin) — dual indication for BPH + HTNDirect vasodilators (minoxidil, many side effects — not first-line)Central agents (clonidine, Parkinsonian side effects — not first-line)
Combination strategy (2018 ESC/ESH):
Most patients start with two-drug combinations (single-pill combinations improve adherence)Classic combinations: ACEi/ARB + CCB / diuretic (synergy + complementary side-effect profile)"ABCD" initiation: A (ACEi/ARB) + B (β-blocker, selective) + C (CCB) + D (diuretic)
New drugs (2024-2025):
Zilebesiran: liver-targeted RNAi silencing angiotensinogen → one injection lowers BP for months (positive Phase II, awaiting Phase III)Aprocitentan: dual endothelin antagonist — resistant HTN, FDA-approved 2023glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar. (semaglutide): lowers BP partly indirectly via weight loss
Adherence is the biggest clinical challenge:
50% of patients stop or skip doses within 1 yearSingle-pill combinations + long-acting + morning dosing + app reminders → ↑ adherence"Drugs for life" is not absolute — some early-stage + large-weight-loss + smoking-cessation + alcohol-limiting patients can taper
① ACEi / ARB (renin–angiotensin–aldosterone system: A hormone chain that controls blood pressure and fluid — when tense it narrows vessels and holds water and sodium. inhibition):
ACEi: captopril / enalapril / perindopril / ramiprilARB: valsartan / irbesartan / losartan / telmisartanMechanism: blocks angiotensin II formation (ACEi) or receptor (ARB)Indications: HTN + HF + CKD + diabetic nephropathy protectionSide effects: ACEi → dry cough (10-20%) (bradykinin accumulation) — switch to ARB; hyperkalemia + acute kidney injury (contraindicated in bilateral renal-artery stenosis)Pregnancy contraindicated (teratogenic)
② Calcium channel blockers (CCB):
Dihydropyridines: amlodipine / nifedipine / lacidipine — primarily vasodilatorsNon-dihydropyridines: verapamil / diltiazem — also reduce heart rateIndications: HTN + the elderly + anginaSide effects: ankle edema (amlodipine 5-15%) + tachycardia + gingival hyperplasiaStrengths: especially effective in older patients + Black populations (relatively weak RAAS suppression in these groups)
③ Diuretics:
Thiazides: hydrochlorothiazide / indapamide — reduce blood volume + moderate BP-loweringLoop diuretics: furosemide — HF / emergencyK-sparing diuretics: spironolactone / eplerenone — aldosterone antagonists (resistant HTN + HF)Side effects: hypokalemia + hyponatremia + gout (thiazides) + hyperglycemiaStrengths: cheap + long safety record + synergistic when combined
④ β-blockers:
Bisoprolol / metoprolol / atenololMechanism: ↓ heart rate + ↓ cardiac output + ↓ reninIndications: HTN + angina + arrhythmia + post-MISide effects: fatigue + cold extremities + asthma worsening + sexual dysfunctionNo longer first choice for uncomplicated HTN (unless a comorbid indication exists)
⑤ Others:
α-blockers (prazosin) — dual indication for BPH + HTNDirect vasodilators (minoxidil, many side effects — not first-line)Central agents (clonidine, Parkinsonian side effects — not first-line)
Combination strategy (2018 ESC/ESH):
Most patients start with two-drug combinations (single-pill combinations improve adherence)Classic combinations: ACEi/ARB + CCB / diuretic (synergy + complementary side-effect profile)"ABCD" initiation: A (ACEi/ARB) + B (β-blocker, selective) + C (CCB) + D (diuretic)
New drugs (2024-2025):
Zilebesiran: liver-targeted RNAi silencing angiotensinogen → one injection lowers BP for months (positive Phase II, awaiting Phase III)Aprocitentan: dual endothelin antagonist — resistant HTN, FDA-approved 2023glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar. (semaglutide): lowers BP partly indirectly via weight loss
Adherence is the biggest clinical challenge:
50% of patients stop or skip doses within 1 yearSingle-pill combinations + long-acting + morning dosing + app reminders → ↑ adherence"Drugs for life" is not absolute — some early-stage + large-weight-loss + smoking-cessation + alcohol-limiting patients can taper
Chapter 5
Decision tree
Decision tree
"My BP is 130-140 / 150 — what do I do?":
Q1: What is your BP range?
120-129 / < 80 (elevated): lifestyle is sufficient130-139 / 80-89 (Stage 1 HTN): 3-6 months of lifestyle; if not at goal, add medication140-159 / 90-99 (Stage 2 HTN): start lifestyle and medication together≥ 160 / 100: immediate medication + lifestyle≥ 180 / 120: emergency, seek care
Q2: What additional risks do you have?
CVD history / diabetes / CKD / ≥ 65 y/o: tighter target (< 130/80)Smoking / high LDL / high BMI / family history: weighted aggressivenessPregnancy: managed separately (preeclampsia risk, ACEi/ARB contraindicated)
Q3: 5 lifestyle levers (ordered by ROI):
① Weight loss (BMI > 25): every 1 kg loss → SBP ↓ 1 mmHg
② Salt reduction (China: mainly cooking salt): 6 g → 3 g → SBP ↓ 5-8 mmHg
③ More potassium (greens + banana + sweet potato + legumes): SBP ↓ 4-5 mmHg
④ Exercise (150 min/week moderate aerobic): SBP ↓ 5-7 mmHg
⑤ Alcohol limitation (< 1 drink/day): SBP ↓ 3-5 mmHg
Q1: What is your BP range?
120-129 / < 80 (elevated): lifestyle is sufficient130-139 / 80-89 (Stage 1 HTN): 3-6 months of lifestyle; if not at goal, add medication140-159 / 90-99 (Stage 2 HTN): start lifestyle and medication together≥ 160 / 100: immediate medication + lifestyle≥ 180 / 120: emergency, seek care
Q2: What additional risks do you have?
CVD history / diabetes / CKD / ≥ 65 y/o: tighter target (< 130/80)Smoking / high LDL / high BMI / family history: weighted aggressivenessPregnancy: managed separately (preeclampsia risk, ACEi/ARB contraindicated)
Q3: 5 lifestyle levers (ordered by ROI):
① Weight loss (BMI > 25): every 1 kg loss → SBP ↓ 1 mmHg
② Salt reduction (China: mainly cooking salt): 6 g → 3 g → SBP ↓ 5-8 mmHg
③ More potassium (greens + banana + sweet potato + legumes): SBP ↓ 4-5 mmHg
④ Exercise (150 min/week moderate aerobic): SBP ↓ 5-7 mmHg
⑤ Alcohol limitation (< 1 drink/day): SBP ↓ 3-5 mmHg
Monitoring + complications + warnings + atlas
Q4: Monitoring:Home BP monitor (upper-arm, calibrated yearly)Two readings in the morning and two before bed, take the averageNot at goal = 3-month average still ≥ 130/80 (not a single reading)"White-coat HTN": high in office + normal at home — no drugs needed"Masked HTN": normal in office + high at home — must be treated (high-risk phenotype, CV events similar to sustained HTN)
Q5: Monitoring for complications:
Heart: ECG + echocardiogram (LVH)Kidney: urine albumin / creatinine + eGFREye: fundoscopy (hypertensive retinopathy)Brain: only if symptomatic
Q6: Commonly overlooked:
Obstructive sleep apnea (OSA) (atlas sleep-apnea L4): snoring + daytime sleepiness + HTN → polysomnographyPrimary aldosteronism (Conn's): resistant HTN + hypokalemia + unilateral adrenal adenoma — check renin / aldosteroneHyperthyroidism / hypothyroidism / Hashimoto's (atlas hashimoto L4)Depression / anxiety + chronic stress: hypothalamic–pituitary–adrenal axis: The body's stress-response chain (hypothalamus → pituitary → adrenal) that releases cortisol. + sympathetic activation → HTN
Important warnings:
"BP drugs are for life" is not absolute — some early-stage + weight-loss + smoking-cessation patients can taper (with physician supervision, do not stop on your own)Self-discontinuation = acute rebound + cardiovascular events — forbiddenChronic NSAIDs / decongestants / some TCM (liquorice) / certain supplements can raise BP — take note
Self-check checklist:
Annually: home BP self-measurement + physical examPriority 35+ y/oAny "elevated" or Stage 1 → 6 months of lifestyle intervention + re-measurementNot at goal → internal-medicine consultation
Atlas connections:
alcohol-metabolism + UPF + fructose-metabolism (dietary drivers)sleep-apnea + shift-work + insomnia (sleep drivers)endocrine/metabolic-syndrome (MetSyn)cardiovascular/atherosclerosis L4 (complication mechanisms)citrulline + magnesium + K-Na (nutritional tools)
Atlas position: hypertension is China's leading modifiable cardiovascular risk — early detection + early intervention + long-term management is one of the highest-ROI interventions for both the healthcare system and the individual. It is not a "disease of the elderly"; it is a metabolic-vascular state that begins at 35.